Fluoride: The Ultimate Cluster Flux Folder 2A

Fluoride: The Ultimate Cluster-Flux

And the Players Involved

A Compilation of Documents and Articles

Relating to Fluoride

This collection is dedicated to those who wrote the original works and

made them available on the internet. I have spent countless hours

searching for information on fluoride and it is my wish, by assembling

these works, to enable others to save time looking and make available

more time for them to ‘do’.

If you are sickened and appalled by the approved use of fluoride in

food, beverage and other consumer products then I ask that you spread

this knowledge on to others and contact your local representatives in the

hopes that one day fluoride will be more strictly regulated or, banned

altogether.

These documents are listed in roughly the order I found them. It would

be nearly impossible to group them in some kind of order since they are

all linked together – a cluster-flux of monumental proportions.

I would like to thank (or curse) Christopher Bryson whose excellent

book, The Fluoride Deception, opened my eyes to fluoride and started

me on this journey of uncovering the truth.

For more information on fluoride, I would recommend the Fluoride Action

Network (FAN) http://www.fluoridealert.org/ as a good place to start.

NOTICE

In accordance with Title 17 U.S.C., section 107, some material on this web site is provided without permission from the copyright owner, only for purposes of criticism, comment, news reporting,

teaching, scholarship and research under the "fair use" provisions of federal copyright laws. These materials may not be distributed further, except for "fair use" non-profit educational purposes,

without permission of the copyright owner.

About Heinz College http://www.heinz.cmu.edu/about-heinz/index.aspx

The Heinz College was founded as the School of Urban and Public Affairs in 1968. The animating vision that lead to the founding of the school was to bring a systems analytic approach (inspired by engineering and the mathematical social sciences) to the study of important questions of public interest – at that time particularly questions related to U.S. urban environments. At the time, no similar academic institution even contemplated the possibility that engineering, operations research, or computing systems had even the remotest relation to the conduct of policy and public management. Indeed, even more traditional mathematically-based social science disciplines brought into the School at that time - economics and statistics, in particular – were quite unusual in the environment of schools of “public affairs”.

Despite the significant changes in the world since 1968, our basic approach to solving real problems has remained incredibly durable and is the soul of who we are today. But the contexts in which we have chosen to apply that approach have expanded remarkably. They include the expansion of public interest domains beyond urban development and poverty to areas like health, globalization and social innovation. We have also gone beyond the traditional boundaries of the domain of the public interest to explore deeply the impact of information technology on organizations, markets and societies. Finally, we have persistently explored the ways in which we could make our educational programs more relevant and effective in their curriculum, in their delivery models, and in their degree of connection to external partners.

Unlike many graduate schools, we are not organized along academic departments. Faculty collaborate in instruction and research, an operating model we believe leads to innovation in research and a superior educational experience. Our strengths span the applied disciplines of empirical methods and statistics, economics, information systems and technology, operations research and organizational behavior.

Our faculty focus their research efforts on a vast array of issues. They have established worldwide reputations for excellence in areas such as the study of crime and criminal justice, urban policy, health care policy and management, arts management, information security policy, and information systems management.

In addition to full-time, on-campus programs in Pittsburgh and Adelaide, Heinz College offers graduate-level programs to nontraditional students through part-time on-campus and distance programs, customized programs delivered virtually anywhere in the world, and executive education programs for senior managers.

Heinz College exists to improve the ability of public, not-for-profit and private organizations to address the most difficult challenges facing society, as well as to strengthen and exploit our cultural resources through skilled leadership and management.

Our success is reflected in the contributions our more than 5,000 graduates have made to society, through their work in international, national, state and local public agencies, not-for-profit organizations, and private corporations.

Oct., 1952

American Journal of Public Healthand THE NATION'S HEALTH

Official Monthly Publication of the American Public Health Association, Inc.

Volume 42 October, 1952 Number 10

C.-E. A. WINSLOW, DR.P.H., EditorREGINALD M. ATWATER, M.D., Managing Editor

Editorial BoardMARK D. HOLLIS, C.E. JOHN D. PORTERFIELD, M.D.RUTH W. HUBBARD, R.N. GEORGE ROSEN, M.D.RAYMOND S. PATTERSON, PH.D. HOWARD J. SHAUGHNESSY, PH.D.

C.-E. A. WINSLOW, DR.P.H.REGINALD M. ATWATER, M.D.. Ckairman

StaffWrLLIMINA RAYNE WALSH FRANCES TOOROCK LYDIA GARi

THE BATTLE FOR SOUND TEETHTHE effects of adding fluorine to community water supplies-on the dental status

of. the population have been the subject of study for some time. It has beendetermined that too high a concentration of fluorine produces mottling of theenamel; and that a complete lack is conducive to excessive caries formation. Ithas been conclusively demonstrated that an optimum fluoride content, of the orderof one part per million, will reduce caries in children to about one-half its normalincidence, while failing to produce mottling. The optimum amount is as effectivewhether water supplies have been blended to reduce the natural fluoride content tothe desired level or fluorides have been artificially added to bring the content upto the established concentration. No harmful effects whatever have been observedfrom drinking waters containing the recommended amount of fluoride, either inthose who have been exposed to it naturally for as long as 80 years, or in those whohave received it on a planned basis for over 5 years.

An impressive number of professional health organizations have reviewed theliterature-independently, it must be added-and have concluded that artificialfluoridation of public water supplies in controlled amounts is desirable as oneeffective means for the partial control of dental caries in the young. In view ofits far-reaching effect on a staggeringly massive problem, and in the absence ofdemonstrable ill-effects, fluoridation of water supplies must be reckoned with asone of the most significant tools of preventive medicine which has been devised inrecent years.

Debate between the conservative and the progressive elements is traditional inour society and is desirable to maintain good balance; but the instinctive tendencyof certain minds to fear any departure from the supposedly beneficent processes

[13041

EDITORIALS

of nature cannot be indefinitely condoned, in the face of accumulating mountainsof evidence. Furthermore, it is uinfortunate that the case of the conservative shouldbe intensified-as in this instance-by the support of vested interests and of fanaticsand members of the lunatic fringe who appear to consider dental caries as an essen-tial part of the "American Way of Life" and any attempt to alter its incidence as

Communist-inspired mass-poisoning.A particularly striking example of the unfortunate effects of such opposition was

described at the Denver meeting of the Western Branch of the APHA last June.'The movement for fluoridation in Seattle, Wash., began with a revealing study

by the PTA in 1950 which disclosed that the average child in the eleventh andtwelfth grades had nearly 15 decayed, missing, or filled teeth. The director of theSeattle-King County Department of Public Health, after thorough consideration ofthe evidence, and with the approval of the local medical and dental societies,recommended to the City Council in February, 1951, the introduction of fluorida-tion. At first there was no opposition except from some representatives of the WaterDepartment. The Water Department produced a fantastically high estimate ofcost ($1.20 per year for each of the premises served); and, a local election being insight, the City Council dodged its responsibilities by submitting the desirabilityof fluoridation (at this assumed cost) to the people in a referendum in March.

The Department of Public Health, with the approval of the medical and dentalsocieties, secured the appointment of a highly representative Committee forFluoridation with a Speaker's Bureau (on which 37 dentists served). At thebeginning of the campaign, however, persons vocal in opposing fluoridation formedthe Washington State Council Against Fluoridation which was backed by theNational Nutrition League, Inc. Most of these were owners, operators, andpatrons of so-called "health food" stores. Later, about the first of Februarv,Christian Scientists, deploring "'compulsory medication," took the lead in formingthe Anti-Fluoridation Committee. An attorney served as chairman, a trainedpublicity man worked with him, and a Speaker's Bureau was formed. Billboardsopposing fluoridation appeared during the last week or so of the campaign.

Following the formation of the Anti-Fluoridation Committee in February,opposition speakers appeared on a wide variety of programs. Added to the ranksof the opposition were three physicians from the Medical Society, and severalwell known attorneys who appeared at meetings, on the radio, and on televisionto debate the issue on the basis of invasion of individual rights, and alleged pressurefor the program from Oscar Ewing and the U. S. Public Health Service. Theirsuggested alternative was to add fluorides to salt.

Although a great deal of nonsense has been talked about the subject, perhapsthe climax of absurdity was reached in this debate by the claim that the addition offluoride was "Socialized Medicine."

Radio and television stations became active instruments for local propaganda.The Committee for Fluoridation issued 10,000 copies of a pamphlet and theopposition distributed great quantities of literature. The first of these pamphletscarried a skull and crossbones on the front. Reprints were distributed includingaccusations of "Socialized Medicine" and recommendations for a "campaign forbetter systemic health through natural nutritious foods." Fluorine was describedas 'rat poison" which would cause hardening of the arteries, would interfere withkidney excretion, cause bones to become brittle, and might cause cancer. It wasalleged that fluorine was used in Germany after World War I to "weaken the willsof the people."

Vol. 42 1305

AMERICAN JOURNAL OF PUBLIC HEALTH

The battle continued for nine weeks; and on March 11 the fluoridation proposalwas defeated by a vote of two to one.

The reader will be inclined to say that such a campaign could not take place-and certainly could not succeed-in an educated American community. But it didand the teeth of Seattle children must continue to ache.

In reading about this case, one is forcibly reminded of the outcry whichoccurred in Boston in 1721 against smallpox inoculation. Cotton Mather, thelearned divine who played a courageous part in defending the practice, says he"never saw the Devil so let loose.... A lying spirit was gone forth at such a ratethat there was no believing anything one heard. . . . The people who made theloudest cry . . . had a very Satanic Fury activating them. They were, like thepossessed people in the Gospel, exceeding fierce."

Perhaps even more menacing, in view of its national import, is the recent displayof the same prejudiced thinking in the setting of that recurrent phenomenon, aCongressional investigating committee. The House Select Committee To Investi-gate the Use of Chemicals in Foods and Cosmetics, more easily known as theDelaney Committee, has just published over 600 pages of its hearings on fluorida-tion of water supplies. The saddest part of the hearings reports the mentalgymnastics of a physician member of the Committee, formerly a public healthofficial, who proclaimed for the record that public health officials force state healthofficials to carry out programs presumably against their will by means of bribery;and, finally, that "you can prove most anything you want to by the statisticalfigures on morbidity and mortality." This gentleman may-or may not-haverevealed his own personal motivations in these statements. He certainly did notrepresent the public health profession, with which he was for a short time allied.

The opposition to fluoridation is not easy to understand. Perhaps only thepsychiatrist can find an adequate explanation for the phenomenon, since an exag-gerated fear of change is a common symptom of insecurity. The primary interestsinvolved are those of the dentist; and with a vision and a public spirit worthy ofthe highest praise, they are precisely the people who have led in this campaign. Allhonor to them!

The Friends of Dental Caries won in Seattle and showed strength in the HouseCommittee to which we have referred. They won the battle of Seattle; but theycannot win the war. "Truth is Mighty" and, in the long run, it will prevail.

1. Lehman, S. P., and Kahn, B. L. Seattle Votes on Fluoridation. Seattle, Wash.: Seattle-King County Depart-ment of Public Health, 1500 Public Safety Building.

OPERATIONS RESEARCH AND PUBLIC HEALTH

THE problem of translating theory into practice is usually beset with difficulty,even in the more exact natural sciences. In the past, this problem has suffered

from neglect, perhaps because it was assumed that practical men could apply inpractice any clearly stated theory, and needed no special agency to facilitate andaccelerate this process. During World War II, however, a rapid reciprocal adjust-ment between theory and practice became necessary in the conduct of certain

Oct., 19521306

TOXICOLOGICAL PROFILE FOR

FLUORIDES, HYDROGEN FLUORIDE, AND FLUORINE

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service

Agency for Toxic Substances and Disease Registry

September 2003

FLUORIDES, HYDROGEN FLUORIDE, AND FLUORINE ii

DISCLAIMER The use of company or product name(s) is for identification only and does not imply endorsement by the Agency for Toxic Substances and Disease Registry.

FLUORIDES, HYDROGEN FLUORIDE, AND FLUORINE iii

UPDATE STATEMENT A Toxicological Profile for Hydrogen Fluoride, and Fluorine, Draft for Public Comment was released in September 2001. This edition supersedes any previously released draft or final profile. Toxicological profiles are revised and republished as necessary. For information regarding the update status of previously released profiles, contact ATSDR at:

Agency for Toxic Substances and Disease Registry Division of Toxicology/Toxicology Information Branch

1600 Clifton Road NE, Mailstop E-29

Atlanta, Georgia 30333

FLUORIDES, HYDROGEN FLUORIDE, AND FLUORINE vii

QUICK REFERENCE FOR HEALTH CARE PROVIDERS Toxicological Profiles are a unique compilation of toxicological information on a given hazardous substance. Each profile reflects a comprehensive and extensive evaluation, summary, and interpretation of available toxicologic and epidemiologic information on a substance. Health care providers treating patients potentially exposed to hazardous substances will find the following information helpful for fast answers to often-asked questions. Primary Chapters/Sections of Interest Chapter 1: Public Health Statement: The Public Health Statement can be a useful tool for educating

patients about possible exposure to a hazardous substance. It explains a substance’s relevant toxicologic properties in a nontechnical, question-and-answer format, and it includes a review of the general health effects observed following exposure.

Chapter 2: Relevance to Public Health: The Relevance to Public Health Section evaluates, interprets,

and assesses the significance of toxicity data to human health. Chapter 3: Health Effects: Specific health effects of a given hazardous compound are reported by type

of health effect (death, systemic, immunologic, reproductive), by route of exposure, and by length of exposure (acute, intermediate, and chronic). In addition, both human and animal studies are reported in this section.

NOTE: Not all health effects reported in this section are necessarily observed in the clinical setting. Please refer to the Public Health Statement to identify general health effects observed following exposure.

Pediatrics: Four new sections have been added to each Toxicological Profile to address child health

issues: Section 1.6 How Can (Chemical X) Affect Children? Section 1.7 How Can Families Reduce the Risk of Exposure to (Chemical X)? Section 3.7 Children’s Susceptibility Section 6.6 Exposures of Children Other Sections of Interest: Section 3.8 Biomarkers of Exposure and Effect Section 3.11 Methods for Reducing Toxic Effects ATSDR Information Center Phone: 1-888-42-ATSDR or (404) 498-0110 Fax: (404) 498-0093 E-mail: [email protected] Internet: http://www.atsdr.cdc.gov The following additional material can be ordered through the ATSDR Information Center: Case Studies in Environmental Medicine: Taking an Exposure History—The importance of taking an

exposure history and how to conduct one are described, and an example of a thorough exposure history is provided. Other case studies of interest include Reproductive and Developmental Hazards; Skin Lesions and Environmental Exposures; Cholinesterase-Inhibiting Pesticide Toxicity; and numerous chemical-specific case studies.

FLUORIDES, HYDROGEN FLUORIDE, AND FLUORINE viii

Managing Hazardous Materials Incidents is a three-volume set of recommendations for on-scene (prehospital) and hospital medical management of patients exposed during a hazardous materials incident. Volumes I and II are planning guides to assist first responders and hospital emergency department personnel in planning for incidents that involve hazardous materials. Volume III—Medical Management Guidelines for Acute Chemical Exposures—is a guide for health care professionals treating patients exposed to hazardous materials.

Fact Sheets (ToxFAQs) provide answers to frequently asked questions about toxic substances. Other Agencies and Organizations The National Center for Environmental Health (NCEH) focuses on preventing or controlling disease,

injury, and disability related to the interactions between people and their environment outside the workplace. Contact: NCEH, Mailstop F-29, 4770 Buford Highway, NE, Atlanta, GA 30341-3724 • Phone: 770-488-7000 • FAX: 770-488-7015.

The National Institute for Occupational Safety and Health (NIOSH) conducts research on occupational

diseases and injuries, responds to requests for assistance by investigating problems of health and safety in the workplace, recommends standards to the Occupational Safety and Health Administration (OSHA) and the Mine Safety and Health Administration (MSHA), and trains professionals in occupational safety and health. Contact: NIOSH, 200 Independence Avenue, SW, Washington, DC 20201 • Phone: 800-356-4674 or NIOSH Technical Information Branch, Robert A. Taft Laboratory, Mailstop C-19, 4676 Columbia Parkway, Cincinnati, OH 45226-1998 • Phone: 800-35-NIOSH.

The National Institute of Environmental Health Sciences (NIEHS) is the principal federal agency for

biomedical research on the effects of chemical, physical, and biologic environmental agents on human health and well-being. Contact: NIEHS, PO Box 12233, 104 T.W. Alexander Drive, Research Triangle Park, NC 27709 • Phone: 919-541-3212.

Referrals The Association of Occupational and Environmental Clinics (AOEC) has developed a network of clinics

in the United States to provide expertise in occupational and environmental issues. Contact: AOEC, 1010 Vermont Avenue, NW, #513, Washington, DC 20005 • Phone: 202-347-4976 • FAX: 202-347-4950 • e-mail: [email protected] • Web Page: http://www.aoec.org/.

The American College of Occupational and Environmental Medicine (ACOEM) is an association of

physicians and other health care providers specializing in the field of occupational and environmental medicine. Contact: ACOEM, 55 West Seegers Road, Arlington Heights, IL 60005 • Phone: 847-818-1800 • FAX: 847-818-9266.

FLUORIDES, HYDROGEN FLUORIDE, AND FLUORINE ix

CONTRIBUTORS CHEMICAL MANAGER(S)/AUTHOR(S): Carolyn A. Tylenda, D.M.D., Ph.D. ATSDR, Division of Toxicology, Atlanta, GA Dennis Jones, D.V.M. ATSDR, Division of Toxicology, Atlanta, GA Lisa Ingerman, Ph.D. Gloria Sage, Ph.D. Lara Chappell, Ph.D. Syracuse Research Corporation, North Syracuse, NY THE PROFILE HAS UNDERGONE THE FOLLOWING ATSDR INTERNAL REVIEWS: 1. Health Effects Review. The Health Effects Review Committee examines the health effects

chapter of each profile for consistency and accuracy in interpreting health effects and classifying end points.

2. Minimal Risk Level Review. The Minimal Risk Level Workgroup considers issues relevant to

substance-specific Minimal Risk Levels (MRLs), reviews the health effects database of each profile, and makes recommendations for derivation of MRLs.

3. Data Needs Review. The Research Implementation Branch reviews data needs sections to assure

consistency across profiles and adherence to instructions in the Guidance.

FLUORIDES, HYDROGEN FLUORIDE, AND FLUORINE xi

PEER REVIEW A peer review panel was assembled for fluorides, hydrogen fluoride, and fluorine. The panel consisted of the following members: 1. Jan Ekstrand, Professor & Vice Dean, Board of Research and Postgraduate Education, Nobels

väg 5, Karolinska Institutet, Stockholm, Sweden; 2. Julie Glowacki, Ph.D., Department of Orthopedic Surgery, Brigham and Women's Hospital,

Harvard Medical School, Boston, MA; 3. Michael Kleerekoper, M.B., B.S., F.A.C.P., F.A.C.E., Departments of Internal Medicine,

Obstetrics & Gynecology, and Pathology Wayne State University School of Medicine, Detroit, MI;

4. Gary Whitford, Ph.D., D.M.D., School of Dentistry, Medical College of Georgia, Augusta, GA. These experts collectively have knowledge of fluorides, hydrogen fluoride, and fluorine's physical and chemical properties, toxicokinetics, key health end points, mechanisms of action, human and animal exposure, and quantification of risk to humans. All reviewers were selected in conformity with the conditions for peer review specified in Section 104(I)(13) of the Comprehensive Environmental Response, Compensation, and Liability Act, as amended. Scientists from the Agency for Toxic Substances and Disease Registry (ATSDR) have reviewed the peer reviewers' comments and determined which comments will be included in the profile. A listing of the peer reviewers' comments not incorporated in the profile, with a brief explanation of the rationale for their exclusion, exists as part of the administrative record for this compound. A list of databases reviewed and a list of unpublished documents cited are also included in the administrative record. The citation of the peer review panel should not be understood to imply its approval of the profile's final content. The responsibility for the content of this profile lies with the ATSDR.

FLUORIDES, HYDROGEN FLUORIDE, AND FLUORINE xiii

CONTENTS DISCLAIMER ..............................................................................................................................................ii UPDATE STATEMENT .............................................................................................................................iii FOREWORD ................................................................................................................................................ v QUICK REFERENCE FOR HEALTH CARE PROVIDERS....................................................................vii CONTRIBUTORS....................................................................................................................................... ix PEER REVIEW ...........................................................................................................................................xi CONTENTS...............................................................................................................................................xiii LIST OF FIGURES ..................................................................................................................................xvii LIST OF TABLES.....................................................................................................................................xix 1. PUBLIC HEALTH STATEMENT.......................................................................................................... 1

1.1 WHAT ARE FLUORIDES, HYDROGEN FLUORIDE, AND FLUORINE? ........................... 1 1.2 WHAT HAPPENS TO FLUORIDES, HYDROGEN FLUORIDE, AND FLUORINE WHEN THEY ENTER THE ENVIRONMENT?....................................................................... 3 1.3 HOW MIGHT I BE EXPOSED TO FLUORIDES, HYDROGEN FLUORIDE, AND FLUORINE?................................................................................................................................ 4 1.4 HOW CAN FLUORIDES, HYDROGEN FLUORIDE, AND FLUORINE ENTER AND LEAVE MY BODY? .................................................................................................................. 6 1.5 HOW CAN FLUORIDES, HYDROGEN FLUORIDE, AND FLUORINE AFFECT MY HEALTH? ................................................................................................................................... 7 1.6 HOW CAN FLUORIDES, HYDROGEN FLUORIDE, AND FLUORINE AFFECT CHILDREN? ............................................................................................................................... 9 1.7 HOW CAN FAMILIES REDUCE THE RISK OF EXPOSURE TO FLUORIDES, HYDROGEN FLUORIDE, AND FLUORINE?....................................................................... 10 1.8 IS THERE A MEDICAL TEST TO DETERMINE WHETHER I HAVE BEEN EXPOSED TO FLUORIDES, HYDROGEN FLUORIDE, AND FLUORINE?...................... 11 1.9 WHAT RECOMMENDATIONS HAS THE FEDERAL GOVERNMENT MADE TO PROTECT HUMAN HEALTH?............................................................................................... 12 1.10 WHERE CAN I GET MORE INFORMATION? ..................................................................... 13

2. RELEVANCE TO PUBLIC HEALTH ................................................................................................. 15

2.1 BACKGROUND AND ENVIRONMENTAL EXPOSURES TO FLUORIDES, HYDROGEN FLUORIDE, AND FLUORINE IN THE UNITED STATES ........................... 15 2.2 SUMMARY OF HEALTH EFFECTS...................................................................................... 17 2.3 MINIMAL RISK LEVELS ....................................................................................................... 22

3. HEALTH EFFECTS.............................................................................................................................. 29

3.1 INTRODUCTION..................................................................................................................... 29 3.2 DISCUSSION OF HEALTH EFFECTS BY ROUTE OF EXPOSURE .................................. 31

3.2.1 Inhalation Exposure .............................................................................................................. 32 3.2.1.1 Death................................................................................................................................. 33 3.2.1.2 Systemic Effects ............................................................................................................... 36 3.2.1.3 Immunological and Lymphoreticular Effects ................................................................... 69 3.2.1.4 Neurological Effects ......................................................................................................... 70 3.2.1.5 Reproductive Effects......................................................................................................... 70 3.2.1.6 Developmental Effects...................................................................................................... 71 3.2.1.7 Cancer ............................................................................................................................... 71

FLUORIDES, HYDROGEN FLUORIDE, AND FLUORINE xiv

3.2.2 Oral Exposure........................................................................................................................ 72 3.2.2.1 Death................................................................................................................................. 74 3.2.2.2 Systemic Effects ............................................................................................................... 75 3.2.2.3 Immunological and Lymphoreticular Effects ................................................................. 110 3.2.2.4 Neurological Effects ....................................................................................................... 110 3.2.2.5 Reproductive Effects....................................................................................................... 111 3.2.2.6 Developmental Effects.................................................................................................... 114 3.2.2.7 Cancer ............................................................................................................................. 117

3.2.3 Dermal Exposure................................................................................................................. 125 3.2.3.1 Death............................................................................................................................... 126 3.2.3.2 Systemic Effects ............................................................................................................. 127 3.2.3.3 Immunological and Lymphoreticular Effects ................................................................. 132 3.2.3.4 Neurological Effects ....................................................................................................... 132 3.2.3.5 Reproductive Effects....................................................................................................... 132 3.2.3.6 Developmental Effects.................................................................................................... 132 3.2.3.7 Cancer ............................................................................................................................. 132

3.3 GENOTOXICITY ................................................................................................................... 132 3.4 TOXICOKINETICS................................................................................................................ 136

3.4.1 Absorption........................................................................................................................... 136 3.4.1.1 Inhalation Exposure ........................................................................................................ 136 3.4.1.2 Oral Exposure ................................................................................................................. 138 3.4.1.3 Dermal Exposure ............................................................................................................ 139

3.4.2 Distribution ......................................................................................................................... 140 3.4.2.1 Inhalation Exposure ........................................................................................................ 140 3.4.2.2 Oral Exposure ................................................................................................................. 141 3.4.2.3 Dermal Exposure ............................................................................................................ 144 3.4.2.4 Other Routes of Exposure............................................................................................... 144

3.4.3 Metabolism.......................................................................................................................... 145 3.4.4 Elimination and Excretion................................................................................................... 145

3.4.4.1 Inhalation Exposure ........................................................................................................ 145 3.4.4.2 Oral Exposure ................................................................................................................. 146 3.4.4.3 Dermal Exposure ............................................................................................................ 147

3.4.5 Physiologically Based Pharmacokinetic (PBPK)/Pharmacodynamic (PD) Models ........... 147 3.5 MECHANISMS OF ACTION ................................................................................................ 151 3.6 TOXICITIES MEDIATED THROUGH THE NEUROENDOCRINE AXIS ........................ 153 3.7 CHILDREN’S SUSCEPTIBILITY......................................................................................... 154 3.8 BIOMARKERS OF EXPOSURE AND EFFECT .................................................................. 157

3.8.1 Biomarkers Used to Identify or Quantify Exposure to Fluorides, Hydrogen Fluoride, and Fluorine ........................................................................................................................ 158 3.8.2 Biomarkers Used to Characterize Effects Caused by Fluorides, Hydrogen Fluoride, and Fluorine ........................................................................................................................ 160

3.9 INTERACTIONS WITH OTHER CHEMICALS .................................................................. 162 3.10 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE............................................ 162 3.11 METHODS FOR REDUCING TOXIC EFFECTS................................................................ 164

3.11.1 Reducing Peak Absorption Following Exposure ................................................................ 165 3.11.2 Reducing Body Burden ....................................................................................................... 166 3.11.3 Interfering with the Mechanism of Action for Toxic Effects.............................................. 167

3.12 ADEQUACY OF THE DATABASE..................................................................................... 168 3.12.1 Existing Information on Health Effects of Fluorides, Hydrogen Fluoride, and Fluorine ............................................................................................................................... 169 3.12.2 Identification of Data Needs ............................................................................................... 173

FLUORIDES, HYDROGEN FLUORIDE, AND FLUORINE xv

3.12.3 Ongoing Studies .................................................................................................................. 185 4. CHEMICAL AND PHYSICAL INFORMATION.............................................................................. 187

4.1 CHEMICAL IDENTITY......................................................................................................... 187 4.2 PHYSICAL AND CHEMICAL PROPERTIES...................................................................... 187

5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL.......................................................... 193

5.1 PRODUCTION ....................................................................................................................... 193 5.2 IMPORT/EXPORT ................................................................................................................. 194 5.3 USE.......................................................................................................................................... 199 5.4 DISPOSAL .............................................................................................................................. 200

6. POTENTIAL FOR HUMAN EXPOSURE ......................................................................................... 203

6.1 OVERVIEW............................................................................................................................ 203 6.2 RELEASES TO THE ENVIRONMENT ................................................................................ 206

6.2.1 Air ....................................................................................................................................... 209 6.2.2 Water ................................................................................................................................... 213 6.2.3 Soil ...................................................................................................................................... 214

6.3 ENVIRONMENTAL FATE.................................................................................................... 215 6.3.1 Transport and Partitioning................................................................................................... 215 6.3.2 Transformation and Degradation ........................................................................................ 216

6.3.2.1 Air ................................................................................................................................... 216 6.3.2.2 Water............................................................................................................................... 217 6.3.2.3 Sediment and Soil ........................................................................................................... 218 6.3.2.4 Other Media .................................................................................................................... 218

6.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT ............................... 218 6.4.1 Air ....................................................................................................................................... 218 6.4.2 Water ................................................................................................................................... 219 6.4.3 Sediment and Soil ............................................................................................................... 222 6.4.4 Other Environmental Media................................................................................................ 223

6.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE ..................................... 225 6.6 EXPOSURES OF CHILDREN............................................................................................... 230 6.7 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES ........................................... 234 6.8 ADEQUACY OF THE DATABASE...................................................................................... 237

6.8.1 Identification of Data Needs ............................................................................................... 237 6.8.2 Ongoing Studies .................................................................................................................. 241

7. ANALYTICAL METHODS ............................................................................................................... 243

7.1 BIOLOGICAL MATERIALS................................................................................................. 243 7.2 ENVIRONMENTAL SAMPLES............................................................................................ 246 7.3 ADEQUACY OF THE DATABASE...................................................................................... 251

7.3.1 Identification of Data Needs ............................................................................................... 252 7.3.2 Ongoing Studies .................................................................................................................. 253

8. REGULATIONS AND ADVISORIES ............................................................................................... 255 9. REFERENCES .................................................................................................................................... 265 10. GLOSSARY ...................................................................................................................................... 351

FLUORIDES, HYDROGEN FLUORIDE, AND FLUORINE xvi

APPENDICES A. ATSDR MINIMAL RISK LEVEL AND WORKSHEETS ...............................................................A-1 B. USER'S GUIDE .................................................................................................................................. B-1 C. ACRONYMS, ABBREVIATIONS, AND SYMBOLS...................................................................... C-1 D. FLUORIDE AND DENTAL CARIES ...............................................................................................D-1

FLUORIDES, HYDROGEN FLUORIDE, AND FLUORINE xvii

LIST OF FIGURES 3-1. Levels of Significant Exposure to Hydrogen Fluoride – Inhalation ................................................... 41 3-2. Levels of Significant Exposure to Fluorine – Inhalation.................................................................... 50 3-3. Levels of Significant Exposure to Fluoride – Inhalation.................................................................... 54 3-4. Levels of Significant Exposure to Fluoride – Oral ............................................................................. 87 3-5. Conceptual Representation of a Physiologically Based Pharmacokinetic (PBPK) Model for a Hypothetical Chemical Substance .................................................................................................... 150 3-6. Existing Information on Health Effects of Fluoride ......................................................................... 170 3-7. Existing Information on Health Effects of Hydrogen Fluoride/Hydrofluoric Acid.......................... 171 3-8. Existing Information on Health Effects of Fluorine ......................................................................... 172 6-1. Frequency of NPL Sites with Fluoride, Hydrogen Fluoride, and Fluorine Contamination.............. 204

FLUORIDES, HYDROGEN FLUORIDE, AND FLUORINE xix

LIST OF TABLES 2-1. Adequate Intake Levels for Fluoride .................................................................................................. 16 3-1. Levels of Significant Exposure to Hydrogen Fluoride – Inhalation ................................................... 37 3-2. Levels of Significant Exposure to Fluorine – Inhalation.................................................................... 43 3-3. Levels of Significant Exposure to Fluoride – Inhalation.................................................................... 53 3-4. Levels of Significant Exposure to Fluoride – Oral ............................................................................. 76 3-5. Levels of Significant Exposure to Hydrogen Fluoride – Dermal ..................................................... 128 3-6. Levels of Significant Exposure to Fluoride – Dermal ...................................................................... 129 3-7. Genotoxicity of Fluoride In Vitro ..................................................................................................... 133 3-8. Genotoxicity of Fluoride In Vivo ...................................................................................................... 135 3-9. Ongoing Studies on the Health Effects of Fluoride, Hydrogen Fluoride, or Fluorine...................... 186 4-1. Chemical Identity of Fluorine, Hydrogen Fluoride, Sodium Fluoride, Fluosilicic Acid, and Sodium Silicofluoride ................................................................................................................ 188 4-2. Physical and Chemical Properties of Fluorine, Hydrogen Fluoride, Sodium Fluoride, Fluosilicic Acid, and Sodium Silicofluoride..................................................................................... 190 5-1. U.S. Manufacturers of Hydrogen Fluoride, Fluorine, Sodium Fluoride, Fluosilicic Acid, and Sodium Silicofluoride ................................................................................................................ 195 5-2. Facilities that Produce, Process, or Use Hydrogen Fluoride ............................................................ 196 5-3. Facilities that Produce, Process, or Use Fluorine ............................................................................. 198 6-1. Releases to the Environment from Facilities that Produce, Process, or Use Hydrogen Fluoride............................................................................................................................................. 207 6-2. Releases to the Environment from Facilities that Produce, Process, or Use Fluorine...................... 210 6-3. Mean Daily Dietary Intake of Fluoride for Selected Canadian Population Groups ......................... 227 6-4. Comparison of Fluoride Levels (µg/g) in Cow Milk and Infant Formulas....................................... 232 6-5. Levels of Fluoride in Human Tissue and Urine—Selected Studies ................................................. 235 7-1. Analytical Methods for Determining Fluoride in Biological Materials............................................ 245 7-2. Analytical Methods for Determining Fluoride in Environmental Samples ...................................... 247

FLUORIDES, HYDROGEN FLUORIDE, AND FLUORINE xx

7-3. Analytical Methods for Determining Hydrogen Fluoride in Environmental Samples ..................... 249 8-1. Regulations and Guidelines Applicable to Fluoride, Sodium Fluoride, Hydrogen Fluoride, and Fluorine ...................................................................................................................................... 256

FLUORIDES, HYDROGEN FLUORIDE, AND FLUORINE 1

1. PUBLIC HEALTH STATEMENT

This public health statement tells you about fluorides, hydrogen fluoride, and fluorine and the

effects of exposure presented in the toxicological profile. These profiles were specifically

prepared by ATSDR for hazardous substances which are most commonly found at facilities on

the CERCLA National Priorities List (Superfund sites) and are intended to describe the effects of

exposure from chemicals at these sites.

The Environmental Protection Agency (EPA) identifies the most serious hazardous waste sites in

the nation. These sites make up the National Priorities List (NPL) and are the sites targeted for

long-term federal cleanup activities. Fluorides, hydrogen fluoride, and fluorine have been found

in at least 188 of the 1,636 current or former NPL sites. However, the total number of NPL sites

evaluated for these substances is not known. As more sites are evaluated, the sites at which

fluorides, hydrogen fluoride, and fluorine is found may increase. This information is important

because exposure to these substances may harm you and because these sites may be sources of

exposure.

When a substance is released from a large area, such as an industrial plant, or from a container,

such as a drum or bottle, it enters the environment. This release does not always lead to

exposure. You are exposed to a substance only when you come in contact with it. You may be

exposed by breathing, eating, or drinking the substance, or by skin contact.

If you are exposed to fluorides, hydrogen fluoride, and fluorine, many factors determine whether

you'll be harmed. These factors include the dose (how much), the duration (how long), and how

you come in contact with it/them. You must also consider the other chemicals you're exposed to

and your age, sex, diet, family traits, lifestyle, and state of health.

1.1 WHAT ARE FLUORIDES, HYDROGEN FLUORIDE, AND FLUORINE?

Fluorides are properly defined as binary compounds or salts of fluorine and another element.

Examples of fluorides include sodium fluoride and calcium fluoride. Both are white solids.



Sodium fluoride readily dissolves in water, but calcium fluoride does not. Sodium fluoride is

often added to drinking water supplies and to a variety of dental products, including toothpastes

and mouth rinses to prevent dental cavities. Other fluoride compounds that are commonly used

for water fluoridation are fluorosilicic acid and sodium fluorosilicate. Calcium fluoride is the

compound in the common minerals fluorite and fluorspar. Fluorspar is the mineral from which

hydrogen fluoride is produced. It is also used in the production of glass and enamel and in the

steel industry. In this profile, we will often use the term “fluoride” to include substances that

contain the element fluorine. The reason for this is that we generally measure the amount of

fluorine in a substance rather than the amount of a particular fluorine compound.

Fluorine is a naturally occurring, widely distributed element and a member of the halogen

family, which includes chlorine, bromine, and iodine. However, the elemental form of fluorine,

a pale yellow-green, irritating gas with a sharp odor, is so chemically reactive that it rarely

occurs naturally in the elemental state. Fluorine occurs in ionic forms, or combined with other

chemicals in minerals like fluorspar, fluorapatite, and cryolite, and other compounds. (Ions are

atoms, collections of atoms, or molecules containing a positive or negative electric charge.)

Fluorine gas reacts with most organic and inorganic substances; with metals, it forms fluorides

and with water, it forms hydrofluoric acid. Fluorine gas is primarily used to make certain

chemical compounds, the most important of which is uranium hexafluoride, used in separating

isotopes of uranium for use in nuclear reactors and nuclear weapons.

Hydrogen fluoride is a colorless, corrosive gas or liquid (it boils at 19.5 °C) that is made up of a

hydrogen atom and a fluorine atom. It fumes strongly, readily dissolves in water, and both the

liquid and vapor will cause severe burns upon contact. The dissolved form is called hydrofluoric

acid. It is known for its ability to etch glass. Commercially, hydrogen fluoride is the most

important fluorine compound. Its largest use is in the manufacture of fluorocarbons, which are

used as refrigerants, solvents, and aerosols.

For more information on the chemical properties of fluorides, hydrogen fluoride, and fluorine,

and their production and use, see Chapters 4 and 5.



1.2 WHAT HAPPENS TO FLUORIDES, HYDROGEN FLUORIDE, AND FLUORINE WHEN THEY ENTER THE ENVIRONMENT?

Fluorides occur naturally in the earth’s crust where they are found in rocks, coal, clay, and soil.

They are released into the air in wind-blown soil. Hydrogen fluoride is released to the air from

fluoride-containing substances, including coal, minerals, and clays, when they are heated to high

temperatures. This may occur in coal-fired power plants; aluminum smelters; phosphate

fertilizer plants; glass, brick, and tile works; and plastics factories. These facilities may also

release fluorides attached to particles. The biggest natural source of hydrogen fluoride and other

fluorides released to the air is volcanic eruptions.

Fluorine cannot be destroyed in the environment; it can only change its form. Fluorides released

into the atmosphere from volcanoes, power plants, and other high temperature processes are

usually hydrogen fluoride gas or attached to very small particles. Fluorides contained in wind-

blown soil are generally found in larger particles. These particles settle to the ground or are

washed out of the air by rain. Fluorides that are attached to very small particles may stay in the

air for many days. Hydrogen fluoride gas will be absorbed by rain and into clouds and fog to

form aqueous hydrofluoric acid, which will fall to the ground mainly in precipitation. The

fluorides released into air will eventually fall on land or water.

In water, fluorides associate with various elements present in the water, mainly with aluminum in

freshwater and calcium and magnesium in seawater, and settle into the sediment where they are

strongly attached to sediment particles. When deposited on land, fluorides are strongly retained

by soil, forming strong associations with soil components. Leaching removes only a small

amount of fluorides from soils. Fluorides may be taken up from soil and accumulate in plants, or

they may be deposited on the upper parts of the plants in dust. The amount of fluoride taken up

by plants depends on the type of plant, the nature of the soil, and the amount and form of fluoride

in the soil. Tea plants are known to accumulate fluoride in their leaves. Animals that eat

fluoride-containing plants may accumulate fluoride. However, the fluoride accumulates

primarily in the bones or shell rather than in edible meat.

For more information about what happens to fluorides in the environment, see Chapter 6.



1.3 HOW MIGHT I BE EXPOSED TO FLUORIDES, HYDROGEN FLUORIDE, AND FLUORINE?

Fluoride is a natural component of the earth’s crust and soil. Small amounts of fluorides are

present in water, air, plants, and animals. You may be exposed to small amounts of fluoride by

breathing air, drinking water, and eating food. In particular, fluorides are frequently added to

drinking water supplies at approximately 1 part of fluoride per million parts of water (ppm) and

to toothpaste and mouth rinses to prevent dental decay. Analytical methods used by scientists to

determine the levels of fluoride in the environment generally do not determine the specific form

of fluoride present. Therefore, we do not always know the form of fluoride that a person may be

exposed to. Similarly, we do not know what forms of fluoride are present at hazardous waste

sites. Some forms of fluoride may be insoluble or so tightly attached to particles or embedded in

minerals that they are not taken up by plants or animals.

Fluorides are normally found in very small amounts in the air. Levels measured in areas around

cities are usually less than 1 microgram (one millionth of a gram) of fluoride per cubic meter

(µg/m3) of air. Rural areas have even lower levels. The amount of fluoride that you breathe in a

day is much less than what you consume in food and water. You may breathe in higher levels of

fluoride in areas near coal-fired power plants or fluoride-related industries (e.g., aluminum

smelters, phosphorus fertilizer plants) or near hazardous waste sites.

Levels of fluorides in surface water average about 0.2 parts of fluoride per million parts of water

(ppm). Levels of fluorides in well water generally range from 0.02 to 1.5 ppm, but often exceed

1.5 ppm in parts of the southwest United States. Many communities fluoridate their water

supplies; the recommended level of fluoride is around 1 ppm. In the United States,

approximately 15,000 water systems serving about 162 million people are fluoridated in the

optimal range of 0.7–1.2 ppm, either occurring naturally or through adjustment. Persons living

in non-fluoridated areas may receive water exposure through beverages and foods processed in

fluoridated areas. You will be exposed to fluorides in the water that you drink or in beverages

prepared with fluoridated water.



The concentration of fluorides in soils is usually between 200 and 300 ppm. However, levels

may be higher in areas containing fluoride-containing mineral deposits. Higher levels may also

occur where phosphate fertilizers are used, where coal-fired power plants or fluoride-releasing

industries are located, or in the vicinity of hazardous waste sites. You may be exposed to

fluorides through dermal contact with these soils.

You may also be exposed to fluorides in your diet. While food generally contains low levels of

fluoride, food grown in areas where soils have high amounts of fluorides or where phosphate

fertilizers are used may have higher levels of fluorides. Tea and some seafoods have been found

to have high levels of fluorides. The average daily fluoride intake by adults from food and water

is estimated to be 1 milligram (mg) if you live in a community with <0.7 ppm in your water, and

about 2.7 mg if you have fluoridated water. You can contact your local water system to

determine the level of fluoride in your drinking water or refer to the annual Consumer

Confidence Report furnished by your water system operators. You may also be exposed to

fluoride in dental products, such as toothpastes, fluoride gels, and fluoride rinses. Dental

products used in the home such as toothpastes, rinses, and topically applied gels contain high

concentrations of fluoride (range 230–12,300 ppm) and are not intended to be ingested. The

most commonly used dental products, toothpastes, contain 900–1,100 ppm fluoride (ca. 0.10%),

most often as sodium fluoride. If you swallow these products, you will be exposed to higher

levels of fluoride. Swallowing toothpaste can account for a large percentage of the fluoride to

which a child <8 years of age might be exposed The Food and Drug Administration requires that

toothpaste tubes be labeled with instructions to minimize ingestion of fluoride by children

including the use of a “pea-sized” amount of paste and parental supervision of brushing.

You may also be exposed to higher levels of fluoride if you work in industries where fluoride-

containing substances are used, most notably in the electronics industry where hydrogen fluoride

may be used to etch glass in TV picture tubes or to clean silicon chips and in aluminum and

phosphate fertilizer plants. Exposure will primarily result from breathing in hydrogen fluoride or

fluoride-containing dust. Exposure will be reduced if exhaust systems or protective masks are

used in the workplace.



For more information on how you can be exposed to fluorides, hydrogen fluoride, or fluorine,

see Chapter 6.

1.4 HOW CAN FLUORIDES, HYDROGEN FLUORIDE, AND FLUORINE ENTER AND LEAVE MY BODY?

Generally, most of the fluoride in food or water that you swallow enters your bloodstream

quickly through the digestive tract. However, the amount that enters your bloodstream also

depends on factors such as how much of the fluoride you swallowed, how well the fluoride

dissolves in water, whether you ate or drank recently, and what you ate or drank. Factors such as

age and health status affect what happens to the fluoride ion once it is in your body. After

entering your body, about half of the fluoride leaves the body quickly in urine, usually within

24 hours unless large amounts (20 mg or more, which is the amount in 20 or more liters of

optimally fluoridated water) are ingested. Most of the fluoride ion that stays in your body is

stored in your bones and teeth.

When you breathe in air containing hydrogen fluoride or fluoride dusts, it enters your

bloodstream quickly through your lungs. When hydrofluoric acid touches skin, most of it can

quickly pass through the skin into the blood. How much of it enters your bloodstream depends

on how concentrated the hydrofluoric acid is and how long it stays on your skin. Almost all of

the fluoride that enters the body in these ways is quickly removed from the body in the urine, but

some is stored in your bones and teeth.

When you breathe in air containing fluorine, fluoride can enter your bloodstream through your

lungs, but it is not known how quickly this happens. Much of the fluoride leaves your body in

urine, but some is stored in your bones and teeth. Exposure to fluorine gas is uncommon, except

in industrial settings.

For more information on how fluorides, hydrogen fluoride, and fluorine enter and leave your

body, see Chapter 3.



1.5 HOW CAN FLUORIDES, HYDROGEN FLUORIDE, AND FLUORINE AFFECT MY HEALTH?

To protect the public from the harmful effects of toxic chemicals and to find ways to treat people

who have been harmed, scientists use many tests.

One way to see if a chemical will hurt people is to learn how the chemical is absorbed, used, and

released by the body; for some chemicals, animal testing may be necessary. Animal testing may

also be used to identify health effects such as cancer or birth defects. Without laboratory

animals, scientists would lose a basic method to get information needed to make wise decisions

to protect public health. Scientists have the responsibility to treat research animals with care and

compassion. Laws today protect the welfare of research animals, and scientists must comply

with strict animal care guidelines and must be recertified regularly with training in updated and

new guidelines.

Fluorides. Several medicines that contain fluoride are used for treating skin diseases (e.g.,

flucytosine, an antifungal) and some cancers (e.g., fluorouracil, an antimetabolite).

Small amounts of fluoride are added to toothpaste or drinking water to help prevent dental decay.

However, exposure to higher levels of fluoride may harm your health. Skeletal fluorosis can be

caused by eating, drinking, or breathing very large amounts of fluorides. This disease only

occurs after long-term exposures and can cause denser bones, joint pain, and a limited range of

joint movement. In the most severe cases, the spine is completely rigid. Skeletal fluorosis is

extremely rare in the United States; it has occurred in some people consuming greater than

30 times the amount of fluoride typically found in fluoridated water. It is more common in

places where people do not get proper nutrition. At fluoride levels 5 times greater than levels

typically found in fluoridated water, fluoride can result in denser bones. However, these bones

are often more brittle or fragile than normal bone and there is an increased risk of older men and

women breaking a bone. Some studies have also found a higher risk of bone fractures in older

men and women at fluoride levels typically found in fluoridated water. However, other studies

have not found an effect at this fluoride dose. If you eat large amounts of sodium fluoride at one



time, it can cause stomachaches, vomiting, and diarrhea. Extremely large amounts can cause

death by affecting your heart.

We do not know if eating, drinking, or breathing fluoride can cause reproductive effects in

humans. Reproductive effects, such as decreased fertility and sperm and testes damage, have

been seen in laboratory animals at extremely high doses (more than 100 times higher than levels

found in fluoridated water). However, other studies have not found any reproductive effects in

laboratory animals.

A number of studies have been done to assess whether there is an association between fluoride

and cancer in people who live in areas with fluoridated water or naturally high levels of fluoride

in drinking water, or people who work in jobs where they may be exposed to fluorides. Most

studies have not found any association between fluoride and cancer in people. A study in rats

and mice found that a small number of male rats developed bone cancer after drinking water with

high levels of fluoride in it throughout their lives. This was considered equivocal evidence that

fluoride causes cancer in male rats. Fluoride did not cause cancer in mice or female rats.

Another study found no evidence that even higher doses of fluoride caused cancer in rats. Both

animal studies had problems that limited their usefulness in showing whether fluoride can cause

cancer in humans. The International Agency for Research on Cancer (IARC) has determined

that the carcinogenicity of fluoride to humans is not classifiable.

Hydrogen Fluoride. Hydrogen fluoride is also a very irritating gas. Hydrogen fluoride is not as

dangerous as fluorine, but large amounts of it can also cause death. People breathing hydrogen

fluoride have complained of eye, nose, and skin irritation. Breathing in a large amount of

hydrogen fluoride with air can also harm the lungs and heart. Kidney and testes damage have

been observed in animals breathing hydrogen fluoride.

Hydrofluoric acid is dangerous to humans because it can burn the eyes and skin. The initial

exposure to hydrofluoric acid may not look like a typical acid burn. Skin may only appear red

and may not be painful at first. Damage to skin may happen over several hours or days, and

deep, painful wounds may develop. When not treated properly, serious skin damage and tissue



loss can occur. In the worst cases, getting a large amount of hydrofluoric acid on your skin can

lead to death caused by the fluoride affecting your lungs or heart.

Fluorine. Fluorine gas is very irritating and very dangerous to the eyes, skin, and lungs. Fluorine

gas at low concentrations makes your eyes and nose hurt. At higher concentrations, it becomes

hard to breathe. Exposure to high concentrations of fluorine can cause death due to lung

damage.

For more information on the health effects of fluorides, hydrogen fluoride, and fluorine, see

Chapter 3. For more information on fluoride and dental caries, see Appendix D.

1.6 HOW CAN FLUORIDES, HYDROGEN FLUORIDE, AND FLUORINE AFFECT CHILDREN?

This section discusses potential health effects from exposures during the period from conception

to maturity at 18 years of age in humans.

When used appropriately, fluoride is effective in preventing and controlling dental caries.

Drinking or eating excessive fluoride during the time teeth are being formed can cause visible

changes in teeth. The condition is called dental fluorosis. The changes increase in severity with

increasing levels of fluoride. Dental fluorosis develops only while the teeth are forming in the

jaw and before they erupt into the mouth (age <8 years). After the teeth have developed and

erupted, they cannot become fluorosed. Most enamel fluorosis seen today is of the mildest form,

in which there are a few almost invisible white spots on the teeth. In moderate cases, there are

large white spots on the teeth (mottled teeth), and some brown spots. In severe cases, the teeth

are pitted and are fragile, and sometimes the teeth can break. The appearance of affected teeth is

not identical for all children exposed to the same level of fluoride in the drinking water.

Exposure to fluoride from other sources, such as fluoride tablets or rinses, may account for these

differences. In general, some children who drink water with 1 ppm fluoride may get a few small

spots or slight discolorations on their teeth. Some children who drink water with 4 ppm fluoride

in it for long periods before their permanent teeth are in place may develop a more severe form

of dental fluorosis.



Fluoride can cross the placenta from the mother’s blood to the developing fetus. Only a very

small portion of fluoride ingested by women is transferred to a child through breast milk.

Several human studies found an increase in birth defects or lower IQ scores in children living in

areas with very high levels of fluoride in the drinking water. Those studies did not adequately

access other factors that could have contributed to the effects. Another study did not find birth

defects in children living in areas with low levels of fluoride. Birth defects have not been found

in most studies of laboratory animals.

1.7 HOW CAN FAMILIES REDUCE THE RISK OF EXPOSURE TO FLUORIDES, HYDROGEN FLUORIDE, AND FLUORINE?

If your doctor finds that you have been exposed to significant amounts of fluorides, hydrogen

fluoride, and fluorine, ask whether your children might also be exposed. Your doctor might need

to ask your state health department to investigate.

It is unlikely that the general population would be exposed to fluorine gas or hydrogen fluoride.

Because fluorides are found naturally in the environment, we cannot avoid being exposed to

them. Some areas of the United States, such as the Southwest, naturally have high levels of

fluorides in well water. There has been an increase in the cosmetic condition of tooth enamel

fluorosis in children in both fluoridated and non-fluoridated communities. Ask your health

department whether your area has naturally high levels of fluorides in the drinking water. If you

live in such an area, you should use bottled drinking water and consult your dentist for guidance

on the need for appropriate alternative fluoride supplements.

These areas may also contain high levels of fluorides in soil. A few hazardous waste sites may

contain high levels of fluorides in soil. By limiting your contact with such soil (for example,

reducing recreational activities that raise dust), you would reduce your family’s exposure to

fluoride. Some children eat a lot of dirt. You should prevent your children from eating dirt.

You should discourage your children from putting their hands or objects in their mouths or

engaging in other hand-to-mouth activity. Make sure they wash their hands frequently and

always before eating.



If you work in a phosphate fertilizer plant or other industry that uses minerals high in fluorides, it

is sometimes possible to carry fluorides home from work on your clothing, skin, hair, tools, or

other objects removed from the workplace. You may contaminate your car, home, or other

locations outside work where children might be exposed to fluoride-containing dust. Your

occupational health and safety officer at work can and should tell you whether the chemicals that

you work with are likely to be carried home on your clothes, body, or tools as well as whether

you should be showering and changing clothes before you leave work, storing your street clothes

in a separate area of the workplace, or laundering your work clothes at home separately from

other clothes.

Children may be exposed to high levels of fluorides if they swallow dental products containing

fluoridated toothpaste, gels, or rinses. Swallowing toothpaste can account for a large percentage

of the fluoride to which a small child might be exposed. You should teach your children not to

swallow these products. For children under age 8, parents should supervise brushing and place,

at most, a small pea size dab of toothpaste on the brush.

1.8 IS THERE A MEDICAL TEST TO DETERMINE WHETHER I HAVE BEEN EXPOSED TO FLUORIDES, HYDROGEN FLUORIDE, AND FLUORINE?

Urine and blood samples can be analyzed to find out if you have been exposed to fluorides. The

fluoride level in the sample is compared with the level of fluoride usually found in urine or

blood. This will show if a person has been exposed recently to higher-than-normal levels of

fluorides. However, this test cannot be used to predict any specific health effects that may occur

after fluoride exposure. The test must be performed soon after exposure because fluoride that is

not stored in the bones leaves the body within a few days. This test can be done at most

laboratories that test for chemical exposure. Bone sampling can be done in special cases to

measure long-term exposure to fluorides. Because fluorides, hydrogen fluoride, and fluorine all

enter the body as fluoride, these tests cannot distinguish among exposure to these different

chemicals.



For more information on medical tests to determine exposure to fluorides, hydrogen fluoride, and

fluorine, see Chapters 3 and 6.

1.9 WHAT RECOMMENDATIONS HAS THE FEDERAL GOVERNMENT MADE TO PROTECT HUMAN HEALTH?

The federal government develops regulations and recommendations to protect public health.

Regulations can be enforced by law. Federal agencies that develop regulations for toxic

substances include the Environmental Protection Agency (EPA), the Occupational Safety and

Health Administration (OSHA), and the Food and Drug Administration (FDA).

Recommendations provide valuable guidelines to protect public health but cannot be enforced by

law. Federal organizations that develop recommendations for toxic substances include the

Agency for Toxic Substances and Disease Registry (ATSDR) and the National Institute for

Occupational Safety and Health (NIOSH).

Regulations and recommendations can be expressed in not-to-exceed levels in air, water, soil, or

food that are usually based on levels that affect animals; then they are adjusted to help protect

people. Sometimes these not-to-exceed levels differ among federal organizations because of

different exposure times (an 8-hour workday or a 24-hour day), the use of different animal

studies, or other factors.

Recommendations and regulations are also periodically updated as more information becomes

available. For the most current information, check with the federal agency or organization that

provides it. Some regulations and recommendations for fluorides, hydrogen fluoride, and

fluorine include the following:

Sodium fluoride, hydrogen fluoride, and fluorine have been named hazardous substances by the

EPA. The federal government has set regulatory standards and guidelines to protect workers

from the possible health effects of fluorides, hydrogen fluoride, and fluorine in air. OSHA has

set a legally enforceable limit of 0.2 milligrams per cubic meter (mg/m3) for fluorine, 2.0 mg/m3

for hydrogen fluoride, and 2.5 mg/m3 for fluoride in workroom air to protect workers during an

8-hour shift over a 40-hour work week. NIOSH recommends air levels of 0.2 mg/m3 for



fluorine, 2.5 mg/m3 for hydrogen fluoride, and 2.5 mg/m3 for sodium fluoride in workroom air to

protect workers during an 8-hour shift over a 40-hour work week.

The federal government has also set regulatory standards and guidelines to protect the public

from the possible health effects of fluoride in drinking water. EPA determined that the

maximum amount of fluoride allowed in drinking water is 4.0 milligrams per liter (mg/L).

For the prevention of dental decay, the Public Health Service (PHS) has, since 1962,

recommended that public water supplies contain fluoride at concentrations between 0.7 and

1.2 mg/L. PHS scientists representing the National Institutes of Health, the Centers for Disease

Control and Prevention, the FDA, ATSDR, and other government agencies conducted an

extensive examination of the worldwide biomedical literature on the public health risks and

benefits of fluoride in 1991. The PHS report stated that fluoride in the drinking water

substantially reduces tooth decay.

For more information on recommendations regarding exposure to fluorides, hydrogen fluoride,

and fluorine, see Chapter 8.

1.10 WHERE CAN I GET MORE INFORMATION?

If you have any more questions or concerns, please contact your community or state health or

environmental quality department or

Agency for Toxic Substances and Disease Registry Division of Toxicology 1600 Clifton Road NE Mailstop E-29 Atlanta, GA 30333

* Information line and technical assistance

Phone: 1-888-42-ATSDR (1-888-422-8737) Fax: 1-404-498-0057



ATSDR can also tell you the location of occupational and environmental health clinics. These

clinics specialize in recognizing, evaluating, and treating illnesses resulting from exposure to

hazardous substances.

* To order toxicological profiles, contact National Technical Information Service 5285 Port Royal Road Springfield, VA 22161 Phone: (800) 553-6847 or (703) 605-6000 Web site: http://www.ntis.gov/


2. RELEVANCE TO PUBLIC HEALTH

2.1 BACKGROUND AND ENVIRONMENTAL EXPOSURES TO FLUORIDES, HYDROGEN FLUORIDE, AND FLUORINE IN THE UNITED STATES

Fluorine is the most electronegative and reactive of all elements; fluoride is the ionic form of fluorine.

Fluorine and anhydrous hydrogen fluoride are naturally occurring gases that have a variety of industrial

uses including the production of fluorine-containing chemicals, pharmaceuticals, high octane gasoline,

and fluorescent light bulbs; aqueous hydrofluoric acid is a liquid used for stainless steel pickling, glass

etching, and metal coatings. The general population is typically exposed to very low levels of gaseous

fluoride (primarily as hydrogen fluoride); in the United States and Canada, the levels ranged from 0.01 to

1.65 µg/m3. Populations living near industrial sources of hydrogen fluoride, including coal burning

facilities, may be exposed to higher levels of hydrogen fluoride in the air. Additionally, vegetables and

fruits grown near these sources may contain higher levels of fluoride, particularly from fluoride-

containing dust settling on the plants.

Fluoride salts, generically referred to as fluorides, are naturally occurring components of rocks and soil.

One of the more commonly used fluoride salt is sodium fluoride; its principal use is for the prevention of

dental caries. Sodium fluoride and other fluoride compounds, such as fluorosilicic acid and sodium

hexafluorisilicate, are used in the fluoridation of public water. Sodium monofluorophosphate and

stanneous fluoride are commonly used in dentifrices such as toothpaste. The general population can be

exposed to fluoride through the consumption of fluoridated drinking water, food, and dentifrices. The

average dietary intake (including water) of fluoride ranges between 1.4 and 3.4 mg/day (0.02–

0.048 mg/kg/day) for adults living in areas with 1.0 mg/L fluoride in the water. In areas with <0.3 mg/L

fluoride in water, the adult dietary intakes ranged from 0.3 to 1.0 mg/day (0.004–0.014 mg/kg/day). In

children, the dietary intakes ranged from 0.03 to 0.06 mg/kg/day in areas with fluoridated water and from

0.01 to 0.04 mg/kg/day in areas without fluoridated water. The Food and Nutrition Board of the Institute

of Medicine has developed adequate intakes (AIs) for fluoride. The AI is the “estimated fluoride intake

that has been shown to reduce the occurrence of dental caries maximally in a population without causing

unwanted side effects including moderate dental fluorosis.” The AIs for each age group are presented in

Table 2-1.



Table 2-1. Adequate Intake Levels for Fluoridea

Age range Adequate intake level (mg/day) Adequate intake level (mg/kg/day)b 0–6 months 0.01 0.0014 6–12 months 0.5 0.056 1–3 years 0.7 0.054 4–8 years 1 0.045 9–13 years (males and females) 2 0.05 14–18 years (males) 3 0.046 14–18 years (females) 3 0.053 >18 years (males) 4 0.052 >18 years (females) 3 0.049 aSource: IOM 1997 bmg/kg/day doses were calculated by using reference body weights reported by IOM (1997)



2.2 SUMMARY OF HEALTH EFFECTS

Fluoride. The main health concern regarding fluoride is likely to be from excessive chronic oral

exposure in drinking water. Due to the deposition of significant amounts of fluoride in bone, the primary

target system for intermediate and chronic exposures of both humans and several laboratory animal

species is the skeletal system (including teeth). Both beneficial and detrimental dental and skeletal effects

have been observed in humans. Fluoride has been shown to decrease the prevalence of dental caries and,

under certain conditions, has been used for the treatment of osteoporosis. However, excess fluoride can

also result in dental fluorosis and can result in an increased prevalence of bone fractures in the elderly or

skeletal fluorosis. Both the beneficial and detrimental effects of fluoride appear to be related to fluoride-

induced alterations in tooth and bone mineralization.

Direct contact with fluoride can result in tissue damage. At high concentrations, fluoride can cause

irritation and damage to the respiratory tract, stomach, and skin following inhalation, oral, and dermal

exposure, respectively. At very high fluoride doses, fluoride can bind with serum calcium resulting in

hypocalcemia and possibly hyperkalcemia; the severe cardiac effects (e.g., tetany, decreased myocardial

contractility, cardiovascular collapse, ventricular fibrillation) observed at or near lethal doses are probably

due to this electrolyte imbalance.

The available data on the potential of fluoride to induce reproductive and/or developmental effects is

inconclusive. A study of birth records found a significant association between high levels of fluoride in

municipal drinking water (3 ppm and greater) and decreases in fertility rates; another study found

decreases in serum testosterone levels in men with skeletal fluorosis (fluoride concentration in water was

3.9 ppm). However, design limitations of these studies, particularly the use of poorly matched controls,

limits the usefulness of these studies. Some animal studies have found alterations in reproductive

hormone levels, histology of the testes, spermatogenesis, and fertility following exposure to relatively

high oral doses of sodium fluoride, roughly equivalent to a human exposure level of >150 ppm in

drinking water. However, other animal studies, including two-generation studies, have not found

alterations in serum hormone levels in male rats, testicular histopathology, sperm morphology, or fertility.

None of the available laboratory animal studies examined reproductive toxicity at low fluoride doses.

The inadequate human studies and conflicting animal studies do not allow for an assessment of the

potential of fluoride to induce reproductive effects in humans. Available human studies provide

suggestive evidence that exposure to elevated levels of fluoride in drinking water may decrease IQ in



children; however, neither study controlled for other confounding variables. Animal studies have not

found increases in the incidences of birth defects in the absence of maternal toxicity; at doses that caused

maternal toxicity (decreases in body weight gain and food consumption), increases in abnormalities were

found.

Numerous community-based studies have examined the possible association between fluoridated water

and cancer. Most of these studies did not find significant associations between water fluoridation and

cancer mortality or site-specific cancer incidence. Some studies have found associations between water

fluoridation and cancer mortality/incidence or site-specific cancer incidence (osteosarcoma or bone

cancer). The lack of control for potential confounding variables (i.e., age, race) limits the interpretation

of the total cancer study results. The weight of the evidence indicates that fluoridation of water does not

increase the risk of developing cancer. A 2-year study in rats found a weak, equivocal fluoride-related

increase in the occurrence of osteosarcomas in male rats, and no evidence of carcinogenicity in female

rats or male or female mice. IARC has determined that the carcinogenicity of fluoride to humans is not

classifiable.

Hydrogen Fluoride. Hydrogen fluoride is highly corrosive, the primary effects are tissue damage

resulting from direct contact. Acute inhalation exposure can result in irritation, inflammation, bronchiolar

ulceration, pulmonary hemorrhage and edema, and death. Gastrointestinal irritation has also been

observed in humans exposed to low levels of hydrogen fluoride. Direct contact of hydrogen

fluoride/hydrofluoric acid with the eyes or skin can produce skin burns, “burning sensation”, and

lacrimation. In addition to these direct contact effects, exposure to hydrogen fluoride can result in

skeletal and cardiac effects. Some evidence of early skeletal fluorosis has been observed in workers

exposed to hydrogen fluoride and fluoride dusts. These studies did not adequately characterize fluoride

exposure levels and, in most of the studies, there is some uncertainty regarding the diagnosis of skeletal

fibrosis. Exposure to very high levels of hydrogen fluoride/hydrofluoric acid can result in severe

cardiovascular effects, which are attributed to a combination of hypocalcemia and hyperkalemia; cardiac

arrhythmias have been seen in humans following hydrofluoric acid splashes in the face region, and

myocardial necrosis and congestion were observed in rabbits. Hepatic (fatty degeneration and necrosis)

and renal effects (tubular degeneration and necrosis) have also been observed in animal studies.

Although elevated cancer rates have been reported in some occupational groups exposed to hydrogen

fluoride and fluoride dusts, these studies were not controlled for the multiple substance exposures to

which industrial workers are generally exposed. Because of these multiple exposures and the problems



inherent in all occupational studies in identifying appropriate reference populations, only limited evidence

from such studies is specifically relevant to the investigation of possible carcinogenic effects of long-term

dermal exposure to hydrofluoric acid and inhalation exposure to hydrogen fluoride and/or fluoride dusts

in human beings. As noted previously, IARC has determined that the carcinogenicity of fluoride to

humans is not classifiable.

Fluorine. Limited data exist on the toxicity of fluorine; the two possible routes of exposure to fluorine

are inhalation or dermal contact with the gas. Fluorine gas is extremely irritating; human and animal data

suggest that the primary health effects of acute fluorine inhalation are nasal and eye irritation (at low

levels), and death due to pulmonary edema (at high levels). In animals, renal and hepatic damage have

also been observed.

A greater detailed discussion of fluoride-induced skeletal effects and portal of entry effects following

exposure to fluorides, hydrogen fluoride, hydrofluoric acid, or fluorine follows. The reader is referred to

Section 3.2, Discussion of Health Effects by Route of Exposure, for additional information on other

health effects.

Dental and Skeletal Effects. Human and animal data clearly indicate that fluoride accumulates in

the teeth and bone resulting in beneficial and detrimental alterations in the structure. There is strong

evidence that oral exposure to fluoride can reduce the risk of dental caries. However, elevated fluoride

levels during enamel maturation can also result in dental fluorosis, which is characterized by hypo-

mineralization of subsurface layers of enamel. In the mildest forms of dental fluorosis, the tooth is fully

functional but has cosmetic alterations, almost invisible opaque white spots. In more severely fluorosed

teeth, the enamel is pitted and discolored and is prone to fracture and wear. Several studies have found

significant increases in the number of decayed, missing, or filled tooth surfaces in children with severe

dental fluorosis. The prevalence and severity of dental fluorosis is strongly associated with fluoride

exposure levels. Dose-response relationships cannot be established from most of these studies because all

sources of fluoride were not considered and most studies used fluoride levels in drinking water as the

dosimetric. A recent meta-analysis estimated that 48% of children living in communities with 1 ppm

fluoride in the water would have evidence of dental fluorosis, most of it considered very mild. The

predicted incidence of dental fluorosis of aesthetic concern was 12.5%. Although the exact mechanism of

dental fluorosis is not known, it is generally believed to result in a fluoride-induced delay in the

hydrolysis of the enamel matrix protein amelogenin during the early enamel maturation phase of tooth

development.



In bone, fluoride replaces the hydroxyl ion in hydroxyapatite to form fluorapatite, thus changing the

physicochemical properties of the bone. Ingestion (and inhalation) of large doses of fluoride for an

extended period of time can result in thickened bones and exostoses (skeletal fluorosis). Signs of skeletal

fluorosis range from increased bone density to severe deformity, known as crippling skeletal fluorosis. In

the more severe cases of crippling fluorosis, complete rigidity of the spine can occur. Reported cases are

found almost exclusively in developing countries, particularly India and China, and are often associated

with malnutrition. It is generally stated that a dose of 10–20 mg/day (equivalent to 5–10 ppm in the

water, for a person who ingests 2 L/day) for at least 10 years is necessary for the development of crippling

skeletal fluorosis, but individual variation, variation in nutritional status, and the difficulty of determining

water fluoride levels in such situations make it difficult to determine the critical dose.

At lower doses, fluoride can cause an increase in bone density and fragility. A large number of

epidemiology studies have attempted to examine the relationship between fluoride in drinking water and

the risk of bone fracture. The results of these predominantly ecological studies are inconsistent. Studies

have found increases and decreases in hip fracture rates among older women living in areas with fluoride

in the drinking water (typically about 1 ppm), as compared to women living in areas with very low levels

of fluoride in the drinking water (<0.3 ppm). Other studies have not found an effect of fluoride on

fracture risk. A relationship between exposure to 1 ppm fluoride in drinking water and the risk of bone

fractures cannot be established from these studies. Studies involving exposure to higher doses of fluoride

have consistently found significant increases in the risk of nonvertebral fractures, particularly hip

fractures. A study involving lifetime exposure to 4.3–8 ppm fluoride in drinking water found an elevated

risk of hip fractures among elderly men and women; this elevated risk of hip fracture was also observed in

a community with very low fluoride (0.25–0.34 ppm) in the water. Studies of individuals using sodium

fluoride for the treatment of osteoporosis also found significant increases in bone mineral density.

Studies in laboratory animals have found defects in bone growth, fracture healing, and bone strength.

Respiratory, Gastrointestinal, Dermal, and Ocular Effects. Fluoride, hydrogen fluoride,

hydrofluoric acid, and fluorine are extremely irritating chemicals and can cause tissue damage after direct

contact. The respiratory tract is the primary target of toxicity following inhalation exposure to hydrogen

fluoride or fluorine. Single exposures to relatively low concentrations of hydrogen fluoride (≥0.5 ppm) or

fluorine (≥10 ppm) can result in upper respiratory tract irritation in humans. At higher concentrations

pulmonary congestion, necrosis and/or edema have been observed in laboratory animals; pulmonary

edema has also been observed in humans exposed to lethal concentrations of hydrogen fluoride.



Pulmonary and nasal irritations have also been reported following repeated exposures for about 30 days.

Chronic exposure to hydrogen fluoride and cryolite dust has resulted in impaired lung function in

workers. The observed respiratory effects are attributed to its highly corrosive properties. Human and

animal data suggest that preexposure to lower levels can reduce the respiratory effects.

Acute and chronic oral exposure to high doses of sodium fluoride, typically >1 mg fluoride/kg, can result

in nausea, vomiting, and gastric pain. Nausea, loss of appetite, and vomiting has also been reported by

workers exposed to cryolite dust for >2 years. The effects occur shortly after ingestion and are likely due

to the formation of hydrofluoric acid in the stomach. There is some evidence to suggest that these overt

signs of gastric irritation may not be sensitive indicators of gastric mucosa damage. Petechiae and/or

erosions were observed in most subjects exposed to sodium fluoride or a dental gel; however, nausea was

only reported by 33% of the subjects. Similar findings were reported in animal studies; thickening of the

glandular stomach mucosa and punctate hemorrhages were observed in rats ingesting high doses of

sodium fluoride in drinking water for an intermediate duration. Gastrointestinal effects have been

observed following inhalation and oral exposure to hydrogen fluoride. Populations living near a smelter

emitting hydrogen fluoride or exposed during an accidental release of hydrogen fluoride have reported

gastrointestinal effects, including nausea, gastrointestinal distress, and vomiting.

Fluorine and hydrogen fluoride are highly reactive chemicals; direct contact can result in severe damage

to the skin or eyes. The severity of the damage is directly related to the concentration and duration of

exposure. Humans exposed to hydrogen fluoride gas for an acute duration have reported symptoms of

skin irritation (itching and burning sensation) and eye irritation. Most of these human data are inadequate

for establishing concentration-response relationships; the data on ocular irritation do provide some

information of the threshold of toxicity. Very mild eye irritation was observed in subjects exposed to

0.5–4.5 ppm hydrogen fluoride for 1 hour, mild eye irritation was reported during a 15–50-day,

6-hour/day exposure to 3 ppm. Aqueous hydrofluoric acid applied directly to the skin can cause

extensive damage; it is quickly absorbed through the epidermis causing necrosis in underlying tissues

(Chela et al. 1989). In rabbits, a 1-minute exposure to 2% hydrofluoric acid did not produce skin lesions;

however, necrotic lesions were observed after a 1–4-hour exposure to this concentration.

There are limited data on the dermal and ocular toxicity of fluorine. A human study reported slight eye

irritation following a repeated exposure to 10 ppm fluorine (no irritation was reported a during 15-minute

exposure to this concentration), mild eye irritation during a 3-minute exposure to 30–50 ppm, and marked

irritation during a <1-minute exposure to 100 ppm.



2.3 MINIMAL RISK LEVELS

Fluorides

Inhalation MRLs

No inhalation MRLs were derived for fluoride. Several occupational exposure studies examined fluoride

toxicity in aluminum potroom workers (Carnow and Conibear 1981; Chan-Yeung et al. 1983b;

Czerwinski et al. 1988; Dinman et al. 1976c; Kaltreider et al. 1972). Interpretation of these studies is

limited by co-exposure to hydrogen fluoride and other chemicals including aluminum. There are limited

data on the inhaled toxicity of fluoride. Significant increases in lung weight and pulmonary edema have

been observed in mice exposed to 10 mg fluoride/m3 as sodium fluoride 4 hours/day, for 10–14 days

(Chen et al. 1999; Yamamoto et al. 2001). Impaired pulmonary bactericidal activity has also been

observed in mice exposed to 5 mg fluoride/m3 as sodium fluoride (Yamamoto et al. 2001). These studies

cannot be used for MRL derivation because none of the studies examined the skeletal system, which has

been shown to be a sensitive target following oral exposure.

Oral MRLs

A limited number of end points have been examined in humans and animals following acute oral

exposure to fluorides. Most of the available data involved exposure to lethal doses of fluoride; other

examined potential targets of toxicity include the gastrointestinal tract, bone, sperm morphology, and the

developing organism. Symptoms of gastric irritation, such as nausea, vomiting, and gastric pain, have

been observed shortly after exposure to fluoride in drinking water (Hoffman et al. 1980; Spak et al. 1989,

1990; Spoerke et al. 1980). Spak et al. (1989) reported macroscopic and microscopic signs of gastric

irritation in subjects ingesting 20 mg fluoride (1,000 ppm) as sodium fluoride; other studies have not

reliably identified exposure concentrations. A decrease in modulus of elasticity was observed in the

bones of weanling rats exposed to 9.5 mg fluoride/kg/day as sodium fluoride in drinking water for

2 weeks (Guggenheim et al. 1976). No alterations in sperm morphology were observed in mice exposed

to 32 mg fluoride/kg/day as sodium fluoride (Li et al. 1987a). In the absence of maternal toxicity, no

adverse effects in rat or rabbit offsprings were observed (Heindel et al. 1996); skeletal and visceral

alterations were observed in the offspring of rat dams with decreases in body weight and feed

consumption (Guna Sherlin and Verma 2001). From the available data, it appears that the stomach is a



sensitive target of fluoride toxicity following consumption of a bolus dose of fluoride. However, the

observed effect (gastric irritation) is likely due to the fluoride concentration rather than a daily dose

(expressed as mg/kg/day). It is not known whether the gastric mucosa would adapt to repeated exposure

to this concentration of fluoride. An acute-duration oral MRL for fluorides was not derived due to the

previously mentioned uncertainties in basing the MRL on a study that administered a single bolus dose of

sodium fluoride and because the resultant MRL would be lower than the chronic-duration oral MRL.

Several studies have examined the toxicity of sodium fluoride following intermediate-duration exposure

in laboratory animals. These studies have identified a number of potentially sensitive targets of fluoride

toxicity. The lowest identified lowest-observed-adverse-effect levels (LOAELs) are 0.5 mg

fluoride/kg/day for thyroid effects in rats exposed to sodium fluoride in drinking water for 2 months

(Bobek et al. 1976) and 0.80 mg fluoride/kg/day for increased bone formation in mice exposed to sodium

fluoride in drinking water for 4 weeks (Marie and Hott 1986). Neither study identified a no-observed-

adverse-effect level (NOAEL). Derivation of an intermediate-duration MRL from either study would

result in an MRL that is lower than the chronic-duration oral MRL.

• A chronic-duration oral MRL of 0.05 mg fluoride/kg/day was derived for fluoride.

A number of studies have examined the possible association between exposure to fluoridated water and

the risk of increased bone fractures, particularly hip fractures. In general, the studies involved comparing

the incidence of hip fractures among residents aged 55 years and older living in a community with

fluoridated water (around 1 ppm) with the incidence in a comparable community with lower levels of

fluoride in the water. Inconsistent results have been found, with studies finding decreases (Lehmann et al.

1998; Phipps et al. 2000; Simonen and Laittinen 1985), increases (Cooper et al. 1990, 1991; Danielson et

al. 1992; Jacobsen et al. 1990, 1992; Kurttio et al. 1999), or no effect (Arnala et al. 1986; Cauley et al.

1995; Goggin et al. 1965; Jacobsen et al. 1993; Karagas et al. 1996; Kröger et al 1994; Suarez-Almazor et

al. 1993) on hip fracture risk. Studies by Li et al. (2001) and Sowers et al. (1986) have examined

communities with higher levels of naturally occurring fluoride in the water. Both studies found increases

in the incidence of hip fractures in residents exposed to 4 ppm fluoride and higher (Li et al. 2001; Sowers

et al. 1986, 1991); the hip fracture incidence in the highly exposed community was compared to the rates

in communities with approximately 1 ppm fluoride in the water. Significant increases in the occurrence

of nonvertebral fractures were also observed in postmenopausal women ingesting sodium fluoride (34 mg

fluoride/day; 0.56 mg fluoride/kg/day) for the treatment of osteoporosis (Riggs et al. 1990, 1994). This

result was not found in another study of postmenopausal women with spinal osteoporosis treated with

34 mg fluoride/day as sodium fluoride (Kleerekoper et al. 1991). A meta-analysis of these data, as well



as other clinical studies, found a significant correlation between exposure to high levels of fluoride and an

increased relative risk of nonvertebral fractures (Haguenauer et al. 2000). The Li et al. (2001) study was

selected as the basis for the chronic-duration oral MRL. This study was selected because other potential

sources of fluoride were considered (the Riggs et al. [1990] study did not provide information on the level

of fluoride in the drinking water or other sources of fluoride) and calcium levels were similar among the

different communities (the Sowers et al. [1986] study did not control for calcium intake). The Li et al.

(2001) study identified a NOAEL of 2.62–3.56 ppm (0.15 mg fluoride/kg/day) and LOAEL of 4.32–

7.97 ppm (0.25 mg fluoride/kg/day). An MRL of 0.05 mg fluoride/kg/day is calculated by dividing the

NOAEL of 0.15 mg/kg/day by an uncertainty factor of 3 to account for human variability; a partial

uncertainty factor was used because the most sensitive subpopulation, elderly men and women, was

examined.

Hydrogen Fluoride/Hydrofluoric Acid

Inhalation MRLs

• An acute-duration inhalation MRL of 0.02 ppm fluoride was derived for hydrogen fluoride.

The respiratory tract appears to be the primary target of hydrogen fluoride toxicity. Upper respiratory

tract irritation and inflammation and lower respiratory tract inflammation have been observed in several

human studies. Nasal irritation was reported by one subject exposed to 3.22 ppm fluoride as hydrogen

fluoride 6 hours/day for 10 days (Largent 1960). Very mild to moderate upper respiratory symptoms

were reported by healthy men exposed to 0.5 ppm fluoride as hydrogen fluoride for 1 hour (Lund et al.

1997). At higher concentrations, 4.2–4.5 ppm fluoride as hydrogen fluoride for 1 hour, more severe

symptoms of upper respiratory irritation were noted (Lund et al. 1997, 2002). In subjects exposed to

4.2 ppm for 1 hour, analysis of nasal lavage fluid provided suggestive evidence that hydrogen fluoride

induces an inflammatory response in the nasal cavity (Lund et al. 2002). Similarly, bronchoalveolar

lavage fluid analysis revealed suggestive evidence of bronchial inflammation in another study of subjects

exposed to 1.9 ppm fluoride as hydrogen fluoride for 1 hour (Lund et al. 1999); no alterations were

observed at 0.5 ppm. Respiratory effects have also been reported in rats acutely exposed to hydrogen

fluoride. Mild nasal irritation was observed during a 60-minute exposure to 120 ppm fluoride

(Rosenholtz et al. 1963), and respiratory distress was observed at 2,310, 1,339, 1,308, and 465 ppm

fluoride for 5, 15, 30, or 60 minutes, respectively (Rosenholtz et al. 1963). Midtracheal necrosis was

reported in rats exposed to 902 or 1,509 ppm fluoride as hydrogen fluoride for 2 or 10 minutes using a



mouth breathing model with a tracheal cannula (Dalbey et al. 1998a, 1998b). These effects were not

observed when the tracheal cannula was not used.

The Lund et al. (1997, 1999) study was selected as the basis of the acute-duration inhalation MRL for

hydrogen fluoride. As reported in the 1997 publication, a trend (p=0.06) toward increased upper

respiratory tract symptom score, as compared to pre-exposure symptom scores, was observed at the

lowest concentration tested (0.5 ppm). A significant increase in the total symptom score was also

observed at this concentration. No significant alterations in symptom scores were observed at the mid

concentration (1.9 ppm), and increases in upper respiratory and total symptom scores were observed at

the high concentration (4.5 ppm). Suggestive evidence of bronchial inflammation was also observed at

≥1.9 ppm fluoride (Lund et al. 1999), although no alterations in lower respiratory tract symptoms (Lund

et al. 1997) or lung function (Lund et al. 1997) were observed at any of the tested concentrations. The

MRL is based on the minimal LOAEL of 0.5 ppm fluoride for upper respiratory tract irritation. Data on

nasal irritation from the Largent (1960) report, the Lund et al. (2002) study, and the intermediate-duration

study by Largent (1960) provide suggestive evidence that the severity of nasal irritation does not increase

with increasing exposure duration. These three studies identified similar LOAEL values for different

exposure durations: 3.22 ppm 6 hours/day for 10 days (Largent 1960), 3.8 ppm 1 hour/day for 1 day

(Lund et al. 2002), and 2.98 ppm 6 hours/day, 6 days/week for 15–50 days (Largent 1960). Thus, time

scaling was not used to derive the acute MRL. The MRL of 0.02 ppm was calculated by dividing the

minimal LOAEL of 0.5 ppm by an uncertainty factor of 30 (3 for the use of a minimal LOAEL and 10 to

account for human variability).

There are limited data on the long-term toxicity of hydrogen fluoride. Slight nasal irritation was reported

by volunteers exposed to an average concentration of 2.98 ppm fluoride, 6 hours/day for 15–50 days

(Largent 1960). In rats, rabbits, and dogs, pulmonary hemorrhages were observed after exposure to

31 ppm fluoride for 6 hours/day, 6 days/week for 5 weeks (Stokinger 1949). An intermediate-duration

inhalation MRL was not derived for hydrogen fluoride because an MRL based on the Largent (1960)

study is higher than the acute-duration inhalation MRL derived from the Lund et al. (1997, 1999) study.

No chronic-duration studies were located for hydrogen fluoride; thus, a chronic-duration inhalation MRL

was not derived.

Oral MRLs



No oral MRLs were derived for hydrogen fluoride/hydrofluoric acid. Only lethality studies were

identified for hydrogen fluoride/hydrofluoric acid, precluding derivation of oral MRLs for this chemical.

Fluorine

Inhalation MRLs

• An acute-duration inhalation MRL of 0.01 ppm fluorine was derived for fluorine.

Irritation appears to be the primary effect following acute inhalation exposure to fluorine. The observed

effects include eye, skin, and nasal irritation in humans intermittently exposed to ≥10 ppm for 0.5–

15 minutes (Keplinger and Suissa 1968) and dyspnea and lung congestion in rats and mice exposed to 47–

175 ppm fluorine for 5–60 minutes (Keplinger and Suissa 1968). The threshold for the respiratory effects

appears to be duration-related. Necrosis was also observed in the liver parenchymal tissue and in the

renal tubules of rodents acutely exposed to fluorine. In general, the liver and kidney effects occurred at

higher concentrations than the respiratory effects.

The NOAEL and LOAEL values for nasal irritation identified in the human study by Keplinger and

Suissa (1968) were selected as the basis of an acute-duration inhalation MRL for fluorine. Subjects did

not report nasal or eye irritation following a 3-, 5-, or 15-minute exposure to 10 ppm. Eye irritation was

observed at ≥23 ppm; nose irritation at ≥50 ppm, and skin irritation at ≥78 ppm. The severity of the

irritation was concentration related. Exposure to 100 ppm was considered very irritating and the subjects

did not inhale during the exposure period. The NOAEL of 10 ppm was adjusted for intermittent exposure

(0.25 hour/24 hours) and divided by an uncertainty factor of 10 to account for human variability to derive

an acute-duration inhalation MRL of 0.01 ppm fluorine.

Longer-duration exposure studies are limited to a multi-species intermediate-duration study (Stokinger

1949) and an occupational exposure study (Lyon 1962). As with acute-duration exposure, the primary

effect of intermediate-duration exposure to fluorine was eye, nose, and mouth irritation, which was

observed in rats and dogs (Stokinger 1949). Evidence of pulmonary damage (bronchitis, hemorrhage, and

edema) was also observed in rats, rabbits, and dogs. The study author noted that there was some

difficulty in measuring the exposure concentrations and considered the measurements of exposure

concentrations to be questionable. The chronic-duration study of workers exposed to fluorine (Lyon

1962) was not considered for MRL derivation because it used a relatively insensitive measure of



respiratory effects (absences from work and visits to the medical department with respiratory complaints)

and the workers and the controls were exposed to uranium hexafluoride and hydrogen fluoride.


3. HEALTH EFFECTS

3.1 INTRODUCTION

The primary purpose of this chapter is to provide public health officials, physicians, toxicologists, and

other interested individuals and groups with an overall perspective on the toxicology of fluorides,

hydrogen fluoride, and fluorine. It contains descriptions and evaluations of toxicological studies and

epidemiological investigations and provides conclusions, where possible, on the relevance of toxicity and

toxicokinetic data to public health.

A glossary and list of acronyms, abbreviations, and symbols can be found at the end of this profile.

The term fluoride properly refers to numerous natural and synthesized compounds that are derived from

hydrofluoric acid. This class of chemicals is commonly referred to as fluorides. Some of these

compounds, such as oxygen difluoride, are very reactive and highly toxic. Because of their reactivity,

these compounds would not migrate unchanged from a hazardous waste site. Fluoride salts, such as

sodium fluoride and calcium fluoride, are much less reactive and much less toxic. Since the fluoride ion

is the toxicologically active agent, and discussion of water fluoridation uses the term fluoride, the term

fluoride is used generically in this profile to refer to toxicology of fluoride salts. Because numerous

different fluoride compounds exist naturally in the environment and have varying chemical properties, the

term fluorides is used in the discussion of environmental media. Most of the available literature on

fluoride toxicity concerns sodium fluoride. Additional toxicity literature is available on some other forms

of fluoride, such as stannous fluoride. Other forms of fluoride are discussed only if exposure is likely to

occur at a hazardous waste site. (Such exposure to stannous fluoride is not likely.) Wherever the form of

fluoride exposure is known, that salt is identified in the profile.

Hydrogen fluoride is also a gas and is very water soluble. It dissolves readily in any water present in the

air or other media. When hydrogen fluoride is dissolved in water, it is called hydrofluoric acid. Although

hydrofluoric acid is very corrosive and can etch glass, it is a weak acid, meaning that it can be present in

water as an undissociated molecule. However, in dilute solutions, it is almost completely ionized; salts

are formed if cations are available. Due to formation of complexes, very concentrated solutions of

hydrofluoric acid are also largely ionic in nature. Therefore, a hydrogen fluoride or hydrofluoric acid

spill would result in contamination with fluoride ion, but hydrogen fluoride or hydrofluoric acid would


3. HEALTH EFFECTS

not be of concern outside the immediate vicinity of the spill. However, while members of the public are

only likely to come into contact with fluoride contamination, clean-up workers could be exposed to

hydrogen fluoride/hydrofluoric acid. In this profile, hydrogen fluoride is used to refer to the gas, while

hydrofluoric acid is used to refer to the liquid form. When both forms are included, the term hydrogen

fluoride is used.

Fluorine is a gaseous element that occurs only in very low concentrations in the environment in the

absence of anthropogenic sources (see Chapter 6 for further discussion). Because it is strongly

electronegative, it is rarely found in the environment in the elemental state, nor is it likely to be found in

the environment near toxic waste sites as molecular fluorine.

Limited information also exists concerning occupational exposure to the mineral cryolite (Na3AlF6),

sometimes with concomitant exposure to hydrogen fluoride. Because these exposures usually involve

exposure to both hydrogen fluoride and cryolite, sometimes along with exposure to other fluoride dusts,

they are discussed separately in the profile.

This profile will discuss data, or the absence of data, concerning the toxicity of inorganic compounds of

fluorine that people could be exposed to at a hazardous waste site. Exposure and toxicity are discussed

separately for fluoride, hydrogen fluoride/hydrofluoric acid, and fluorine. Toxic effects of occupational

exposure in aluminum reduction plants, where exposures to hydrogen fluoride, fluoride dusts, and cryolite

all occur, are also discussed separately. Because the toxic effects of fluorine are largely due to the action

of the fluorine molecule on the respiratory tract or other exposed surfaces, fluorine exposure is reported as

exposure to a level of diatomic fluorine. By contrast, systemic effects of hydrogen fluoride are due to the

fluoride ion, so concentrations of hydrogen fluoride are converted to fluoride equivalents. All doses of

fluoride are reported as the amount of fluoride ion.

The primary routes and durations of concern vary with the different fluorine compounds. In general, the

more soluble the fluoride, the more that can be absorbed by oral ingestion, and the more toxic it is. The

primary exposure routes and duration for hydrofluoric acid are the inhalation or dermal routes, related to

acute occupational exposure, while the primary exposure route and duration for fluoride is chronic oral

exposure to fluoride in the drinking water, food, and fluoride-containing dental products. Therefore, most

of the information for the inhalation and dermal routes comes from studies of acute exposure to fluorine

or hydrofluoric acid, while most of the information regarding the oral route is based on sodium fluoride.

The toxicity following inhalation or dermal exposure to other inorganic fluorine compounds differs from


3. HEALTH EFFECTS

that of hydrofluoric acid. Similarly, oral exposure to various fluorides other than sodium fluoride may

result in different toxic effects.

3.2 DISCUSSION OF HEALTH EFFECTS BY ROUTE OF EXPOSURE

To help public health professionals and others address the needs of persons living or working near

hazardous waste sites, the information in this section is organized first by route of exposure (inhalation,

oral, and dermal) and then by health effect (death, systemic, immunological, neurological, reproductive,

developmental, genotoxic, and carcinogenic effects). These data are discussed in terms of three exposure

periods: acute (14 days or less), intermediate (15–364 days), and chronic (365 days or more).

Levels of significant exposure for each route and duration are presented in tables and illustrated in

figures. The points in the figures showing no-observed-adverse-effect levels (NOAELs) or lowest-

observed-adverse-effect levels (LOAELs) reflect the actual doses (levels of exposure) used in the studies.

LOAELs have been classified into "less serious" or "serious" effects. "Serious" effects are those that

evoke failure in a biological system and can lead to morbidity or mortality (e.g., acute respiratory distress

or death). "Less serious" effects are those that are not expected to cause significant dysfunction or death,

or those whose significance to the organism is not entirely clear. ATSDR acknowledges that a

considerable amount of judgment may be required in establishing whether an end point should be

classified as a NOAEL, "less serious" LOAEL, or "serious" LOAEL, and that in some cases, there will be

insufficient data to decide whether the effect is indicative of significant dysfunction. However, the

Agency has established guidelines and policies that are used to classify these end points. ATSDR

believes that there is sufficient merit in this approach to warrant an attempt at distinguishing between

"less serious" and "serious" effects. The distinction between "less serious" effects and "serious" effects is

considered to be important because it helps the users of the profiles to identify levels of exposure at which

major health effects start to appear. LOAELs or NOAELs should also help in determining whether or not

the effects vary with dose and/or duration, and place into perspective the possible significance of these

effects to human health.

The significance of the exposure levels shown in the Levels of Significant Exposure (LSE) tables and

figures may differ depending on the user's perspective. Public health officials and others concerned with

appropriate actions to take at hazardous waste sites may want information on levels of exposure

associated with more subtle effects in humans or animals (LOAELs) or exposure levels below which no


3. HEALTH EFFECTS

adverse effects (NOAELs) have been observed. Estimates of levels posing minimal risk to humans

(Minimal Risk Levels or MRLs) may be of interest to health professionals and citizens alike.

Estimates of exposure levels posing minimal risk to humans (Minimal Risk Levels or MRLs) have been

made for fluorides, hydrogen fluoride, and fluorine. An MRL is defined as an estimate of daily human

exposure to a substance that is likely to be without an appreciable risk of adverse effects (noncarcino-

genic) over a specified duration of exposure. MRLs are derived when reliable and sufficient data exist to

identify the target organ(s) of effect or the most sensitive health effect(s) for a specific duration within a

given route of exposure. MRLs are based on noncancerous health effects only and do not consider

carcinogenic effects. MRLs can be derived for acute, intermediate, and chronic duration exposures for

inhalation and oral routes. Appropriate methodology does not exist to develop MRLs for dermal

exposure.

Although methods have been established to derive these levels (Barnes and Dourson 1988; EPA 1990),

uncertainties are associated with these techniques. Furthermore, ATSDR acknowledges additional

uncertainties inherent in the application of the procedures to derive less than lifetime MRLs. As an

example, acute inhalation MRLs may not be protective for health effects that are delayed in development

or are acquired following repeated acute insults, such as hypersensitivity reactions, asthma, or chronic

bronchitis. As these kinds of health effects data become available and methods to assess levels of

significant human exposure improve, these MRLs will be revised.

A User's Guide has been provided at the end of this profile (see Appendix B). This guide should aid in

the interpretation of the tables and figures for Levels of Significant Exposure and the MRLs.

3.2.1 Inhalation Exposure

Inhalation exposure most commonly occurs in an occupational setting. As discussed above, most of the

available information concerning toxic effects of fluorine and its compounds following inhalation

exposure comes from studies of exposure to hydrogen fluoride or hydrofluoric acid. There are also a

limited number of useful studies concerning inhalation exposure to fluorine or particulates of inorganic

fluoride compounds. However, no animal studies were located regarding toxic effects of exposure to the

particulate fluoride compounds. Toxic effects of hydrogen fluoride are discussed in all of the following

sections. Where toxicity data exist for fluoride or fluorine, these substances are also discussed.


3. HEALTH EFFECTS

Acute inhalation of hydrogen fluoride following facial splashes with hydrofluoric acid can cause

bronchiolar ulceration, pulmonary hemorrhage and edema, and death. In addition, renal and hepatic

damage have been observed in animal studies. Many of the human studies regarding inhalation of

hydrogen fluoride fumes also involved dermal exposure; in such cases, it is difficult to determine which

effects are specific to the inhalation route. However, the respiratory effects of hydrogen fluoride appear

to be inhalation-specific, because they have not been reported in cases where there was clearly no

inhalation exposure. The effects of combined inhalation and dermal exposure to hydrofluoric acid are

also discussed in Section 3.2.3.

Fluorine gas is extremely irritating. The primary health effects of acute fluorine inhalation are nasal and

eye irritation (at low levels), and death due to pulmonary edema (at high levels). In animals, renal and

hepatic damage have also been observed.

The major health effect of chronic inhalation exposure to fluoride is skeletal fluorosis, which has been

reported in cases of exposure to fluoride dusts and hydrogen fluoride, either individually or in

combination.

3.2.1.1 Death

Both hydrogen fluoride and fluorine can cause lethal pulmonary edema, although cardiac effects also

contribute to the toxicity of hydrogen fluoride. The reported LC50 values for hydrogen fluoride in rats for

a given duration are generally at least 3.5 times higher than the value for fluorine (as diatomic fluorine) in

rats for the same duration. Although strain differences could account for some of this difference, the

LC50 values of hydrogen fluoride in Crl:CD®BR and Wistar-derived rats were very similar.

Hydrogen Fluoride. Acute inhalation of hydrogen fluoride fumes in combination with dermal exposure

to hydrofluoric acid has been reported to cause death in humans. Actual exposure concentrations are not

known in any of these cases. Death was generally due to pulmonary edema (resulting from irritation and

constriction of the airways) or to cardiac arrhythmias with pronounced hyperkalemia, hypocalcemia, and

hypomagnesemia.

The death of a chemist who sustained first- and second-degree burns of the face, hands, and arms when a

vat containing hydrofluoric acid accidentally ruptured has been described (Kleinfeld 1965). This 29-year-

old male died 10 hours after admission to the hospital. Postmortem examination revealed severe


3. HEALTH EFFECTS

tracheobronchitis and hemorrhagic pulmonary edema. A petroleum refinery worker was splashed in the

face with 100% anhydrous hydrofluoric acid (Tepperman 1980). The absorption of fluoride produced

acute systemic fluoride poisoning with profound hypocalcemia and hypomagnesemia and cardiac

arrhythmias. The patient died <24 hours after exposure; autopsy revealed pulmonary edema. A young

woman splashed in the face with hydrofluoric acid died of respiratory insufficiency a few hours after

exposure (Chela et al. 1989). The autopsy revealed severe burns of the skin and lungs, with hemorrhagic

pulmonary edema produced by hydrofluoric acid and its vapor.

The lethal concentration of hydrogen fluoride has been investigated in rats, mice, and guinea pigs. It

appears that mice are more sensitive to the acute effects of hydrogen fluoride than rats, and rats are more

sensitive than guinea pigs. The 15-minute LC50 values for hydrogen fluoride were 4,327 ppm fluoride for

guinea pigs and 2,555 ppm fluoride for Wistar-derived rats (Rosenholtz et al. 1963). The 60-minute

LC50 values for hydrogen fluoride were 325 ppm fluoride in ICR-derived mice (Wohlslagel et al. 1976),

1,325 ppm fluoride in Sprague-Dawley-derived rats (Wohlslagel et al. 1976), and 1,242 ppm fluoride in

Wistar-derived rats (Rosenholtz et al. 1963). In a study (Dalbey et al. 1998a) comparing the toxicity of

hydrogen fluoride in rats using mouth-breathing (rats fitted with a tracheal cannula) and nose-breathing

models, dramatic differences in lethality were observed. In the mouth-breathing rats, 50 and 80% of the

animals died within 2 weeks of a 10-minute mouth breathing exposure to 3,655 or 6,663 ppm fluoride,

respectively. In contrast, no deaths were noted following exposure to these concentrations using the nose-

breathing model. The difference in lethality between the two models is probably due to the higher dose of

hydrogen fluoride reaching the lower airways in the mouth-breathing model.

The LC50 values reported by Haskell Laboratory (1988) for Crl:CD®BR rats were much higher than the

values reported by the above investigators, although the size of the discrepancy decreased with longer

exposure durations. For example, the 15-minute LC50 was reported as 6,620 ppm, while the 60-minute

LC50 was 1,610 ppm. Although the concentration of hydrogen fluoride that produced death was reported

to be lower when it was administered to rats in humid air (Haskell Laboratory 1988), the method for

measuring fluoride in humid air may not have given accurate results. This limitation was recognized by

the authors, who stated that the collection efficiency of the sampling train for aerosols was not evaluated.

Longer-term effects of hydrogen fluoride were investigated by exposing various species to 8.2 or 31 ppm

fluoride as hydrogen fluoride for 6 hours/day, 6 days/week for 5 weeks (Stokinger 1949). Humidity was

47–97% at the lower concentration and 48–66% at the higher concentration. Marked species differences

were observed. All rats and mice exposed to 31 ppm died, but no guinea pigs, rabbits, or dogs exposed at


3. HEALTH EFFECTS

this level died. No animal of any species died following exposure to 8.2 ppm. In an experiment where

five rabbits, three guinea pigs, and two Rhesus monkeys were exposed to 18 ppm for 6–7 hours/day,

5 days/week for 50 days (309 hours total), the only deaths observed were two guinea pigs (Machle and

Kitzmiller 1935). Exposure of one of these animals stopped after 134 hours of exposure, and exposure of

the other one stopped after 160 hours, when marked weight loss was observed. Nevertheless, the animals

died about 2 weeks later.

Fluorine. No information was located on death in humans caused by fluorine. Fluorine toxicity has been

investigated in Osborne-Mendel rats, Swiss-Webster mice, New England guinea pigs, and New Zealand

rabbits (Keplinger and Suissa 1968). Similar values for the LC50 were calculated for the different species.

In the rats, the LC50 values for exposures of 5, 15, 30, and 60 minutes were 700, 390, 270, and 185 ppm,

respectively. At concentrations near the LC50, few signs of intoxication were observed immediately after

exposure, except for irritation of the eyes and nose. Several hours after exposure, the animals exhibited

lethargy, dyspnea, and general weakness. Except at concentrations above the LC90, death generally

occurred 12–18 hours after exposure. Animals that survived for 48 hours generally survived for the

duration of the observation period. Loss of body weight was also observed, but was considered

nonspecific and was attributed to anorexia.

Toxic effects of inhalation exposure to fluorine and hydrogen fluoride were compared in rats, mice,

rabbits, and guinea pigs (Stokinger 1949). Lethal doses from fluorine exposure determined by this group

are about 3–4 times those determined by Keplinger and Suissa (1968), but quantitative exposure level

data from these experiments are not reliable due to technical problems in monitoring fluorine gas levels.

However, qualitative results from these experiments are useful. These experiments also found that

fluorine was more toxic than hydrogen fluoride.

There are some indications that preexposure to low levels of fluorine may provide resistance to lethal

effects of fluorine. Increases in survival time were observed in rabbits exposed to 50 ppm fluorine for

30 minutes, 1 day/week for 4 weeks prior to exposure to a lethal concentration of fluorine (400 ppm for

30 minutes) (Keplinger 1969). Survival time in the rabbits was 48 hours, as compared to 18 hours or less

in similarly exposed rabbits not preexposed to fluorine. In mice, slight increases in LC50 values were

found in animals receiving a single exposure to 30–45 ppm fluorine prior to exposure to lethal

concentrations. However, slight decreases in LC50 values were seen in mice preexposed to 25 ppm

fluorine (Keplinger 1969). No mechanism for the possible tolerance was suggested.


3. HEALTH EFFECTS

Repeated exposures of rats, mice, guinea pigs, and rabbits to 0.5, 2, 5, or 18 ppm fluorine were conducted

for up to 178 hours over 35 days (Stokinger 1949). The exposure regimen was not stated, but appears to

be 6 hours/day, 6 days/week. The exposure levels at these lower concentrations were considered fairly

reliable. Guinea pigs and rats were less sensitive to lethal effects than were rabbits or dogs. All of the

rabbits and dogs exposed to 5 ppm and mice exposed to 18 ppm died, while only half of the rats and

guinea pigs exposed to 18 ppm died. Most animals exposed to 2 ppm survived.

The LC50 values for each species and duration category of exposure to hydrogen fluoride are recorded in

Table 3-1 and plotted in Figure 3-1. The LC50 values for each species and duration category of exposure

to fluorine are recorded in Table 3-2 and plotted in Figure 3-2.

3.2.1.2 Systemic Effects

The highest NOAEL values and all reliable LOAEL values for systemic effects in each species and

duration category of exposure to hydrogen fluoride are recorded in Table 3-1 and plotted in Figure 3-1.


duration category of exposure to fluorine are recorded in Table 3-2 and plotted in Figure 3-2. The highest

NOAEL values and all reliable LOAEL values for systemic effects in each species and duration category

of exposure to fluoride are recorded in Table 3-3 and plotted in Figure 3-3.

Respiratory Effects.

Hydrogen Fluoride. Acute inhalation of 122 ppm fluoride as hydrogen fluoride by two male volunteers

produced marked respiratory irritation within 1 minute (Machle et al. 1934). Pulmonary edema,

pulmonary hemorrhagic edema, and tracheobronchitis have been reported in cases of people being

splashed in the face with hydrofluoric acid, where concurrent inhalation and dermal exposures are likely

(Chan et al. 1987; Chela et al. 1989; Dieffenbacher and Thompson 1962; Kleinfeld 1965; Tepperman

1980). Exposure concentrations were not known in these cases. In another case, a women developed

herrhagic alveolitis and adult respiratory disease syndrome following exposure to a presumably high

concentration of hydrogen fluoride from a cleaning product (Bennion and Franzblau 1997).

Two human experimental studies have been conducted to assess the ability of hydrogen fluoride to induce

respiratory tract inflammation. In the first study, increases in upper airway symptoms were observed in

LOAEL

Less SeriousNOAEL(ppm) (ppm)

Seriousa

(ppm)System

Exposure/Duration/

Frequency(Specific Route)

Species(Strain)

Key tofigure

Reference

Table 3-1 Levels of Significant Exposure to Hydrogen Fluoride - Inhalation

Chemical Form

ACUTE EXPOSUREDeath

1 1 d5-60min/d

Haskell Laboratory 1988

hydrogen fluoride2890 (30-minute LC50)

6620 (15-minute LC50)

14600 (5-minute LC50)

1610 (60-minute LC50)

Rat

2(Wistar)

1 d5-60min/day

Rosenholtz et al. 1963


2555 (15-minute LC50)

4722 (5-minute LC50)

1242 (60-minute LC50)

Rat

3 1 d60 min/d

Wohlslagel et al. 1976

hydrogen fluoride1325 (60-minuteLC50)

Rat

4 1 d60min/d

Wohlslagel et al. 1976


Mouse

5(Hartley)

1 d5-60min/d



Gn Pig

Systemic6

Resp1 hour Lund et al. 1999; Lund et al. 1997

hydrogen fluoride1.9 (lower respiratory inflammation)M

0.5b

(upper respiratory irritation)M

Human

LOAEL


Seriousa

(ppm)System

Exposure/Duration/


Species(Strain)

Key tofigure

Reference

(continued)Table 3-1 Levels of Significant Exposure to Hydrogen Fluoride - Inhalation

Chemical Form

7Resp

1 hour Lund et al. 2002

hydrogen fluoride4.2 (upper airway irritation and

inflammation)M

Human

8Dermal

1 to sevminutesseecomments

Machle et al. 1934

hydrogen fluoride122 (smarting of the skin)

Human

Ocular 122 (conjunctival irritation)

9563

(Sprague-Dawley)

Resp2 min Dalbey et al. 1998a, b

hydrogen fluoride1509 (mucosal necrosis in mid

trachea)

Rat

4643Hemato 8190 (incr RBC, hemoglobin, andhematocrit levels)

563Hepatic 1509 (incr asparate aminotransferaseactivity)

10257

(Sprague-Dawley)

Resp10 min Dalbey et al. 1998a, b

hydrogen fluoride902 (minimal midtracheal necrosis)

Rat

Hemato 1676 (incr hemoglobin and hematocritlevels)

1676Hepatic

11Resp

1 d5 min/d


hydrogen fluoride712 (mild nasal irritation) 2310 (temporary respiratory distress

and nasal discharge)

Rat

Ocular 712 (moderate lacrimation)

LOAEL


Seriousa

(ppm)System

Exposure/Duration/


Species(Strain)

Key tofigure

Reference


Chemical Form

12292Resp

1 d15min/d


hydrogen fluoride357 (nasal irritation) 1339 (temporary respiratory distress


Rat

292Ocular 357 (lacrimation)

1398Resp

1 d60min/d


hydrogen fluoride120 (nasal irritation) 465 (temporary respiratory distress


Rat

98Ocular 120 (lacrimation)

14(Fischer- 344)

Resp30 min Stavert et al. 1991

hydrogen fluoride1235 (fibrinonecrotic rhinitis in nose

breathing rats; tracheal andbronchial necrosis in mouthbreathing rats)

Rat

Bd Wt 1235 (10% body weight reduction)

INTERMEDIATE EXPOSUREDeath

15(NS)

5 wks6d/wk6hr/d

Stokinger 1949

hydrogen fluoride31 (100% mortality)

Rat

16(NS)

5 wks6d/wk6hr/d

Stokinger 1949

hydrogen fluoride31 (100% mortality)

Mouse

Systemic17

Resp15-50 d6 hr/d

Largent 1960

hydrogen fluoride2.98 (slight nasal irritation)

Human

Dermal 2.98 (stinging sensation on skin)

Ocular 2.98 (stinging sensation in eyes)

LOAEL


Seriousa

(ppm)System

Exposure/Duration/


Species(Strain)

Key tofigure

Reference


Chemical Form

188.2

(NS)Resp

5 wks6hr/d

Stokinger 1949

hydrogen fluoride31 (pulmonary hemorrhage)

Rat

31Hemato

8.2Renal 31 (cortical necrosis)

Ocular 8.2 (subcutaneous hemorrhagearound the eyes and on thefeet)

19(NS)

Dermal5 wks6d/wk6hr/d

Stokinger 1949

hydrogen fluoride8.2 (subcutaneous hemorrhage

around the eyes and on thefeet)

Mouse

20(NS)

Resp5 wks6d/wk6hr/d

Stokinger 1949


Dog

31Hemato

218.2

(NS)Resp

5 wks6d/wk6hr/d

Stokinger 1949


Rabbit

31HematoNeurological

220.01

(albino)

a The number corresponds to entries in Figure 3-1.

b Used to derive an acute-duration inhalation minimal risk level (MRL) of 0.02 ppm; the concentration was divided by an uncertainty factor of 30 (3 for use of a minimal LOAEL and 10to account for human variability).

Bd = body weight; d = day(s); Hemato = hematological; hr = hour(s); incr = increase; LC50 = lethal concentration, 50% kill; LOAEL = lowest-observed-adverse-effect level; min =minute(s); mo = month(s); NOAEL = no-observed-adverse-effect level; ppm = parts per million; RBC = red blood cell; Resp = respiratory; wk = week(s)

5mo24hr/d

Sadilova et al. 1965

hydrogen fluoride0.03 (disturbances in conditioned

reflexes; lengthened latentperiods)

Rat

0.01

0.1

1

10

100

1000

10000

100000

Death

5g

4m

1r

1r

1r1r

2r2r2r2r 3r

Respiratory

6

6

7

9r

9r10r

10r

11r

11r

12r

12r

12r13r

13r 13r

14r

Hematological

9r9r

10r

Hepatic

9r

9r 10r

Dermal

8

Ocular

8

11r

12r 12r

13r 13r

Body Weight

14r

ppm

Figure 3-1. Levels of Significant Exposure to Hydrogen Fluoride - InhalationAcute (≤14 days)

c-Catd-Dogr-Ratp-Pigq-Cow

k-Monkeym-Mouseh-Rabbita-Sheep

f-Ferretj-Pigeone-Gerbils-Hamsterg-Guinea Pig

n-Minko-Other

Cancer Effect Level-Animals LOAEL, More Serious-Animals LOAEL, Less Serious-Animals NOAEL - Animals

Cancer Effect Level-Humans LOAEL, More Serious-Humans LOAEL, Less Serious-Humans NOAEL - Humans

LD50/LC50 Minimal Risk Level for effects other than Cancer

Systemic

0.01

0.1

1

10

100

Death

16m 15r

Respiratory

20d

17

18r

18r

21h

21h

Hematological

20d 18r 21h

Renal

18r

18r

Dermal

17

19m

Ocular

17

18r

Neurological

22r

22r

ppm

Figure 3-1. Levels of Significant Exposure to Hydrogen Fluoride - Inhalation (Continued)Intermediate (15-364 days)




n-Minko-Other




Systemic

LOAEL


Seriousa

(ppm)System

Exposure/Duration/


Species(Strain)

Key tofigure

Reference

Table 3-2 Levels of Significant Exposure to Fluorine - Inhalation

Chemical Form

ACUTE EXPOSUREDeath

1(Osborne-Mendel)

1d5-60min/d

Keplinger and Suissa 1968

fluorine270 (30-minute LC50)


700 (5-minute LC50)


Rat

2(Swiss-Webster)

1d15-60min/d




600 (5-minute LC50)


Mouse

3(NewEngland)

1d15-60min/d




Gn Pig

4(NewZealand)

1d5-30min/d




Rabbit

Systemic5

Dermal2-3 days3-5 minutes every 15minutes


fluorine10 (slight skin irritation)

Human

Ocular 10 (slight eye irritation)

LOAEL


Seriousa

(ppm)System

Exposure/Duration/


Species(Strain)

Key tofigure

Reference

(continued)Table 3-2 Levels of Significant Exposure to Fluorine - Inhalation

Chemical Form

610b

Resp15 minutes Keplinger and Suissa 1968

fluorine

Human

10Dermal

10Ocular

7Resp

1d0.5min/d


fluorine100 (nasal irritation)

Human

Ocular 100 (eye irritation)

8Resp

1d1min/d



Human

67Dermal 67 (skin irritation)

Ocular 67 (eye irritation)

910Resp

1d3min/d


fluorine50 (slight nasal irritation)

Human

10Ocular 50 (eye irritation)

1023Resp

1d5min/d


fluorine

Human

23Dermal

10Ocular 23 (slight eye irritation)

LOAEL


Seriousa

(ppm)System

Exposure/Duration/


Species(Strain)

Key tofigure

Reference


Chemical Form

1188

(Osborne-Mendel)

Resp1d5min/d


fluorine350 (irritation)

175 (dyspnea; mild lung congestion)

Rat


1249

(Osborne-Mendel)

Resp1d15min/d



98 (very mild lung congestion)

Rat

195Ocular

1335

(Osborne-Mendel)

Resp1d30min/d




Rat


1428

(Osborne-Mendel)

Resp1d60min/d




Rat

93Ocular

1579

(Swiss-Webster)

Resp1d5min/d


fluorine174 (dyspnea; nasal irritation;

diffuse lung congestion; alveolarnecrosis)

Mouse

174Hepatic 195 (necrosis and cloudy swelling)

79Renal 114 (necrosis)


LOAEL


Seriousa

(ppm)System

Exposure/Duration/


Species(Strain)

Key tofigure

Reference


Chemical Form

1665

(Swiss-Webster)

Resp1d15min/d




Mouse

188Ocular

1765

(Swiss-Webster)

Resp1d15min/d


fluorine82 (alveolar necrosis and

hemorrhage)

Mouse

128Hepatic 144 (coagulation, necrosis, andcloudy swelling)

65Renal 82 (coagulation, necrosis)

1851

(Swiss-Webster)

Resp1d30min/d



hemorrhage)

Mouse

82Hepatic 116 (coagulation, necrosis, andcloudy swelling)

51Renal 82 (coagulation, necrosis)

1967

32(Swiss-Webster)

Resp1d30min/d




Mouse

113Ocular

2030

(Swiss-Webster)

Resp1d60min/d




Mouse

LOAEL


Seriousa

(ppm)System

Exposure/Duration/


Species(Strain)

Key tofigure

Reference


Chemical Form

2130

(Swiss-Webster)

Resp1d60min/d



hemorrhage)

Mouse

55Hepatic 80 (necrosis and cloudy swelling)

50Renal 55 (necrosis)

2270

(NewEngland)

Resp1d15min/d




Gn Pig

2373

(NewEngland)

Resp1d60min/d


fluorine135 (mild lung congestion, irritation,

dyspnea)

Gn Pig

2439

(NS)Resp

1d15min/d


fluorine93 (slight lung congestion)

Dog


2568

(NS)Resp

1d60min/d


fluorine93 (irritation, cough, and slight

dyspnea)

Dog


2679

(NewZealand)

Resp1d5min/d



134 (slight dyspnea)

Rabbit

LOAEL


Seriousa

(ppm)System

Exposure/Duration/


Species(Strain)

Key tofigure

Reference


Chemical Form

2732

(NewZealand)

Resp1d30min/d




Rabbit


28(NS)

5 wks6d/wk6hr/d

Stokinger 1949

fluorine18 (100% mortality)

Rat

29(NS)

5 wks6d/wk6hr/d

Stokinger 1949


Dog

30(NS)

5 wks6d/wk6hr/d

Stokinger 1949


Rabbit

Systemic31

5(NS)

Resp5 wks6d/wk6hr/d

Stokinger 1949

fluorine18 (severe pulmonary irritation)

Rat

Bd Wt 18 (weight loss)

320.5

(NS)Resp

5 wks6d/wk6hr/d

Stokinger 1949

fluorine2 (pulmonary hemorrhage and

edema)

Dog

5Hepatic 18 (liver congestion)

330.5

(NS)Resp

5 wks6d/wk6hr/d

Stokinger 1949

fluorine2 (mild bronchial inflammation) 18 (hemorrhage in the lungs)

Rabbit

2Hepatic 5 (hyperemia of the liver)

LOAEL


Seriousa

(ppm)System

Exposure/Duration/


Species(Strain)

Key tofigure

Reference


Chemical Form

Reproductive34

5(NS)


b Used to derive an acute inhalation minimal risk level of 0.01 ppm; the concentration was adjusted for intermittent exposure (0.25 hours/24 hours) and divided by an uncertaintyfactor of 10 to account for human variability.

d = day(s); Gn Pig = Guinea pig; LC50 = lethal concentration, 50% kill; LOAEL; lowest-observed-adverse-effect-level; min = minute(s); NOAEL = no-observed-adverse-effect level;ppm = parts per million; Resp = respiratory

5 wks6d/wk6hr/d

Stokinger 1949

fluorine18 (testicular degeneration)

Rat

0.01

0.1

1

10

100

1000

Death

3g

3g

2m

2m

2m2m

1r

1r1r1r

4h

4h

Respiratory

24d

24d

25d25d 22g

22g

22g

23g

23g

6

789

9

10

15m

15m

16m

16m

16m17m17m

18m

18m19m

19m

19m

19m

20m

20m

20m 21m

21m

11r

11r

11r

12r

12r

12r

13r

13r

13r

14r

14r

14r

26h

26h

26h

27h

27h

27h

ppm

Figure 3-2. Levels of Significant Exposure to Fluorine - InhalationAcute (≤14 days)




n-Minko-Other




Systemic

0.01

0.1

1

10

100

1000

17m

18m18m

21m21m

Renal

15m15m

17m17m

18m

18m

21m 21m

Dermal

5 6

8 8

10

Ocular

24d

24d 25d

25d

5 6

789

9

10

10

15m15m

16m

19m11r

11r

12r13r

13r14r

ppm

Figure 3-2. Levels of Significant Exposure to Fluorine - Inhalation (Continued)Acute (≤14 days)




n-Minko-Other




Hepatic

15m 15m17m

Systemic

0.1

1

10

100

Death

29d

28r

30h

Respiratory

32d

32d

31r

31r 33h

33h

33h

Hepatic

32d

32d

33h

33h

Body Weight

31r

Reproductive

34r

34r

ppm

Figure 3-2. Levels of Significant Exposure to Fluorine - Inhalation (Continued)Intermediate (15-364 days)




n-Minko-Other




Systemic

LOAEL

Less SeriousNOAEL(mg/m³) (mg/m³)

Seriousa

(mg/m³)System

Exposure/Duration/


Species(Strain)

Key tofigure

Reference

Table 3-3 Levels of Significant Exposure to Fluoride - Inhalation

Chemical Form

ACUTE EXPOSURESystemic

1(ICR)

Resp4 hours/day10 days

Chen et al. 1999

sodium fluoride13.3 (increased relative lung weight)M

Mouse

22 M

(BALB/c)Resp

4 hour/day14 days

Yamamoto et al. 2001

sodium fluoride10 (pulmonary edema)M

Mouse

Immuno/ Lymphoret3

2 M(BALB/c)

4 hour/day14 days

Yamamoto et al. 2001

sodium fluoride5 (decreased pulmonary

bactericidal activity)M

Mouse

INTERMEDIATE EXPOSURESystemic

4(ICR)

Resp


LOAEL = lowest-observed-adverse-effect level; M = male; NOAEL = no-observed-adverse-effect level; Resp = respiratory

4 hours/day20-30 days

Chen et al. 1999

sodium fluoride13.3 (increased relative lung weight)M

Mouse

1

10

100

Respiratory

1m

2m

2m

Immuno/Lymphor

3m

3m

mg/m3

Figure 3-3. Levels of Significant Exposure to Fluoride - InhalationAcute (≤14 days)




n-Minko-Other




Systemic

10

100

Respiratory

4m

mg/m3

Figure 3-3. Levels of Significant Exposure to Fluoride - Inhalation (Continued)Intermediate (15-364 days)




n-Minko-Other




Systemic


3. HEALTH EFFECTS

individuals exposed to 0.5 or 4.5 ppm hydrogen fluoride for 1 hour (Lund et al. 1997). Significant

increases in the percentage of CD3-positive cells and lymphocytes in the bronchial portion of the lower

respiratory tract, as assessed via bronchoalveolar lavage performed 3 weeks prior to exposure and

24 hours after exposure, was also observed at 4.5 ppm, but not at 0.5 ppm (Lund et al. 1999). However,

no significant alterations in lung function or lower airway symptoms were observed (Lund et al. 1997).

The second study with a similar study design assessed upper airway inflammation via nasal lavage (Lund

et al. 2002). An inflammatory response in the nasal mucosa was observed following a 1-hour exposure to

3.8–4.5 ppm hydrogen fluoride. Seven of the 10 tested subjects also reported upper airway symptoms

(specific symptoms were not presented); most of the subjects scored the severity of the symptoms as very

mild to mild.

A number of residents of Texas City, Texas, reported respiratory symptoms following the accidental

release of hydrogen fluoride. It was estimated that most of the hydrogen fluoride was released in the first

2 hours after the accident, and evacuation of residents within 0.5 miles of the facility began within

20 minutes of the accident. Many of the 939 people who went to the emergency room within 24 hours of

the accident reported signs of respiratory irritation: throat burning (21.0%), shortness of breath (19.4%),

sore throat (17.5%), and cough (16.4%) (Wing et al. 1991). Forced expiratory volume in 1 second

(FEV1) was <80% of predicted values in 42.3% of the 130 individuals who underwent pulmonary

function testing. In another study of the Texas City residents, health effects within 1 month of the

accident and 2 years after the accident were assessed in 1,994 residents who were asked to complete

health questionnaires 2 years after the accident (Dayal et al. 1992). A large number of highly exposed

residents reported severe symptoms of breathing problems (e.g., coughing, difficulty breathing, shortness

of breath), throat problems (e.g., difficulty swallowing, burning irritation, phlegm, voice changes), and

nose problems (e.g., sneezing, runny nose, problems smelling food); the prevalence of severe symptoms

were 60.2, 51.9, and 40.7% for breathing, throat, and nose problems, respectively, within the first month

of the accident. High prevalence of these effects was still reported 2 years after the accident; 38.5, 22.1,

and 26.5% for severe breathing, throat, and nose problems, respectively. The prevalence of severe

breathing, throat, and nose problems in the nonexposed population were 11.3, 6.2, and 6.4%, respectively,

within 1 month of the accident and 8.2, 3.3, and 4.1%, respectively, 2 years after the accident. The

prevalence of the breathing problems were higher in a subgroup of the high exposure group that had pre-

existing respiratory problems or smoked more than two packs of cigarettes per day. Although this study

(Dayal et al. 1992) provides suggestive evidence that acute exposure to hydrogen fluoride can result in

long-term damage to the respiratory tract, the study results should be interpreted with caution. The


3. HEALTH EFFECTS

symptom survey was administered 2 years after the accident, there was no medical confirmation of the

effects, and the study authors did not provide a definition for severe symptoms.

Lethality studies in animals have also reported respiratory effects in rats, mice, and guinea pigs from

acute inhalation exposure to hydrogen fluoride. True respiratory effects, such as respiratory distress,

pulmonary congestion, and intra-alveolar edema were generally observed at levels of at least ~50% of the

LC50 (Haskell Laboratory 1988; Rosenholtz et al. 1963; Wohlslagel et al. 1976). These effects appear to

be reversible within a week upon cessation of exposure.

A series of experiments by Dalbey et al. (1998a, 1998b) examined the acute toxicity of nonlethal

concentrations of hydrogen fluoride in rats following a 2- or 10-minute exposure. In most of the

experiments, a mouth-breathing model with a tracheal cannula was used to maximize delivery of

hydrogen fluoride to the lower respiratory tract. A number of respiratory tract effects were found in the

mouth-breathing rats, including alterations in bronchioalveolar lavage (BAL) parameters (increased total

protein, myeloperoxidase, lactate dehydrogenase, β-glucuronidase, and glucose-6-phosphate

dehydrogenase), impaired lung function (decreased total lung capacity, vital capacity, peak expiratory

flow, forced expiratory flow at 50 and 25% of the forced vital capacity, forced expiratory volume at

0.1 second, forced vital capacity, and diffusing capacity and increased pulmonary resistance), and

histological damage (necrosis and acute inflammation in trachea and acute alveolitis and perivascular/

peribronchial edema and inflammation in the lung). Rats exposed for 2 minutes manifested histological

damage and BAL parameter alterations at 1,509 ppm fluoride and impaired lung function at 4,643 ppm.

No adverse respiratory effects were observed at 563 ppm fluoride. In the rats exposed for 10 minutes,

histopathological alterations (necrosis of the trachea only) and BAL parameters (polymorphonuclear

leukocytes and myeloperoxidase levels only) were observed at 903 ppm fluoride; impaired respiratory

function was observed at 1,676 ppm fluoride. No adverse effects were observed at 257 ppm fluoride.

The respiratory effects were consistently more severe in the rats exposed for 2 minutes as compared to

10 minutes, when exposure was expressed as the product of concentration x time. In other experiments,

rats were exposed for 60 minutes to hydrogen fluoride. No adverse respiratory effects were observed at

19 or 46 ppm. Respiratory effects observed in nose-breathing rats were limited to the nose. Necrosis and

acute inflammation of the ventral meatus, nasal septum, and nasoturbinates were observed in rats exposed

to 6,072 ppm for 2 minutes and 1,586 ppm for 10 minutes. A dramatic decrease in breathing frequency

was also observed in the nose-breathing rats; within the first minute of exposure, breathing frequency was

32–35% of the preexposure levels. The decrease in breathing frequency, which is a component of reflex

apnea, is a response to sensory irritation.


3. HEALTH EFFECTS

Similar results were observed in rats exposed to 1,235 ppm fluoride for 30 minutes. Moderate to severe

fibronecrotic rhinitis and large fibrin thrombi in the submucosa and hemorrhage were observed in the

nasal cavity of nose-breathing rats; no nasal lesions were observed in similarly exposed rats fitted with a

tracheal cannula to simulate mouth-breathing. Epithelial, submucusal, and cartilage necrosis in the

trachea, trace levels of neutrophils in the alveoli, and necrosis of the bronchi were observed in the mouth-

breathing rats, but not in the nose-breathing rats, suggesting that the toxicity of hydrogen fluoride occurs

at the point of entry. Reflex apnea, as evidenced by a marked decrease in breathing frequency, was

observed in the nose-breathing rats. Based on differences in minute ventilation rates, the study authors

estimated that the mouth-breathing rats inhaled 27% more hydrogen fluoride than the nose-breathing rats.

Pulmonary hemorrhage was noted in dogs, rabbits, and rats exposed to 31 ppm fluoride as hydrogen

fluoride for 6 hours/day, 6 days/week for 5 weeks (Stokinger 1949). At 8.2 ppm fluoride, no effect was

seen in rats or rabbits, and localized hemorrhages were seen in only 1/5 dogs.

Pulmonary hemorrhage, alveolar inflammation, and hyperplasia of the bronchial epithelium were

observed in guinea pigs that died due to exposure to 18 ppm fluoride as hydrogen fluoride for 6–

7 hours/day, 5 days/week for about 35 days (Machle and Kitzmiller 1935). This effect was not readily

reversible. The one surviving guinea pig had alveolar exudates, thickening of the alveolar walls, and

hemorrhages of the lungs when necropsied 9 months after the conclusion of the full 50-day exposure

period. Similarly, all four rabbits exposed under the same conditions had lobular pneumonia and

leucocytic infiltration of the alveolar walls, sometimes with edema and thickening of the walls, when

necropsied 7–8 months after the last exposure. No clinical signs of toxicity were reported in rabbits and

weight gain was generally similar to the controls. This study is limited by the small number of animals

used and the incomplete reporting of the data.

Hydrogen Fluoride and Fluoride Dusts. A study of an occupational cohort exposed to hydrogen

fluoride and fluoride dusts in the pot rooms of an aluminum smelter reported a significantly lower forced

expiratory volume and increased cough and sputum production in the highest exposure group, compared

with controls who worked in the office or casting department and were reported to have no significant

occupational exposure to air contaminants. Corrections were made for age, height, and smoking habits.

The ambient air fluoride concentration in the high-exposure area was 0.2 mg fluoride/m3 as vapor

(presumably hydrogen fluoride) and 0.28 mg/m3 "particulate fluoride." It is not clear whether the latter

value represented the air concentration of fluoride in particulates or the concentration of the particulates


3. HEALTH EFFECTS

that contain fluoride. Actual exposure was unknown because the workers wore respirators. Although

urinary fluoride levels increased over the course of one work shift in the high-exposure group and not in

the control group, the decrease in respiratory volume in the same time period was about the same in both

groups (Chan-Yeung et al. 1983a). This effect was attributed to the fact that the exposed workers wore

respirators; historical use of respirators was not reported. Because actual exposure was not known, no

quantitative relationship between clinical symptoms and environmental or urinary fluoride levels could be

established. There also may have been concomitant exposure to other respiratory irritants.

Fluoride Particulates. There is limited information on the respiratory toxicity of fluorides. Significant

increases in relative lung weight were observed in mice exposed to 13.3 mg F/m3 as sodium fluoride

4 hours/day for 10, 20, or 30 days (Chen et al. 1999). The toxicological significance of this effect is not

known because histopathology was not conducted. In another study of mice (Yamamoto et al. 2001),

lung damage, as evidenced by significant decreases in total cells and alveolar macrophages and increases

in polymorphocytic neutrophils and lymphocytes in the bronchoalveolar lavage fluid, was found in mice

exposed to 10 mg F/m3 as sodium fluoride 4 hours/day for 14 days. An increase in polymorphocytic

neutrophils was also observed at 5 mg/m3.

Fluorine. Limited data are available regarding respiratory effects of fluorine on humans. Five volunteers

(19–50 years of age; gender not specified) were exposed to fluorine through a face mask that covered the

eyes and nose but not the mouth (Keplinger and Suissa 1968). A concentration of 10 ppm was not

irritating to the respiratory tract for at least 15 minutes. Slight nasal irritation was reported following a

3-minute exposure to 50 ppm, and exposure to 100 ppm for 0.5 or 1 minute was very irritating to the

nose. Intermittent inhalation (3–5-minute exposure every 15 minutes for 2–3 hours) of 23 ppm did not

cause respiratory difficulty.

An occupational cohort study comparing the incidence of respiratory complaints by 61 exposed workers

with over 2,000 "unexposed" workers found no increase in the exposed group (Lyon 1962). The average

fluorine level was 0.9 ppm, and the maximum measured value was 24 ppm. The study author concluded

that the workers became "hardened" to the irritating effects of fluorine. The study is limited in that both

groups were also exposed to uranium hexafluoride and hydrogen fluoride. The method of measuring

respiratory complaints (visits to the plant medical department) was also not very sensitive. However, the

observation of tolerance caused by repeated low level exposures is supported by the results from animal

studies discussed in Section 3.2.1.1 and later in this section (Keplinger 1969).


3. HEALTH EFFECTS

Diffuse lung congestion has been reported in rats, mice, guinea pigs, dogs, and rabbits exposed to fluorine

for 5–60 minutes (Keplinger and Suissa 1968). The severity was concentrated-related. The adverse

effect levels for each exposure duration did not appear to vary across species. The ranges of adverse

effect levels for each exposure duration were 174–175 ppm for 5 minutes, 87–100 ppm for 15 minutes,

67–71 ppm for 30 minutes, and 47–135 ppm for 60 minutes. Other respiratory effects that were observed

in these animals included dyspnea, irritation, and alveolar necrosis.

In 5-week exposure studies conducted by Stokinger (1949), pulmonary hemorrhage, edema, and bronchial

inflammation were reported. These studies found species differences in sensitivity to fluorine-induced

respiratory effects. Exposure to 2 ppm, 6 hours/day, 6 days/week for 5 weeks resulted in no effects in

rats, pulmonary hemorrhage and edema in dogs, and mild bronchial inflammation in rabbits; respiratory

effects (severe pulmonary irritation) were observed in rats exposed to 18 ppm.

Swiss-Webster mice that were preexposed once to 30 ppm fluorine for 60 minutes and then exposed to

118–410 ppm fluorine for 15 minutes after an interval of 4–96 hours showed markedly less lung

pathology than animals that were not pretreated (Keplinger 1969). At the highest level (410 ppm),

exposure 4 hours prior to the challenge reduced the lung pathology from the most severe rating to a rating

of normal–mild. Preexposure also reduced the increased lung weight otherwise seen following fluorine

exposure. However, a similar preexposure regimen only resulted in slight increases in the LC50, as

discussed in Section 3.2.1.1.

Cardiovascular Effects.

Hydrogen Fluoride. Cardiac arrhythmias have been seen in humans following hydrofluoric acid splashes

in the face region, where both dermal and inhalation exposures were involved (Chan et al. 1987;

Tepperman 1980). It is not known whether inhalation exposure alone would cause these effects.

However, myocardial necrosis and congestion were observed in three rabbits following inhalation

exposure of 26 ppm fluoride as anhydrous hydrogen fluoride for an unspecified period (Machle et al.

1934). The study was limited by the small sample size and undetermined exposure period.

Gastrointestinal Effects.

Hydrogen Fluoride. A population exposed to airborne hydrogen fluoride near a smelter reported nausea

(22.6%) and diarrhea (21.7%). The corresponding levels reported by a control population were 6.9 and

12.1%, respectively. The total levels of gastrointestinal complaints were 70.5 and 36.2% in the subject


3. HEALTH EFFECTS

and control populations, respectively. The subject population appears to have been derived by self-

selection and random house-to-house sampling, while the control population lived in a nonindustrial area.

Although atmospheric concentrations were not presented, concentrations of fluoride in animals and plants

in the area surrounding the smelter were substantially above normal. The smelter was also reported to

emit metallic oxide fumes (Waldbott 1979).

Similar gastrointestinal effects (diarrhea, nausea, and vomiting) were reported by Texas residents exposed

to an accidental 2-hour release of hydrogen fluoride (Dayal et al. 1992). During the first month after the

accident, 38.5% of the highly exposed residents reported severe gastrointestinal effects; 15.5% of the

residents still reported severe gastrointestinal effects 2 years after the accident. The occurrence of severe

gastrointestinal effects among nonexposed residents was 4.5 and 2.7%, respectively, for these time

periods.

Hematological Effects.

Hydrogen Fluoride. Hemograms of 20 variables (not specified) determined in the rat (30/group), rabbit

(10/group), and dog (4/group) following exposure to 18 ppm fluoride for 6 hours/day, 6 days/week, for

5 weeks showed no clear changes (Stokinger 1949).

Five rabbits and two Rhesus monkeys were exposed to 18 ppm fluoride as hydrogen fluoride via

inhalation 6–7 hours/day, for 50 days (Machle and Kitzmiller 1935). Blood counts were done beginning

1 week prior to exposure and ending 3 months after the final exposure. There was a small but significant

decrease in erythrocyte levels in both species, but the study authors considered that the result may have

been due to biological variation. Significant increases in hemoglobin levels were seen in monkeys. There

was no effect on hemoglobin levels in rabbits or on leukocyte levels in either species. These experiments

used only a few animals from each species, and the exposure measurement technology was not very

precise.

Hydrogen Fluoride and Fluoride Dusts. No signs of hematological effects, as measured by routine

blood counts, were seen in a large cohort of aluminum workers exposed to total fluoride levels below

2.5 mg/m3 for durations of at least 10 years (Chan-Yeung et al. 1983b). Similarly, no increase in

abnormal findings was seen in 74 workers exposed at a phosphate fertilizer plant (Derryberry et al. 1963).

The average urinary fluoride level in the exposed group was 4.6 mg/L. Significantly reduced levels of

hemoglobin were reported in Slovak children aged 6–14 years living near an aluminum smelter (Macuch

et al. 1963), but no information was provided on any statistical tests used. No information was provided


3. HEALTH EFFECTS

on air fluoride concentrations, but urinary fluoride levels were about 0.8 mg/L for 6–11-year-old children

and about 0.4 mg/L for 12–14-year-old children. In an outdated study of 78 workers exposed to cryolite,

anemia was present in 11/30 subjects with pathological bone changes (Moller and Gudjonsson 1932).

Blood parameters were not analyzed for the workers without bone changes.

Fluorine. No studies were located on hematological effects of inhalation exposure of humans to fluorine.

No effect on complete blood count parameters was observed in Osborne-Mendel rats exposed to 142 ppm

for 60 minutes or 329 ppm for 15 minutes or in dogs exposed to 109 ppm for 60 minutes or 93 ppm for

15 minutes (Keplinger and Suissa 1968). These concentrations were higher than the corresponding

LC50 values. Blood counts were monitored for 21 days postexposure. Similarly, Stokinger (1949) saw no

effect on hematological parameters in dogs, rabbits, or rats following repeated exposures at

concentrations up to lethal levels (31 ppm). This study did not specify which parameters were measured.

Musculoskeletal Effects.

Fluoride. There are several case reports of radiological alterations (primarily thickening of the bone) in

workers exposed to sodium fluoride (McGarvey and Ernstene 1947), rock phosphate dust containing

3.88% fluoride (Wolff and Kerr 1938), or cryolite (Roholm 1937). In the two cryolite workers, the

fluorine content of the costa bone was 10-fold higher than in non-exposed individuals. Roholm (1937)

also examined 68 cryolite workers exposed to high levels (35 mg/m3) of cryolite dust. Approximately

35% of the workers complained of “rheumatic attacks, pains, or feeling of stiffness” and reduced mobility

was found in approximately 21% of the workers. Radiological examinations revealed diffuse

osteosclerosis in approximately 84% of the workers.

No studies were located regarding musculoskeletal effects in animals after inhalation exposure to fluoride.

Hydrogen Fluoride. Human data on the musculoskeletal effects of hydrogen fluoride (in the absence of

concomitant exposure to fluoride dusts) are limited to a case report of a worker employed at an alkylation

unit of an oil company (Waldbott and Lee 1978). The worker complained of back pains, leg pains, and

loss of memory and was diagnosed with advanced osteoarthritis of the spine. The data presented in this

report are inadequate to assess whether the back and leg pains were related to hydrogen fluoride exposure,

the osteoarthritis, or a petroleum product.

Duration- and concentration-related increases in tooth and bone fluoride levels were reported in the rat

following exposure to 8.2 or 31 ppm fluoride as hydrogen fluoride for 6 hours/day, 6 days/week for


3. HEALTH EFFECTS

5 weeks (Stokinger 1949). The study author did not report whether there were any visible or radiological

signs of dental or skeletal fluorosis.

Hydrogen Fluoride and Fluoride Dusts. Marked evidence of skeletal fluorosis was reported in workers

exposed to gaseous fluoride (largely hydrogen fluoride) and fluoride dust in the pot rooms of the

aluminum industry (Kaltreider et al. 1972). Individual exposure concentrations and durations were not

presented. However, the estimated time-weighted average (TWA) 8-hour exposure to total fluorides for

one plant ranged from 2.4 to 6.0 mg/m3. Average post-shift urinary fluoride levels were about 9 mg/L.

Exposure at a second plant was lower as a result of industrial hygiene measures; no TWA was available,

but post-shift urinary fluoride levels ranged from 1.4 to 4.6 mg/L. No skeletal changes were observed at

the second plant, and detailed physical examinations of the workers at both plants revealed no general

health impairment. No data were presented that correlated urinary fluoride levels to the presence or

absence of fluorosis.

In a follow-up study of 59 of the potroom workers at the second plant, the average preshift (after 48 hours

away from work) urinary fluoride level was 2.24 mg/L (range, 1.4–3.1). The average level after 3–

5 working days (postshift) was 5.68 mg/L (range, 2.7–10.4). In spite of this evidence of fluoride

exposure, there was no radiological evidence of any fluoride-related bone abnormalities (Dinman et al.

1976c). Total occupational exposure ranged from 10 to 43 years. This study may provide urinary

fluoride levels that are not associated with any bone effects in healthy adults. However, because only

workers who remained at the high-exposure tasks for the duration of the study were examined, any

sensitive population that may have found work elsewhere because of adverse health effects might have

been missed.

Clinical and radiological investigations were performed for 2,258 aluminum workers exposed to fluoride

for an average of 17.6 years (Czerwinski et al. 1988). The form of fluoride was not reported, but it was

probably hydrogen fluoride and fluoride dust. Possible fluorosis (multiple joint pains, limited motion in

at least two joints or in the spine, and initial ossifications visible on x-ray films) was found in 14% of the

workers. Indications of early skeletal fluorosis (advanced painful symptoms, advanced limitation of

motion in at least two joints or spine, marked ossifications on two or more x-rays, initial osteosclerosis,

slight periosteal reaction, and thickening of long bone cortices ) were found in 5.12% of the workers and

definite fluorosis (stage I) was found in 1.0% of the workers. The study authors reported finding a close

positive correlation between the occurrence of fluorosis and the time and level of fluoride exposure.

Another health study of 2,066 workers in an aluminum smelter reported early signs of skeletal fluorosis


3. HEALTH EFFECTS

(mild increase in bone density, periosteal changes, calcifications of ligaments) in a few pot room workers

employed for >10 years. The study authors noted that there was poor agreement on early signs of

fluorosis among the two radiologists reading the x-ray films. No effects were seen in workers exposed for

<10 years. Actual airborne fluoride levels measured at the time of the health assessment were 0.2 mg/m3

hydrogen fluoride and 0.28 mg/m3 fluoride dusts. Historical fluoride levels were not reported; although

the study authors implied that exposure levels had been below 2.5 mg/m3 for some period (Chan-Yeung et

al. 1983b).

Skeletal fluorosis was also observed in workers involved in study the crushing and refining of cryolite

(Moller and Gudjonsson 1932). Thirty-nine of the 78 examined workers showed evidence of skeletal

fluorosis in the form of dense calcification in the long bones, cartilage, and in extreme cases, of the skull

as well. Although an average exposure period was not presented, no workers with <2 years of exposure

were included; some workers had been exposed for as long as 40 years.

While the above studies generally found radiologically-apparent skeletal fluorosis appearing prior to or

concurrent with musculoskeletal symptoms, Carnow and Conibear (1981) found musculoskeletal

symptoms in aluminum workers in the absence of radiological findings. Questionnaire answers suggested

a significant increase in incidence and severity of musculoskeletal disease and fracture frequency with

fluoride exposure. By contrast, there was no exposure-related increase in evidence of skeletal fluorosis

on chest and spinal x-ray films. Neither radiologic data nor actual exposure levels or durations were

reported. As the authors recognized, the exposure group was heterogeneous and was exposed to other

chemicals, and some of the musculoskeletal symptoms may have actually been due to heavy physical

labor.

Fluorine. No data were located regarding musculoskeletal effects of fluorine inhalation on humans.

Fluoride levels in the teeth of rats exposed to 18 ppm fluorine for approximately 6 hours/day, 6 days/week

for 5 weeks were about 14 times the levels in controls; fluoride levels in the femur were about 6 times that

of the controls (Stokinger 1949). The appearance of the teeth was characterized as corresponding to that

of very mild to mild dental fluorosis. The fluoride levels in the teeth and bone at lower concentrations

decreased in a concentration-related manner. Pigment changes were reported as just perceptible in

animals exposed to 2 ppm fluorine.


3. HEALTH EFFECTS

Hepatic Effects.

Hydrogen Fluoride. Ten animals (five rabbits, three guinea pigs, and two Rhesus monkeys) were

exposed via inhalation to 18 ppm fluoride as hydrogen fluoride 6–7 hours/day for 50 days (Machle and

Kitzmiller 1935). Fatty degeneration of the liver parenchyma, scattered focal necroses, and fibroblastic

encroachment of periportal spaces were observed in the guinea pigs. Two of the three guinea pigs began

losing weight after about 145 hours of exposure, were withdrawn from the exposure regimen, and died

about 2 weeks later. Generalized fatty changes were also seen in two of four rabbits sacrificed 7 months

after exposure termination. These experiments used only a few animals from each species, and the

exposure measurement technology was not very precise.

Hydrogen Fluoride and Fluoride Dusts. The occupational health study by Chan-Yeung et al. (1983b)

discussed above revealed no adverse effects on liver function, as measured by levels of total bilirubin,

serum glutamic oxaloacetic transaminase (SGOT), and alkaline phosphatase.

Fluorine. No studies were located regarding hepatic effects of fluorine inhalation in humans. Mice

exposed to fluorine exhibited coagulation necrosis of the liver, periportal hemorrhages, and diffuse cloudy

swelling (Keplinger and Suissa 1968). These effects were generally observed after exposure to

concentrations of 195, 144, 116, or 80 ppm fluoride for 5, 15, 30, or 60 minutes, respectively. Damage

became apparent 7–14 days after exposure. Liver congestion was reported in dogs, but not in other

species subjected to repeated exposures to a lethal concentration of fluorine (18 ppm 6 hours/day,

6 days/week for 5 weeks) (Stokinger 1949).

Renal Effects.

Hydrogen Fluoride. Pathologically elevated serum creatinine and urea levels were seen 24 hours after

accidental dermal and inhalation exposure to a mixture of 70–80% sulfuric acid and 10% hydrofluoric

acid at 150 °C (Braun et al. 1984). Neither the effect of the sulfuric acid nor the exposure levels were

known.

Degeneration and necrosis of the renal cortex was reported in 27/30 rats exposed to 31 ppm fluoride as

hydrogen fluoride for 6 hours/day, 6 days/week for 5 weeks, but not in rats exposed to 8.2 ppm fluoride

(Stokinger 1949). Pathological examination of rabbits and guinea pigs (n=3/species/exposure level)

exposed to hydrogen fluoride revealed tubular necrosis, congestion, and edema (Machle et al. 1934). A

variety of different exposure levels and durations were tested, but the levels at which exposure-related


3. HEALTH EFFECTS

effects were seen were not reported. Rabbits (n=4) exposed via inhalation to 18 ppm fluoride as

hydrogen fluoride 6–7 hours/day for 50 days developed degeneration and necrosis of convoluted tubules,

accompanied by fibrous tissue replacement of cortical tissues (Machle and Kitzmiller 1935).

Degenerative and inflammatory changes were also seen in the single exposed monkey at necropsy. The

experiments described in both of these papers used a small number of animals and no control data were

presented.

Hydrogen Fluoride and Fluoride Dusts. Increased incidence of albuminuria (p<0.1) was observed in

phosphate fertilizer plant workers with an average urinary fluoride level of 4.6 mg/L (Derryberry et al.

1963). However, the testing method used in this study is considered to be hypersensitive (Dinman et al.

1976a), and several other studies have found no effects. No signs of renal effects, as measured by

standard renal function tests, were seen in a large cohort of aluminum workers exposed to total fluoride

levels estimated to be below 2.5 mg/m3 (Chan-Yeung et al. 1983b). Two other studies of aluminum

workers failed to find an increase in the incidence of albuminuria (Dinman et al. 1976c; Kaltreider et al.

1972). Average postshift urinary fluoride levels were ≤5.68 mg/L (Dinman et al. 1976c) and ≤9.6 mg/L

(Kaltreider et al. 1972). The exposed population included workers exposed to estimated air fluoride

levels of 4–6 mg/m3 (time-weighted average), of which 50% was gaseous fluoride (presumably hydrogen

fluoride) (Kaltreider et al. 1972).

The weight-of-evidence indicates that typical inhalation occupational exposure to hydrogen fluoride and

fluoride dust is not nephrotoxic. The overall animal data indicate that inhalation exposure to sufficiently

high levels of hydrogen fluoride or fluorine can cause kidney damage, but the relevance to human health

and the potential nephrotoxic level cannot be determined because of generally incomplete human and

animal data. In addition, only one animal experiment was located that conducted a histopathic exam

following fluorine exposure.

Fluorine. No studies were located regarding renal effects of fluorine inhalation in humans. Mice

exposed to fluorine exhibited focal areas of coagulation necrosis in the renal cortex and focal areas of

lymphocyte infiltration in the cortex and medulla following exposure to 114 ppm for 5 minutes, 82 ppm

for 15 or 30 minutes, or 55 ppm for 60 minutes (Keplinger and Suissa 1968). Damage became apparent

7–14 days postexposure.

Endocrine Effects. No studies were located regarding endocrine effects in humans or animals after

inhalation exposure to fluoride, hydrogen fluoride, or fluorine.


3. HEALTH EFFECTS

Dermal Effects.

Hydrogen Fluoride/Hydrofluoric Acid. Dermal exposure to hydrogen fluoride can cause irritation of the

skin and mucous membranes. Residents exposed to hydrogen fluoride following an accidental release

reported a number of skin effects including itching, burning, and rash; 43.8% of the highly exposed

residents reported severe skin problems, as compared to 5.3% of nonexposed residents (Dayal et al.

1992). Two years after the accident, severe skin problems were reported by 21.9% of the high-exposure

group compared to 2.7% of the control group. “Smarting" of exposed skin occurred in humans within

1 minute of exposure to hydrogen fluoride at about 122 ppm fluoride (Machle et al. 1934). This was the

highest concentration that two male volunteers could tolerate for >1 minute. Repeated exposures did not

reveal any habituation.

Exposure to hydrogen fluoride levels approaching the LC50 can cause lesions of the face in rats (Haskell

Laboratory 1988). Rats exposed to hydrogen fluoride (whole body) at a concentration of approximately

1,395 ppm fluoride for 60 minutes were observed to have erythema of an unspecified severity of the

exposed skin (Wohlslagel et al. 1976). Subcutaneous hemorrhages around the eyes and on the feet

developed in rats exposed to 8.2 or 31 ppm fluoride as hydrogen fluoride for 6 hours/day, 6 days/week for

5 weeks (Stokinger 1949). The effect was more severe at the higher exposure level. Dogs exposed to

31 ppm fluoride for the same time periods developed inflammation of the scrotal epithelium.

Fluorine. When the shaved backs of New Zealand rabbits were exposed to fluorine gas under 40 pounds

of pressure for 0.2–0.6 seconds at distances of 0.5–1.5 inches, the resulting burn appeared to be thermal,

rather than chemical in nature (Stokinger 1949). Exposure for 0.2 seconds produced an ischemic area

about ¼ inch in diameter, surrounded by an erythematous area. This became a superficial eschar that

sloughed off within 4 days, revealing normal epidermis. The longer exposures produced a flash of flame

that resulted in combustion of hair, singeing, and erythema over an area several times the area of the

primary burn. Coagulation necrosis and charring of the epidermis was also reported. The wound healed

within 13 days. The burns resembled those produced by an oxyacetylene flame, rather than those made

by hydrofluoric acid, and so were characterized as thermal, rather than chemical. However, it is not clear

if the difference from the hydrofluoric acid burn is due to the shorter exposure to fluorine.


3. HEALTH EFFECTS

Ocular Effects.

Hydrogen Fluoride. Marked conjunctival irritation was noted in humans within 1 minute of exposure to

hydrogen fluoride at about 122 ppm fluoride (Machle et al. 1934). This was the highest concentration

that two male volunteers could tolerate for >1 minute. At 61 ppm fluoride, conjunctival and nasal

irritations were still marked, and tickling and discomfort of the nasal passages were reported. A

concentration of 32 ppm fluoride produced mild irritation of the nose and eyes and irritation of the larger

air passages. This concentration could be tolerated for "several" minutes (at least 3 minutes). The

authors of this study reported some difficulties with their measurements of exposure. Repeated exposures

did not reveal any habituation.

Severe symptoms of eye problems were reported by 63.2% of Texas residents exposed to high levels of

hydrogen fluoride following an accidental release (Dayal et al. 1992). The most commonly reported eye

effects were redness, itching, and burning or irritation. Two years after the accident, 11.5% of the

population still reported severe eye problems. In nonexposed residents, the prevalence of severe

symptoms within the first month of the accident was 7.4; 2 years later, the prevalence was 4.9.

Mild eye irritation was observed in five volunteers exposed 6 hours/day for 15–50 days, to hydrogen

fluoride at concentrations averaging from approximately 0.85 to 7.7 ppm fluoride; the mean of the

average concentrations was 2.98 ppm (Largent 1960). This study is limited by the inadequacy of both the

experimental details and the description of effects observed.

Hydrogen fluoride levels approaching the LC50 can cause corneal opacity in rats (Haskell Laboratory

1988), while slight ocular irritation was observed in rats exposed to levels as low as 6% of the LC50

(Rosenholtz et al. 1963). Eye irritation, evidenced by pawing of eyes, was observed in rats exposed to

140 or 175 ppm fluorine for 30 or 5 minutes, respectively, and in dogs exposed to 68 or 93 ppm fluorine

for 60 or 15 minutes, respectively. In experiments with exposure for durations of 15–60 minutes, eye and

nose irritation was reported only at ~50% of the LC50. Similar results were obtained with Swiss-Webster

mice, New England guinea pigs, and New Zealand rabbits (Keplinger and Suissa 1968).

Fluorine. Volunteers (19–50 years of age) were exposed to 10 ppm fluorine for 15 minutes without

discomfort or irritation of the eyes or nose (Keplinger and Suissa 1968). However, repeated exposures to

10 or 23 ppm fluorine for 3–5 minutes every 15 minutes over a 2–3-hour period caused slight eye

irritation. Exposure was through a face mask that covered the eyes and nose but not the mouth. Eye

irritation was also reported following exposure to 50 ppm for 3 minutes and 67 and 78 ppm for 1 minute.


3. HEALTH EFFECTS

Exposure to 100 ppm was very irritating and became uncomfortable after a few seconds. At this

concentration, the subjects reported that the eyes burned and felt as though they were covered by a film.

Body Weight Effects.

Hydrogen Fluoride. Pronounced weight loss shortly before death was observed in rats exposed to a

lethal level of hydrogen fluoride (31 ppm fluoride for 6 hours/day, 6 days/week for 5 weeks). Guinea

pigs exposed under the same conditions lost weight following the third exposure week, even though there

were no deaths (Stokinger 1949). While a decrease compared to the low-exposure level group is clear, no

control animals were used and the lowest exposure level that would result in a significant change was not

established. Animals surviving a lethal exposure exhibited a body weight loss of 10–15% for up to a

week after exposure (Rosenholtz et al. 1963; Stavert et al. 1991).

Fluorine. Decreased weight gain was observed in rats, guinea pigs, and rabbits exposed to 18 ppm

fluorine for about 6 hours/day, 6 days/week for 5 weeks (Stokinger 1949). While a decreased weight gain

in the high-exposure group compared to the low-exposure groups is clear, no control animals were used

and the lowest exposure level that would result in a significant change was not established.

3.2.1.3 Immunological and Lymphoreticular Effects

No studies were located regarding immunological effects in humans or animals after inhalation exposure

to hydrogen fluoride or fluorine.

Fluoride Particulates. A significant decrease in pulmonary bactericidal activity was observed in mice

challenged for 30 minutes with aerosol inhalation of Staphylococcus aureus following a 14-day exposure

(4 hours/day) to 5 or 10 mg F/m3 as sodium fluoride (Yamamoto et al. 2001). Bactericidal activity was

not significantly altered in mice exposed to 2 mg/m3. The highest NOAEL values and all reliable LOAEL

values for immunologic effects in each species and duration category of inhalation exposure to fluoride

are recorded in Table 3-3 and plotted in Figure 3-3.


3. HEALTH EFFECTS

3.2.1.4 Neurological Effects

Hydrogen Fluoride. The threshold of the light adaptive reflex was measured as a marker for neurological

effects in three subjects following exposure to hydrogen fluoride at concentrations of 0.02, 0.03, or

0.06 ppm fluoride (Sadilova et al. 1965). While the threshold level was determined to be 0.03 ppm, it is

not clear whether this response is due to irritation of mucous membranes or is the result of an effect on

cerebral cortical function. The toxicological significance of a change in light adaptive reflex is not

known.

Exposure to concentrations at about 50% of the LC50 values was reported to cause general weakness and

decreased activity in Wistar rats (Rosenholtz et al. 1963). Albino rats given 24-hour exposures to either

0.03 or 0.1 ppm fluoride as hydrogen fluoride for 5 months developed central nervous system

dysfunctions, as evidenced by diminished conditioned responses and increased time before motor nerve

response. Histological studies showed changes in the nerve cell synapses of only those animals exposed

to 0.1 ppm. A concentration of 0.01 ppm was found to be without effect on conditioned responses,

latency in motor nerve response, or neurohistological parameters. When additional stresses were added

(alcohol, 24-hour starvation), the conditioned responses were extinguished more frequently (Sadilova et

al. 1965). Some recovery in conditioned responses was seen following a 1-month recovery period in the

animals exposed to 0.1 ppm. Animals exposed to 0.03 ppm recovered completely.

All reliable LOAEL values for neurological effects of exposure to hydrogen fluoride in each species and

duration category are recorded in Table 3-1 and plotted in Figure 3-1.

Fluorine. No studies were located regarding neurological effects in humans of fluorine following

inhalation exposure. Dogs exposed to 5 or 18 ppm for 6 hours/day, 6 days/week for up to 35 days had

seizures prior to death (Stokinger 1949). Because no further details were available, the neurotoxic

potential of fluorine cannot be evaluated.

3.2.1.5 Reproductive Effects

No studies were located regarding reproductive effects in humans after inhalation exposure to fluoride,

hydrogen fluoride, or fluorine, and no studies were located regarding reproductive effects in animals after

inhalation exposure to fluoride.


3. HEALTH EFFECTS

Hydrogen Fluoride. All four dogs exposed to 18 ppm fluoride as hydrogen fluoride for 6 hours/day,

6 days/week for 5 weeks developed degenerative testicular changes and ulceration of the scrotum

(Stokinger 1949). This effect was not seen at 8.2 ppm, or in rabbits or rats at either exposure level. No

further details were available. Furthermore, it is not clear whether this is a systemic effect or a result of

irritation from dermal contact with the gas.

Fluorine. Rats exposed to 18 ppm fluorine, 6 hours/day, 6 days/week for 5 weeks showed testicular

degeneration (Stokinger 1949). No further details were available. It is not clear whether this effect was

seen both in animals that died and in those that survived.

3.2.1.6 Developmental Effects

No studies were located regarding developmental effects in humans or animals after inhalation exposure

to fluoride, hydrogen fluoride, or fluorine.

3.2.1.7 Cancer

Hydrogen Fluoride and Fluoride Dusts. Most occupational exposure to fluoride occurs as a result of

inhalation of hydrofluoric acid fumes or dust from cryolite or fluorspar. A cohort of cryolite workers in

Denmark was reported to have an increase in mortality and morbidity from respiratory cancer compared

with the national average (standardized mortality ratio [SMR] of 2.52, 95% confidence interval of 1.40–

4.12, Standardized Incidence Ratio of 2.5 , 95% confidence interval of 1.6–3.5) (Grandjean et al. 1985).

The study authors stated that the increase can be explained by the fact that the respiratory cancer death

rate for the Copenhagen area is about twice the national average for the birth cohorts from 1890 to 1929,

so that comparison with national rates may not be appropriate. Respiratory cancer rates for the workers

were slightly higher than those of the general population of Copenhagen (standardized incidence ratio of

1.5, 95% confidence interval of 1.0–2.1). No apparent relationship between incidence of all cancers and

the length of employment or latency period was found. Significant increases in cancer mortality,

particularly respiratory cancer, were also found in a follow-up study of this cohort (Grandjean et al.

1992). The SMR for all cancer was 1.34 (95% confidence interval of 1.2–1.50) compared to Danish

national rates and the standardized incidence ratio for lung cancer was 1.40 (95% confidence interval

of 1.01–1.90) compared with rates for Copenhagen. Additionally, a significant increase in bladder cancer


3. HEALTH EFFECTS

incidence was seen (standardized incidence ratio of 1.84, 95% confidence interval of 1.08–2.96). The

investigators noted that smoking habits may have accounted for some of the lung cancer risk.

Increased lung cancer rates have been reported in several studies of aluminum industry workers

(Andersen et al. 1982; Gibbs and Horowitz 1979; Milham 1979), but no correction was made for smoking

or concurrent exposure to tars and polycyclic aromatic hydrocarbons. Similarly, fluorspar miners had

increased lung cancer rates, but they were also exposed to elevated radon levels (deVilliers and Windish

1964). A cohort study of 21,829 workers in aluminum reduction plants for ≥5 years did not find an

increase in lung cancer, but did report an increase in mortality due to pancreatic cancer, lymphohemato-

poietic cancers, genitourinary cancer, and nonmalignant respiratory disease (Rockette and Arena 1983).

Only the effect on pancreatic cancer rates was statistically significant. Increases in incidence of

hematopoietic cancers and respiratory disease were also reported by Milham (1979). Because of the

confounding factors mentioned above, and because no breakdown was done by fluoride exposure, these

studies are of questionable relevance to the issue of possible carcinogenicity of inhalation exposure to

hydrogen fluoride and/or fluorides.

A study was published describing a positive relationship between increased lung cancer occurrence and

exposure to fluoride among individuals residing near, or working in, the steel industry (Cecilioni 1972).

Possible occupational exposures to other carcinogenic substances from steel and other industries were not

considered. Carcinogenicity via inhalation of fluoride is not considered to be likely by most investigators

reporting in the existing literature.

No studies were located regarding cancer in animals after inhalation exposure to fluoride, hydrogen

fluoride, or fluorine.

3.2.2 Oral Exposure

Because hydrogen fluoride and fluorine are gases, oral exposure to these substances occurs only

concomitant with inhalation exposure. Oral exposure to hydrofluoric acid has been reported very rarely.

Except where otherwise indicated, the following sections on oral exposure refer to oral exposure to

fluoride.

The oral toxicity of fluoride has been investigated in humans and animals. The human database mostly

consists of epidemiology studies designed to assess whether consumption of fluoridated water is


3. HEALTH EFFECTS

associated with adverse health effects, particularly skeletal effects and cancer. Most of these studies are

community-based and do not provide data on individual exposure levels or the particular fluoride

compound. Fluorosilicic acid and sodium hexafluorosilicate are the primary fluoride compounds used in

water fluoridation programs, although exposure to other fluoride compounds, such as

monofluorophosphate, used in dental products also contribute to total fluoride exposure. Additional

information on the toxicity of fluoride in humans comes from studies of communities with naturally high

levels of fluoride in the drinking water and experimental studies typically involving exposure to sodium

fluoride. Animal studies have primarily involved exposure to sodium fluoride in drinking water or the

diet. A few animal studies also examined the toxicity of fluoride following exposure to calcium fluoride,

cryolite, and fluoride from rock phosphate. For all forms of fluoride discussed, doses are reported as

amount of the fluoride ion.

Conflicting results have been obtained from animal experiments addressing whether fluorine is an

essential element. Much of this conflict appears to result from the great difficulty in preparing an animal

diet that has negligible amounts of fluoride, but otherwise allows normal animal growth and development.

As discussed in Section 3.2.2.6, there have been suggestions that fluoride can aid fertility by improving

intestinal absorption of iron and other trace elements (Messer et al. 1973; Tao and Suttie 1976). In a

study where fluoride was rigorously removed from dietary components, a total of 110 Wistar rats were

observed over the course of four generations (Maurer and Day 1957). There were no adverse effects

compared to controls that received the same diet and 0.28 mg fluoride/kg/day in drinking water. Animals

fed the low-fluoride diet were healthy, had sleek coats and healthy teeth, and had similar weight gains to

those of the controls. Low success in bringing pups to weaning (50%) was reported for both the low-

fluoride and control groups. No fluoride was detectable in the diet (detection limit not reported), and

fluoride levels in femurs were ≤8.8 ppm fluoride in bone ash. In a more recent study, dose-dependent

increases in daily weight gain of F344 rats were observed when a low-fluoride diet was supplemented

with fluoride (Schwarz and Milne 1972). The fluoride provided by the basal diet varied, but was

sometimes 0.023 mg/kg/day and occasionally dropped below 0.002 mg/kg/day. However, the results are

likely to be due to other nutritional deficiencies that were partially compensated by fluoride. Rats in both

the control and low-fluoride groups had shaggy fur, loss of hair, and seborrhea. Fluoride was only

partially effective in correcting the bleached incisors found in the low-fluoride group. Bleached incisors

have been related to deficiencies of calcium, phosphorus, magnesium, iron, and vitamins E, D, and A.

None of these studies provide strong evidence that fluoride is an essential element.


3. HEALTH EFFECTS

Several organizations consider fluoride to be an important dietary element for humans. The Institute of

Medicine (IOM 1997) has derived adequate intake values ranging from 0.01 to 4 mg/day to reduce the

occurrence of dental caries. Adequate intake values broken down by age group are 0–6 months,

0.01 mg/day; 7–12 months, 0.5 mg/day; 1–3 years, 0.7 mg/day; 4–8 years, 1 mg/day; 9–13, 2 mg/day;

14–18 years, 3 mg/day; 19 years and older, 4 mg/day (males) and 3 mg/day (females); pregnancy,

3 mg/day; and lactation, 3 mg/day. Using body weight data reported by IOM (2000), these dietary intakes

are equivalent to doses of approximately 0.05 mg/kg/day for ages 6 months to >18 years; the dose in

infants 0–6 months is 0.0014 mg/kg/day. The World Health Organization (WHO) considers fluoride to

be “essential” because it considered “resistance to dental caries to be a physiologically important

function” (WHO 2002).

3.2.2.1 Death

Fluoride. Fatal ingestion of sodium fluoride has been reported as early as 1899 (Sharkey and Simpson

1933). A summary of early fatalities indicates that the primary symptoms were the sudden onset of

nausea and vomiting, accompanied by burning, cramp-like abdominal pains and diarrhea. Clonic

convulsions and pulmonary edema were reported in some cases; the pulmonary edema may have been

due to aspiration of vomitus. While a few of these deaths were suicides, most of them resulted from

accidental exposure to sodium fluoride when containers of insecticide were mistaken for baking powder

or epsom salts. Based on numerous incidents of fatal fluoride poisoning, Hodge and Smith (1965)

estimated the certainly lethal dose to be 5–10 g sodium fluoride (32–64 mg fluoride/kg) in adults.

More recent information includes the case report of a 3-year-old boy who swallowed 200 sodium fluoride

tablets (1 mg fluoride each) for a dose of 16 mg fluoride/kg body weight (Eichler et al. 1982).

Immediately after ingestion, he vomited and appeared to recover, but he collapsed 4 hours later. The boy

died 7 hours after fluoride ingestion. Upon autopsy, hemorrhagic edema of the lungs, hemorrhagic

gastritis, and massive cerebral edema were observed. The hemorrhagic edema observed in the lungs was

probably due to aspiration of the gastric contents. Cloudy swelling was observed in the cells of the liver,

heart, and kidney. In another case, a 27-month-old child died 5 days after ingesting about 100 fluoride

tablets, for a dose of about 8 mg fluoride/kg body weight (Whitford 1990). Based on this case and weight

tables for 3-year-old boys, Whitford (1990) calculated a probable toxic dose of about 5 mg fluoride/kg

body weight.


3. HEALTH EFFECTS

Erickson (1978) examined the possible relationship between water fluoridation and increased death rate

among residents of 24 cities with fluoridation and 22 cities without water fluoridation. Although there

was a difference in crude death rates for all causes between the two study populations (1,109.9 and

1,053.6/100,000 person-years for the fluoridation and non-fluoridation populations, respectively), similar

death rates (1,123.9 and 1,137.1/100,000 person-years, respectively) were found after adjustment for

differences in age, sex, race, and analysis of covariance (median education and city population density

In rats, LD50 values for sodium fluoride administered by oral gavage range from 31 to 126.3 mg

fluoride/kg (DeLopez et al. 1976; Lim et al. 1978; Skare et al. 1986; Whitford et al. 1990). Differences in

rat strains, variations in weight (and presumably differences in ages), and gender differences may account

for the reported differences in LD50 values. LD50 values were higher in younger female rats (52–

54 mg/kg) than in older female rats (31 mg/kg) (DeLopez et al. 1976). LD50 values (84.3–146.3 mg

fluoride/kg) were also estimated in rats administered monofluorophosphate (Whitford et al. 1990). These

LD50 values were similar to the LD50 values for sodium fluoride (85.5-126.3 mg fluoride/kg) measured in

the same study. An LD50 of 44.3 mg fluoride/kg was reported for mice (Lim et al. 1978).

All reliable LD50 and LOAEL values for death in each species and duration category are recorded in

Table 3-4 and plotted in Figure 3-4.

Hydrofluoric Acid. Six deaths were reported to have occurred between 1 and 6 hours following

accidental or intentional ingestion of a rust remover containing hydrofluoric acid (Menchel and Dunn

1984). No dose levels of fluoride were reported. At autopsy, severe hemorrhagic gastritis was noted in

all cases. In one case, hemorrhage and necrosis of the pancreas were also noted. A fatal case of

hydrofluoric acid ingestion occurred when a 29-year-old man drank a mouthful, thinking it was water

(Manoguerra and Neuman 1986). In spite of immediate vomiting, respirations were shallow within an

hour, and the patient died within 2 hours of exposure. Serum calcium and SGOT levels were markedly

depressed. Serum fluoride level was 35 ppm. Another study reported six deaths due to hydrofluoric acid

ingestion (Menchel and Dunn 1984). The major symptoms reported were nausea, thirst, and ulcerations

of the buccal mucosa, followed by the rapid onset of tetany and coma.


No studies were located regarding dermal or ocular effects in humans or animals after oral exposure to

fluoride, hydrogen fluoride, or fluorine.

LOAEL

Less SeriousNOAEL(mg/kg/day) (mg/kg/day)

Seriousa

(mg/kg/day)System

Exposure/Duration/


Species(Strain)

Key tofigure

Reference

Table 3-4 Levels of Significant Exposure to Fluoride - Oral

Chemical Form

ACUTE EXPOSUREDeath

1

(C)

1d1x/d

Eichler et al. 1982

sodium fluoride16 (1 child)

Human

2(Sprague-Dawley) (GW)

1 d1x/d

DeLopez et al. 1976

sodium fluoride52 (LD50 for 150g rats)

54 (LD50 for 80g rats)

31b

(LD50 for 250g rats)

Rat

3(Rochester)

(GW)

1 d1x/d

Lim et al. 1978

sodium fluoride51.6 (LD50)

Rat

4(Sprague-Dawley) (GW)

1 d1x/d

Skare et al. 1986


Rat

5(Sprague-Dawley)

(GW)once Whitford et al. 1990

sodium fluoride126.3 (LD50)M

Rat

6(Sprague-Dawley)


sodium fluoride85.5 (LD50)M

Rat

7(Sprague-Dawley)


Monofluorophosphate146.3 (LD50)M

Rat

8(Sprague-Dawley)


Monofluorophosphate84.3 (LD50)M

Rat

LOAEL


Seriousa

(mg/kg/day)System

Exposure/Duration/


Species(Strain)

Key tofigure

Reference

(continued)Table 3-4 Levels of Significant Exposure to Fluoride - Oral

Chemical Form

9(Swiss)

1 d1x/d

Lim et al. 1978


Mouse

Systemic10

Musc/skel(W)2wk Guggenheim et al. 1976

sodium fluoride9.5 (decreased modulus of

elasticity)

Rat

Reproductive11

32

(G)

5d1x/d

Li et al. 1987a

sodium fluoride

Mouse

Developmental12

(Wistar) (GW)GD 6-19 Guna Sherlin and Verma 2001

sodium fluoride18 (increased percentage of

skeletal and visceralabnormalities)

FRat

1313.21

(Sprague-Dawley) (W)

Gd 6-15daily

Heindel et al. 1996

sodium fluoride

Rat

1413.72

(NewZealand) (W)

Gd 6-19daily

Heindel et al. 1996

sodium fluoride

Rabbit


15(B6C3F1)

(W)

6 modaily

NTP 1990

sodium fluoride67 (increased mortality)

Mouse

16

(W)

6moad lib

NTP 1990

sodium fluoride300c

(increased mortality)M

600 (increased mortality)F

Mouse

LOAEL


Seriousa

(mg/kg/day)System

Exposure/Duration/


Species(Strain)

Key tofigure

Reference


Chemical Form

Systemic17

Endocr

(W)

2 mo7d/wk24hr/d

Bobek et al. 1976

sodium fluoride0.5 (decreased thyroxine levels;

increased T3- resin uptakeratio)

Rat

188.25 F

(CD)Musc/skel

(W)

daily16-19 weeks

Collins et al. 2001a

sodium fluoride10.7 (prominent growth lines on

upper incisors)F

Rat

19(Sprague-Dawley)

Musc/skel

(W)

7d/wk24hr/d

DenBesten and Crenshaw 1984

sodium fluoride10.5 (decr mineral content and incr

proline in tooth enamel matrix)

Rat

2013

(Wistar)Musc/skel

(W)5 wk Harrison et al. 1984

sodium fluoride19 (histological fluorosis; decr

bone growth)

Rat

21(Fischer- 344)

Gastro

(W)

6 modaily

NTP 1990

sodium fluoride7 (hyperplasia of glandular

stomach)

Rat

20Hepatic

20Renal

220.15 M

(Sprague-Dawley)

Musc/skel

(W)

daily16 or 48 weeks

Turner et al. 2001

sodium fluoride0.5 (decreased vertebral strength

and bone mineralization)M

Rat

23Musc/skel

(W)30d Uslu 1983

sodium fluoride14 (delayed healing of broken

bones)

Rat

LOAEL


Seriousa

(mg/kg/day)System

Exposure/Duration/


Species(Strain)

Key tofigure

Reference


Chemical Form

24Hepatic

(W)

280 ddaily

Greenberg 1982a

sodium fluoride0.95 (pale, granular hepatocytes

with fatty vacuoles)

Mouse

25Renal

(W)280d Greenberg 1986

sodium fluoride1.9 (nephron degeneration)

Mouse

26Musc/skel

(W)

4 wk7d/wkdaily

Marie and Hott 1986

sodium fluoride0.8 (incr bone formation rate; slight

decr bone calcium)

Mouse

27(B6C3F1)

Cardio

(W)

6 modaily

NTP 1990

sodium fluoride67 (multifocal mineralization and

degeneration of themyocardium)

Mouse

Musc/skel 5.6 (increased osteoid in femur andtibia)

M

Hepatic 67 (megaolocytosis and syncytialalteration)

Renal 67 (multifocal nephrosis)

Bd Wt 67 (20% decr bw gain)

28Hemato

(GW)

35 d1x/d

Pillai et al. 1988

sodium fluoride5.2 (decr RBC and hemoglobin, incr

WBC)

Mouse

Bd Wt 5.2 (decr body weight)

LOAEL


Seriousa

(mg/kg/day)System

Exposure/Duration/


Species(Strain)

Key tofigure

Reference


Chemical Form

290.06 M

(Kunmin)Musc/skel

(W)

daily100-150 days

Zhao et al. 1998

sodium fluoride3.2 (incisor fluorosis)M

Mouse

0.06 MEndocr 3.2 (decreased radiolabelled iodineuptake)

M

3.2 MBd Wt

30(NS)

Resp

(F)

6 modaily

Purohit et al. 1999

sodium fluoride4.5 (congestion, edema fluid,

desquamation of respiratoryepithelium in lungs)

Rabbit

Neurological31


6 wkdaily

Mullenix et al. 1995

sodium fluoride6 (altered spontaneous behavior)F

Rat

325.5 F


6 wkdaily

Mullenix et al. 1995

sodium fluoride7.5 (altered spontaneous behavior)F

Rat

33(Wistar)

(GW)

60 ddaily

Paul et al. 1998

sodium fluoride9 (decr spontaneous activity)

Rat

Reproductive34


daily30 days

Al-Hiyasat et al. 2000

sodium fluoride10.21 (decreased number of viable

fetuses, increased resorptions)F

Rat

35(CD)

(F)

60 d7d/wk

Araibi et al. 1989

sodium fluoride2.3 (decr seminiferous tubule

diameter)4.5 (50% reduction in fertility, decr

in percentage of seminiferoustubules containing spermatozoaand decr testosterone levels)

Rat

LOAEL


Seriousa

(mg/kg/day)System

Exposure/Duration/


Species(Strain)

Key tofigure

Reference


Chemical Form

36(NS)

(GW)

daily30 d

Chinoy et al. 1992

sodium fluoride2.3 (decreased fertility and sperm

counts)

Rat

37(CharlesFoster) (F)

30 or 50 daysd

Chinoy et al. 1995

sodium fluoride4.5 (decreased sperm motility and

count)

Rat

3810.7 F

(CD)(W)

daily16-19 weeks

Collins et al. 2001a

sodium fluoride

Rat

3921

(Wistar)(W)

daily6 wk

Krasowska and Wlostowski 1992

sodium fluoride

Rat

40(Wistar)

(W)

daily16 wk

Krasowska and Wlostowski 1992

sodium fluoride7.5 (seminiferous tubule atrophy)

Rat

4123

(F)

3 mo7d/wk

Marks et al. 1984

sodium fluoride

Rat

42CharlesFoster (GW)

daily50 d

Narayana and Chinoy 1994

sodium fluoride4.5 (decr testosterone levels and

Leydig cell diameter)

Rat

4316

(Sprague-Dawley)

(W)daily Sprando et al. 1997

sodium fluoride

Rat

LOAEL


Seriousa

(mg/kg/day)System

Exposure/Duration/


Species(Strain)

Key tofigure

Reference


Chemical Form

4416

(Sprague-Dawley)

(W)daily Sprando et al. 1998

sodium fluoride

Rat

45(Swiss)

(F)

30 ddaily

Chinoy and Sequeira 1992

sodium fluoride4.5 (decr sperm motility and count

and infertility)

Mouse

469.5

(Swiss-Webster)

(W)25 wks Messer et al. 1973

sodium fluoride19 (nearly complete infertility)

Mouse

475.2

(GW)

35 d1x/d

Pillai et al. 1988

sodium fluoride

Mouse

48(NS)

(GW)

30 ddaily

Chinoy et al. 1997

sodium fluoride4.5 (decr sperm motility and

viability)

Gn Pig

Developmental49

11.2(CD)

(W)

Gd 1-20daily

Collins et al. 1995

sodium fluoride11.4 (incr in average number of

fetuses per litter with 3+ skeletalvariations)

Rat

5012.2 F

(CD)(W)

daily16-19 weeks

Collins et al. 2001b

sodium fluoride

Rat

5121

(Sprague-Dawley)

(W)

28 wk7d/wk24hr/d

Ream et al. 1983

sodium fluoride

Rat

LOAEL


Seriousa

(mg/kg/day)System

Exposure/Duration/


Species(Strain)

Key tofigure

Reference


Chemical Form

CHRONIC EXPOSURESystemic

520.04Musc/skel

(W)daily Hillier et al. 2000

sodium fluoride

Human

530.15

dMusc/skel

(W)Daily Li et al. 2001

sodium fluoride0.25 (Increased prevalence of bone

fractures)

Human

54Musc/skel

(C)4 yr Riggs et al. 1990

sodium fluoride0.56 (increased fracture rate)

Human

553.9

(Fischer- 344)Resp

(W)103 wk NTP 1990

sodium fluoride

Rat

3.9Cardio

3.9Gastro

3.9Hemato

2.5Musc/skel 4.3 (osteoscleosis)

3.9Hepatic

3.9Renal

3.9Bd Wt

LOAEL


Seriousa

(mg/kg/day)System

Exposure/Duration/


Species(Strain)

Key tofigure

Reference


Chemical Form

567.6

(B6C3F1)Resp

(W)103 wk NTP 1990

sodium fluoride

Mouse

7.6Cardio

7.6Gastro

7.6Hemato

4.3 MMusc/skel 7.6 (dentine dysplasia)M

7.6Hepatic

7.6Renal

7.6Bd Wt

57Gastro

(GW)

24 mo1x/d

Susheela and Das 1988

sodium fluoride5 (roughened duodena mucosa)

Rabbit

58Hemato

(G)

7-12 mo1x/d

Susheela and Jain 1983

sodium fluoride4.52 (decr leukocyte and hemoglobin

levels)

Rabbit

59Musc/skel

(F)

382 d24hr/d

Aulerich et al. 1987

sodium fluoride5 (mottled and brittle kit teeth) 9.1 (sagittal crests deformed, 3/6

adults)

Mink

Immuno/ Lymphoret60

(albino)(G)

18 mo1x/d

Jain and Susheela 1987

sodium fluoride4.5 (decr primary and secondary

antibody titers)

Rabbit

LOAEL


Seriousa

(mg/kg/day)System

Exposure/Duration/


Species(Strain)

Key tofigure

Reference


Chemical Form

Reproductive61

13(F)3 gen Tao and Suttle 1976

sodium fluoride

Mouse

62(NS)

(GW)

daily18 mo

Kumar and Susheela 1994

sodium fluoride4.5 (structural damage of the

spermatid and epididymalspermatozoa)

MRabbit

63(NS)

(GW)

daily20 or 23 mo

Kumar and Susheela 1995

sodium fluoride4.5 (structural damage of the

spermatid and epididymalspermatozoa)

MRabbit

64(NS)

(GW)

daily18 or 29 mo

Susheela and Kumar 1991

sodium fluoride4.5 (complete cessation of

spermatogenesis)

Rabbit

65(NewZealand) (GW)

daily18 or 23 mo

Susheela and Kumar 1997

sodium fluoride4.5 (Leydig cell damage)

Rabbit

669.1

(F)

382 ddaily

Aulerich et al. 1987

sodium fluoride

Mink

LOAEL


Seriousa

(mg/kg/day)System

Exposure/Duration/


Species(Strain)

Key tofigure

Reference


Chemical Form

Cancer67

(Fischer- 344) (W)


b Only this dose level, for the most sensitive group, is plotted in Figure 3-4.

c Differences in levels of health effects and cancer effects between males and females are not indicated in Figure 3-4. Where such differences exist, only the levels of effect for themost sensitive gender are presented.

d Used to derive a chronic-duration oral minimal risk level (MRL) of 0.05 mg fluoride/kg/day; the dose was divided by an uncertainty factor of 3 to account for human variability.

ad lib = ad libitum; Bd Wt = body weight; (C) = capsule); d = day(s); decr = decrease; Endocr = endocrine; (F) = feed; F = female(s); (G) = gavage; Gastro = gastrointestinal; Gd =gestational day; gen = generation(s); (GW) = gavage in water; Hemato = hematological; hr = hour(s); incr = increase; LD50 = lethal dose, 50% kill; LOAEL =lowest-observed-adverse-effect level; M = males; mg/kg/day = milligram per kilogram per day; mo = month(s); Musc/skel = muscular/skeletal; NOAEL = no-observed-adverse-effectlevel; RBC = red blood cell(s); Resp = respiratory; T3 = triiodothyronine; (W) = water; WBC = white blood cell(s); wk = week(s); x = time

103 wk NTP 1990

sodium fluoride2.4 (osteosarcoma of bone)M

Rat

1

10

100

1000

Death

1

9m

2r

2r 2r 3r

4r5r

6r

7r

8r

Musculoske

letal

10r

Reproductive

11m

Developmental

12r

13r 14h

mg/kg/day

Figure 3-4. Levels of Significant Exposure to Fluoride - OralAcute (≤14 days)




n-Minko-Other




Systemic

0.01

0.1

1

10

100

1000

Death

15m

16m

16m

Respiratory

30h

Cardiovascular

27m

Gastrointestin

al

21r

Hematological

28m

Musculoske

letal

26m

27m

29m

29m

18r18r 19r

20r20r

22r

22r

23r

Hepatic

24m

27m

21r

Renal

25m

27m

21r

Endocrine

29m

29m

17r

mg/kg/day

Figure 3-4. Levels of Significant Exposure to Fluoride - Oral (Continued)Intermediate (15-364 days)




n-Minko-Other




Systemic

0.01

0.1

1

10

100

1000

44r

Developmental

49r 49r 50r

51r

mg/kg/day

Figure 3-4. Levels of Significant Exposure to Fluoride - Oral (Continued)Intermediate (15-364 days)




n-Minko-Other




Body Weight

27m

28m

29m

Neurological

31r 32r32r33r

Reproductive

48g 45m

46m

46m

47m

34r

35r

35r 36r

37r

38r

39r

40r

41r

42r

43r

Systemic

0.01

0.1

1

10

100

Respiratory

56m

55r

Cardiovascular

56m

55r

Gastrointestin

al

56m

55r57h

Hematological

56m

55r58h

Musculoske

letal

52

53

53

54

59n

59n56m

56m

55r

55r

Hepatic

56m

55r

Renal

56m

55r

Body Weight

56m

55r

Immuno/Lymphor

60h

Reproductive

66n

61m

62h 63h 64h 65h

Cancer *

67r

mg/kg/day

Figure 3-4 Levels of Significant Exposure to Fluoride - Oral (Continued)Chronic (≥365 days)




n-Minko-Other




Systemic

*Doses represent the lowest dose tested per study that produced a tumorigenicresponse and do not imply the existence of a threshold for the cancer endpoint.


3. HEALTH EFFECTS



Respiratory Effects. No studies were located regarding respiratory effects in humans after oral

exposure to fluoride, hydrogen fluoride, or fluorine.

Congestion, the presence of edema fluid, and desquamation of respiratory epithelium were observed in

the lungs of rabbits exposed to 4.5 or 9 mg fluoride/kg/day as sodium fluoride in the diet for 6 months

(Purohit et al. 1999). Inflammatory cell infiltrates, congestion, and desquamated epithelium were also

observed in the large bronchi and trachea of rabbits fed 9 mg fluoride/kg/day. Necrosis of the lung

parenchyma was also observed in two high-dose rabbits that died before the end of the study.

Cardiovascular Effects. The cardiovascular effects of fluoride have been attributed to hypocalcemia

and hyperkalemia caused by high fluoride levels. Fluoride can bind with serum calcium if the dose is

sufficient and cause hypocalcemia. Calcium is necessary for the functional integrity of the voluntary and

autonomic nervous systems. Hypocalcemia can cause tetany, decreased myocardial contractility, and

possibly cardiovascular collapse (Bayless and Tinanoff 1985). Hyperkalemia has been suggested as the

cause of the repeated episodes of ventricular fibrillation and eventual death that are often encountered in

cases of fluoride poisoning (Baltazar et al. 1980).

Approximately 2 hours after ingestion of 120 g of roach powder (97% sodium fluoride) in an

unsuccessful suicide attempt, a 25-year-old male had severe toxic reactions that included tetany, multiple

episodes of ventricular fibrillation, and esophageal stricture (Abukurah et al. 1972). Within 14 hours

following exposure, the patient experienced 63 episodes of ventricular fibrillation. In a study of adults

with skeletal fluorosis living in an area of China with high levels of fluoride in the drinking water (4.1–

8.6 ppm) (Xu and Xu 1997), a higher percentage of electrocardiogram abnormalities was observed in

individuals with skeletal fluorosis (50.73%), as compared to a control group (0.1–0.6 ppm fluoride in

water) (20.0%).

In two epidemiological studies, fluoride in the drinking water did not increase the mortality rates from

cardiovascular effects. One of these studies was a report of 428,960 people in 18 areas of "high" natural

fluoride (0.4–>3.5 ppm) in England and Wales and 368,580 people in control areas (<0.2 ppm fluoride).

The water supply for 52% of the "high" fluoride population had average fluoride levels of ≥1 ppm

(Heasman and Martin 1962). Results indicated that there were no significant differences between areas


3. HEALTH EFFECTS

with different fluoride levels in mortality due to coronary disease, angina, and other heart disease, as

evidenced by standard mortality ratios (SMRs). The second study (Hagan et al. 1954) examined 32 pairs

of cities in the United States that contained 892,625 people in the high fluoride areas and

1,297,500 people in the control cities. A positive relationship between heart disease and water

fluoridation was reported, but these authors did not adjust for a doubling of the members of this

population over 75 years old during the period of fluoridation under study (Jansen and Thomson 1974).

In addition, this study lacked statistical analysis and drew conclusions regarding trends that were not

obvious from the data presented. The large variation in the presented data was not discussed. Doses of

fluoride are difficult to estimate for large populations, however, because most people are potentially

exposed to fluoride through a variety of sources, such as food, beverages, medicine, and dental products.

Similarly, no significant alterations in the rate of cardiovascular system abnormalities were observed in a

community with 8 ppm fluoride in the water supply, as compared to a community with 0.4 ppm (Leone et

al. 1954).

The results of other studies have suggested a role for fluoride in reducing cardiovascular disease. A study

of 300 North Dakota residents who drank water containing 4–5.8 ppm and 715 people who drank water

containing 0.15–0.3 ppm found a lower incidence of calcification of the aorta in the high-fluoride group

(Bernstein et al. 1966). Significant differences were found in 45–54-year-old males (p<0.05), as well as

in males aged 55–64 and 65+ years (p<0.01). This effect was not due solely to differences in age

distribution, because the incidence in the 55–64-year-old, high-fluoride group was lower than the

incidence in the 45–54-year-old, low-fluoride group. A crude analysis also found no association with

milk and cheese consumption. In a study of four towns in Finland, Luoma (1980) found that incidence of

cardiovascular disease correlated negatively with water fluoride concentration. Taves (1978) likewise

found that standard mortality ratios decreased to a greater extent in fluoridated cities from 1950 to

1970 as compared to non-fluoridated control cities. Both studies, however, relied on population-summary

information for disease rates. A mechanism for this potential reduction in cardiovascular disease could be

the ability of fluoride to inhibit the calcification of soft tissue such as the aorta, as demonstrated in in vitro

studies (Taves and Neuman 1964; Zipkin et al. 1970).

About half of the male and female B6C3F1 mice that died as a result of exposure to 67–71 mg

fluoride/kg/day for 6 months as sodium fluoride in drinking water had mineralization of the myocardium

(NTP 1990); some female mice also had myocardial degeneration. Electrocardiogram alterations and


3. HEALTH EFFECTS

histological alterations in the myocardium were observed in rabbits exposed to sodium fluoride (Okushi

1971).

Gastrointestinal Effects. The primary gastrointestinal effects following both acute and chronic oral

exposure to fluoride consist of nausea, vomiting, and gastric pain. The irritation of the gastric mucosa is

attributed to fluoride (as sodium fluoride) forming hydrofluoric acid in the acidic environment of the

stomach (Hoffman et al. 1980; Waldbott 1981). The uncharged hydrogen fluoride molecule can then

penetrate cell membranes and enter the neutral environment of the cytoplasm where it dissociates to

release both fluoride and hydrogen ions.

Thirty-four students (kindergarten through third grade) exhibited acute gastrointestinal effects after

drinking water from school water fountains that provided a fluoride supplement designed to raise the

water level to a range of 1–5 ppm (Hoffman et al. 1980). An accident with the delivery system resulted in

the water levels reaching 375 ppm; specific doses could not be calculated, but were estimated to range

from 1.4 to 90 mg per child. In two other cases, individuals vomited and had abdominal pain

immediately after accidentally consuming 1 tablespoon of sodium fluoride (used as a dusting powder for

poultry) (Rao et al. 1969) or sodium fluorosilicate (Dadej et al. 1987).

Of the 150 cases involving fluoride intake reported to a poison control center from 1978 to 1979, most of

the cases involved ingestion of <1 mg/kg fluoride, although exact doses could not be determined (Spoerke

et al. 1980). Effects included nausea (13.9%), vomiting (77.8%), and diarrhea (8.3%). These effects

usually subsided within 24 hours. Symptoms of a more serious nature were not reported.

Endoscopies were performed and biopsy samples were taken from healthy volunteers either after no

treatment (control), or 2 hours after drinking 20 mL of a solution containing 20 mg fluoride (1,000 ppm)

as sodium fluoride (Spak et al. 1989), or application of 0.42% fluoride dental gel (5.1 mg fluoride

ingested) (Spak et al. 1990). Fluoride treatment resulted in petechiae (minute hemorrhages) or erosions in

most of the subjects. Histological examination of biopsied stomach tissue revealed signs of irritation.

Nausea was present in one-third of the subjects drinking the sodium fluoride solution, suggesting that

nausea may not be the first sign of fluoride irritation of the gastric mucosa.

While high levels of fluoride clearly can cause gastrointestinal irritation, it is unclear whether there are

any gastrointestinal effects of chronic exposure to fluoride in drinking water. Gastrointestinal tract

disorders were not evaluated in the Bartlett-Cameron study of the effect of water containing 8 ppm


3. HEALTH EFFECTS

fluoride (Leone et al. 1954). The sole evidence of an effect comes from a study of 20 non-ulcer dyspepsia

patients at an outpatient clinic in India and 10 volunteers without gastrointestinal problems from the

surgical clinic (Susheela et al. 1992). While none of the drinking water supplies of the controls had

fluoride levels >1 ppm, the water supplies of 55% of the dyspepsia patients were at this level. In addition,

all of the dyspepsia patients and 30% of the controls had serum fluoride levels >0.02 ppm (mean of the

dyspepsia group, 0.1 ppm); all of the dyspepsia patients and none of the controls had urine fluoride levels

>0.1 ppm (mean, 1.34 ppm). The study was compromised by small treatment size, undetermined total

fluoride doses, undetermined nutritional status of the subjects, and lack of statistical comparisons. In

addition, the appropriateness of the control population was not clear.

Seventy-eight workers engaged in the crushing and refining of cryolite, a mineral compound composed of

sodium, aluminum, and fluoride, were examined (Moller and Gudjonsson 1932). Although an average

exposure period was not presented, no workers with <2 years of exposure were included; 18 workers had

been exposed for >10 years. Forty-two workers reported evidence of gastrointestinal effects. The

primary effect was nausea, followed by loss of appetite and vomiting. Chronic indigestion was also

reported in these workers. The study authors stated that the effects were due only to cryolite dust being

swallowed (either due to dust being deposited in the mouth during mouth-breathing, or due to deposition

on the bronchial tree followed by mucociliary action bringing the material to the epiglottis) and absorbed

through the gastrointestinal tract. They based this conclusion on the fact that 21 enamel-, glass-, and

sulphuric acid-industry workers exposed by inhalation to fluorine gas (some for up to 40 years) revealed

no evidence of any effect on the stomach. In light of what is now known about the absorption of fluorides

through the lung, the cryolite workers probably were exposed by both the oral and inhalation routes.

Decreased appetite, congestion of the duodenum, and mild diarrhea were reported in sheep given a single

intragastric dose of 28.5 mg fluoride/kg in the form of sodium fluoride via nasoesophageal catheter

(Kessabi et al. 1985). It is difficult to extrapolate possible human effects from this study because the

gastrointestinal system of ruminants (sheep, cows, goats) is quite different from that of humans.

Thickening of the mucosa of the glandular stomach and punctate hemorrhages were seen in F344/N rats

given 20 mg fluoride/kg/day as sodium fluoride in drinking water for 26 weeks (NTP 1990). Similar, but

less severe, alterations were seen in some rats that received 7 mg fluoride/kg/day. Stomach ulcers were

also seen in some high-dose males and females. Histologically identified stomach lesions included

necrosis and hyperplasia. No gastrointestinal effects were reported in B6C3F1 mice in this study at doses

up to 67–71 mg fluoride/kg/day. No gastrointestinal effects were reported in the chronic portion of this


3. HEALTH EFFECTS

study at doses up to 9.1 mg/kg/day (mice) or 4.5 mg/kg/day (rats). Roughened duodenal mucosa and a

"cracked-clay" appearance of the absorptive cells were observed following daily dosage of nine rabbits

with 5 mg/kg fluoride via oral gavage for 24 months (Susheela and Das 1988). The rabbit gastrointestinal

system also differs from that of humans, and the study is limited by the small number of rabbits per group

and the use of only one dose.

Hematological Effects. The incidence of abnormal white blood cell counts was significantly higher

in a community with high levels of naturally occurring fluoride (8 ppm) as compared to a community

with low levels of fluoride (0.4 ppm fluoride). However, the study authors did not consider this finding

as necessarily an effect of fluoride (Leone et al. 1954). No other significant hematological effects were

observed. No significant alterations in hemoglobin, erythrocyte, and total leukocyte levels were found in

children living in a community with fluoridated water (1.2 ppm), as compared to children living in a

community with nonfluoridated water (Schlesinger et al. 1956).

As part of the 2-year National Toxicology Program (NTP) study of fluoride (NTP 1990), hematological

analyses were conducted at 27 and 66 weeks. No treatment-related effects were observed at doses up to

4.5 and 9.1 mg/kg/day in F344/N rats and B6C3F1 mice, respectively.

Lactating Holstein cows were fed a mineral supplement containing soft rock phosphate (6,000 ppm

fluoride) and a protein supplement containing 1,088 ppm fluoride (Hillman et al. 1979). Because

consumption of minerals fed ad libitum could not be determined accurately under farm conditions, no

dose estimates could be made. After 9 months, red blood cells per unit volume, blood hemoglobin,

hematocrit, and mean corpuscular volume were significantly lower (p<0.05) in herds exhibiting evidence

of high fluoride exposure. The number of eosinophils increased with increasing urinary fluoride. Rabbits

administered 4.52 mg fluoride/kg/day by gavage for 6–12 months had significantly decreased numbers of

blood cells (e.g., erythrocytes, leukocytes, thrombocytes, monocytes, neutrophils) and hemoglobin

(Susheela and Jain 1983). Similar, although not identical, results were seen in mice fed 5.2 mg

fluoride/kg body weight (Pillai et al. 1988). These animals showed a significant decrease in red blood

cell count, but a significant increase in white cells. Although a dose-effect relationship cannot be

determined from single-dose studies, these studies suggest that the hematopoietic system may be affected

by oral exposure to high levels of fluoride.

Musculoskeletal Effects. The skeletal system is the primary site of fluoride deposition in the body

resulting in both beneficial and adverse effects. Oral exposure to fluoride has been shown to decrease the


3. HEALTH EFFECTS

prevalence of dental caries in children (the relationship between fluoride and dental caries is discussed in

greater detail in Appendix D); however, at higher doses, fluoride can also result in non-beneficial effects

on the teeth, dental fluorosis. Dental or enamel fluorosis occurs when excess amounts of fluoride are

ingested during tooth development (1–8 years of age). It is characterized by increased porosity (or

hypomineralization) of the subsurface enamel and well mineralized surface layer of enamel. Mildly

fluorosed enamel is full functional (denBesten and Thariani 1992), but may be cosmetically

objectionable. As the severity of dental fluorosis increases, the depth of the enamel involvement and the

degree of porosity increases (Fejerskov et al. 1990). More severely fluorosed enamel is more porous,

pitted, and discolored and is prone to fracture and wear because the well mineralized zone is very fragile

to mechanical stress (denBesten and Thariani 1992; Fejerskov et al. 1990). Not all teeth are similarly

affected by elevated fluoride levels. Teeth that develop earlier in life appear to be less affected than those

that develop later (Fejerskov et al. 1990). Several methods have been developed for quantifying dental

fluorosis. The most commonly used method is Dean's index (Dean 1934), which classifies fluorosis as a

scale of from 0 to 4 as follows: class 0, no fluorosis; class 1, very mild fluorosis (opaque white areas

irregularly covering ≤25% of the tooth surface); class 2, mild fluorosis (white areas covering 25–50% of

the tooth surface); class 3, moderate fluorosis (all surfaces affected, with some brown spots and marked

wear on surfaces subject to attrition); and class 4, severe fluorosis (widespread brown stains and pitting).

The average score of the two most severely affected teeth is used to derive the classification. Other

commonly used methods to rate dental fluorosis include the Thylstrup-Fejerskov (TF) index (Thylstrup

and Fejerskov 1978) and the tooth surface index of fluorosis (TSIF) (Horowitz et al. 1984). Unlike the

Dean’s index, the TF and TSIF indexes use all tooth surfaces to develop the final index score.

The development and severity of dental fluorosis is dependent on the amount of fluoride ingested, the

duration of exposure, and the stage of amelogenesis at the time of exposure. The relationship between

fluoride exposure levels and the prevalence and severity of dental fluorosis was first established in the

1930s and 1940s. There is an extensive amount of literature on the relationship between the prevalence of

dental fluorosis and the concentration of fluoride in municipal water (e.g., Alarcón-Herrera et al. 2001;

DHHS 1991; Eklund et al. 1987; Heifetz et al. 1988; Jackson et al. 1995; Selwitz et al. 1995; Teotia and

Teotia 1994) and the use of fluoridated dentifrices (as reviewed by Warren and Levy 1999). Studies

examining children living in communities with different fluoride levels found that the severity of dental

fluorosis is directly related to fluoride exposure levels. Higher fluorosis severity scores were found in

children living in communities with 4 ppm fluoride in drinking water compared to children living in

communities with 1 ppm fluoride in drinking water (Heifetz et al. 1988; Jackson et al. 1995; Selwitz et al.

1995). No signs of dental fluorosis (using the TSIF scoring method) were found in 81.8, 54.7, and 7.9%


3. HEALTH EFFECTS

of the children aged 7–14 years living in communities with 0.2, 1, or 4 ppm, fluoride in drinking water,

respectively (Jackson et al. 1995). Moderate dental fluorosis (TSIF score of 3) was observed in 0, 0.9,

and 25.7%, respectively, of the children. The maximum TSIF score was 2 (3.2% of the children received

this score) in the 0.2 ppm community, 4 (0.9% of children) in the 1 ppm community, and 7 (6.9% of

children) in the 4 ppm community. Studies in adults have not always found a direct relationship between

severity of dental fluorosis and prevalence of dental caries (Eklund et al. 1987). A recent meta-analysis

of 88 studies on dental fluorosis (McDonagh et al. 2000) found a dose-related response relationship

between the levels of fluoride in drinking water and the prevalence of dental fluorosis. At a water

fluoride concentration of 1 ppm, the estimated prevalence of dental fluorosis is 48% (95% confidence

interval of 40–57%) and the prevalence of fluorosis of aesthetic concern would be 12.5% (95%

confidence interval of 7.0–21.5%). Another meta-analysis found a significant association between dental

fluorosis and use of fluoride supplements (Ismail and Bandekar 1999).

There is also evidence that the prevalence of dental fluorosis has increased over time due to the multiple,

widespread sources of fluoride in food processed with fluoridated water and dentifrices containing

fluoride, which has resulted in higher fluoride exposure levels. The DHHS (1991) compared the

prevalence of dental fluorosis in three cities (Kingston, New York, Kewanee, Illinois, and Newburgh,

New York) measured in 1939 or 1955 with prevalence in those cities in 1980 or 1985. In Kingston,

which had a municipal fluoride level of 0 ppm, the prevalence of dental fluorosis (using the Dean’s index)

increased from 0.0 to 7.3%, primarily in the very mild (4.4% received this score) category. In the other

two cities (0.9 or 1.0 ppm fluoride in water), there was only a slight change in the overall prevalence

(12.2 versus 14.6% for Kewanee and 7.3 versus 7.7% in Newburgh) of dental fluorosis. However, there

was a shift toward higher severity scores. For example in Kewanee, the prevalence in the very mild, mild,

moderate, and severe categories was 10.6, 1.6, 0.0, and 0.0%, respectively, in 1939 and 7.4, 4.8, 1.8, and

0.6%, respectively, in 1980. In another comparison conducted by DHHS (1991), the prevalence and

severity of dental fluorosis measured in children living in 21 cities in the 1940s were compared with the

prevalence and severity of dental fluorosis measured in 28 cities in the 1980s. During the 40-year period,

the prevalence of fluorosis in areas with <0.4 ppm fluoride increased from <1% to about 6%; nearly all of

the increase was in the very mild and mild categories. Both the prevalence and severity of fluorosis

increased in communities with 0.7–1.2 ppm fluoride, with prevalence increasing from about 13% to about

22%. Most of the increase was in the very mild and mild categories, which increased from 12.3% to

17.7% and from 1.4% to 4.4% of the population, respectively. The combined prevalence of the severe

and moderate categories increased from 0.0% to 0.9%. While there were some differences between the

studies in the 1940s and those in the 1980s, such as the subject population and examination conditions,


3. HEALTH EFFECTS

they do not affect the overall trends. Although total fluoride intake was not measured, these studies

indicate that intake by children at risk has increased since the 1940s, because fluorosis levels increased

for all water fluoride levels. Another series of studies compared the prevalence and severity of dental

fluorosis in 8–10 and 13–15-year-old children living in communities with 1, 2, 3, or 4 ppm fluoride in

drinking water in 1980 to the prevalence in 1985 (Heifetz et al. 1988) and 1990 (Selwitz et al. 1995).

While there were no marked changes in fluorosis levels in 8–10-year-old children, both the prevalence

and severity increased in the 13–15-year-old children (this group of children also participated in the 1980

study). Increases in the 1-ppm communities were mostly in the category of barely visible white spots.

However, the percentage of labial surfaces of incisors and canines from children in the 2-ppm group that

had brown mottling increased from 0 to 7.6%. Less marked increases in mottled and pitted teeth were

seen in the higher exposure groups. The increased levels of fluorosis were attributed to increased fluoride

exposure from multiple sources. However, the apparent increase in fluorosis did not continue from 1985

to 1990 (Selwitz et al. 1995); in many cases, the severity of the fluorosis declined in the period of 1985–

1990 compared to the 1985 levels.

There is some evidence to suggest that exposure to very high levels of fluoride can increase the

susceptibility to dental caries. Studies in children and adolescents aged 8–16 years (Driscoll et al. 1986;

Mann et al. 1987) found higher incidences of dental caries in individuals with severe dental fluorosis than

in individuals with less severe dental fluorosis. However, for children with very mild, mild, or moderate

fluorosis, no significant associations were found. Driscoll et al. (1986) reported a mean decayed, missing,

and filled surface (DMFS) score of 2.96 for children with severe fluorosis (TSIF score of 4) compared to

1.40 for children with very mild dental fluorosis (TSIF score of 0.5) or 1.58 for children with mild to

moderate fluorosis (TSIF score of 1–3). It is possible that the higher prevalence of filled teeth was due to

the increased rate of fracture and wear in severely fluorosed teeth rather than a higher risk of tooth decay.

As with the dental effects, fluoride has both beneficial and adverse effects on bone. Because fluoride

stimulates bone formation, and increases bone mass, especially in cancellous bone, and inhibit bone

resorption, fluoride has been used as a treatment for osteoporosis. However, the effect of fluoride on the

bone varies in different parts of the body. It increases bone formation earlier and to a larger extent in

trabecular bone than in cortical bone (Gruber and Baylink 1991). There is an excellent response in the

spine, slight response in the hip, and poor response in the wrist as a result of fluoride treatment. Studies

examining the efficiency of fluoride treatment for osteoporosis have found an increased risk of hip

fractures; the prevailing view is that the beneficial increase in spinal bone mass is at the expense of an

increasing risk of hip fractures. There is some evidence that exposure to low doses of slow released


3. HEALTH EFFECTS

sodium fluoride can significantly reduce the occurrence of spinal fractures in individuals with

osteoporosis (Pak et al. 1995). A large number of studies have examined the adverse skeletal effects of

fluoride; the human studies primarily consist of clinical trials of elderly subjects administered fluoride for

the treatment of osteoporosis and community-based studies of populations exposed to fluoride in drinking

water. The observed effects include increases in bone density, increased risk of bone non-vertebral

fractures, and skeletal fluorosis.

Skeletal fluorosis is a condition associated with an accumulation of fluoride in the bone resulting in brittle

bones and decreased tensile strength. In severe cases (crippling skeletal fluorosis), complete rigidity of

the spine, often accompanied by kyphosis (humpbacked) or lordosis (arched back), is observed. Skeletal

fluorosis is associated with long-term exposure to very high oral doses of fluoride or occupational

exposure to cryolite (AlF6Na2) dust (which would involve inhalation and oral exposure to fluoride).

Cases of skeletal fluorosis are predominantly found in developing countries, particularly India and China,

and are associated with high fluoride intakes coupled with malnutrition (WHO 2002). High tea

consumption and increased consumption of water with high levels of naturally occurring fluoride are the

primary contributors to the elevated fluoride intake; in China, the indoor burning of fluoride-rich coal also

contributes to the overall fluoride intake. Most reports of skeletal fluorosis are inadequate for establishing

dose-response relationships. Choubisa et al. (1997) examined the prevalence of skeletal fluorosis in

residents of 15 villages in India. At 1.4 ppm fluoride in drinking water, the prevalence of skeletal

fluorosis was 4.4%; at 6.0 ppm fluoride, the prevalence was 63.0%. Another investigator found that

skeletal fluorosis occurred 10 years after the initiation of increased fluoride consumption; the average

water concentration was 9.2 ppm fluoride and daily water consumption was 4.6 L/day (42 mg

fluoride/day) (Saralakumari and Ramakrishna Rao 1993); after 20 years of exposure, the prevalence of

skeletal fluorosis was 100%. A limited number of cases of skeletal fluorosis have been reported in the

United States (Bruns and Tytle 1988; Fisher et al. 1981; Goldman et al. 1971; Sauerbrunn et al. 1965);

where doses are known, they are generally 15–20 mg fluoride/day for over 20 years. In a study of

116 people who had lived in an area with an average of 8 ppm fluoride in the drinking water for at least

15 years, a 10–15% incidence of fluoride-related bone changes was observed (Leone et al. 1955).

Coarsened trabeculation and thickened bone were observed, but no exostoses were evident, and the

subjects were asymptomatic. The severity of the skeletal fluorosis appears to be related to bone fluoride

levels. Among persons whose drinking water contains about 1 ppm fluoride, bone ash fluoride

concentrations trypically range from 500 to 1,500 ppm. The higher values are generally found among

older persons since the concentrations tend to increase gradually throughout life. Bone from people with

preclinical skeletal fluorosis, which is generally asymptomatic and characterized by slight radiologically


3. HEALTH EFFECTS

detectable increases in bone mass, contains 3,500–5,500 ppm fluoride. Sporadic pain, joint stiffness, and

osteosclerosis of the pelvis are observed at 6,000–7,000 ppm, while chronic joint pain, increased

osteosclerosis, and slight calcification of ligaments occur at 7,500–9,000 ppm. Crippling fluorosis is

observed at fluoride bone concentrations >10,000 ppm (Franke et al. 1975).

Studies of individuals undergoing fluoride treatment for osteoporosis, epidemiology studies of

communities with high levels of fluoride in drinking water, and community-based studies of populations

with different fluoride levels in the water have examined the possible relationship between exposure to

fluoride and alterations in bone mineral density and/or the risk of bone fractures. The effect of fluoride

on bone fracture rate and mineralization has alos been investigated in children.

A prospective, randomized of 135 women with postmenopausal osteoporosis ascertained the effect of

administering 34 mg fluoride/day as sodium fluoride (0.56 mg fluoride/kg/day) for 4 years (Riggs et al.

1990). The fluoride treated and the placebo control groups received 1,500 mg calcium/day. Although

bone mineral density in the lumbar spine, femoral neck, and femoral trochanter increased markedly in the

treatment group, bone mineral density in the shaft of the radius decreased 4%. There was no significant

difference in the number of new vertebral fractures between the treatment and control groups, although

the number of vertebral fractures in the fluoride group was slightly elevated in the first year. In contrast,

the level of nonvertebral fractures in the fluoride group was 3.2 times that of the control group, with

significant increases in both the frequency and rate of fractures. Most of the increase was due to

increased incidences of incomplete ("stress") fractures, which occurred 16.8 times more often in the

treatment group. In a follow-up to this study, Riggs et al. (1994) examined 50 of the women in the

fluoride treatment group after an additional 2 years of treatment with 34 mg fluoride/day as sodium

fluoride. The lumbar spine, femoral neck, and femoral trochanter bone mineral density continued to

increase and the bone mineral density of the radius continued to decrease during years 4–6 of treatment.

The vertebral fracture rate decreased during years 4–6 as compared to years 0–4. The nonvertebral

fracture rate also decreased during the last 2 years, but the rate for the full 6-year period was still 3 times

higher than the rate in the placebo control group. In addition to extending the study for an additional

2 years, Riggs et al. (1994) also re-examined the data from the previous study. Vertebral fracture rate was

influenced by several factors. Vertebral fracture rate decreased with increasing lumbar spine bone

mineral density except in the cases where the higher bone mineral density was associated with a rapid rate

of increase in the lumbar spine bone mineral density or a large increase from baseline serum fluoride

level.


3. HEALTH EFFECTS

In a similar study by Kleerekoper et al. (1991), the anti-fracture efficacy of 34 mg fluoride/day as sodium

fluoride was examined in 46 postmenopausal women (mean age of 66.2 years) with spinal osteoporosis.

A daily dose of 1,500 mg calcium was also administered to this group as well as a placebo control group

of 38 postmenopausal women with spinal osteoporosis (mean age of 67.9 years). No significant

differences in bone mineral density of the forearm, vertebral fractures, or peripheral fractures were found.

A significant increase in painful lower extremity syndrome was observed in the fluoride group. It should

be noted that Riggs et al. (1990, 1994) considered the lower extremity syndrome to be incomplete

fractures and the incidence of incomplete fractures was added to the complete fracture incidence to

calculate nonvertebral fracture incidence.

Haguenauer et al. (2000) performed a meta-analysis to examine the effects of fluoride on the treatment

and prevention of postmenopausal osteoporosis using the data from the Riggs et al. (1990, 1994),

Kleerekoper et al. (1991), and 10 other studies. The meta-analysis showed a significant increase in bone

mineral density in the lumbar spine and hip and a decrease in bone mineral density in the forearm after

2 or 4 years of fluoride treatment. When the data from all studies were used, fluoride treatment for 2–

4 years did not affect the relative risk of vertebral fractures. However, in studies in which the subjects

were exposed to low levels of fluoride or a slow-release formulation for 4 years, a significant decrease in

vertebral fracture relative risk was seen. An increase in the relative risk of nonvertebral fracture was

observed when data from all studies were used; no effect was seen in studies using low levels of fluoride

(<30 mg/day) or slow-release fluoride.

Conflicting findings on whether fluoride exposure in drinking water results in increased bone mineral

density have been reported, with studies finding increases in spine and femur bone mineral density

(Kröger et al. 1994; Phipps et al. 1998, 2000), decreases in radius mineral density (Phipps et al. 1998), or

no effect on bone mineral density (Cauley et al. 1995; Lehmann et al. 1998; Sowers et al. 1991). Lumbar

spine, proximal femur, and forearm bone mineral densities were measured in men and women 60 years

and older living in one of three cities with different levels of naturally occurring fluoride in drinking

water (Phipps et al. 1998). After adjusting for a number of non-fluoride related risk factors, significant

elevations in bone mineral density of the lumbar spine (men and women) and proximal femur (women

only) were observed in residents with the highest levels of fluoride (2.5 mg/L), as compared to densities

in residents with the lowest fluoride concentration (0.03 mg/L); no significant differences in bone mineral

density were found between residents with the mid-level fluoride concentration (0.7 mg/L) and the lowest

concentration. In contrast to this finding, a negative correlation between bone mineral density of the

forearm and an individual’s fluoride intake from drinking water and toothpaste was found. Significant


3. HEALTH EFFECTS

increases in bone mineral density were also reported in another study by this group (Phipps et al. 2000).

Adjusted (age, weight, education, knee/grip strength, surgical menopause, calcium intake, alcohol

consumption, estrogen use, thiazide use, diabetes, thyroid hormone levels, exercise, and smoking) mineral

densities were higher in the lumbar spine and femur and lower in the radius in women aged 65 years and

older exposed to fluoridated drinking water, as compared to women with no reported exposure to

fluoridated water. Kröger et al. (1994) also found significant increases in bone mineral density (adjusted

for confounding factors such as age, weight, menopausal status, calcium intake, physical activity) of the

femoral neck and lumbar spine among women aged 47–56 years exposed to fluoridated drinking water

(1.2 mg/L) for >10 years (mean exposure duration was 25.9 years), as compared to women exposed to

fluoridated drinking water for <10 years.

In a study of women aged 65 years and older, no significant alterations in bone mineral density of the

radius, calcaneus, hip, or lumbar spine were found between women with no exposure to fluoridated water

(n=1,248), 1–10 years of exposure (n=438), 11–20 years of exposure (n=198), or greater than 20 years of

exposure (n=192) (Cauley et al. 1995). Total calcium intake was significantly higher in the >20-year

group and lower in the 11–20-year group. Lehmann et al. (1998) also found no difference in age- and

weight-adjusted bone mineral density of the spine and femur of women aged 20–69 years living in an area

with fluoridated water (1 mg/L). In the men living in the fluoridated water a community, there was a

significant increase in age- and weight-adjusted bone mineral density of the Ward’s triangle portion of the

femur, but no effect on neck or trochanter portions of the femur or the spine. The lack of adjustment for

other risk factors limits the interpretation of this study; significantly higher alcohol consumption and

lower calcium intakes were found in the fluoride-exposed group. Sowers et al. (1991) also found no

significant alterations in bone mass in women aged 20–80 years living in a community with naturally

high fluoride levels (4 mg/L) as compared to women living in a community with fluoridated water

(1 mg/L). However, radius bone mass was significantly lower in the high fluoride group.

As with bone mineral density, conflicting results have been found on the effect of low levels of fluoride

on the risk of fractures, particularly hip fractures. These studies have found conflicting results, with

studies finding a lower or higher incidence of hip fractures or no differences in hip fracture between

humans exposed to fluoride in drinking water.

Several studies have found decreases in hip fracture incidences in communities with fluoride in the

drinking water, suggesting that there may be a beneficial effect. Simonen and Laittinen (1985) examined

male and female residents older than 50 years living in two cities in Finland with either trace amounts of


3. HEALTH EFFECTS

fluoride in the water or with 1 ppm fluoride in the water. The occurrence of femoral neck fractures was

lower in the men 50–80 years old and women >70 years old living in the area with fluoridated water, as

compared to the low fluoride community. No difference in femoral neck fracture was observed in women

50–69 years of age. In a prospective study of older women, Phipps et al. (2000) examined the possible

relationship between living in an area with fluoridated water and the risk of fractures among women

≥65 years old. Fewer spine, hip, and humerus fractures were observed in this group. However, a

nonsignificant trend toward higher incidences of wrist fractures was observed in the continuous exposure

group. Lehmann et al. (1998) also found a significant decrease in the occurrence of hip fractures

(adjusted for age) in men and women living in an area with fluoridated water (approximately 1 ppm), as

compared to residents living in a city with low levels of fluoride in the water.

In contrast to the results of these studies, other studies have found an increase in the incidence of hip

fractures in communities with fluoride in the drinking water. Sowers et al. (1986) found a higher

incidence of hip fractures among women aged 55–80 years living in a community with high levels of

naturally occurring fluoride (4 ppm) in the water, as compared to women living in an area with

fluoridated water (1 ppm). The lower calcium intake in the high fluoride group may have influenced

these results. A geographical correlational study of 541,985 white women hospitalized for hip fractures

found a weak association (regression coefficient=0.001, p=0.1) between hip fracture incidence and

fluoridation of water (Jacobsen et al. 1990). The association was strengthened (regression

coefficient=0.003, p=0.0009) after correcting by county for other factors found to correlate with hip

fracture incidence (latitude, hours of sunlight, water hardness, income level, and percentage of land in

farms). Another study by this group (Jacobsen et al. 1992) also found a significantly elevated risk of hip

fractures in residents living in counties with fluoridated water. The relative risks were

1.17 (95% CI=1.13–1.22) and 1.08 (95% CI=1.06–1.10) for men and women aged 65 years and older.

The highest prevalence of hip fractures was found in counties that began a fluoridation program within

the last 5 years. Madans et al. (1983) examined the association between fluoride in drinking water and

risk of hip fractures using hip fracture data from the National Health Interview Surveys of 1973–1977 and

Centers for Disease Control and Prevention (CDC) data on the percent of a population in each U.S.

county served with water having a natural or adjusted fluoride content of at least 0.7 ppm in 1973.

Female residents over 45 years of age living in areas with lower fluoride levels in the drinking water had

9% more hip fractures than women living in high fluoride areas; however, the difference was not

statistically significant. An increase in the risk of hip fractures (age, sex, and quatelet index-adjusted

odds ratio of 1.86, 95% CI=1.02–3.36) was also observed in adults aged 65 years and older living in areas


3. HEALTH EFFECTS

with drinking water fluoride levels ranging from 0.11 to 1.83 ppm (Jacqmin-Gadda et al. 1995); these

data were reported as a letter to the editor and limited study details were provided.

A study in England and Wales also found increased rates of hip fractures in men and women over

age 45 as water fluoride levels increased up to 0.93 ppm (Cooper et al. 1991). Hip fracture rates in

39 counties (standardized by age and sex) were compared with water fluoride levels in those counties. In

the original analysis (Cooper et al. 1990), no significant correlation was found. However, when the

authors reanalyzed the data using a weighted least-squares technique (weighting by the size of the

population aged ≥45 years) to account for differences in the precision of the county-specific rates, a

significant positive correlation between water fluoride levels and hip fracture rates was found (r=0.41,

p=0.009). The correlation existed for both women (r=0.39, p=0.014) and men (r=0.42, p=0.007) (Cooper

et al. 1991). Kurttio et al. (1999) studied over 144,000 residents living in rural areas of Finland from

1967 to –1980. When all age groups were considered together, no relationship between fluoride levels in

drinking water and the risk of hip fractures was found. However, among women aged 50–64 years with

higher fluoride levels, an increase in the risk of hip fractures was found. No consistent relationships were

found in men or in older women. The study authors suggested that other risk factors for hip fracture may

be more important than fluoride exposure in determining risk of hip fractures in older women. An

ecologic cohort study compared the hip fracture rate for men and women in a Utah community that had

water fluoridated to 1 ppm with the rate in two communities with water containing <0.3 ppm fluoride

(Danielson et al. 1992). The age-adjusted rate was significantly elevated in both women (relative risk

1.27, 95% CI=1.08–1.46) and men (relative risk 1.41, 95% CI=1.00–1.81). In men, the rates in the

fluoridated and nonfluoridated communities were similar until age 70. After age 75, the difference

between the rates in the fluoridated and nonfluoridated areas increased with age. The difference between

the hip fracture rates in the fluoridated and nonfluoridated areas increased for women in the 70- and

75-year age groups. However, the fracture rates in women at ages ≥80 years old were similar in the

fluoridated and nonfluoridated towns. The study authors attributed this to the fact that women older than

80 years would have already gone through menopause by the beginning of fluoridation, and so would

have had less bone remodeling and less incorporation of fluoride into the bone. The study authors also

suggested that the reason that they found an effect when other investigators have not was the low levels of

exposure to risk factors for osteoporosis (smoking and alcohol) in the Utah populations. This was a well-

conducted study that suggests that communities with fluoridated water have an elevated risk of hip

fracture. However, several possible confounding factors were not examined. Calcium levels in the water,

total calcium and vitamin D intake, and individual fluoride intake were not determined. Estrogen use was


3. HEALTH EFFECTS

not evaluated, but was assumed to be similar since the communities were similar distances from larger

medical centers. In addition, estrogen levels would not cause the effect in men.

A study by Li et al. (2001) found a U-shaped pattern for the prevalence of overall bone fractures and the

level of fluoride in the drinking water of six communities in rural China. The prevalence of bone

fractures (adjusted for age and gender) was significantly elevated in the communities with 0.25–0.34 ppm

fluoride (7.41%) or 4.32–7.97 ppm fluoride (7.40%), as compared to the prevalence (5.11%) in the

community with 1.00–1.06 ppm fluoride in the water. When only hip fractures since age 20 years were

examined, the age- and body mass index (BMI)-adjusted prevalence was only significantly higher in the

4.32–7.97 ppm group; prevalence of 1.20% compared to 0.37% in the 1.00–1.06 ppm group. A similar

pattern was found for overall fractures since age of 50 years; the age-adjusted prevalences were 4.80 and

3.28% in the 4.32–7.97 and 1.00–1.06 ppm groups, respectively.

Other studies have not found a relationship between fluoride in drinking water and hip fracture

prevalence. No significant differences in the incidence or type of upper femoral fracture were observed

when groups of subjects living in communities with low fluoride (<0.3 ppm), fluoridated (1.0–1.2 ppm),

or high fluoride (>1.5 ppm) drinking water (Arnala et al. 1986). Kröger et al. (1994) found no effect on

self-reported fractures among a group of older Finnish residents (mean age of approximately 53 years)

living in an area with fluoridated water (1.0–1.2 mg/L), as compared to residents living in an area with

low fluoride levels in the drinking water (<0.3 ppm). Similarly, Avorn and Niessen (1986) found no

statistically significant alteration in the occurrence of long bone fractures among women aged 65 years

and older living in counties with fluoridated water (fluoride concentrations were not reported) as

compared to residents living in counties without fluoridated water. No alteration in the occurrence of hip

or ankle fractures were observed in men and women aged 65 years or older residents living in

communities with fluoridated water, as compared to residents living in communities without a water

fluoridation program (Karagas et al. 1996). In men, the risk of proximal humerus fracture (relative risk

1.23, 95% CI=1.06–1.43) and distal forearm fractures (relative risk of 1.16, 95% CI=1.02–1.33) were

higher in the fluoridated water areas; the relative risks of these fractures in women living in fluoridated

areas were not significantly altered. Cauley et al. (1995) found no effect on the risk of vertebral or

nonvertebral fractures among women aged 65 years and older exposed to fluoridated water for 13 years

(mean exposure duration).

Jacobsen et al. (1993) compared hip fractures rates in the 10-year period prior to fluoridation to the rates

in the 10-year period after fluoridation of a city’s water source (fluoride concentration of 1.1 ppm). No


3. HEALTH EFFECTS

significant differences in the risk of hip fractures were found in men or women aged 50 years and older;

the relative risks, after adjusting for other risk factors, were 0.78 (95% CI=0.37–1.66) and 0.60 (95%

CI=0.42–0.85) for men and women, respectively. No significant alterations in the risk of hip fracture

were found among male and female residents aged 45 and older living in a city with fluoridated water

(Suarez-Almazor et al. 1993). However, when male residents were considered separately, the relative risk

of hip fracture was statistically significant in the 65 years and older age bracket (risk ratio of 1.13, 95%

CI=1.00–1.24) and all men combined (risk ratio of 1.12, 95% CI=1.01–1.24).

With the exception of studies examining skeletal fluorosis, most of the studies on the skeletal effects of

fluoride involved older adult populations. There is also some limited evidence that fluoride may affect

bone mineralization in children. Increased trabecular height and area were observed in the distal radial

metaphysis of boys (11–12 years of age) with dental fluorosis living in an area with 2.7 ppm fluoride in

water (Chlebna-Sokol and Czerwinski 1993). No alterations were observed in similarly aged girls or

older (13.5–15 years) boys and girls. The trabecular changes were correlated with lower serum calcium

levels and higher alkaline phosphatase activity levels. Alarcón-Herrera et al. (2001) found a significant

correlation between bone fracture incidence and Dean’s index of dental fluorosis among children aged 6–

12 years and adults aged 13–60 years.

Evidence from animal experiments supports the association of high levels of fluoride and adverse effects

on bone. The femurs of weanling male rats of a Wistar-derived strain that were given ≥9.5 mg

fluoride/kg/day as sodium fluoride for 2 weeks exhibited a marked decrease in the modulus of elasticity.

It is not clear if the change was analyzed statistically. No lower doses were tested (Guggenheim et al.

1976). Musculoskeletal effects in albino rats (strain not identified) following oral exposure of

intermediate duration have been investigated. After 30 days of exposure to 100 ppm of fluoride in water

(14 mg fluoride/kg/day), tibia bones were broken and allowed to heal (Uslu 1983). Collagen synthesis

was determined to be defective, and fracture healing was delayed, when compared to the controls.

Decreased bone growth and signs of fluorosis were observed in rats given 19 mg fluoride/kg/day as

sodium fluoride in their drinking water and adequate calcium for 5 weeks; with elevated calcium levels,

fluorosis was not observed until the fluoride level reached 35 mg fluoride/kg/day (Harrison et al. 1984).

Male mice administered 0.80 mg fluoride/kg/day for 4 weeks exhibited a statistically significant increase

in the bone formation rate and a slight but statistically significant decrease in bone calcium levels (Marie

and Hott 1986). The authors concluded that 0.80 mg fluoride/kg increased the population of osteoblasts

under the conditions of this experiment. Turner et al. (1992) found a biphasic relationship between bone

strength and bone fluoride content in rats. At lower fluoride intakes, increased bone strength was


3. HEALTH EFFECTS

observed; the maximum bone strength was achieved at 1,000–1,500 ppm fluoride in the bone. At fluoride

concentrations >1,000 ppm bone strength started to decrease. The sagittal crests were enlarged and/or

deformed in three of six adult female mink fed 9.1 mg fluoride/kg/day as sodium fluoride for 382 days

(Aulerich et al. 1987). The authors attributed the abnormalities of the sagittal crests to increased

osteoblastic activity. An increase in the diameter of the femur bone and decreased breaking strength was

observed in pigs administered sodium fluoride or rock phosphate in the diet (Kick et al. 1933).

Hepatic Effects. No studies were located regarding hepatic effects in humans after oral exposure to

fluoride, hydrogen fluoride, or fluorine.

Pale, granular hepatocytes, compatible with parenchymal degeneration, were observed in mice

administered 0.95 mg fluoride/kg/day in drinking water for 7–280 days (Greenberg 1982a). Fatty

granules were observed after 3 weeks. Liver congestion was observed in sheep given a single intragastric

dose of fluoride as low as 9.5 mg fluoride/kg. Mild serum increases of liver enzymes (glutamate

dehydrogenase [GDH] and gamma-glutamyl transferase [GGT]) also occurred in sheep administered

38 mg fluoride/kg (Kessabi et al. 1985). It is difficult to use this result to predict to possible human

effects because ruminants (sheep, cows, goats) have gastrointestinal systems quite different from that of

humans.

Enlarged liver cells with multiple foci were seen in about half of the male B6C3F1 mice that died after

receiving 33–36 or 67–71 mg fluoride/kg/day for up to 6 months as sodium fluoride in drinking water

(NTP 1990). This change was seen in all of the female mice that died at the 71 mg/kg/day dose level. No

liver effects were seen in a parallel experiment with F344/N rats at doses up to 20 mg/kg/day. Similarly,

no liver histopathology was seen in the chronic portion of this study (NTP 1990), in which rats received

total fluoride doses (amount added to water plus endogenous fluoride in food) of about 4.5 mg/kg/day

(rats) or up to 9.1 mg/kg/day (mice). Alkaline phosphatase levels were significantly increased in male

and female mice at the 66-week interim sacrifice of the chronic study.

Renal Effects. One study was located in which ingestion of fluoride appeared to be linked with renal

insufficiency (Lantz et al. 1987). A 32-year-old man ingested 2–4 L of Vichy water (a highly gaseous

mineral water containing sodium bicarbonate and approximately 8.5 mg/L of fluoride) every day for

about 21 years. This exposure ended 4 years before his hospital admission. The patient also had

osteosclerosis and a moderate increase in blood and urinary levels of fluoride. No teeth mottling was

observed. The authors could not find factors, other than fluoride, related to his interstitial nephritis. No


3. HEALTH EFFECTS

effect on the incidence of urinary tract calculi or the incidence of albuminuria was found in the Bartlett-

Cameron study of people drinking water containing 8 ppm fluoride (Leone et al. 1954).

Congestion of the kidney was observed in sheep given a single intragastric dose of fluoride as low as

9.5 mg fluoride/kg (Kessabi et al. 1985). An intermediate exposure study tested the effect of

administering up to 67–71 mg fluoride/kg/day to B6C3F1 mice (8–9/group) as sodium fluoride in drinking

water for 26 weeks (NTP 1990). Acute nephrosis characterized by extensive multifocal degeneration and

necrosis of the tubular epithelium was believed to be the main cause of death in two of the four males

exposed to 67 mg/kg/day that died, the single male that died after exposure to 33 mg/kg/day, and two of

the four females in the high dose group that died. No kidney histopathology was observed in surviving

mice or in rats exposed to 20 mg fluoride/kg/day and higher (NTP 1990). Significant increases in water

consumption and apparent (based on qualitative descriptions) increases in acid phosphatase activity in the

glomeruli were observed in monkeys exposed to 0.46 mg fluoride/kg/day as hydrofluosilicic acid for

180 days (Manocha et al. 1975). The toxicological significance of these changes is not known.

Changes in kidney histology were seen in mature Swiss mice given a dose of sodium fluoride in drinking

water for up to 280 days that was described as the maximum dose that could be chronically tolerated, i.e.,

1.9 mg/kg/day (Greenberg 1986). Using a sensitive staining technique, increased collagen levels were

seen after about 45 days. Thickening of the Bowman's capsule, edematous swelling of the tubules, and

infiltrations of mononuclear cells were also noticed. No kidney pathology was seen in a 2-year study in

B6C3F1 mice at doses up to 8.1 mg/kg/day (males) or 9.1 mg/kg/day (females), or in F344/N rats at doses

up to 4.1 mg/kg/day (males) or 4.5 mg/kg/day (females) (NTP 1990).

Endocrine Effects. Significant increases in serum thyroxine levels were observed in residents of

North Gujarat, India with high levels of fluoride in the drinking water (range of 1.0–6.53 mg/L; mean of

2.70 mg/L) (Michael et al. 1996). No significant changes in serum triiodothyronine or thyroid stimulating

hormone levels were found. Increases in serum epinephrine and norepinephrine levels were also

observed. In another study conducted in India, a positive dose-response relationship between parathyroid

hormone and fluoride intake from drinking water was observed in children aged 6–12 years (Gupta et al.

2001). It is unclear if nutritional deficiencies played a contributing role to the observed endocrine effects.

Jooste et al. (1999) found a higher goiter prevalence among children (6–15 years of age) living in two

towns in South Africa with high levels of fluoride in the water (1.7 or 2.6 ppm), as compared to children

living in towns with low (0.3 or 0.5 ppm) or optimal (0.9 or 1.1 ppm) fluoride levels in the water. The

prevalence of goiter was also elevated in three of the other four towns, although the prevalence was lower


3. HEALTH EFFECTS

than in the high fluoride towns; suggesting that the children were exposed to other goitrogens. Iodine

deficiency was not the likely etiological agent because the median urinary iodine levels were higher than

iodine sufficiency standards. These data are inadequate to assess the relationship between elevated

fluoride intake and goiter formation.

Fluoride has been shown to affect the endocrine system in rats given 0.5 mg fluoride/kg/day as sodium

fluoride in drinking water every day for 2 months (Bobek et al. 1976). These animals showed decreased

thyroxine levels and an increased T3-resin uptake ratio. In contrast, Zhao et al. (1998) did not find any

alterations in serum T3 or T4 levels in mice exposed to 3.2 mg fluoride/kg/day as sodium fluoride in

drinking water for 100 or 150 days. However, a decrease in thyroid radiolabelled iodine uptake was

observed at 3.2 mg fluoride/kg/day, but not at 0.06 mg fluoride/kg/day.

No significant alterations in parathyroid hormone levels or morphological alterations in the parathyroid

gland were observed in rats exposed to 3.3 mg fluoride/kg in drinking water for 46 weeks (Rosenquist et

al. 1983).

Body Weight Effects. Final body weight was reduced by >40% relative to the controls in female

F344/N rats administered 25 mg fluoride/kg/day as sodium fluoride in drinking water for 14 days; body

weight in males was reduced by >10% at doses ≥6.3 mg/kg/day (NTP 1990). A clear and consistent

effect on body weight of B6C3F1 mice was seen only at the high dose (69 mg/kg/day), which was lethal

to males (3/5), but not to females. In the intermediate-duration (6 months) phase of the study, the body

weight of mice administered 17 mg fluoride/kg/day was reduced by 20%; it was reduced by 10% at

19 mg/kg/day in male and female rats.

F344/N rats and B6C3F1 mice given large doses of sodium fluoride in drinking water for 14 days had

reduced water intake (NTP 1990). Male and female rats given 25 mg fluoride/kg/day drank about 30%

less water than the controls. Water consumption by male rats given 51 mg fluoride/kg/day was 50% of

controls, while it was 25% of controls for females. Similarly, mice given 69 mg fluoride/kg/day drank

≤60% the volume of water consumed by the controls. This means that actual fluoride doses are lower

than the estimates given here, since these values were calculated assuming normal water intake.

However, the reduced water intake may have been due to the disagreeable taste of fluoride at high

concentrations in the water.


3. HEALTH EFFECTS


A request to the American Academy of Allergy was made by the U.S. Public Health Service for an

evaluation of suspected allergic reactions to fluoride as used in the fluoridation of community water

supplies (Austen et al. 1971). The response to this request included a review of clinical reports and an

opinion as to whether these reports constituted valid evidence of a hypersensitivity reaction to fluoride

exposure of types I, II, III, or IV (Austen et al. 1971), which are, respectively, anaphylactic or reaginic,

cytotoxic, toxic complex, and delayed-type reactivity. The Academy reviewed the wide variety of

symptoms presented (vomiting, abdominal pain, headaches, scotomata [blind, or partially blind areas in

the visual field], personality change, muscular weakness, painful numbness in extremities, joint pain,

migraine headaches, dryness in the mouth, oral ulcers, convulsions, mental deterioration, colitis, pelvic

hemorrhages, urticaria, nasal congestion, skin rashes, epigastric distress, and hematemesis) and concluded

that none of these symptoms were likely to be immunologically mediated reactions of types I–IV. No

studies were located that investigated alterations in immune response following fluoride exposure in

humans.

In a study with rabbits administered 4.5 mg fluoride/kg/day as sodium fluoride for 18 months, decreased

antibody titers were observed (Jain and Susheela 1987). These results were observed after 6 months of

treatment; the authors hypothesized that a threshold level is reached at which time the immune system is

impaired. However, as only one dose level (4.5 mg fluoride/kg/day) was tested, no dose-effect

relationships can be established. An increase in the cellularity of Peyer’s patches and mesenteric lymph

nodes was observed in rats administered sodium fluoride (Butler et al. 1990).


There are limited data on the neurological toxicity of fluoride in humans. Exposure to very high doses of

fluoride can result in neuromuscular symptoms (e.g., tetany, paresthesia, paresis, convulsions). These

effects are probably due to hypocalcemia caused by fluoride binding of calcium causes these symptoms

(Eichler et al. 1982). As discussed in the Developmental Effects section, decreases in intelligence were

reported in children living in areas of China with high levels of fluoride in the drinking water, as

compared to matched groups of children living in areas with low levels of fluoride in the drinking water

(Li et al. 1995a; Lu et al. 2000), but these studies are weak inasmuch as they do not address important

confounding factors. Using dental fluorosis as a surrogate for high fluoride intake, Morgan et al. (1998)


3. HEALTH EFFECTS

examined the possible correlation between dental fluorosis and behavioral problems in children aged 7–

11 years. No significant correlations were found.

There are limited animal data on the neurotoxicity of fluoride. Significant decreases in spontaneous

motor activity were observed in rats exposed via gavage to 9 mg fluoride/kg/day as sodium fluoride in

saline for 60 days (Paul et al. 1998). No alterations in motor coordination, as assessed with the rotarod

test, were found. A decrease in blood cholinesterase activity was also observed in these rats. Another

study (Mullenix et al. 1995a) found alterations in spontaneous behavior in female rats exposed to 7.5 mg

fluoride/kg/day as sodium fluoride in drinking water for 6 weeks beginning at 3 weeks of age and in

female rats exposed to 6.0 mg fluoride/kg/day as sodium fluoride in drinking water for 6 weeks beginning

at 13 weeks of age. The study authors noted that the observed effects were consistent with hyperactivity

and cognitive deficits. In a recent study only available as an abstract (Whitford et al. 2003), no significant

alterations in performance on operant behavior tests were observed in female rats exposed to 2.9–11.5 mg

fluoride/kg/day in drinking water for 7 months. Varner et al. (1998) found increases in the frequency of

neuronal abnormalities in the neocortex and a bilateral accumulation of β-amyloid in the thalamus of rats

exposed to 0.11 mg fluoride/kg/day as sodium fluoride in drinking water. This study did not assess

neurofunction; thus, it is difficult to assess the toxicological significance of these effects.


There are limited data on the potential of fluoride to induce reproductive effects in humans following oral

exposure. A meta-analysis found a statistically significant association between decreasing total fertility

rate and increasing fluoride levels in municipal drinking water (Freni 1994). Annual county birth data

(obtained from the National Center for Health Statistics) for over 525,000 women aged 10–49 years living

in areas with high fluoride levels in community drinking water were compared to a control population

approximately 985,000 women) living in adjacent counties with low fluoride drinking water levels. The

fluoride-exposed population lived in counties reporting a fluoride level of 3 ppm or higher in at least one

system. The weighted mean fluoride concentration (county mean fluoride level weighted by the 1980 size

of the population served by the water system) was 1.51 ppm (approximately 0.04 mg fluoride/kg/day

calculated using a reference water intake of 2 L/day and body weight of 70 kg), and 10.40% of the

population was served by water systems with at least 3 ppm fluoride. The mean weighted mean fluoride

concentration in the control population was 1.08 ppm (approximately 0.03 mg fluoride/kg/day).

However, this meta-analysis relied on a comparison of two quite disparate data sets, inasmuch as the

fluoridation population often did not correlate well with the population for whom health statistics was


3. HEALTH EFFECTS

available. The ecologic nature of this study design does not allow an evaluation of the nature of the total

fertility rate and fluoride association. Another study found significantly decreased serum testosterone

levels in 30 men diagnosed with skeletal fluorosis and in 16 men related to men with fluorosis and living

in the same house as the patient (Susheela and Jethanandani 1996). The mean drinking water fluoride

levels were 3.9 ppm (approximately 0.11 mg fluoride/kg/day), 4.5 ppm (0.13 mg fluoride/kg/day), and

0.5 ppm (0.014 mg fluoride/kg/day) in the patients with skeletal fluorosis, related men, and a control

group of 26 men living in areas with low endemic fluoride levels. No correlations between serum

testosterone and urinary fluoride levels or serum testosterone and serum fluoride levels were found. One

limitation of this study is that the control men were younger (28.7 years) than the men with skeletal

fluorosis (39.6 years) and the related men (38.7 years). In addition, the groups are small and potentially

confounding factors are not well addressed.

Animal studies have examined the effect of fluoride on reproductive hormone levels, histology of the

testes, spermatogenesis, and fertility. No alterations in mean serum levels of testosterone, luteinizing

hormone, or follicle stimulating hormone were found in male rats exposed to 16 mg fluoride/kg/day as

sodium fluoride in drinking water for 14 weeks or in their male offspring exposed during gestation,

lactation, and for 14 weeks after weaning (Sprando et al. 1997). In contrast, significant decreases in

serum testosterone levels were observed in rats receiving daily gavage doses of 4.5 mg fluoride/kg/day as

sodium fluoride for 50 days (Narayana and Chinoy 1994) and in rats exposed for 60 days to 4.5 mg

fluoride/kg/day as sodium fluoride in the diet (Araibi et al. 1989).

No alterations in Sertoli cells or in the seminiferous tubules were observed in the male offspring of rats

exposed during gestation, lactation, and for 14 weeks post weaning to 16 mg fluoride/kg/day as sodium

fluoride in drinking water (Sprando et al. 1998). However, other studies have reported testicular damage,

which appears to be directly related to the length of exposure. No histological alterations were observed

in the testes of rats exposed to 21 mg fluoride/kg/day as sodium fluoride for 6 weeks (Krasowska and

Wlostowski 1992). However, after 16 weeks of exposure, seminiferous tubule atrophy was observed at

7.5 mg fluoride/kg/day and higher (Krasowska and Wlostowski 1992). A decrease in the mean diameter

of the seminiferous tubules was observed in rats exposed to 2.3 or 4.5 mg fluoride/kg/day as sodium

fluoride in the diet for 60 days (Araibi et al. 1989); thickening of the peritubular membrane of the

seminiferous tubules was also observed at 4.5 mg fluoride/kg/day. Consistent with the decreases in serum

testosterone levels, significant decreases in Leydig cell diameter were observed in rats (Narayana and

Chinoy 1994) and rabbits (Susheela and Kumar 1991) receiving 4.5 mg fluoride/kg/day via gavage as

sodium fluoride in water for 50 days or 18–23 months, respectively.


3. HEALTH EFFECTS

Although some studies have not found significant alterations in spermatogenesis or sperm morphology, a

number of studies have reported adverse effects. No alterations in sperm head abnormalities (Li et al.

1987a) or sperm morphology (Dunipace et al. 1989) were observed in B6C3F1 mice administered sodium

fluoride by gavage at doses up to 32 mg fluoride/kg/day for 5 days and killed 30 days later or in

B6C3F1 mice administered 23 mg fluoride/kg/day as sodium fluoride in water. In CD rats administered

4.5 mg fluoride/kg/day as sodium fluoride in the diet for 60 days, a significant decrease in the percentage

of seminiferous tubules containing spermatozoa was observed (Araibi et al. 1989). Damage to the

spermatid and epididymal spermatozoa were observed in rabbits administered by gavage 4.5 mg

fluoride/kg/day as sodium fluoride in water for at least 18 months (Kumar and Susheela 1994, 1995), and

complete cessation of spermatogenesis was observed after 29 months of exposure (Susheela and Kumar

1991). A number of studies have found significant alterations in cauda epididymal and vas deferens

sperm. Decreased sperm counts, sperm motility, and sperm viability (the ratio of live to dead sperm) have

been observed in rats exposed to 2.3 mg fluoride/kg/day and higher (Chinoy et al. 1992, 1995) and mice

(Chinoy and Sequeira 1992) and guinea pigs (Chinoy et al. 1997) exposed to 4.5 mg fluoride/kg/day and

higher. When exposed male rats were mated with unexposed females, decreased fertility was observed at

2.3 mg fluoride/kg/day as sodium fluoride and higher (Chinoy and Sequeira 1992; Chinoy et al. 1992).

The alterations in sperm and the infertility were reversible 30–60 days after termination of a 30-day

exposure period (Chinoy and Sequeira 1992).

Adverse reproductive effects have also been observed in females. Nearly complete infertility was

observed in female Swiss-Webster mice exposed to 19 mg fluoride/kg/day as sodium fluoride in the

drinking water for 25 weeks (Messer et al. 1973). However, this effect was not repeated in another study

of Webster mice exposed to 13 mg fluoride/kg/day as sodium fluoride in the diet for three generations

(Tao and Suttie 1976). The study authors attributed the difference between this study and the Messer et

al. (1973) study to the higher iron levels in the Tao and Suttie (1976) study, as anemia was reported by

Messer et al. (1973), but not by Tao and Suttie (1976). Significant decreases in the number of viable

fetuses and increases in the resorption rate were observed in female Sprague-Dawley rats exposed to

10.21 mg fluoride/kg/day as sodium fluoride in drinking water for 30 days prior to mating with

unexposed males (Al-Hiyasat et al. 2000); it is not known if these effects were directly related to fluoride

exposure or were secondary to the severe decreases in body weight (31% lower than controls) and water

consumption. In contrast, a two-generation study by Collins et al. (2001a) did not find any significant

alterations in reproductive performance in CD rats exposed to 10.7 mg fluoride/kg/day as sodium fluoride

in drinking water for 10 weeks prior to mating with similarly exposed males. This study only found a


3. HEALTH EFFECTS

small decrease in body weight gain (approximately 6%) in the rats exposed to a similar sodium fluoride

concentration as used by Al-Hiyasat et al. (2000). Decreased estrus rate and increased incidence of

missed pregnancies was observed in Sheltie dogs fed dog food supplemented with rock phosphate at a

level of 11.5 mg fluoride/kg/day (Shellenberg et al. 1990). However, these changes were also observed in

groups provided with distilled water rather than well water. No adverse effects on reproduction were

observed in a two-generation rat study in which male and female rats were fed diets containing 23 mg

fluoride/kg/day (Marks et al. 1984). Additional evidence that fluoride adversely affects female

reproduction includes decreased lactation in rats exposed to 21 mg fluoride/kg/day in drinking water for

88 days (Yuan et al. 1994) and decreased calving rate (Van Rensburg and de Vos 1966) and decreased

milk production (Maylin and Krook 1982) in cows ingesting large amounts of fluoride.

The highest NOAEL values and all reliable LOAEL values for reproductive effects for each species and



Fluoride readily crosses the placenta and is found in fetal and placental tissue (Armstrong et al. 1970;

Gupta et al. 1993; Malhotra et al. 1993; Shen and Taves 1974). A number of human and animal studies

have examined the potential of fluoride to induce developmental effects.

Analysis of birth certificates and hospital records for over 200,000 babies born in an area with fluoridated

water and over 1,000,000 babies born in a low fluoride area found no difference in the incidence of birth

defects attributable to fluoride (Erickson et al. 1976). Exposure to high levels of fluoride has been

described together with an increased incidence of spina bifida (Gupta et al. 1995). The occurrence of

spina bifida was examined in a group of 50 children aged 5–12 years living in an area of India with high

levels of fluoride in the drinking water (4.5–8.5 ppm) and manifesting either clinical (bone and joint pain,

stiffness, and rigidity), dental, or skeletal fluorosis. An age- and weight-matched group of children living

in areas with lower fluoride levels (≤1.5 ppm) served as a control group. Spina bifida was found in

22 (44%) of the children in the high fluoride area and in 6 (12%) of the children in the control group.

This study did not examine the possible role of potentially important nutrients such as folic acid,

however, and had other study design flaws.

Three studies (Li et al. 1995a; Lu et al. 2000; Zhao et al. 1996) conducted in China have found significant

decreases in intelligence score in children living in areas with high endemic levels of fluoride in the


3. HEALTH EFFECTS

water. As noted below, these studies have a number of design limitations, which restrict the interpretation

of the results. A fourth study did not find significant alterations in IQ scores in Mexican children

(Calderon et al. 2000). The study by Li et al. (1995a) examined intelligence in children living in areas

with high fluoride levels due to soot from coal burning. A group of 907 children aged 8–13 years were

divided into four groups depending on the existence and severity of dental fluorosis; 20–24 children in

each age group for each area were examined for intelligence. A significant decrease in IQ was measured

in children living in the medium- (mean IQ of 79.7) and severe- (mean of 80.3) fluorosis areas, as

compared to the children living in the non- (mean of 89.9) or slight- (mean of 89.7) fluorosis areas. More

children with IQs of <70 and 70–79 and fewer children with IQs of 90–109 and 110–119 were found in

the medium- and severe-fluorosis areas than in the non- or slight-fluorosis areas. No information on

exposure levels were provided; the mean urinary fluoride levels were 1.02, 1.81, 2.01, and 2.69 mg/L in

the non-, slight-, medium-, and severe-fluorosis areas, respectively. Numerous potentially confounding

variables were not mentioned in this study, however, which raises questions regarding the validity of the

study’s findings. A study by Lu et al. (2000) also examined exposure to high fluoride levels and

decreased intelligence. Sixty children aged 10–12 years living in an area with high fluoride levels in the

drinking water (3.15 mg/L) were examined for intelligence. The test results were compared to a group of

58 children with similar social, education, and economic backgrounds who lived in an area with low

fluoride levels in water (0.37 mg/L). A significant decrease in IQ was observed in the high fluoride area

(mean IQ of 92.27) as compared to the control group (103.05). Additionally, there was a significantly

higher number of children from the high exposure area with IQ scores of <70 (retarded) and 70–

79 (borderline retarded) than in the control group. A significant inverse relationship between urinary

fluoride levels and IQ was also found. Nevertheless, because this study relied on small groups and

presented scant discussion of numerous potential confounders, the strength of its conclusions are

questionable. Zhao et al. (1996) found significantly lower IQ scores in children living in a village with

high levels of fluoride in drinking water (4.12 ppm) as compared to children living in a village with

0.91 ppm fluoride in water. The study authors noted that IQ levels in children were correlated with the

educational levels of the parents; however, the educational level of parents in the village with low fluoride

levels was higher than those in the high fluoride village.

No significant alterations in IQ scores were found in Mexican children (6–8 years of age) exposed to 1.2–

3 ppm fluoride in drinking water (Calderon et al. 2000; only available as an abstract). However, increases

in reaction time and decreases in visuospatial organization were found; the scores on these tests were

correlated with urinary fluoride levels.


3. HEALTH EFFECTS

Rapaport (1956) reported an increased prevalence of Down’s syndrome in areas with fluoridated water.

However, this finding has not been replicated by several other investigations (Berry 1958; Erickson et al.

1976; Needleman et al. 1974). No correlation was found between fluoridation and Down's syndrome

incidence (corrected for maternal age) in a study of over 234,000 children in fluoridated areas and over

1,000,000 children in low-fluoride areas (Erickson et al. 1976). Ascertainment was based on birth

certificates and hospital records, but was probably incomplete. Takahashi (1998) criticized the methods

used by Erickson et al. (1976) to analyze the data. Using the same dataset and combining Down’s

syndrome prevalence for the three youngest maternal ages, Takahashi (1998) found a significant

association between water fluoridation and Down’s syndrome. Similar to Erickson et al. (1976),

Needleman et al. (1974) found no maternal age-specific increases in Down’s syndrome; ascertainment

was nearly complete in this study of over 80,000 children in fluoride areas and over 1,700,000 children in

low-fluoride areas. Similarly, a study of the incidence of Down's syndrome in England did not find an

association with the level of fluoride in water, but age-specific rates were not determined and tea was not

taken into account as a source of fluoride (Berry 1958).

No alterations in the number of live births, sex ratio, fetal body weights, or the occurrence of external,

visceral, or skeletal malformations were observed in the offspring of rats and rabbits exposed to doses as

high as 13.21 or 13.72 mg fluoride/kg/day, respectively, as sodium fluoride in drinking water consumed

on gestational days 6–15 or 6–19, respectively (Heindel et al. 1996) or in the offspring of F0 or F1 rats

exposed to 12.2 mg fluoride/kg/day as sodium fluoride in drinking water for 10 weeks prior to mating and

during gestation (Collins et al. 2001b). Similarly, no developmental effects were observed in offspring of

rats drinking water containing at least 11.2 mg fluoride/kg/day as sodium fluoride on gestational days 1–

20 (Collins et al. 1995). An increase in the average number of fetuses per litter with at least three skeletal

variations was seen at the highest dose tested (11.4 mg fluoride/kg/day); however, this was associated

with decreased maternal water and food consumption and decreased body weight gain. Significant

increases in the percentage of fetuses with skeletal or visceral abnormalities were also observed in the

fetuses of rats receiving gavage doses of 18 mg fluoride/kg/day as sodium fluoride on gestational days 6–

19 (Guna Sherlin and Verma 2001). As with the Collins et al. (1995) study, significant decreases in

maternal body weight and food consumption were also observed in the dams.

Bone morphology of weanling Sprague-Dawley rats from dams that received 21 mg fluoride/kg day for

10 weeks prior to breeding and during gestation was examined with both light and electron microscopy.

No pathological changes were seen, suggesting that although fluoride is transported across the placenta,

the amount transported was not sufficient to affect fetal bone development (Ream et al. 1983). There


3. HEALTH EFFECTS

were no developmental effects of fluoride in the first litter of an extended two-litter reproduction study in

rats that were fed diets containing 23 or 2.8 mg fluoride/kg/day (two litters from each dam) (Marks et al.

1984). However, the second litters born to mothers in the high-fluoride group had a higher number of

abnormal newborns and affected litters than were found in the low-fluoride group. The significance of

this finding is unclear because the effect was not analyzed statistically.

Wild and domestic animals may be more sensitive than laboratory animals to developmental effects of

fluoride. Stunted growth (Krook and Maylin 1979) and lameness (Maylin and Krook 1982) have been

reported in calves that foraged on land downwind of an aluminum plant. Severe dental fluorosis

confirmed high levels of fluoride ingestion. Mink kits that were born to mothers fed 9.1 mg

fluoride/kg/day and fed the same feed after weaning exhibited a marked decrease in survivability (14% at

3 weeks, compared with 86% for the control) (Aulerich et al. 1987). There was no effect at the next

lower dose. No further clinical details were provided for these pups. However, survival of the females

exposed to that level was also decreased (17% at the end of the trial [382 days], compared with 100% for

the control), so it is not clear if the kit effects were secondary to maternal toxicity. The only clinical signs

in the adult mink were general unhealthiness, hyperexcitability, and lethargy a few days before they died.

No lameness was observed.

3.2.2.7 Cancer

Numerous epidemiological studies have examined the issue of a connection between fluoridated water

and cancer. Most studies have not found significant increases in cancer mortality (Erickson 1978; Hoover

et al. 1976; Rogot et al. 1978; Taves 1977) or site-specific cancer incidence (Freni and Gaylor 1992;

Gelberg et al. 1995; Hoover et al. 1976; Mahoney et al. 1991; McGuire et al. 1991). However, a couple

of studies have reported significant fluoridation-related increases in cancer mortality (Yiamouyiannis and

Burk 1977) or incidence (Takahashi et al. 2001). The lack of control for potential confounding variables

(i.e., age, race) limits the interpretation of these study results. Most of the investigations were

community-based studies, and the sensitivity limit of even the most sensitive analysis in these studies

appears to be a 10–20% increase.

Yiamouyiannis and Burk (1977) were the first investigators to suggest a relationship between water

fluoridation and increased cancer risk. In their study, cancer death rates for 1940–1950 were compared to

rates for 1953–1969 for residents of the 10 largest cities in the United States with fluoridated water.

Similar comparisons were made in 10 cities without fluoridated water. The investigators noted that prior


3. HEALTH EFFECTS

to fluoridation (1940–1950) the crude cancer deaths were similar in the two groups of cities. After

fluoridation (1953–1969), a sharp increase in cancer deaths was observed in the cities with fluoridated

water. The increases in cancer deaths among residents aged 45–64 years and ≥65 years living in cities

with fluoridated water were significantly higher than in residents of cities with nonfluoridated water.

Yiamouyiannis and Burk (1977) noted that there was a greater increase in nonwhites in the fluoridated

cities than in the nonfluoridated cities. Because they found no correlation between the increase in age-

adjusted cancer death rate and the increase in the number of nonwhites living in each city, they concluded

that the change in racial composition did not contribute to the fluoridation-related increase in cancer death

rates.

A number of investigators have criticized the methods used by Yiamouyiannis and Burk and have re-

analyzed the data (Chilvers 1982, 1983; Doll and Kinlen 1977; Hoover et al. 1976; Kinlen and Doll 1981;

Oldham and Newell 1977; Smith 1980; Taves 1977). The study was primarily criticized for the

dissimilarity of the age, sex, and race distribution between the fluoridated and nonfluoridated cities and

the rather short cancer latency period. Chilvers (1983) and Smith (1980) noted that the divergence in

crude cancer deaths began almost immediately after fluoridation was initiated. The latency period (the

period of time between first exposure and the discovery of cancer) is usually >5 years and the period

between first exposure and death from cancer is typically >15 years. Thus, Chilvers (1983) and Smith

(1980) suggested that exposure to fluoridated water was not the likely cause of the divergence in cancer

mortality between the two groups of cities that began shortly after initiation of a water fluoridation

program. Smith (1980) noted that using age bands of 20 years is problematic for cancer studies because

cancer mortality dramatically increases with age so that small differences in the age distribution between

two populations can result in apparently significant differences in cancer mortality.

Smith (1980) also criticized Yiamouyiannis and Burk’s dismissal of the potential confounding variable of

race based on the lack of significant correlation relationships. Additionally, he noted that the appropriate

analytical method should account for race, age, and sex differences at the same time. Between 1950 and

1970, the proportion of nonwhites and individuals over the age of 65 years increased more rapidly in the

fluoridated cities than in the nonfluoridated cities (Doll and Kinlen 1977). This change in demographics

would have likely resulted in increased cancer deaths independent of fluoridation. Oldham and Newell

(1977) noted that although the crude cancer rates in the two groups of cities were similar, the 1950 excess

cancer rate (which accounts for race, sex, and age differences) in the fluoridated cities was 10.3 per

100,000 higher than in the nonfluoridated cities. The higher excess cancer rate in the fluoridated cities

was attributed to the smaller number of white elderly women and greater number of elderly white males.


3. HEALTH EFFECTS

Oldham and Newell (1977) estimated that in 1970, the excess cancer rate increased by 1% in the

fluoridated cities and 4% in the nonfluoridated cities; the increases in absolute deaths were 8.8 per

100,000 and 7.7 per 100,000 in the fluoridated and nonfluoridated cities, respectively. In re-examining

the data used by Yiamouyiannis and Burk (1977), Hoover et al. (1976) noted that when fluoride was the

only variable used in the regression analysis, it was a significant predictor of cancer mortality rate.

However, when other demographic variables (population density, education level, race, employment in

manufacturing, and geographic section of the country) were also entered into the equation, fluoride only

statistically predicted stomach cancer mortality rate. Re-analysis of stomach cancer data with adjustment

for high-risk ethnic groups resulted in a nonsignificant association for females and a significant

association for males.

Yiamouyiannis and Burk’s selection of nonfluoridated cities has also been criticized because they did not

select the 10 largest cities (the criteria used for selecting fluoridated cities), rather they selected the

10 largest cities with a crude cancer death rate exceeding 155 per 100,000 (the average in fluoridated

cities). Comparison of the SMRs for 1950, 1960, and 1970 and the change from 1950 to 1970 using

cancer mortality analysis of data from the original 10 largest fluoridated cities and the 10 largest

nonfluoridated cities did not result in any relevant changes in cancer mortality (Kinlen and Doll 1981).

Similarly, Taves (1977) calculated SMRs for three 2-year periods (1949–1951, 1959–1961, and 1969–

1971) for all cancers in the fluoridated and nonfluoridated cities examined by Yiamouyiannis and Burk

and for the next 10 largest fluoridated cities and 5 nonfluoridated cities. The SMRs for the 20 fluoridated

cities, as well as the SMRs for the 15 nonfluoridated cities, were relatively constant for the three time

periods, suggesting that water fluoridation did not increase the cancer risk.

A number of other population studies have examined the possible association between water fluoridation

and increased risk of all cancers or site-specific cancers. Hoover et al. (1976) examined cancer mortality

data for counties in Texas with varying levels of naturally occurring fluoride. For white males and

females, no significant increases in SMRs for all cancers combined or site-specific cancers were found in

the three groups of counties with high levels of fluoride (0.7–1.2 ppm, 1.3–1.9 ppm, and ≥2.0 ppm) as

compared to counties with very low fluoride levels in the drinking water. Hoover et al. (1976) also

examined the effect of artificial fluoridation on cancer mortality. SMRs were calculated for residents of

counties in the United States that were 67% urban. No significant differences in the SMRs for all cancer

combined between the fluoridated and nonfluoridated counties were seen prior to fluoridation or 5, 10, or

15 years after fluoridation. Similarly, no significant differences in SMRs were seen for individual cancer

sites. A third study conducted by Hoover et al. (1976) examined cancer incidence data from Birmingham,


3. HEALTH EFFECTS

Alabama (nonfluoridated) and Denver, Colorado (fluoridated after 1947–1948). No fluoridation-related

increases in age-adjusted, site-specific cancer incidence rates were found prior to fluoridation (1947–

1948) or after fluoridation (1969–1971).

Using mortality data from 22 nonfluoridated and 24 fluoridated cities with populations greater than

250,000, Erickson (1978) calculated crude and adjusted death rates for all malignant neoplasms and

several site-specific cancers (digestive, respiratory, breast, genital, urinary, leukemia). Slightly higher

crude mortality rates were seen in the fluoridated cities (206.6 versus 183.0); however, when the mortality

rates were adjusted for age, sex, and race, and demographic, social, and economic variables, no

significant differences were found. Rogot et al. (1978) also found no association between fluoridation

and cancer mortality among cities with populations of 25,000 or more in 1950. Mortality rates for 1950,

1960, and 1970 and the change from 1950 to 1970 were compared for fluoridated and nonfluoridated

cities. In a study of cancer mortality rates in three counties in Kansas with fluoridated water, and one

county with nonfluoridated water, no consistent fluoridation-related increases in age-adjusted mortality

from all cancers were found (Neuberger 1982). In one fluoridated county, there was a significant increase

in mortality; however, in another county, cancer mortality was significantly lower than in the

nonfluoridated county and in the third county, there were no significant differences. Examination of

cancer mortality data for individual tumor sites revealed slightly higher rates of rectum cancer in females,

higher rates of pancreatic cancer in females living in the county with the longest history of fluoridation,

and bone cancer in males with the longest history of fluoridation exposure; the statistical significance of

these findings was not reported. Using data from the NCI Surveillance, Epidemiology and End Result

(SEER) program, Hoover et al. (1991a) evaluated cancer mortality data for 36 years and incidence data

for 15 years. No consistent evidence of a relationship between site-specific cancer mortality or incidence

and the pattern of fluoridation was found. A suggestive relationship between renal cancer incidence and

duration of fluoridation was found. However, when the incidence data were divided into two time periods

(1973–1980, 1981–1987), no relationship between renal cancer incidence and duration of fluoridation was

found.

A more recent study has also examined cancer incidence in populations with fluoridated water. Using

data from three states (Connecticut, Iowa, and Utah) and six cities (Atlanta, Detroit, New Orleans, Seattle,

San Francisco, and Los Angeles), Takahashi et al. (2001) conducted regression analysis of site-specific

cancers. Statistically significant positive associations between fluoridation index (percentage of

population with naturally or artificially fluoridated water) and cancer at a number of sites including the

oral cavity, esophagus, colon, liver, pancreas, bronchus, lungs, kidney, urinary bladder, and bone were


3. HEALTH EFFECTS

found. However, interpretation of these data is limited by the lack of control for potential confounding

variables (particularly age and race) between the fluoridated and nonfluoridated communities.

In the early 1990s, two population-based studies found increases in the incidence of bone and joint cancer

or osteosarcoma among males under the age of 20 living in areas with fluoridated water (Cohn 1992;

Hoover et al. 1991b). Based on the NCI SEER program data, Hoover et al. (1991b) found 47 and 79%

increases in the incidences of bone and joint cancer and osteosarcoma, respectively, among males and

females living in areas with fluoridated water. In contrast, 34 and 4% declines in bone and joint cancer

and osteosarcoma, respectively, were found in the nonfluoridated areas. The investigators questioned the

biological significance of this finding because no relationship between the increased incidence and the

initiation of fluoridation was found (Hoover et al. 1991b). In the Cohn (1992) study of the New Jersey

cancer registry data, significant increases in the osteosarcoma incidence risk ratios were found among

males under the age of 20 years living in areas with fluoridated water. The investigator cautioned that

these results were based on a small number of cases. Other population-based studies (Freni and Gaylor

1992; Mahoney et al. 1991) did not find significant associations between fluoridation and bone cancer.

Freni and Gaylor (1992) reported significant increases in the cumulative risk of bone cancer among young

men aged 10–29 years in 40 cancer registry areas in the United States, Canada, and Europe for the period

of 1958–1987. However, when registry data for areas with known fluoridation status were examined, no

consistent pattern was observed; both increases and decreases in cumulative risk were found in areas with

fluoridated water. Similarly, Mahoney et al. (1991) reported a significant trend for increasing incidence

of bone cancer among young men (<30 years of age) living in New York State, exclusive of New York

City. A significant trend was not observed in young females or for osteosarcomas. Comparisons between

bone cancer and osteosarcoma incidence rates among residents of counties with fluoridated water and

residents of counties with nonfluoridated water did not reveal any statistically significant associations. A

case-control study of New York residents, excluding New York City, also failed to show an association

between fluoridated water and increased risk of osteosarcoma (Gelberg et al. 1995). A significant

protective trend (odds ratio decreased with increased fluoride intake) was observed for males, although

the authors noted that this may be due to good health practices rather than fluoride because a significant

trend was not observed when only fluoridated water was considered. A small-scale case-control study

(22 cases examined) also failed to find a significant association between fluoridated water and

osteosarcoma occurrence (McGuire et al. 1991).

The NTP conducted two chronic oral bioassays of fluoride administered as sodium fluoride (0, 25, 100, or

175 ppm) in drinking water for 103 weeks, using F344/N rats and B6C3F1 mice (Bucher et al. 1991; NTP


3. HEALTH EFFECTS

1990). The first study was considered compromised for reasons that will be discussed below. However,

pathology data from the first study were used in determining the doses for the second study. The

specially formulated diet used in the second study contained 8.6 ppm fluoride; daily fluoride amounts

administered in the food for control and experimental groups were 0.43 mg/kg/day in rats and

1.1 mg/kg/day in mice. Based on the total amount of fluoride ingested and the amount in the feces, and

apparently assuming that none of the fluoride found in the feces was absorbed, Bucher et al. (1991)

calculated that the average bioavailability of fluoride in the food over the course of the experiment was

60%. Assuming complete absorption of fluoride in the water, they estimated total fluoride intake

(including fluoride in both water and diet) of control, low-, medium-, and high-dose male rats as 0.2, 0.8,

2.5, and 4.1 mg/kg/day, respectively. Similarly, the high doses for female rats, male mice, and female

mice were 4.5, 8.1, and 9.1 mg/kg/day, respectively.

The study found osteosarcomas in the bone of 1/50 male rats in the mid-dose group and 3/80 of the high-

dose male rats. An additional high-dose male had an extraskeletal osteosarcoma in subcutaneous tissue.

Examination of radiographs did not reveal a primary site in bone for the extraskeletal tumor, suggesting

that it was a soft-tissue tumor that later ossified. No osteosarcomas were found in the low-dose or control

rats. One of the osteosarcomas in the high-dose group was missed on radiographic examination and in the

necropsy, and found only on microscopic examination. Three of the tumors were in the vertebra and only

one was in a long bone. This is unusual, as Bucher et al. (1991) stated that chemically-induced

osteosarcomas usually appear in the long bones, rather than in the vertebrae. Statistical analysis found a

significant dose-response trend in the four osteosarcomas of the bone (p=0.027), but no significant

difference (p=0.099) in a pairwise comparison of the controls with the high-dose group. The probability

value for the trend test was decreased (p=0.010) when the extraskeletal osteosarcoma was included, but

the pairwise test was still not significant (p=0.057). Osteosarcomas are rarely observed in control male

rats in NTP studies; the historical incidence is 0.6% (range 0–6%). The rate in the high-dose group in this

study was 3.75 or 5%, depending on whether or not the extraskeletal tumor is included. Tumor rates

could not be compared with the historical controls because the diet generally used for NTP studies

contains >20 ppm fluoride. Assuming the same bioavailability of 60%, the study report states that this

would place the historical controls between the low- and mid-dose groups in the fluoride study.

Conversely, the more extensive bone examinations used in the fluoride study, both at the macroscopic

level and histologically, could have led to higher bone tumor levels being observed than in historical

controls.


3. HEALTH EFFECTS

The average fluoride level in the bones of male rats in the high-dose group was 5,260 ppm. While similar

bone fluoride levels were found in the bones of female rats and male and female mice, there was no

evidence of treatment-related osteosarcomas in these groups. Osteosclerosis was observed in high-dose

female rats, suggesting a stimulatory or mitogenic effect on osteoblasts (Marie and Hott 1986).

Osteosclerosis was not observed in mice, despite the higher dose. Osteosarcomas were observed in one

low-dose male mouse, one low-dose female mouse, and one control female mouse. There was also one

osteoma in a control female mouse. No osteosarcomas were observed at mid- or high-dose levels in

female rats or male or female mice. The study authors stated that the absence of treatment-related

osteosarcomas in female rats and male and female mice may have limited relevance to the findings in

male rats. Results in the literature are mixed as to whether there is a sex-linked response in bone tumor

formation (Litvinov and Sikivuev 1973; NCI 1978).

Increased tumor incidence in rats or mice was noted in a few other tissues, but was not considered

biologically significant. For example, the combined incidence of squamous cell papillomas and

carcinomas in the oral mucosa was marginally increased in the high-dose male and female rats and

thyroid follicular cell neoplasms were marginally increased in the high-dose male rats. Neither increase

was statistically significant, and both types of neoplasms lacked a supporting pattern of increased

preneoplastic lesions. Similarly, increased levels of keratoacanthomas were observed in high-dose female

rats, but were not considered biologically significant because other benign neoplasms arising from

stratified squamous epithelium was found in the controls. Malignant lymphoma and histiocytic sarcoma

incidence in female high-dose mice was marginally increased (combined rate 30%), but the increase was

not considered biologically significant. The incidence was well within the range of historical controls at

the study laboratory (18–48%) and at all NTP laboratories (10–74%). The incidence of hepatocellular

neoplasms in male and female mice of the treatment and control groups was higher than in historical

controls. The study authors noted similar increases in other NTP studies that were conducted

contemporaneously, and suggested that they may be associated with increased animal weight. Hepato-

cholangiocarcinomas, which are rare liver neoplasms, were identified in the original pathology

examination in five treated male mice, four treated female mice, and one control female mouse. The

Pathology Working Group reclassified all of the neoplasms (except one in a high-dose female mouse and

one in a control female mouse) as hepatoblastomas, because they contained well-defined populations of

cells that resembled embryonal liver cells more closely than they did biliary cells. The dose levels at

which the reclassified hepatocholangiocarcinomas were found were not reported.


3. HEALTH EFFECTS

Interpretation of this study is further complicated because higher doses might have been tolerated in both

the rat and the mouse studies (NTP 1990). Fluoride-related tooth abnormalities found in the study

included dental attrition in males of both species that was dose-related in rats but not in mice, dentine

dysplasia in both genders of both species, and tooth deformities in male rats. No other treatment-related

toxic effects were found in any group, and there was no evidence of decreased body weight gain in any

group. Higher fluoride levels may have affected the teeth of the male rats so severely as to interfere with

the animals' ability to eat. However, it appears that the mice and possibly the female rats could have

tolerated a higher dose.

Based on the finding of a rare tumor in a tissue known to accumulate fluoride, but not at the usual site for

chemically-associated osteosarcomas, a weakly significant dose-related trend, and the lack of supporting

data in female rats and mice of either gender, the NTP concluded that there was "equivocal evidence of

carcinogenic activity of sodium fluoride in male F344/N rats." NTP defined equivocal evidence of

carcinogenic activity to be a situation where the results show "a marginal increase in neoplasms that may

be chemically related." NTP further concluded that there was no evidence that fluoride was carcinogenic

at doses up to 4.73 mg/kg/day in female F344/N rats, or at doses up to 17.8 and 19.9 mg/kg/day in male

and female B6C3F1 mice, respectively.

The first chronic study in this series conducted by NTP was a 2-year cancer study in B6C3F1 mice and

F344/N rats using a semisynthetic diet containing 2.1 ppm fluoride and fluoride provided in drinking

water as sodium fluoride at 0, 10, 30, or 100 ppm. Several nontreatment-related clinical signs developed

in rats, including corneal lesions and head tilt. Analysis of the diet revealed marginal to marked

deficiencies in manganese, chromium, choline, and vitamins B12 and D. Based on these findings, the

study was considered compromised, but the results were used to aid in dose selection for the second

study. Only the following unverified pathology findings were reported: (1) one osteosarcoma in the

occipital bone of one low-dose male rat; (2) one osteoma in the vertebra of a male control mouse; (3) one

subcutaneous osteosarcoma in one female high-dose mouse; and (4) no osteosarcomas in female rats

(male mice were not mentioned).

A study sponsored by Procter and Gamble examined the carcinogenic potential of sodium fluoride

administered in feed to Sprague-Dawley rats (Maurer et al. 1990). One group of controls was fed

laboratory chow, and another control group was fed a semisynthetic low-fluoride diet. The control group

fed the low-fluoride diet received 0.14 (males) or 0.18 (females) mg fluoride/kg/day as sodium fluoride.

The fluoride level in the laboratory chow was not determined. Treatment groups ingested 1.8, 4.5, or


3. HEALTH EFFECTS

11.3 mg fluoride/kg/day in the diet as sodium fluoride. Fluoride bioavailability was not determined and

water fluoride levels were not reported. Fluoride-related toxicity included dose-related hyperostoses in

males and females, tooth abnormalities, and stomach inflammation. Fluoride levels in the bone ash of the

high-dose males and females were 16,761 and 14,438 ppm, respectively. Primary tumors in target tissues

as reported by the study authors were one fibroblastic sarcoma with areas of osteoid formation in a high-

dose male, one osteosarcoma in a low-dose female, one chordoma in a mid-dose male, one chondroma

each in a mid-dose male and a low-dose female, one odontoma in a laboratory-chow control, and one

stomach papilloma in a low-fluoride control. Re-examination of tissue slides as part of a review of the

study by the Carcinogenicity Assessment Committee, Center for Drug Evaluation and Research, Food and

Drug Administration (CAC/CDER/FDA) revealed an additional osteosarcoma in a low-dose female and

one osteosarcoma in a high-dose male. Statistical analysis of the incidence of bone tumors found no

dose-response relationship (CDER 1991).

Several limitations of the study were not apparent in the study report, but were noted in the CAC review

(CDER 1991). The low-fluoride diet may not have allowed normal growth and development, since pale

livers and gastric hairballs were observed in all study animals except those fed laboratory chow. The diet

and water were often above specifications for minerals, ions, and vitamins. A virus was found during the

pretest period and its continued presence during the study was suspected; this may have compromised the

health of the animals. The finding of bone tumors missed by the contract laboratory raised questions

about the adequacy of the examination at gross necropsy. Finally, bone sections from only 50–80% of the

mid- and low-dose animals were analyzed microscopically. The CAC review concluded that there are

"flaws and uncertainties in the studies that keep them from providing strongly reassuring data." However,

the committee concluded that the study results reaffirm the negative finding of the NTP study in female

rats, and do not reinforce the equivocal finding in male rats.

3.2.3 Dermal Exposure

Several human and animal studies investigating the health effects following accidental dermal exposure to

hydrofluoric acid were located. In addition, many of the human and animal studies investigating the

health effects of inhalation exposure to hydrogen fluoride or fluorine found dermal/ocular effects due to

the irritating effects of these chemicals. (In this section, hydrogen fluoride refers to the gas while

hydrofluoric acid refers to the liquid.) One study regarding dermal exposure to sodium fluoride was

located. Fluorine causes severe irritation of the eyes and skin and can severely burn the skin at high

concentrations. Hydrofluoric acid is a caustic acid and can produce severe tissue damage either as the


3. HEALTH EFFECTS

water solution, or in the anhydrous form (hydrogen fluoride). Hydrofluoric acid can also rapidly

penetrate the skin and cause systemic effects, especially cardiac arrhythmias. If left untreated, death can

result.

3.2.3.1 Death

Hydrofluoric Acid. Fatalities from dermal fluoride exposure occur most frequently from accidental

exposure to hydrofluoric acid in an occupational setting. The actual systemic doses are seldom known.

However, the extent and severity of the burns, and occasionally, clinical chemistry values are reported.

Death following hydrofluoric acid burns to the extremities, in the absence of inhalation exposure, is due

to cardiac arrhythmias, with pronounced hypocalcemia, hyperkalemia, and hypomagnesemia. Ion pump

disruption is thought to be the mechanism of systemic toxicity. Hydrofluoric acid exposure of the face

has also resulted in death due to respiratory insufficiency, but the respiratory effects are likely to be due to

concurrent inhalation exposure. Depending on the extent of the body surface exposed and the

effectiveness of medical treatment, death usually occurs within a few hours (Chan et al. 1987; Chela et al.

1989; Kleinfeld 1965).

A patient with hydrofluoric acid burns on his leg involving 8% of his body surface area died from

intractable cardiac arrhythmia, presumably secondary to the depletion of ionized calcium by the fluoride

ion (Mullett et al. 1987). Serum fluoride level 4 hours after the burn injury was reported to be

9.42 µg/mL, about 400 times the value reported as normal for that age and sex. A 23-year-old man who

sustained second and third degree burns of his thighs, covering 9–10% of his body surface area died of

cardiac arrhythmia 17 hours after exposure (Mayer and Gross 1985); serum fluoride was 4.17 µg/mL.

The death of a chemist who sustained first- and second-degree burns of the face, hands, and arms when a

vat containing hydrofluoric acid accidentally broke has been reported (Kleinfeld 1965). This 29-year-old

male died 10 hours after admission to the hospital. Postmortem examination showed severe

tracheobronchitis and hemorrhagic pulmonary edema. A petroleum refinery worker was splashed in the

face with 100% anhydrous hydrofluoric acid (Tepperman 1980). The burn produced acute systemic

fluoride poisoning with profound hypocalcemia and hypomagnesemia. The patient died <24 hours after

exposure. A young woman splashed in the face with hydrofluoric acid died a few hours after exposure

occurred (Chela et al. 1989). The autopsy revealed severe burns of the skin and lungs, with pulmonary

hemorrhagic edema produced by hydrofluoric acid and its vapor.


3. HEALTH EFFECTS

No studies were located regarding lethality in humans after dermal exposure to fluorine or fluoride, and

no studies were located regarding lethality in animals after dermal exposure to fluoride, hydrofluoric acid,

or fluorine.


No studies were located regarding gastrointestinal, hematological, musculoskeletal, endocrine, or body

weight effects in humans or animals after dermal exposure to fluoride, hydrofluoric acid, or fluorine.


duration category of exposure to hydrofluoric acid are recorded in Table 3-5. All reliable LOAEL values

for systemic effects in each species and duration category for fluoride are recorded in Table 3-6.

Respiratory Effects.

Hydrofluoric Acid. Respiratory effects including pulmonary edema, tracheobronchitis, and pulmonary

hemorrhagic edema have been reported in humans following acute dermal exposure of the face to

hydrofluoric acid (Chela et al. 1989; Kleinfeld 1965). However, the pulmonary effects are likely to be

due to concomitant inhalation of the acid vapor. As two of these cases were occupational accidents and

the third was a homicide, no doses could be estimated from the information provided.

No studies were located regarding respiratory effects in humans after dermal exposure to fluoride or

fluorine, and no studies were located regarding respiratory effects in animals after dermal exposure to

fluoride, hydrofluoric acid, or fluorine.

Cardiovascular Effects. Cardiac arrhythmias are found following acute dermal exposure to

hydrofluoric acid in humans (Mayer and Gross 1985; Mullett et al. 1987). A man who received a

hydrofluoric acid burn on the arm covering 5% of the body experienced repeated ventricular fibrillation

episodes, but survived following administration of intravenous calcium chloride, subcutaneous calcium

gluconate, and excision of the burn area (Buckingham 1988). These cardiovascular effects are believed to

result from the strong binding of fluoride to calcium, which produces hypocalcemia. Serum calcium is

critical for proper ion transport in neuromuscular synapses; hypocalcemia can cause the ventricles not to

contract properly.

LOAEL

Table 3-5 Levels of Significant Exposure to Hydrogen Fluoride - Dermal

Species(Strain)

Exposure/Duration/

Frequency(Specific Route) System

ReferenceNOAEL Less Serious Serious Chemical Form

ACUTE EXPOSURESystemicRabbit 1 d

1-4hr/dDermal 2

Percent (%) (necrotic lesions)2

Percent (%)Derelanko et al. 1985

hydrogen fluorideINTERMEDIATE EXPOSURESystemic

(NS)Rat 5 wks

6d/wk6hr/d

Dermal(subcutaneoushemorrhage around theeyes and on the feet)

8.2ppm

Stokinger 1949

hydrogen fluoride

Reproductive

(NS)Dog 5 wks

6d/wk6hr/d

8.2ppm

d = day(s); hr = hour(s); LOAEL = lowest-observed-adverse-effect level; min = minute(s); NOAEL = no-observed-adverse-effect level; wk = week(s); ppm = parts per million

(ulceration of thescrotum)

31ppm

Stokinger 1949

hydrogen fluoride

LOAEL

Table 3-6 Levels of Significant Exposure to Fluoride - Dermal

Species(Strain)

Exposure/Duration/

Frequency(Specific Route) System

ReferenceNOAEL Less Serious Serious Chemical Form

ACUTE EXPOSURESystemic

(Sprague- Dawley)Rat 1 d

24hr/dDermal

d = day(s); hr = hour(s); LOAEL = lowest-observed-adverse-effect level; NOAEL = no-observed-adverse-effect level; PMN = polymorphnuclear leukocyte

(superficial necrosis,moderate edema, PMNinfiltration)

0.5Percent (%)

(extensive necrosis,marked edema,degenerating mast cells)

1Percent (%)

Essman et al. 1981

sodium fluoride


3. HEALTH EFFECTS

No studies were located regarding cardiovascular effects in humans after dermal exposure to fluoride or

fluorine, and no studies were located regarding cardiovascular effects in animals after dermal exposure to

fluoride, hydrofluoric acid, or fluorine.

Hepatic Effects.

Hydrofluoric Acid. Elevated SGOT, serum glutamic pyruvic transaminase (SGPT), and lactate dehydro-

genase levels were found in a man who was splashed in the face and on the neck with a mixture of 10%

hydrofluoric acid and sulfuric acid (Braun et al. 1984). The elevated SGOT and SGPT levels were

attributed to either muscle necrosis or temporary liver damage caused by toxic metabolic products from

necrotic tissue.

Renal Effects.

Hydrofluoric Acid. A 49-year-old man who was splashed in the face and on the neck with a mixture of

hydrofluoric acid and sulfuric acid became oliguric for a brief period on the day after the accident, and

then became anuric (Braun et al. 1984). Concomitant inhalation exposure is likely, and the effect of the

sulfuric acid is unknown.

Dermal Effects. Skin irritation and damage has been observed in humans and/or animals exposed to

fluoride, hydrogen fluoride, hydrofluoric acid, or fluorine. Dermal effects related to exposure to

hydrogen fluoride or fluorine are discussed under Inhalation Exposure (Section 3.2.1.2).

Fluoride. Sodium fluoride applied topically to the abraded skin of Sprague-Dawley rats (0.5 or 1.0%) for

24 hours produced both morphological and biochemical changes (Essman et al. 1981). At 0.5%, the

abraded surface showed focal superficial necrosis of the epidermis. At 1.0%, the abraded surface showed

edema and vacuolization. There was marked edema of the dermis with inflammation. Skin histamine

concentrations were also increased following application of 0.5 or 1% sodium fluoride to shaved-only or

epidermally abraded skin, although the variance of these measurements was quite high.

Hydrofluoric Acid. Dermal exposure to hydrofluoric acid results in extensive skin burns (Chela et al.

1989). Hydrofluoric acid quickly penetrates into soft tissues and causes necrosis. As a result of cell

membrane destruction, the fluoride ion has easy access to lymph and the venules, can be distributed

rapidly, and can cause significant adverse effects such as inhibition of glycolytic enzymes, hypocalcemia,

and hypomagnesia. Untreated burns of the fingers can result in loss of fingers. There are many reports of


3. HEALTH EFFECTS

hydrofluoric acid skin burns in humans. In one case, a 23-year-old man received fatal second- and third-

degree burns over 9–10% of his body from a 70% hydrofluoric acid spill (Mayer and Gross 1985). The

patient died 17 hours after exposure due to cardiac arrhythmias. Two case studies of accidental dermal

exposure of the hands to hydrofluoric acid (5–7%) reported serious dermal injury following exposures

from 45 minutes to 6 hours (Roberts and Merigian 1989). Topical treatment with calcium gluconate

prevented loss of nails. Other case reports are discussed in Section 3.2.3.1.

The concentration of hydrofluoric acid and the length of exposure affect the severity of dermal lesions

(Derelanko et al. 1985). Rabbits exposed to a hydrofluoric acid solution of 0.01% for 5 minutes had

visible skin lesions, whereas exposure to 2% hydrofluoric acid for 1 minute did not produce lesions. A

longer exposure of 1–4 hours to 2% hydrofluoric acid solution produced necrotic lesions on the backs of

rabbits (Derelanko et al. 1985). The application of 0.2 mL of a 47% hydrofluoric acid solution to the

shaved backs of New Zealand rabbits over a surface of 1¼ inches produced no immediate reaction

(Stokinger 1949). The material was held in place by lanolin and allowed to dry for 24 hours. Within a

few days of exposure, erythema and dark spots of liquefaction necrosis appeared. Multiple eschars were

formed in the necrotic areas. These wounds healed more slowly than those produced by fluorine gas.

Healing did not near completion until 27 days after exposure.

Ocular Effects. Ocular irritation and damage has been observed in humans and animals exposed to

hydrogen fluoride, hydrofluoric acid, and fluorine. The ocular effects resulting from exposure to

hydrogen fluoride or fluorine are discussed under inhalation exposure (Section 3.2.1.2).

Some evidence of delayed ocular damage due to persistence of the fluoride ion was observed 4 days after

a 3-year-old girl accidentally sprayed a hydrofluoric-acid-containing product in her eyes (Hatai et al.

1986). Opacification of the corneal epithelium and thrombosis of the conjunctival vessels were seen.

These changes were not permanent; after 30 days, the eyes returned to normal, and vision was 20/20.

However, it is difficult to generalize from this report as the product contained both hydrofluoric acid and

phosphoric acid at unspecified concentrations.

McCulley et al. (1983) concluded that the greater severity of hydrofluoric acid eye injuries compared to

injuries from other inorganic acids at comparable strengths probably results from the destruction of the

corneal epithelium allowing substantial penetration of the fluoride ion into the corneal stroma and

underlying structures.


3. HEALTH EFFECTS

No studies were located regarding the following effects in humans and animals after dermal exposure to

fluoride, hydrofluoric acid, or fluorine:





3.2.3.7 Cancer

3.3 GENOTOXICITY

In general, positive genotoxicity findings occurred at doses that are highly toxic to cells and whole

animals. Lower doses were generally negative for genotoxicity. Tables 3-7 and 3-8 present the results of

more recent assays.

The in vivo genotoxicity of fluoride has been tested in humans and animals following inhalation, oral, or

parenteral exposure. No alterations in the occurrence of sister chromatid exchange were observed in a

population living in areas with high levels of fluoride (4.8 ppm) in the drinking water (Li et al. 1995b).

Mixed results have been reported in animal studies examining the clastogenic potential of hydrogen

fluoride and sodium fluoride. Increases in the occurrence of chromosome aberrations were found in the

bone marrow cells of rats exposed by inhalation to 1.0 mg/m3 hydrogen fluoride 6 hours/day, 6 days/week

for 1 month (Voroshilin et al. 1975) and in mouse bone marrow cells following oral, intraperitoneal, or

subcutaneous exposure to sodium fluoride (Pati and Bunya 1987). However, other studies did not find

significant alterations in the occurrence of chromosome aberrations in mouse bone marrow cells

following oral exposure (Kram et al. 1978; Martin et al. 1979). Additionally, no alterations in sister

chromatid exchange occurrence were observed in mouse or Chinese hamster bone marrow cells following

oral exposure (Kram et al. 1978; Li et al. 1987b). Intraperitoneal injection of sodium fluoride resulted in

an increase in micronuclei in mouse bone marrow cells (Pati and Bhunya 1987); no alterations were

observed in rat bone marrow cells following oral exposure (Albanese 1987). Hydrogen fluoride was


3. HEALTH EFFECTS

Table 3-7. Genotoxicity of Fluoride In Vitro

Results

Species (test system) End point With activation

Without activation Reference Form

Prokaryotic organisms: Salmonella typhimurium Gene mutation – – Martin et al. 1979; NTP

1990; Tong et al. 1988 NaF

Eukaryotic organisms: Human lymphocytes Chromosomal

aberrations No data + Albanese 1987 NaF

Human lymphocytes Chromosomal aberrations

No data – Thomson et al. 1985 NaF, KF

Human fibroblasts Chromosome aberrations

No data + Tsutsui et al. 1984c NaF

Human fibroblasts Chromosomal aberrations

No data – Tsutsui et al. 1995 NaF

Human diploid IMR-90 cells

Chromosomal aberrations

No data + Oguro et al. 1995 NaF

Human lymphocytes Sister chromatid exchange

No data – Thomson et al. 1985; Tong et al. 1988

NaF

Human lymphocytes Sister chromatid exchange

No data – Thomson et al. 1985 KF

Human lymphoblasts Gene mutation + + Caspary et al. 1988 NaF Human fibroblasts Unscheduled

DNA synthesis No data + Tsutsui et al. 1984c NaF

Syrian hamster embryo cell


No data + Tsutsui et al. 1984b NaF


Sister chromatid exchange



Unscheduled DNA synthesis


Chinese hamster ovary cells


No data – Li et al. 1987b NaF



No data – Tong et al. 1988 NaF



+ + NTP 1990 NaF



+ + Aardema et al. 1989 NaF



– + NTP 1990 NaF

Chinese hamster V79 cells

Gene mutation No data – Slameńová et al. 1992 NaF

Mouse lymphoma cells Gene mutation No data (+) Cole et al. 1986 NaF Mouse lymphoma cells Gene mutation + + Caspary et al. 1987,

1988; NTP 1990 NaF


3. HEALTH EFFECTS

Table 3-7. Genotoxicity of Fluoride In Vitro

Results

Species (test system) End point With activation

Without activation Reference Form

Mouse lymphoma cells Gene mutation + + Caspary et al. 1987 KF Rat hepatocytes DNA repair No data – Tong et al. 1988 NaF Rat liver epithelium cells Gene mutation No data – Tong et al. 1988 NaF Rat vertebral body

derived cells Chromosome aberrations

No data + Mihashi and Tsutsui 1996

NaF

Rat bone marrow cells Chromosome aberrations

No data (+) Khalil 1995 NaF, KF

Rat bone marrow cells Sister chromatid exchange

No data – Khalil and Da’dara 1994 NaF, KF

– = negative result; + = positive result; (+) = weakly positive result; DNA = deoxyribonucleic acid; KF = potassium fluoride; NaF = sodium fluoride


3. HEALTH EFFECTS

Table 3-8. Genotoxicity of Fluoride In Vivo

Species (test system) End point Results Reference FormHuman lymphocytes (oral exposure) Sister chromatid exchange – Li et al. 1995b NR Rat bone marrow cells (oral exposure)

Micronuclei – Albanese 1987 NaF

Rat bone marrow Chromosome aberrations + Voroshilin et al. 1975 HF Rat testis cells (oral exposure) DNA strand breaks – Skare et al. 1986 NaF Mouse (C57B1) Dominant lethal – Voroshilin et al. 1975 HF Mouse (Harlan Sprague-Dawley) Sperm head abnormality – Li et al. 1987a NaF Mouse bone marrow and testis cells (oral exposure)

Chromosome aberrations – Martin et al. 1979 NaF

Mouse bone marrow cells (oral, intraperitoneal, or subcutaneous exposure)

Chromosome aberrations + Pati and Bhunya 1987 NaF

Mouse bone marrow cells (intraperitoneal exposure)

Micronuclei + Pati and Bhunya 1987 NaF

Mouse bone marrow cells (oral exposure)

Chromosome aberrations – Kram et al. 1978 NaF

Mouse bone marrow cells (oral exposure)

Sister chromatid exchange – Kram et al. 1978 NaF

Chinese hamster bone marrow cells (oral exposure)

Sister chromatid exchange – Li et al. 1987b NaF

– = negative result; + = positive result; DNA = deoxyribonucleic acid; HF = hydrogen fluoride; NaF = sodium fluoride; NR = not reported


3. HEALTH EFFECTS

negative for dominant lethal mutations following inhalation exposure to hydrogen fluoride in C57B1 mice

(Voroshilin et al. 1975). In a study in Drosophila melanogaster in which reproductive parameters were

measured as an indicator of genotoxicity, significant reductions in the number of eggs per female and

male fertility were observed following inhalation exposure to hydrogen fluoride (Gerdes et al. 1971b).

The maximum lethality to adults of one of the two tested strains was 60%; under most of the test

conditions, the lethality was ≤40%.

3.4 TOXICOKINETICS

The majority of data on the toxicokinetics of fluoride focus on sodium fluoride and hydrofluoric acid.

Data regarding the toxicokinetics of calcium fluoride and other fluorides in human or animals are limited.

While radioactive isotopes are useful in toxicokinetic studies, this use is limited in studies of fluoride

because the fluorine isotope 18F has a short half-life (Wallace-Durbin 1954).

3.4.1 Absorption

3.4.1.1 Inhalation Exposure

Data providing information on absorption exist on the inhalation exposure of humans to hydrogen

fluoride or mixtures of hydrogen fluoride and fluoride dusts, and inhalation exposure of animals to

hydrogen fluoride. Animal data also exist showing that fluorine is absorbed.

Hydrogen Fluoride. Increases in plasma fluoride levels were observed in humans inhaling 0.8–2.8 or

2.9–6.0 ppm fluoride as hydrogen fluoride of 60 minutes (Lund et al. 1997); maximum plasma

concentrations were observed 60–90 minutes after exposure initiation. A study in rats suggests that

hydrogen fluoride is absorbed primarily by the upper respiratory tract, and that removal of hydrogen

fluoride from inhaled air by the upper respiratory tract approaches 100% for exposures that range from

30 to 176 mg fluoride/m3 (Morris and Smith 1982). Furthermore, it is apparent that distribution to the

blood is rapid. Immediately following 40 minutes of intermittent exposure, plasma fluoride

concentrations correlated closely (correlation coefficient=0.98; p<0.01) with the concentration of

hydrogen fluoride in the air passed through the surgically isolated upper respiratory tract. Plasma levels

were not measured at time points <40 minutes.


3. HEALTH EFFECTS

Hydrogen Fluoride and Fluoride Dusts. The absorption in humans of inhaled hydrogen fluoride and

fluoride dusts has been demonstrated in several studies. In a study by Collings et al. (1952), two workers

were exposed to approximately 5 mg fluoride/m3 for 6 hours with 15-minute breaks every 2 hours.

Absorption of fluoride was evaluated by monitoring urinary excretion of fluoride during and after

exposure. Analysis of 2-hour serial urine samples showed a peak fluoride level 2–4 hours after cessation

of exposure, which decreased to base levels within 12–16 hours after exposure. Similar results were

obtained using the same protocol to measure urinary fluoride following exposure to air containing 5.0 mg

fluoride/m3 as rock phosphate dust (Collings et al. 1951). Another study reported clinical observations of

employees in the production of phosphate rock and triple superphosphate (Rye 1961). Three employees

were exposed to airborne fluoride (2–4 ppm) composed of approximately 60% dust and 40% hydrogen

fluoride gas. Within 2–3 hours after exposure began, urinary fluoride levels increased from 0.5 to

4.0 mg/L and peaked 10 hours (7–8 mg/L) following cessation of exposure. None of the subjects had

prior occupational exposure to fluoride. Two studies of aluminum potroom workers found elevated

plasma fluoride levels (Ehrnebo and Ekstrand 1986; Søyseth et al. 1994). In workers exposed to

0.910 mg fluoride/m3 total fluoride (34% of which was gasous fluoride) during an 8-hour workshift,

elevated plasma fluoride concentrations and urinary fluoride levels were observed (Ehrnebo and Ekstrand

1986). Although these studies demonstrate absorption of fluoride, none measure the extent of fluoride

absorption.

Fluorine. No data were located regarding the absorption of fluorine in humans. Hepatic and renal effects

were observed in mice following exposure to fluorine for periods up to 60 minutes (Keplinger and Suissa

1968). This indicates that the fluoride ion was systemically available following the exposure. Fluoride,

rather than fluorine, is the agent that is toxicologically active systemically, since fluorine is too reactive to

be absorbed unchanged. Similarly, the finding of elevated fluoride levels in bones, teeth, and urine during

intermediate-duration exposure to fluorine indicates that fluoride is absorbed under these conditions

(Stokinger 1949). No information on absorption rate or extent is available.

Furthermore, although the data presented concern only acute exposures, it is expected that virtually

complete absorption would also be observed during long-term exposure to low levels of fluoride in the

air.


3. HEALTH EFFECTS

3.4.1.2 Oral Exposure

Fluoride. In humans and animals, fluoride is rapidly and efficiently absorbed from the gastrointestinal

tract. Elevated plasma fluoride levels are seen shortly after exposure to sodium fluoride; peak plasma

levels are typically seen within 30–60 minutes of ingestion (Carlson et al. 1960a; Ekstrand et al. 1977,

1978). Fluoride is absorbed from both the stomach and small intestine via passive diffusion. Nopakun et

al. (1989) estimated that in rats, approximately 20% of total absorbed fluoride was absorbed from the

stomach. Absorption of fluoride from the stomach is inversely proportional to pH (Messer and Ophaug

1993; Whitford and Pashley 1984), suggesting that fluoride is absorbed from the stomach as the

undissociated hydrogen fluoride rather than the fluoride ion (Whitford and Pashley 1984). After gastric

emptying, fluoride was rapidly absorbed from the small intestine (Messer and Ophaug 1993). An in vitro

study suggests that in the small intestine, fluoride is primarily absorbed as the fluoride ion (Nopakun and

Messer 1990). The absorption of fluoride does not appear to be homeostatically regulated. A linear

correlation between fluoride (as sodium fluoride) intake and the area under the plasma fluoride

concentration curve was found in humans ingesting 2–10 mg doses of sodium fluoride (Trautner and

Seibert 1986).

A number of dietary factors can influence the absorption of fluoride. Delayed gastric emptying slows the

rate of fluoride absorption, but does not appear to affect the total amount of fluoride absorbed (Messer

and Ophaug 1993). Ingestion of sodium fluoride with food delayed the peak plasma level but did not

significantly alter the total amount of fluoride absorbed, as compared to values when the subjects ingested

sodium fluoride after an 8-hour fast (Shulman and Vallejo 1990; Trautner and Einwag 1987). In contrast,

ingestion of calcium fluoride with a meal dramatically increased (33.5 versus 2.8%) the absorption of

fluoride, as compared to absorption after an 8-hour fast; similar results were found for the fluoride in bone

meal tablets (Trautner and Einwag 1987). It is likely that the increased residence time in the upper

gastrointestinal tract increased absorption. Ingestion of sodium fluoride with milk decreased fluoride

absorption by 13–50% (Ekstrand and Ehrnebo 1979; Shulman and Vallejo 1990; Trautner and Seibert

1986). Other studies have also shown that co-exposure to calcium carbonate or a diet high in calcium

decreases fluoride absorption (Jowsey and Riggs 1978; Whitford 1994). Increased exposure to

magnesium (Stookey et al. 1964; Weddle and Muhler 1954) or aluminum (Stookey et al. 1964; Weddle

and Muhler 1954) also resulted in decreases in fluoride absorption.

Soluble fluoride compounds, such as sodium fluoride, hydrogen fluoride, and fluorosilic acid, are readily

absorbed from the gastrointestinal tract. Studies in humans and animals have found that >80% of an oral


3. HEALTH EFFECTS

dose of soluble fluoride compound is absorbed (Ericsson 1958; McClure et al. 1950, 1945; Zipkin and

Likins 1957); several studies have reported 99–100% absorption efficiencies (Ekstrand et al. 1978;

Trautner and Einwag 1987). Poorly soluble fluoride compounds, such as calcium fluoride, magnesium

fluoride, and aluminum fluoride, do not appear to be well absorbed. Very little (<10%) fluoride was

absorbed in fasting subjects ingesting calcium fluoride (Afseth et al. 1987; Trautner and Einwag 1987).

Compared to sodium fluoride, the fluoride from bone meal (McClure et al. 1945; Trautner and Einwag

1987) and cryolite (McClure et al. 1945) was poorly absorbed.

The absorption of fluoride in infants, children, and adults appears to be similar. A study of four infants

(mean age 8 months) reported mean absorption rates of 88.9–96.0% when a sodium fluoride solution was

administered along with infant formula (Ekstrand et al. 1994b). As discussed previously, the absorption

efficiency in adults usually exceeds 90% (Ekstrand et al. 1978; Trautner and Einwag 1987). As with

adults, peak plasma levels usually occurred in 30–60 minutes (mean of 39 minutes) in infants (Ekstrand et

al. 1994a) and young children aged 3–4 years (Ekstrand et al. 1983). One observed difference between

fluoride absorption in infants and adults is that administration of fluoride with a high calcium diet did not

result in a significant decrease in fluoride absorption (88.9 versus 96.0%) in infants (Ekstrand et al.

1994b); a decrease in absorption has been reported in adults (Ekstrand and Ehrnebo 1979; Shulman and

Vallejo 1990; Trautner and Einwag 1987).

3.4.1.3 Dermal Exposure

Data exist on dermal absorption of hydrofluoric acid in humans and animals, and limited quantitative rate

data are available in animals.

Hydrofluoric Acid. Dermal application of hydrofluoric acid results in rapid penetration of the fluoride

ion into the skin. Sufficiently large amounts cause necrosis of the soft tissue and decalcification and

corrosion of bone in humans (Browne 1974; Dale 1951; Dibbell et al. 1970; Jones 1939; Klauder et al.

1955). Systemic fluoride poisoning has been reported following accidental dermal exposure to anhydrous

hydrogen fluoride (Buckingham 1988; Burke et al. 1973). Although the extent of the contribution of

inhalation exposure in these cases is not known, the reports suggest that hydrogen fluoride is quickly

absorbed into the body following dermal exposure. However, these studies did not provide useful

information concerning the extent of fluoride absorption, or information on absorption of smaller doses.


3. HEALTH EFFECTS

Dermal absorption of hydrofluoric acid in albino mice of the d.d. strain was inferred in a study by

Watanabe et al. (1975). Mice were painted with 0.02 mL of 50% hydrofluoric acid, and the residual acid

was wiped off after 5 minutes. The mice were then injected intraperitoneally with [14C]glucose and

analyzed by whole body radiography. Radioactivity levels in the liver, renal cortex, lungs, and blood

were elevated 30 minutes after injection. This suggests that fluoride was absorbed through the skin and

interfered with the tissue distribution of glucose. No data were located on the extent of absorption of

fluoride in animals exposed dermally to hydrofluoric acid.

These studies indicate that fluoride as hydrofluoric acid is absorbed through the skin in humans and

animals. However, the degree of absorption is not known, nor is it known whether other forms of fluoride

would be absorbed, and to what extent. Furthermore, it is expected that the relationship between duration

or concentration and degree of absorption would be affected by the corrosive action of hydrofluoric acid.

Therefore, prediction of the extent of absorption following exposure to a low concentration of

hydrofluoric acid cannot be made based on the existing data.

Fluorine. Systemic effects have been observed following whole-body exposure to fluorine (Keplinger

and Suissa 1968; Stokinger 1949). However, these effects are likely to be due to inhalation exposure,

rather than dermal exposure.

3.4.2 Distribution


Hydrogen Fluoride. No data were located regarding the distribution of fluoride in humans following

exposure to only hydrogen fluoride. Evidence from studies in animals supports the inference from

occupational studies of exposure to hydrogen fluoride and fluoride dust that fluoride is distributed to the

rest of the body when inhaled. Duration- and concentration-related increases in tooth and bone fluoride

levels were reported in the rat following exposure to 7 or 24 mg/m3 for 6 hours/day, 6 days/week for up to

30 days (Stokinger 1949). Fluoride levels in new bone were up to twice the levels in old bone. The

distribution of the fluoride ion was studied in the tissues of rabbits, a guinea pig, and a monkey exposed

to hydrogen fluoride at various concentrations (1.5–1,050 mg/m3) and exposure times (Machle and Scott

1935). The observation period ranged from 9 to 14 months. As might be expected, based on the

following discussion of human occupational exposure to fluoride compounds, the fluoride ion

accumulated chiefly in the skeleton of all three species.


3. HEALTH EFFECTS

Several studies in animals have demonstrated that fluoride is widely available through the blood, although

actual concentrations in tissues other than blood have, for the most part, not been reported. For example,

whole body exposure of male rats to levels ranging from 11 to 116 mg fluoride/m3 as hydrogen fluoride

for 6 hours resulted in a dose-dependent increase in lung and plasma fluoride concentrations (Morris and

Smith 1983). In another study, rats exposed to 84 mg fluoride/m3 as hydrogen fluoride by whole body

exposure had significantly elevated levels of fluoride in plasma and lungs 6 hours postexposure (Morris

and Smith 1983).

Hydrogen Fluoride and Fluoride Dusts. Limited information was located on the distribution of inhaled

fluoride in humans. However, reports of skeletal fluorosis (Chan-Yeung et al. 1983b; Czerwinski et al.

1988; Kaltreider et al. 1972) and elevated bone fluoride levels (Baud et al. 1978; Boivin et al. 1988) after

occupational exposure to hydrogen fluoride and fluoride dusts indicate that fluoride is distributed to bone

and accumulates there.

Fluoride deposition in bone occurs mainly in regions undergoing active ossification or calcification. If

the source of fluoride exposure has been removed, fluoride levels in bone decrease as the bone undergoes

remodeling. Areas of fluoride deposition during high-level exposure are distinguished by highly elevated

fluoride levels even after the average fluoride level of the bone has returned to normal (Baud et al. 1978).

Fluorine. No data were located regarding the distribution of fluoride following the inhalation exposure

of humans to fluorine. In rats exposed to 25 mg/m3 fluorine for about 5 hours/day, 6 days/week for

21 days, markedly elevated fluoride levels were observed in teeth and bone, the only tissues that were

analyzed (Stokinger 1949). Tooth fluoride levels were about 14 times the levels in controls, and fluoride

levels in the femur were about 6 times those in the controls. Similar concentration-related increases in

bone and tooth fluoride levels were observed at the lower concentrations (3 and 0.8 mg/m3).


Fluoride. Once absorbed, fluoride is rapidly distributed throughout the body via the blood. Fluoride is

distributed between the plasma and blood cells, with plasma levels being twice as high as blood cell levels

(Whitford 1990). After ingestion of sodium fluoride, the plasma fluoride does not appear to be bound to

proteins (Ekstrand et al. 1977a; Rigalli et al. 1996). However, there is evidence that following ingestion

of sodium monofluorophosphate, the plasma contains diffusible fluoride and protein-bound fluoride


3. HEALTH EFFECTS

(Rigalli et al. 1996). The elimination of fluoride from plasma following short-term exposure to sodium

fluoride has been fit to a two-compartment model (Ekstrand et al. 1977a). The half-life of the terminal

phase ranged from 2 to 9 hours. The rapid phase of fluoride distribution represents distribution in soft

tissues, with fluoride being more rapidly distributed to well-perfused tissues. In pigs, the plasma

clearance half-time of fluoride was 0.88 hours (Richards et al. 1982). Fluoride does not accumulate in

most soft tissue; the ratio between tissue fluoride levels and plasma fluoride levels is typically between

0.4 and 0.9 (Whitford et al. 1979a). It is likely that fluoride enters the intracellular fluid of soft tissues as

hydrogen fluoride (Whitford et al. 1979a). Studies in rats and ewes suggest that the blood brain barrier is

effective in preventing fluoride migration into the central nervous system (Spak et al. 1986; Whitford et

al. 1979a); brain fluoride concentrations typically do not exceed 10% of plasma concentrations (Whitford

et al. 1979a). Higher fluoride concentrations are found in the renal tubules, the concentration often

exceeding plasma concentrations.

The largest concentration of fluoride in the body is found in calcified tissues. Approximately 99% of the

fluoride in the body is found in bones and teeth (Hamilton 1990; Kaminsky et al. 1990). The pineal gland

which contains hydroxyapatite also accumulates fluoride (Luke 2001). Fluoride is incorporated into bone

by replacing the hydroxyl ion in hydroxyapatite to form hydroxyfluroapatite (McCann and Bullock 1957;

Neuman et al. 1950). Fluoride is not irreversibly bound to bone and is mobilized from bone through the

continuous process of bone remodeling and to a lesser extent from ionic flux between interstitial fluoride

and the crystalline bone surface (Turner et al. 1993; Whitford 1990). The biological half-life of fluoride

was estimated to be 58.5 days in pigs orally exposed 2 mg fluoride/kg/day as sodium fluoride for

6 months (Richards et al. 1985). A comparison between the retention of sodium fluoride, fluorosilicic

acid, and sodium fluorosilicate did not find significant differences in the percentage of intake retained in

the body of female rats exposed to 24 ppm fluoride in the diet for 5 months; fluoride retentions were 66.2,

68.1, and 64.8, respectively (Whitford and Johnson 2003; only available as an abstract).

Tissue fluoride levels are not homeostatically regulated. In adults, plasma fluoride levels appear to be

directly related to fluoride intake. At higher fluoride intakes, a wide fluctuation of plasma fluoride levels

were found in two adults and three children consuming 9.6 ppm fluoride in water (Ekstrand 1978); the

fluctuation in plasma fluoride levels was smaller in the children, as compared to the adults. Mean plasma

levels in individuals living in areas with a water fluoride concentration of <0.1 ppm was 0.4 µmol/L,

compared to a mean plasma fluoride level of 1 µmol/L in individuals with a water fluoride content of 0.9–

1.0 ppm (Guy et al. 1976). The level of fluoride in bone is influenced by several factors including age,

past and present fluoride intake, and the rate of bone turnover. In adults (mean age, 47–60 years),


3. HEALTH EFFECTS

fluoride levels in the iliac crest ranged from 0.06 to 0.10% of bone ash (Boivin et al. 1988). In contrast,

in subjects undergoing sodium fluoride treatment for osteoporosis for 5–6 years, the fluoride content of

the iliac crest was 0.67% bone ash. Termination of high fluoride exposure can result in a decrease in

bone fluoride levels. In aluminum workers diagnosed with skeletal fluorosis, there was a significant and

progressive decrease in bone fluoride levels (Boivin et al. 1988).

Age strongly influences the distribution of fluoride. The amount of fluoride taken up by bone is inversely

related to age (Lawrenz et al. 1940; Miller and Phillips 1956; Suttie and Phillips 1959; Zipkin and

McClure 1952; Zipkin et al. 1956). In a study of dogs (Ekstrand and Whitford 1984; Whitford 1990), the

fractional uptake of fluoride by bone steadily declined during the first year of life. At weaning, 90% of an

administered dose was taken up by bone compared to 50% at 1 year of age. Similar findings have been

reported in human studies. In infants aged 37–410 days exposed to 0.25 mg fluoride supplement, the

mean retention (bone uptake) of fluoride ranged from 68.1 to 83.4% (Ekstrand et al. 1994a, 1994b). In

contrast, retention in adults receiving a fluoride supplement was 55.3% (Ekstrand et al. 1979).

Human and animal studies have shown that fluoride is readily transferred across the placenta. There

appears to be a direct relationship between maternal blood fluoride levels and cord blood fluoride levels

(Armstrong et al. 1970; Gupta et al. 1993; Malhotra et al. 1993; Shen and Taves 1974). At relatively low

maternal blood levels, the cord blood levels were at least 60% of that of maternal blood (Brambilla et al.

1994; Gupta et al. 1993). Although cord fluoride levels were typically lower than maternal levels, one

study found no statistical difference between maternal and newborn (1 day old) serum fluoride levels

(Shimonovitz et al. 1995). However, a partial placental barrier may exist at high maternal fluoride levels.

At higher maternal blood levels, the cord to maternal fluoride ratio is lower than at lower maternal

fluoride levels (Gupta et al. 1993). Another study found that the use of fluoride supplements markedly

increased placental fluoride levels, while fluoride levels in fetal blood remained relatively constant,

suggesting that the placenta can regulate the transfer of fluoride from maternal blood to fetal blood

(Gedalia 1970). Animal studies also demonstrate that maternal fluoride exposure also results in increased

levels of fluoride in fetal teeth and bones (Bawden et al. 1992b; Nedeljković and Matović 1991; Theuer et

al. 1971).

In humans, fluoride is poorly transferred from plasma to milk (Ekstrand et al. 1981c, 1984b; Esala et al.

1982; Spak et al. 1983). A single dose of 1.5 mg sodium fluoride did not result in a significant rise in

fluoride breast milk concentrations within 3 hours of the exposure (Ekstrand et al. 1981c). Although no

linear correlation between fluoride levels in tap water and fluoride levels in breast milk has been found,


3. HEALTH EFFECTS

significantly higher breast milk fluoride concentrations were found in women living in an area with high

levels of naturally occurring fluoride (1–7 ppm) as compared to women in areas with low fluoride levels

in tap water (0.2 ppm) (Esala et al. 1982). Fluoride levels in human milk of 5–10 µg/L have been

measured (Fomon and Ekstrand 1999).


No information was located in humans or animals regarding the distribution of fluoride, hydrogen

fluoride, or fluorine following dermal absorption.

3.4.2.4 Other Routes of Exposure

Based on the results of a five-compartment computer model, Charkes et al. (1978) calculated that about

60% of intravenously administered radiolabelled fluoride (18F) is taken up by bone; the half-time for this

uptake is about 13 minutes.

Perkinson et al. (1955) found initial rates of removal of fluoride from sheep and cow blood to be 41 and

32%/minute of the intravenously administered dose, respectively. These data suggest a rapid distribution

of fluoride and corroborate findings reported by other routes of administration.

Fluoride distribution in rats was examined during and after continuous intravenous infusion of

radiolabeled sodium fluoride at varying chemical dose rates for 3 hours (Knaus et al. 1976). Blood,

kidneys, and lungs contained the highest fluoride concentrations at doses up to 3.6 mg fluoride/kg/hour,

but at 6 mg/kg/hour, the fluoride content of the liver, spleen, and hollow organs increased sharply,

indicating that the dose exceeded the amount readily processed by the excretory mechanisms of the body.

In rat pups injected intraperitoneally with 0.1 µg fluoride/g body weight as sodium fluoride solution,

significant increases in the fluoride content occurred in the developing enamel and bone (Bawden et

al. 1987). Thus, regardless of the route of administration, some fluoride is deposited in teeth, bone, and

soft tissues of animals, and some is excreted in the urine, sweat, and saliva.


3. HEALTH EFFECTS

3.4.3 Metabolism

Fluoride is believed to replace the hydroxyl ion (OH-) and possibly the bicarbonate ion (HCO3-)

associated with hydroxyapatite—a mineral phase during formation of bone (McCann and Bullock 1957;

Neuman et al. 1950). The resultant material is hydroxyfluorapatite. Once absorbed, a portion of the

fluoride is deposited in the skeleton, and most of the remainder is excreted in the urine, with smaller

amounts in feces, and sweat, and saliva within 24 hours (Dinman et al. 1976a, 1976b; McClure et al.

1945). Urinary excretion is markedly decreased in the presence of decreased renal function (Kono et al.

1984; Spak et al. 1985).

A portion of the circulating inorganic fluoride acts as an enzyme inhibitor because it forms metal-

fluoride-phosphate complexes that interfere with the activity of those enzymes requiring a metal ion

cofactor. In addition, fluoride may interact directly with the enzyme or the substrate. It is a general

inhibitor of the energy production system of the cell (i.e., glycolytic processes and oxidative

phosphorylation enzymes responsible for forming ATP) (Guminska and Sterkowicz 1975; Najjar 1948;

Peters et al. 1964; Slater and Bonner 1952). Although much is known about enzyme inhibition by

fluoride, the human health significance remains to be determined. The studies on enzymatic inhibition by

fluoride were in vitro studies and used fluoride concentrations that were significantly (100–1,000 times)

higher than concentrations that would be normally found in human tissues.

3.4.4 Elimination and Excretion


Hydrogen Fluoride. Overnight urinary fluoride excretion in dogs and rabbits exposed to 7 mg/m3

hydrogen fluoride for 6 hours/day, 6 days/week for 30 days was about 1.5 times that of controls

(Stokinger 1949). No further details were reported.

Hydrogen Fluoride and Fluoride Dusts. Studies in humans indicate that fluoride absorbed from inhaled

hydrogen fluoride and fluoride dusts over an 8-hour work shift is excreted even during exposure, with

urinary excretion peaking approximately 2–4 hours after cessation of exposure (about 10 hours following

beginning of exposure) (Collings et al. 1951; Rye 1961). A significant correlation between urinary

fluoride excretion and the area under the plasma concentration-time curve was found in aluminum


3. HEALTH EFFECTS

workers (Ehrnebo and Ekstrand 1986). A significant correlation between urinary fluoride excretion and

exposure levels of gaseous fluoride, but not particulate fluoride, was also found.

Fluorine. No data were located regarding excretion of fluoride following human inhalation exposure to

fluorine. Urinary fluoride levels were increased in dogs and rabbits exposed to levels as low as 0.8 mg/m3

for 5–6 hours/day, 6 days/week for 35 days (Stokinger 1949). No quantitative data were reported at this

level, but urinary fluoride levels in rabbits exposed to 3 mg/m3 were 1.5 times normal. No further details

were reported.


Fluoride. The primary pathway for fluoride excretion is via the kidneys and urine; to a lesser extent,

fluoride is also excreted in the feces, sweat, and saliva. A study in rats suggests that the source of the

small amount fecal fluoride may be fluoride that has re-entered the more distal portion of the intestine and

became associated with unabsorbed cations (Whitford 1994). It has been estimated that approximately

1% or less of an ingested dose is excreted in saliva (Carlson et al. 1960a; Oliveby et al. 1989), because

saliva is swallowed, this amount does not enter mass balance calculations. The concentration of fluoride

in the saliva appears to mirror plasma fluoride levels (Ekstrand 1977; Oliveby et al. 1989, 1990) and the

ratio of saliva fluoride to plasma fluoride is about 0.5–0.64 (Ekstrand 1977; Oliveby et al. 1989). There

are limited data on fluoride excretion via sweat. An older study (McClure et al. 1945) estimated that 19%

of an ingested fluoride dose (3.7 mg) was excreted in sweat under comfortable conditions. Excretion of

fluoride increased to 42% under hot-moist conditions. However, this study appears to have grossly

overestimated fluoride excretion in sweat. A more recent study (Henschler et al. 1975), reported low

levels of fluoride in sweat, approximately 20% of plasma levels, 2 hours after administration of sodium

fluoride.

Renal excretion is the major route of fluoride removal from the body; it typically equals 35–70% of intake

in adults (Ekstrand et al. 1978; Machle and Largent 1943;). The fluoride ion is filtered from the plasma

as it passes through the glomerular capillaries followed by a varying degree (10–70%) of tubular

reabsorption; there is no evidence of tubular secretion of fluoride (Schiffl and Binswanger 1982; Whitford

1990). Renal clearance rates in humans can range from 12.4 to 71.4 mL/minute with average values of

36.4–41.8 mL/minute (Schiffl and Binswanger 1982; Waterhouse et al. 1980). A number of factors,

including urinary pH, urinary flow, and glomerular filtration rate, can influence urinary fluoride

excretion. Urinary pH appears to be the major determining factor for fluoride reabsorption from the renal


3. HEALTH EFFECTS

tubules (Ekstrand et al. 1980a, 1982; Järnberg et al. 1980, 1981, 1983; Whitford et al. 1976). At lower

pH levels, more fluoride exists in the undissociated form (hydrogen fluoride) than in the ion form; the

uncharged hydrogen fluoride more readily diffuses through the tubular epithelium to the interstitial fluid

than the free charged fluoride ion. In the neutral interstitial fluid, the hydrogen fluoride would rapidly

dissociate and the fluoride ions would be returned to the systemic circulation (Whitford et al. 1976).

Thus, renal clearance of fluoride is directly related to urinary pH. A significant correlation between

urinary flow and urinary fluoride excretion has been reported in humans (Ekstrand et al. 1978, 1982).

Ekstrand et al. (1982) noted that a high flow rate in the renal tubules would likely increase the renal

clearance of a substance that is reabsorbed at a slow rate. Similarly, a decrease in glomerular filtration

rate would result in a decrease in urinary fluoride excretion (Jeandel et al. 1992).

Most of the data on renal clearance of fluoride in humans come from studies of health adults; however,

several studies have examined renal clearance of fluoride at different age levels (Ekstrand et al. 1994a;

Jeandel et al. 1992; Spak et al. 1985; Villa et al. 2000). Whitford (1999) compared the results of many of

these studies in infants and children with those in adults and concluded that there are no apparent age-

related differences in renal clearance rates (adjusted for body weight or surface area) between children

and adults. However, in older adults (>65 years), a significant decline in renal clearance of fluoride has

been reported (Jeandel et al. 1992). This is consistent with the decline in glomerular filtration rate and

renal clearance of many substances that are also observed in the elderly (Whitford 1999).


No studies were located regarding excretion of fluoride, hydrogen fluoride, or fluorine in humans or

animals following dermal exposure. However, in the absence of evidence to the contrary, it is expected

that dermally absorbed fluoride would be sequestered in bone and excreted in urine in a manner similar to

that observed following oral or inhalation exposure.

3.4.5 Physiologically Based Pharmacokinetic (PBPK)/Pharmacodynamic (PD) Models

Physiologically based pharmacokinetic (PBPK) models use mathematical descriptions of the uptake and

disposition of chemical substances to quantitatively describe the relationships among critical biological

processes (Krishnan et al. 1994). PBPK models are also called biologically based tissue dosimetry

models. PBPK models are increasingly used in risk assessments, primarily to predict the concentration of


3. HEALTH EFFECTS

potentially toxic moieties of a chemical that will be delivered to any given target tissue following various

combinations of route, dose level, and test species (Clewell and Andersen 1985). Physiologically based

pharmacodynamic (PBPD) models use mathematical descriptions of the dose-response function to

quantitatively describe the relationship between target tissue dose and toxic end points.

PBPK/PD models refine our understanding of complex quantitative dose behaviors by helping to

delineate and characterize the relationships between: (1) the external/exposure concentration and target

tissue dose of the toxic moiety, and (2) the target tissue dose and observed responses (Andersen et al.

1987; Andersen and Krishnan 1994). These models are biologically and mechanistically based and can

be used to extrapolate the pharmacokinetic behavior of chemical substances from high to low dose, from

route to route, between species, and between subpopulations within a species. The biological basis of

PBPK models results in more meaningful extrapolations than those generated with the more conventional

use of uncertainty factors.

The PBPK model for a chemical substance is developed in four interconnected steps: (1) model

representation, (2) model parametrization, (3) model simulation, and (4) model validation (Krishnan and

Andersen 1994). In the early 1990s, validated PBPK models were developed for a number of

toxicologically important chemical substances, both volatile and nonvolatile (Krishnan and Andersen

1994; Leung 1993). PBPK models for a particular substance require estimates of the chemical substance-

specific physicochemical parameters, and species-specific physiological and biological parameters. The

numerical estimates of these model parameters are incorporated within a set of differential and algebraic

equations that describe the pharmacokinetic processes. Solving these differential and algebraic equations

provides the predictions of tissue dose. Computers then provide process simulations based on these

solutions.

The structure and mathematical expressions used in PBPK models significantly simplify the true

complexities of biological systems. If the uptake and disposition of the chemical substance(s) is

adequately described, however, this simplification is desirable because data are often unavailable for

many biological processes. A simplified scheme reduces the magnitude of cumulative uncertainty. The

adequacy of the model is, therefore, of great importance, and model validation is essential to the use of

PBPK models in risk assessment.

PBPK models improve the pharmacokinetic extrapolations used in risk assessments that identify the

maximal (i.e., the safe) levels for human exposure to chemical substances (Andersen and Krishnan 1994).


3. HEALTH EFFECTS

PBPK models provide a scientifically sound means to predict the target tissue dose of chemicals in

humans who are exposed to environmental levels (for example, levels that might occur at hazardous waste

sites) based on the results of studies where doses were higher or were administered in different species.

Figure 3-5 shows a conceptualized representation of a PBPK model.

Only one published PBPK model has been identified (Rao et al. 1995); it differs from published

compartmental models for fluoride kinetics (Charkes et al. 1978, 1979; Ekstrand et al. 1977a; Hall et al.

1977; Richards et al. 1982, 1985) in that the earlier models were data-based and useful only to simulate

short-term fluoride kinetics. Because the fluoride ion is characterized by its long residence time in the

body, health effects based on long-term fluoride exposure are of concern. In contrast to the earlier

models, the Rao et al. (1995) PBPK model is amenable to extrapolation across species, routes, and doses,

thereby offering an advantage in quantitative risk assessment for fluoride exposure.

In order to assess the complex relationship between extended fluoride exposure, target tissue (bone) dose,

and tissue response, a sex-specific PBPK model has been developed to describe the absorption,

distribution, and elimination of fluorides in rats and humans (Rao et al. 1995). The PBPK model

incorporates age and body weight dependence of the physiological processes that control the uptake of

fluoride by bone and the elimination of fluoride by the kidneys. Six compartments (lung, liver, kidney,

bone, and slowly- and rapidly-perfused compartments) make up the model. The bone compartment

includes two subcompartments: a small, flow-limited, rapidly exchangeable surface bone compartment,

and a bulk, virtually nonexchangeable inner bone compartment. The inner bone compartment contains

nearly all of the whole body content of fluoride, which, in the longer time frame, may be mobilized

through the process of bone modeling and remodeling. This model has been validated by comparing

predictions with experimental data gathered in rats and humans after drinking water and dietary ingestion

of fluoride.

The PBPK model permits the analysis of the combined effect of ingesting and inhaling fluorides on the

target organ, bone. It takes into account the effects of age and growth; in the human model, for instance,

the bone and renal clearance rates accounted for 90 and 10%, respectively, during the growth period,

compared to about 50% each in adulthood. Estimates of fluoride concentrations in bone are calculated

and related to chronic fluoride toxicity. The model incorporates nonlinear binding rates of fluoride to

bone, which has been described at high plasma concentrations. The model is thus useful for predicting

some of the long-term metabolic features and tissue concentrations of fluoride that may be of value in

understanding positive or negative effects of fluoride on human health. In addition, the PBPK model


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Figure 3-5. Conceptual Representation of a Physiologically Based Pharmacokinetic (PBPK) Model for a

Hypothetical Chemical Substance

Source: adapted from Krishnan et al. 1994 Note: This is a conceptual representation of a physiologically based pharmacokinetic (PBPK) model for a hypothetical chemical substance. The chemical substance is shown to be absorbed via the skin, by inhalation, or by ingestion, metabolized in the liver, and excreted in the urine or by exhalation.


3. HEALTH EFFECTS

provides a basis for cross-species extrapolation of the effective fluoride dose at the target tissue (bone) in

the assessment of risk from different exposure conditions.

3.5 MECHANISMS OF ACTION

Skeletal Effects. A number of mechanisms are involved in the toxicity of fluoride to bone. Fluoride ions

are incorporated into bone by substituting for hydroxyl groups in the carbonate-apatite structure to

produce hydroxyfluorapatite, thus altering the mineral structure of the bone (Chachra et al. 1999). Unlike

hydroxyl ions, fluoride ions reside in the plane of the calcium ions, resulting in a structure that is

electrostatically more stable and structurally more compact (Grynpas 1990). Following administration of

fluoride, there is a shift in the mineralization profile towards higher densities and increased hardness

(Chachra et al. 1999). However, the structure of the bone (cortical thickness and the trabecular

architecture of the femoral head) was largely unchanged in rabbits by fluoride administration. Chachra et

al. (1999) suggest that the shift in mineralization could be due to either hypermineralization of older

(denser) fractions or to a greater packing density of the hydroxyapatite crystals. Although high-dose

fluoride administration is associated with an increase in bone mass, in vivo and in vitro animal studies

have found a negative association between fluoride-induced new bone mass and bone strength, suggesting

that the quality of the new bone was impaired by the fluoride (Silva and Ulrich 2000; Turner et al. 1997).

Because bone strength is thought to derive mainly from the interface between the collagen and the

mineral (Catanese and Keavney 1996), alteration in mineralization probably affects strength. The wider

crystals, which are formed after fluoride exposure, are presumably not as well associated with collagen

fibrils and thus, do not contribute to mechanical strength. Turner et al. (1997) found that the crystal width

was inversely correlated with bending strength of the femur. Thus, although there is an increase in

hardness and bone mass and unaltered structure, the mechanical strength of bone is decreased with long-

term, high-dose administration of fluoride (Chachra et al. 1999).

In addition to the physicochemical effect of fluoride on the bone, at high doses, fluoride can be mitogenic

to osteoblasts (Farley et al. 1990; Gruber and Baylink 1991) and inhibitory to osteoclasts. The osteoblasts

are still active, although there are fewer plump, cuboidal, highly secretory osteoblasts; whereas fluoride is

mitogenic to osteoblastic precursors (Bonjour et al. 1993), it is toxic to individual osteoblasts at the same

concentration (Chachra et al. 1999). The effect of fluoride on osteoclasts is not well understood; it

appears that fluoride decreases the amount of bone resorbed by osteoclasts (Chachra et al. 1999).


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Studies in humans and animals suggest that the effect of fluoride on bone strength is biphasic. In rats

administered 1–128 ppm fluoride as sodium fluoride in drinking water for 16 weeks, both increases and

decreases in bone strength were found; the maximum femoral bone strength occurred at 16 ppm (Turner

et al. 1992). A biphasic relationship between femoral bone strength and bone fluoride content was found.

Bone strength increased 18% as the bone fluoride content increased from 100 to 1,216 ppm, and

decreased by 31% as the bone fluoride levels increased from 1,216 to 10,000 ppm. It should be noted that

the bone fluoride levels in this study, as well as other studies discussed in this section, resulted from high

doses of fluoride. Arnala et al. (1986) measured fluoride levels in iliac crest biopsies taken from 18–

25 subjects with hip fractures living in areas with low fluoride (<0.3 ppm), high fluoride (>1.5 ppm), or

with fluoridated (1.0–1.2 ppm) water. The average fluoride levels in the bone were 450, 3,720, and

1,590 ppm, respectively.

The biphasic nature of bone effects is supported by data from clinical trials in women with

postmenopausal osteoporosis (Haguenauer et al. 2000). The meta-analyses of 12 studies found a

significant increase in the relative risk of nonvertebral fractures in subjects ingesting high doses of

fluoride (>30 mg/day); in subjects administered low fluoride doses or slow-release formulations, there

was no effect on nonvertebral fractures. Further,, there was no effect on vertebral fracture risk in high

fluoride dose subjects, but a decrease in this risk in subjects administered low fluoride doses or slow-

release formulations was found.

Dental Fluorosis. Numerous human and animal studies have demonstrated that exposure to elevated

fluoride levels during tooth development can result in dental fluorosis. As described previously,

fluorosed enamel is composed of hypomineralized subsurface enamel covered by well-mineralized

enamel. The exact mechanisms of dental fluorosis development have not been fully elucidated. Although

there are a number of proposed mechanisms, most of the recent research has focused on the theory that

dental fluorosis results from a fluoride-induced delay in the hydrolysis and removal of amelogenin matrix

proteins during enamel maturation and subsequent effects on crystal growth (as reviewed by Aoba 1997;

Bawden et al. 1995; DenBesten and Thariani 1992; Whitford 1997). Amelogenins, proteins secreted by

ameloblasts, comprise >90% of the enamel matrix proteins and are involved in the regulation of the form

and size of hydroxapatite crystallites; large molecular weight amelogenins inhibit the growth of enamel

crystallites. In the early maturation phase of tooth development, the amelogenins are removed from the

enamel matrix by amelogeninases, and crystallite growth dramatically increases. This phase of enamel

maturation appears to be the most sensitive to elevated fluoride levels. The current evidence strongly

suggests that fluoride inhibits amelogeninase activity. In one proposed mechanism, fluoride indirectly


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inhibits amelogeninase, a calcium-dependent metalloenzyme, by binding to calcium in the mineralizing

milieu and thereby decreasing the calcium concentration (or its activities) and the activation of

amelogeninases (Aoba 1997; DenBesten and Thariani 1992; Whitford 1997). Another proposed

mechanism is that amelogeninases are activated by a metalloproteinase and that calcium is required for

this activation (Bawden et al. 1995; DenBesten and Thariani 1992); fluoride thus interferes with the

proteolytic cascade necessary for hydrolysis of amelogenins. The fluoride-calcium interaction is

supported by the findings that the enzymatic cleavage of amelogenins occurs at a slow rate during the

secretory phase when calcium transport is low and dramatically increase during the early maturation

phase (in the absence of excess fluoride) when calcium transport is high (Aoba 1997).

An alternative theory on the mechanism of dental fluorosis is related to the effects of fluoride on

maturation-stage ameloblasts (Bawden et al. 1995; DenBesten and Thariani 1992). Elevated fluoride

exposure results in a decrease in the number of ameloblast modulations, which in turn could reduce the

number of zone refinement cycles. As defined by Bawden et al. (1995), zone refinement is the process by

which impurities (such as magnesium) that have been incorporated into forming crystals are reduced,

resulting in an improvement of the structural characteristics of the crystal. Thus, a reduction in zone

refinement cycles could result in inferior apatite crystalline structure. This theory is not incompatible

with the theory that fluoride interferes with the hydrolysis of amelogenins. The fluoride-induced

inhibition of amelogeninases results in an enamel matrix with a higher organic content, which could

influence ameloblast modulation rate.

3.6 TOXICITIES MEDIATED THROUGH THE NEUROENDOCRINE AXIS

Recently, attention has focused on the potential hazardous effects of certain chemicals on the endocrine

system because of the ability of these chemicals to mimic or block endogenous hormones. Chemicals

with this type of activity are most commonly referred to as endocrine disruptors. However, appropriate

terminology to describe such effects remains controversial. The terminology endocrine disruptors,

initially used by Colborn and Clement (1992), was also used in 1996 when Congress mandated the

Environmental Protection Agency (EPA) to develop a screening program for “...certain substances

[which] may have an effect produced by a naturally occurring estrogen, or other such endocrine

effect[s]...”. To meet this mandate, EPA convened a panel called the Endocrine Disruptors Screening and

Testing Advisory Committee (EDSTAC), which in 1998 completed its deliberations and made

recommendations to EPA concerning endocrine disruptors. In 1999, the National Academy of Sciences

released a report that referred to these same types of chemicals as hormonally active agents. The


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terminology endocrine modulators has also been used to convey the fact that effects caused by such

chemicals may not necessarily be adverse. Many scientists agree that chemicals with the ability to disrupt

or modulate the endocrine system are a potential threat to the health of humans, aquatic animals, and

wildlife. However, others think that endocrine-active chemicals do not pose a significant health risk,

particularly in view of the fact that hormone mimics exist in the natural environment. Examples of

natural hormone mimics are the isoflavinoid phytoestrogens (Adlercreutz 1995; Livingston 1978; Mayr et

al. 1992). These chemicals are derived from plants and are similar in structure and action to endogenous

estrogen. Although the public health significance and descriptive terminology of substances capable of

affecting the endocrine system remains controversial, scientists agree that these chemicals may affect the

synthesis, secretion, transport, binding, action, or elimination of natural hormones in the body responsible

for maintaining homeostasis, reproduction, development, and/or behavior (EPA 1998c). Stated

differently, such compounds may cause toxicities that are mediated through the neuroendocrine axis. As

a result, these chemicals may play a role in altering, for example, metabolic, sexual, immune, and

neurobehavioral function. Such chemicals are also thought to be involved in inducing breast, testicular,

and prostate cancers, as well as endometriosis (Berger 1994; Giwercman et al. 1993; Hoel et al. 1992).

Although there is no evidence that fluoride is an endocrine disruptor, there are some data to suggest that

fluoride does adversely affect some endocrine glands. An increase in serum thyronine levels, in the

absence of changes in triiodothyronine and thyroid stimulating hormone levels, was observed in

individuals living in areas of India with high fluoride levels in the drinking water (Michael et al. 1996).

In contrast, a decrease in thyroxine levels was observed in rats exposed to fluoride in drinking water for

2 months (Bobek et al. 1976). Significant decreases in serum testosterone have been observed in rats

exposed to sodium fluoride for 50–60 days (Araibi et al. 1989; Narayana and Chinoy 1994).

3.7 CHILDREN’S SUSCEPTIBILITY

This section discusses potential health effects from exposures during the period from conception to

maturity at 18 years of age in humans, when all biological systems will have fully developed. Potential

effects on offspring resulting from exposures of parental germ cells are considered, as well as any indirect

effects on the fetus and neonate resulting from maternal exposure during gestation and lactation.

Relevant animal and in vitro models are also discussed.


3. HEALTH EFFECTS

Children are not small adults. They differ from adults in their exposures and may differ in their

susceptibility to hazardous chemicals. Children’s unique physiology and behavior can influence the

extent of their exposure. Exposures of children are discussed in Section 6.6 Exposures of Children.

Children sometimes differ from adults in their susceptibility to hazardous chemicals, but whether there is

a difference depends on the chemical (Guzelian et al. 1992; NRC 1993). Children may be more or less

susceptible than adults to health effects, and the relationship may change with developmental age

(Guzelian et al. 1992; NRC 1993). Vulnerability often depends on developmental stage. There are

critical periods of structural and functional development during both prenatal and postnatal life and a

particular structure or function will be most sensitive to disruption during its critical period(s). Damage

may not be evident until a later stage of development. There are often differences in pharmacokinetics

and metabolism between children and adults. For example, absorption may be different in neonates

because of the immaturity of their gastrointestinal tract and their larger skin surface area in proportion to

body weight (Morselli et al. 1980; NRC 1993); the gastrointestinal absorption of lead is greatest in infants

and young children (Ziegler et al. 1978). Distribution of xenobiotics may be different; for example,

infants have a larger proportion of their bodies as extracellular water and their brains and livers are

proportionately larger (Altman and Dittmer 1974; Fomon 1966; Fomon et al. 1982; Owen and Brozek

1966; Widdowson and Dickerson 1964). The infant also has an immature blood-brain barrier (Adinolfi

1985; Johanson 1980) and probably an immature blood-testis barrier (Setchell and Waites 1975). Many

xenobiotic metabolizing enzymes have distinctive developmental patterns. At various stages of growth

and development, levels of particular enzymes may be higher or lower than those of adults, and

sometimes unique enzymes may exist at particular developmental stages (Komori et al. 1990; Leeder and

Kearns 1997; NRC 1993; Vieira et al. 1996). Whether differences in xenobiotic metabolism make the

child more or less susceptible also depends on whether the relevant enzymes are involved in activation of

the parent compound to its toxic form or in detoxification. There may also be differences in excretion,

particularly in newborns who all have a low glomerular filtration rate and have not developed efficient

tubular secretion and resorption capacities (Altman and Dittmer 1974; NRC 1993; West et al. 1948).

Children and adults may differ in their capacity to repair damage from chemical insults. Children also

have a longer remaining lifetime in which to express damage from chemicals; this potential is particularly

relevant to cancer.

Certain characteristics of the developing human may increase exposure or susceptibility, whereas others

may decrease susceptibility to the same chemical. For example, although infants breathe more air per

kilogram of body weight than adults breathe, this difference might be somewhat counterbalanced by their


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alveoli being less developed, which results in a disproportionately smaller surface area for alveolar

absorption (NRC 1993).

A number of studies have examined the effects of fluoride in children. Due to its cariostatic properties,

several agencies (for example, IOM 1997; WHO 1973) advocate the use of fluoride supplementation in

children. However, there is a delicate balance between prevention of dental caries and the occurrence of

dental fluorosis. Dental fluorosis, which is an increased porosity or hypomineralization of the tooth

enamel, results from excess exposure to fluoride during tooth development (ages 1–8 years). The

development and severity of dental fluorosis are dependent on the amount of fluoride ingested, the

duration of exposure, and the stage of enamel development at the time of exposure. In the more severe

cases, the tooth enamel is discolored, pitted, and prone to fracture and wear. Severe dental fluorosis is not

commonly found in the United States; one study found prevalences of 0.9 and 6.9% in children living in

communities with 1 or 4 ppm fluoride in drinking water, respectively (Jackson et al. 1995). In milder

forms of dental fluorosis, opaque striations can run horizontally across the surface of the teeth, sometimes

becoming confluent giving rise to white opaque patches. In mild dental fluorosis, the tooth enamel is

fully functional; the opaque spots are considered a cosmetic effect. A recent meta-analysis (McDonagh et

al. 2000) estimated the prevalence of dental fluorosis in children consuming 1 ppm fluoride in water to be

48%; in 12.5% of the children, the fluorosis would be of aesthetic concern. Most of the community-based

studies used for the meta-analysis did not consider other sources of fluoride, such as dental products,

manufactured beverages, or food.

Approximately 99% of the body’s fluoride is found in calcified tissues. Chronic exposure to high levels

of fluoride results in bone thickening and exostoses (skeletal fluorosis). Because of the dynamic nature of

growing bone, it is likely that children will deposit more fluoride in bone than adults consuming an equal

amount of fluoride. However, it is not known if children would be more susceptible to skeletal fluorosis

than adults.

Developmental effects have been observed in humans and animals exposed to fluoride. In humans, an

increased occurrence of spina bifida was found in children living in areas of India with high levels of

fluoride in the drinking water (Gupta et al. 1995). However, this study had several deficiencies. For

example, it did not address the nutritional status of the mothers. This is important because folic acid

deficiency has been implicated in the etiology of spina bifida (Hernandez-Diaz et al. 2001; Honein et al.

2000). In addition, the paper did not provide the fluoride levels in the blood of the mothers, nor

radiographic evidence of spina bifida. Studies by Li et al. (1995a) and Lu et al. (2000) concluded that


3. HEALTH EFFECTS

there were decreases in IQ scores in children living in areas of China with high fluoride levels due to soot

from coal burning, but it is not known if other contaminants in the soot also contributed to this effect, and

the adequacy of the design of these studies is highly questionable. In the Gupta et al. (1995) and Li et al.

(1995a) studies, the observed effects occurred in children with dental and/or skeletal fluorosis. In general,

developmental effects have not been observed in rat or rabbit oral exposure studies (Collins et al. 1995;

Heindel et al. 1996). However, the animal studies did not assess potential neurodevelopmental effects.

The available human and animal data suggest that the developing fetus is not a sensitive target of fluoride

toxicity.

Fluoride retention appears to be higher in children than adults; although on a body weight basis, clearance

is about the same in children and adults. Approximately 80% of an absorbed dose of fluoride is retained

in young children compared to 50% in adults (Ekstrand et al. 1994a, 1994b). This is supported by the

finding that renal fluoride excretion rate is lower in children than adults (Gdalia 1958; Spak et al. 1985).

This difference in fluoride retention is due to high fluoride uptake in developing bones. Data on other

potential age-related differences in the toxicokinetic properties of fluoride were not located. Fluoride is

poorly transferred from maternal blood to breast milk (Ekstrand et al. 1981c; 1984b; Escala et al. 1982;

Spak et al. 1983).

Most of the available information on biomarkers, interactions, and methods for reducing toxic effects is

from adults and mature animals; no child-specific information was identified, with the exception of

biomarker data. It is likely that the available information in adults will also be applicable to children.

3.8 BIOMARKERS OF EXPOSURE AND EFFECT

Biomarkers are broadly defined as indicators signaling events in biologic systems or samples. They have

been classified as markers of exposure, markers of effect, and markers of susceptibility (NAS/NRC

1989).

Due to a nascent understanding of the use and interpretation of biomarkers, implementation of biomarkers

as tools of exposure in the general population is very limited. A biomarker of exposure is a xenobiotic

substance or its metabolite(s) or the product of an interaction between a xenobiotic agent and some target

molecule(s) or cell(s) that is measured within a compartment of an organism (NAS/NRC 1989). The

preferred biomarkers of exposure are generally the substance itself or substance-specific metabolites in

readily obtainable body fluid(s), or excreta. However, several factors can confound the use and


3. HEALTH EFFECTS

interpretation of biomarkers of exposure. The body burden of a substance may be the result of exposures

from more than one source. The substance being measured may be a metabolite of another xenobiotic

substance (e.g., high urinary levels of phenol can result from exposure to several different aromatic

compounds). Depending on the properties of the substance (e.g., biologic half-life) and environmental

conditions (e.g., duration and route of exposure), the substance and all of its metabolites may have left the

body by the time samples can be taken. It may be difficult to identify individuals exposed to hazardous

substances that are commonly found in body tissues and fluids (e.g., essential mineral nutrients such as

copper, zinc, and selenium). Biomarkers of exposure to fluorides, hydrogen fluoride, and fluorine are

discussed in Section 3.8.1.

Biomarkers of effect are defined as any measurable biochemical, physiologic, or other alteration within an

organism that, depending on magnitude, can be recognized as an established or potential health

impairment or disease (NAS/NRC 1989). This definition encompasses biochemical or cellular signals of

tissue dysfunction (e.g., increased liver enzyme activity or pathologic changes in female genital epithelial

cells), as well as physiologic signs of dysfunction such as increased blood pressure or decreased lung

capacity. Note that these markers are not often substance specific. They also may not be directly

adverse, but can indicate potential health impairment (e.g., DNA adducts). Biomarkers of effects caused

by fluorides, hydrogen fluoride, and fluorine are discussed in Section 3.8.2.

A biomarker of susceptibility is an indicator of an inherent or acquired limitation of an organism's ability

to respond to the challenge of exposure to a specific xenobiotic substance. It can be an intrinsic genetic or

other characteristic or a preexisting disease that results in an increase in absorbed dose, a decrease in the

biologically effective dose, or a target tissue response. If biomarkers of susceptibility exist, they are

discussed in Section 3.10 “Populations That Are Unusually Susceptible”.

3.8.1 Biomarkers Used to Identify or Quantify Exposure to Fluorides, Hydrogen Fluoride, and Fluorine

There is extensive literature regarding fluoride levels in biological tissues such as urine, teeth, bone, and

fingernails as indices of exposure. Since it does not produce any metabolites, the fluoride ion itself is the

measured indicator. The most commonly used medium for identifying fluoride exposure is urinary levels

(Ekstrand and Ehrnebo 1983). Several investigators have used this parameter to detect exposure to

sodium fluoride through drinking water (Zipkin et al. 1956) or by ingestion (i.e., toothpaste or diet)

(Ekstrand et al. 1983). Villa et al. (2000) found that measurement of fractional urinary fluoride excretion


3. HEALTH EFFECTS

in children is a good predictor of total daily fluoride intake. Occupational exposure to hydrogen fluoride

is also evaluated from urine fluoride levels (Yoshida et al. 1978).

Urinary fluoride levels are generally ≤1 mg/L when the water supply contains ≤1 ppm fluoride

(Schamschula et al. 1985; Venkateswarlu et al. 1971; Zipkin et al. 1956). Only one report was located of

urinary fluoride levels following acute poisoning. Following dermal exposure to about 5 g hydrofluoric

acid over 2.5% of the body surface (along with concomitant inhalation exposure), the urinary fluoride

level in the first sample obtained 3.5 hours after the accident was 87.0 mg/L (Burke et al. 1973). It is

difficult to determine urine levels that are associated with chronic effects such as skeletal fluorosis,

because no studies that report urinary fluoride levels, accurate exposure levels, duration of exposure, and

health effects were located. Probably the most complete study reports average urinary fluoride levels of

9 mg/L following inhalation exposure to 2.4–6.0 mg/m3 for an unspecified period of time (Kaltreider et

al. 1972). Marked evidence of fluorosis was seen in these workers. In another study (Dinman et al.

1976c), the average postshift urinary fluoride level after 3–5 working days was 5.7 mg/L (range, 2.7–

10.4). No exposure levels were available, but they were reported to be lower than in the plant where

urinary fluoride levels were 9 mg/L. In spite of 10–43 years of occupational exposure, no signs of

skeletal fluorosis were seen. This study may provide urinary fluoride levels that are not associated with

skeletal fluorosis, but any sensitive workers may have left such work and not been included in the study.

These studies are described in more detail in Section 3.2.1.2.

Urinary fluoride levels up to 13.5 mg/L have been reported in areas of India where skeletal fluorosis due

to high water fluoride levels (up to 16.2 ppm) is prevalent (Singh et al. 1963).

Other media that have been used to measure fluoride exposure include plasma (Ekstrand et al. 1983),

ductal saliva (Oliveby et al. 1990; Whitford et al. 1999b), nails (Whitford et al. 1999a), and tooth enamel

(McClure and Likins 1951). When using plasma or saliva as a biomarker, the samples should be obtained

under fasting conditions when measuring body burden (long-term intake) of fluoride (Whitford et al.

1999b). Care must be taken when using plasma fluoride as an indicator of exposure; dosage, time, and

duration must be taken into account (Whitford and Williams 1986). A wide range of plasma fluoride

levels have been reported for the general population; the daily intake of fluoride appears to be one of the

major contributors to plasma fluoride levels (Ikenishi et al. 1988; NAS 1971a). One study (Guy et al.

1976) found a mean plasma fluoride concentration of 0.4 µmol/L (7.5 µg/L) in individuals consuming

drinking water containing <0.1 ppm fluoride and an average plasma fluoride level of 1 µmol/L (19 µg/L)

in individuals consuming 0.9–1.0 ppm fluoride in drinking water. Much higher plasma fluoride levels


3. HEALTH EFFECTS

have been reported in poisoning cases. For example, a plasma fluoride level of 2,000 µg/L was reported

in a case of severe oral poisoning with 53 g fluoride as sodium fluoride (Abukurah et al. 1972). Chronic

exposure to high levels of fluoride can result in wide fluctuations in plasma fluoride levels during the day

(Ekstrand 1978).

Urine, plasma, or saliva can be used as biomarkers of acute exposure to fluoride. Concentrations can

peak within 1 hour after exposure since fluoride is rapidly absorbed from all routes of exposure. Fluoride

salts possess a peculiar "soapy-salty" taste that enables some individuals to recognize that they are

consuming large quantities of fluoride. With chronic exposures, such as from drinking water containing

fluoride, urinary fluoride levels initially increase, and then reach a constant level. In workers, postshift

urinary levels differ from preshift levels since fluoride exposure during the work day is absorbed rapidly

into the body. However, these measurements may not always be useful for quantifying chronic exposure

because fluoride can accumulate in bones. It may be retained in the skeletal tissues for a long period after

the end of exposure, and later re-enter circulating blood to be taken up by bone again or excreted in urine.

Furthermore, background tissue/fluid levels may affect these measurements since fluoride is prevalent in

the environment from dietary sources. An important factor in biological fluid fluoride concentration is

urinary pH (Whitford 1990). When urine is alkaline, fluoride urine excretion increases and is followed by

a decline in plasma fluoride.

Bone fluoride levels can be used to quantitate long-term fluoride exposure (Baud et al. 1978; Boivin et al.

1988). However, this requires a bone biopsy, so bone fluoride levels are most frequently measured after

clinical signs appear. As described in Section 3.2.2.2, the fluoride level found in bone varies between

bones and increases with age. That section also describes fluoride levels in normal bone and levels

associated with various effects.

Studies of Hungarian (Schamschula et al. 1985) or Brazilian (Whitford et al. 1999a) children have

demonstrated a direct relationship between fluoride concentrations in drinking water and fluoride levels in

fingernail clippings, suggesting that fluoride in fingernails may be a reliable biomarker of exposure.

3.8.2 Biomarkers Used to Characterize Effects Caused by Fluorides, Hydrogen Fluoride, and Fluorine

Because soft tissues do not accumulate significant levels of fluoride over long periods of time, effects of

chronic exposure to fluoride first appear in the teeth or skeletal system. Chronic oral fluoride exposure


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can produce dental fluorosis (denBesten and Thariani 1992; DHHS 1991; Eklund et al. 1987; Fejerskov et

al. 1990; Heifetz et al. 1988; Ismail and Bandekar 1999; Jackson et al. 1995; McDonagh et al. 2000;

Selwitz et al. 1995; Teotia and Teotia 1994; Warren and Levy 1999), and higher levels of oral or

inhalation exposure can lead to skeletal effects (Kaltreider et al. 1972; Leone et al. 1955). Evidence of

moderate or severe dental fluorosis (pitting, staining, and/or excessive wear) are possible markers of

effect for fluoride exposure (Walton 1988). However, dental fluorosis is reflective of fluoride exposure

during tooth development (typically during ages 1–8 years), rather than current fluoride exposure.

Alteration in bone density or derangement of trabecular structure can be detected by radiographs, and can

indicate fluoride-induced changes. However, these are nonspecific changes and can be associated with

other exposures. Other elements can sequester in the skeleton and produce similar changes observed in

radiographs. Exostoses, apposition of new bone, ossification of ligaments and tendon insertions, and

metastatic aberrant growth of new bone appear to be much more specific and constant findings in severe

cases of skeletal fluorosis (Vischer et al. 1970). Skeletal fluorosis has been reported following inhalation

exposure to 2.4–6.0 mg/m3 for an unspecified duration (Kaltreider et al. 1972). As discussed in

Section 3.2.2.2, nutritional status plays a large role in determining the oral fluoride exposure levels that

lead to this effect. In the few cases of skeletal fluorosis in the United States for which doses are known,

they are generally 15–20 mg/day for over 20 years (Bruns and Tytle 1988; Sauerbrunn et al. 1965).

No well-documented information was located regarding biomarkers of effect for fluoride, although there

are studies in which cellular changes occurred after fluoride exposure. Increases in glucose or lipid

metabolism have been reported in tissues after exposure to fluorides (Dousset et al. 1984; Shearer 1974;

Watanabe et al. 1975). Changes in erythrocyte enzyme activities including enolase, pyruvate kinase, and

ATPase were found in chronically exposed workers in conjunction with slightly increased fluoride levels

in the body (Guminska and Sterkowicz 1975). These alterations may explain the decreased red blood cell

counts observed in other studies (Hillman et al. 1979; Susheela and Jain 1983). However, none of these

enzyme alterations are specific to fluoride exposure. No information is available regarding how long

these effects last after the last exposure. The enzymatic effects were measured within a few hours of a

single fluoride treatment, while the red blood cell effects were seen as a result of chronic exposure.

There is evidence that in patients with skeletal diseases, the proportion of dialyzable and nondialyzable

hydroxyproline peptides serves as an index of bone collagen turnover. A decreased proportion of

nondialyzable hydroxyproline peptides in the urine of fluorosis patients indicates either a decreased rate

of synthesis of new collagen or an increased utilization of newly formed collagen for matrix formation.


3. HEALTH EFFECTS

This marker offers potential for an early, although nonspecific, indication of altered bone metabolism

after long-term fluoride exposure (Anasuya and Narasinga Rao 1974). No information is available

regarding how long this lasts after chronic exposure. Sudden hyperkalemia and hypocalcemia are effects

seen with fluoride intoxication due to the marked potassium efflux from intact cells caused by fluoride

(McIvor et al. 1985). These ionic shifts are the only serologic markers of effect that have been identified,

and these changes are not unique to fluoride. They last for a few hours after exposure. Polydypsia and

polyuria are also nonspecific markers of effect.

3.9 INTERACTIONS WITH OTHER CHEMICALS

The absorption of fluoride from the gastrointestinal tract of humans and/or animals is affected by the

presence of several minerals including calcium, magnesium, phosphorus, and aluminum (Rao 1984).

These effects are discussed in Section 3.11. No reliable data on interactions that exacerbate negative

effects of fluoride were located.

Teotia and Teotia (1994) found that deficient calcium intake and elevated fluoride intake (1.1–4.0 ppm)

resulted in a significant increase in the occurrence of dental fluorosis (100%) and dental caries (74%), as

compared to children with normal calcium intakes and excess fluoride intakes (prevalences of dental

fluorosis and caries were 14.2 and 31.4%, respectively).

3.10 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE

A susceptible population will exhibit a different or enhanced response to fluorides, hydrogen fluoride, and

fluorine than will most persons exposed to the same level of fluorides, hydrogen fluoride, and fluorine in

the environment. Reasons may include genetic makeup, age, health and nutritional status, and exposure

to other toxic substances (e.g., cigarette smoke). These parameters result in reduced detoxification or

excretion of fluorides, hydrogen fluoride, and fluorine, or compromised function of organs affected by

fluorides, hydrogen fluoride, and fluorine. Populations who are at greater risk due to their unusually high

exposure to fluorides, hydrogen fluoride, and fluorine are discussed in Section 6.7, Populations With

Potentially High Exposures.

Some existing data indicate that subsets of the population may be unusually susceptible to the toxic

effects of fluoride and its compounds. These populations include the elderly, people with osteoporosis,

people with deficiencies of calcium, magnesium, vitamin C, and/or protein (Murray and Wilson 1948;


3. HEALTH EFFECTS

Pandit et al. 1940; Parker et al. 1979), and people with kidney problems (Kono et al. 1984, 1985; Schiffl

and Binswanger 1980; Spak et al. 1985). For most of these populations, there are very limited data to

support or refute increased susceptibility to fluoride. Additionally, there are no data to suggest that

exposure to typical fluoride drinking water levels would result in adverse effects in these potentially

susceptible populations.

The major route of fluoride excretion is via the kidney and the urine; fluoride excretion is influenced by a

number of factors, including glomerular filtration rate, urinary flow, and urinary pH (Ekstrand et al. 1978,

1980a, 1982; Järnberg et al. 1980, 1981, 1983; Whitford et al. 1976). In chronic renal failure, there is a

decrease in glomerular filtration rate, which would result in a decrease in urinary fluoride excretion

(Jeandel et al. 1992; Schiffl and Binswanger 1980). Decreases in fluoride excretion have been seen in

adults (Kono et al. 1984; Schiffl and Binswanger 1980) and children (Spak et al. 1985) with impaired

renal function. In children with low glomerular filtration rates (<92 mL/minute), renal fluoride clearance

was 31.4 mL/minute compared to 45.0 mL/minute in children with normal glomerular filtration rates

(Spak et al. 1985). In older adults (>65 years of age), there is a decline in renal function, which results in

a decrease in renal clearance of fluoride (Jeandel et al. 1992; Kono et al. 1985).

Poor nutrition increases the incidence and severity of dental fluorosis (Murray and Wilson 1948; Pandit et

al. 1940) and skeletal fluorosis (Pandit et al. 1940). Comparison of dietary adequacy, water fluoride

levels, and the incidence of skeletal fluorosis in several villages in India suggested that vitamin C

deficiency played a major role in the disease (Pandit et al. 1940). Calcium intake met minimum

standards, although the source was grains and vegetables, rather than milk, and bioavailability was not

determined. Because of the role of calcium in bone formation, calcium deficiency would be expected to

increase susceptibility to effects of fluoride. Calcium deficiency was found to increase bone fluoride

levels in a 2-week study in rats (Guggenheim et al. 1976), but not in a 10-day study in monkeys (Reddy

and Srikantia 1971). Guinea pigs administered fluoride and a low-protein diet had larger increases in

bone fluoride than those given fluoride and a control diet (Parker et al. 1979). Bone changes in monkeys

following fluoride treatment appear to be more marked if the diet is deficient in protein or vitamin C, but

the conclusions are not definitive because of incomplete controls and small sample size (Reddy and

Srikantia 1971). Inadequate dietary levels of magnesium may affect the toxic effects of fluoride.

Fluoride administered to magnesium-deficient dogs prevented soft-tissue calcification, but not muscle

weakness and convulsions (Chiemchaisri and Philips 1963). In rats, fluoride aggravated the

hypomagnesemia condition, which produced convulsive seizures. The symptoms of magnesium


3. HEALTH EFFECTS

deficiency are similar to those produced by fluoride toxicity. This may be because of a fluoride-induced

increase in the uptake of magnesium from plasma into bone.

Although the possible relationship between fluoride in drinking water and the risk of fractures has been

extensively investigated, the data are inconclusive with studies finding beneficial (Madans et al. 1983;

Phipps et al. 2000; Simonen and Laittenen 1985) and deleterious (Cooper et al. 1990, 1991; Danielson et

al. 1992; Jacobsen et al. 1990; Kurttio et al. 1999; Sowers et al. 1986) effects or no effects (Arnala et al.

1984; Cauley et al. 1995; Kröger et al. 1994). Clinical trials of postmenopausal women with osteoporosis

have found an increased risk of nonvertebral fractures following exposure to high doses of fluoride

(34 mg/day) (Haguenauer et al. 2000; Riggs et al. 1990, 1994); no effect on vertebral fracture risk was

found. However, administration of low doses of slow release sodium fluoride medications has been

effective in treating spinal osteoporosis (Pak et al. 1995).

3.11 METHODS FOR REDUCING TOXIC EFFECTS

This section will describe clinical practice and research concerning methods for reducing toxic effects of

exposure to fluorides, hydrogen fluoride, and fluorine. However, because some of the treatments

discussed may be experimental and unproven, this section should not be used as a guide for treatment of

exposures to fluorides, hydrogen fluoride, and fluorine. When specific exposures have occurred, poison

control centers and medical toxicologists should be consulted for medical advice. The following texts

provide specific information about treatment following exposures to fluorides, hydrogen fluoride, and

fluorine:

Bronstein AC, Currance PL. 1988. Emergency care for hazardous materials exposure. St. Louis, MO: The C.V. Mosby Company, 113-114, 165-166. Ellenhorn MJ, Barceloux DG. 1988. Medical toxicology: Diagnosis and treatment of human poisoning. New York, NY: Elsevier Science Publishing Company, Inc. 76, 83, 531-536, 873-874, 924-929. Goldfrank LR, Flomenvaum NE, Lewin NA, et al., eds. 1990. Goldfrank’s toxicologic emergencies. Norwalk, CT: Appleton & Lange, 220-221, 745, 769-779.

In all cases of acute high-level exposure to fluoride, hydrogen fluoride/hydrofluoric acid, or fluorine, the

focus of mitigation is to limit further absorption and to complex or remove the free fluoride ions from the

blood while maintaining the proper electrolyte balances. The majority of relevant acute high-level

exposure situations for which mitigation information is available involve dermal and/or inhalation


3. HEALTH EFFECTS

exposure to hydrofluoric acid or gaseous hydrogen fluoride. Some information is also available regarding

mitigation of chronic oral exposure to fluoride.

3.11.1 Reducing Peak Absorption Following Exposure

Fluoride. Ingested fluoride is rapidly absorbed from the gastrointestinal tract. However, fluoride

absorption is affected by the presence of several minerals including calcium, magnesium, and aluminum

which bind to the fluoride to form less soluble complexes (Ekstrand and Ehrnebo 1979; Kuhr et al. 1987;

Machle and Largent 1943; McClure et al. 1945; Spencer and Lender 1979; Spencer et al. 1980a, 1981;

Whitford 1994). Gastric lavage with solutions of calcium gluconate, calcium carbonate, calcium lactate,

calcium chloride, calcium hydroxide, calcium- or magnesium-based antacid, or aluminum hydroxide gel

have been used in the treatment of fluoride poisoning (Ellenhorn and Barceloux 1988; Goldfrank et al.

1990; Haddad and Winchester 1990; Morgan 1989). Two treatments that are not recommended are

attempting to neutralize the acid with orally administered sodium bicarbonate due to the resulting

exothermic reaction (Bronstein and Currance 1988) and emesis due to the formation of hydrofluoric acid

in the stomach (Bronstein and Currance 1988; Haddad and Winchester 1990).

Hydrogen Fluoride/Hydrofluoric Acid. In cases of dermal and inhalation exposure, the exposed persons

are first removed from the source of exposure, and any particles or excess liquids are removed by

brushing or blotting (Bronstein and Currance 1988). Thorough irrigation with cold water or saline is then

done to further limit absorption through exposed skin and eyes. Irrigation is followed by washing the

affected skin with an alkaline soap and water (Bronstein and Currance 1988; Dibbell et al. 1970).

Persistent pain is an indication that large amounts of free fluoride ions remain. In such cases, magnesium

oxide paste is applied or the exposed skin is soaked in cold solutions of magnesium sulfate, calcium salts,

or quaternary ammonium compounds (benzalkonium chloride, benzethonium) (Browne 1974; Goldfrank

et al. 1990; Haddad and Winchester 1990). However, the evolving standard of treatment for mild to

moderate burns involves massaging the affected area with a penetrating calcium gluconate gel, to avoid

problems with magnesium oxide precipitation (Borak et al. 1991; Browne 1974; Goldfrank et al. 1990).

Fluorine. Inhalation exposure to fluorine is treated very similarly to inhalation exposure to hydrogen

fluoride. The source of exposure is removed and water used to decontaminate the patient. The eyes are

washed with saline if necessary, and magnesium oxide paste can be applied (Bronstein and Currance

1988; Stutz and Janusz 1988).


3. HEALTH EFFECTS

3.11.2 Reducing Body Burden

Fluoride. There is limited information on reducing the body burden of fluoride. Whitford (1994)

demonstrated that a diet high in calcium resulted in a negative fluoride balance in rats due to a significant

increase in fecal excretion of fluoride. Although no significant alterations in plasma fluoride levels were

found, the high calcium diet did result in a significant decrease in fluoride levels in the femur epiphysis.

In a study of 10 individuals with clinical manifestations of fluorosis (Susheela and Bhatnagar 2002), a

diet with adequate levels of calcium, vitamins C and E, and other antioxidants and access to drinking

water with low levels of fluoride (1 ppm or lower) resulted in a decrease in urinary and blood fluoride

levels and a decrease in clinical signs were observed. One year after intervention, there was complete

recovery of gastrointestinal complaints, muscular weakness, polyuria, polydypsea, and pain and rigidity in

the joints. A study by Khandare et al. (2000) provides suggestive evidence that co-administration of

fluoride and tamarind results in increased urinary excretion of fluoride and decreased bone fluoride levels

in dogs.

Hydrogen Fluoride/Hydrofluoric Acid. Hydrogen fluoride burns are characterized by intense pain and

progressive tissue destruction. The damage associated with this burn occurs in two stages. The first stage

is immediate tissue damage caused by a high concentration of hydrogen ions and the second is

liquefaction necrosis that is caused by free fluoride ions (Seyb et al. 1995). There are a number of

recommended forms of therapy; these therapies have the common goal of binding the fluoride ion and/or

altering its reactivity with tissues (Dunn et al. 1992). Recommended forms of therapy include topical

treatments with calcium gluconate paste, magnesium oxide paste, and iced solutions of quaternary

ammonium compounds, alcohol, or magnesium sulfate and intradermal injections of either magnesium

sulfate or calcium gluconate, or intraarterial injection of calcium gluconate (Dunn et al. 1992; Seyb et al.

1995). Intra-arterial infusions of calcium gluconate are often preferred to intradermal injections due to

the ability of the infusions to deliver more calcium to the burn site, better distribution of calcium in the

tissues, and the need for only a single injection, as opposed to an injection for every square centimeter of

affected dermal tissue (Haddad and Winchester 1990). Additionally, in burns involving the hands,

multiple intradermal injections pose the risk of elevating tissue pressures and forcing the removal of the

nails (Ellenhorn and Barceloux 1988; Goldfrank et al. 1990). One source reports that calcium gluconate

injection was successfully used in at least 96 cases without causing damage (Browne 1974).


3. HEALTH EFFECTS

Several studies have compared different therapies in an attempt to identify the most effective treatment.

The therapeutic effects of calcium gluconate, magnesium acetate, and magnesium sulfate on hydrofluoric

acid burns of shaved Sprague-Dawley rats were compared using intradermal and subcutaneous injection

(Harris et al. 1981). Although this study found that injection of calcium gluconate, but not the

magnesium compounds, was irritating in the absence of a burn, and the duration, depth, and area of

lesions were reduced with the magnesium compounds compared with calcium gluconate, no reports were

located of using intradermal injection of magnesium compounds in humans. Seyb et al. (1995) found that

subcutaneous injections of 10% calcium gluconate and magnesium sulfate solution and topically applied

calcium gluconate mixed with dimethyl sulfoxide significantly reduced the damage caused by hydrogen

fluoride exposure in rats exposed to 70% hydrogen fluoride for 60 seconds followed by continuously

rinsing with tap water for 5 minutes. Treatment with topically applied dimethyl sulfoxide only or calcium

gluconate only did not affect the degree of tissue damage. In contrast, Dunn et al. (1992) found that

injection of 10% calcium gluconate was the least effective therapy in pigs following topical application of

38% hydrogen fluoride. The most effective treatments were soaking in calcium acetate or iced Zephiran

(benzalkonium chloride), or injection of 5% calcium gluconate.

3.11.3 Interfering with the Mechanism of Action for Toxic Effects

Fluoride. The major treatment strategies for long-term, low-level exposure to fluorides are removal of

the source of exposure and administration of compounds that reduce intestinal absorption. Skeletal

fluorosis has been reported to be partially reversed 8–15 years after the elevated exposure ended

(Grandjean and Thomsen 1983). Sclerosis of the trabecular bone in ribs, vertebral bodies, and pelvis

faded, but calcification of muscle insertions and ligaments was not altered. Techniques that increase bone

turnover or bone resorption might be effective in reversing skeletal fluorosis. However, no information

on such techniques was located.

Chinoy and associates have examined the effectiveness of calcium, ascorbic acid, vitamin E, and

vitamin D in reversing the reproductive effects associated with oral exposure to sodium fluoride.

Administration of ascorbic acid and/or calcium and cessation of sodium fluoride exposure enhanced the

recovery of sperm function and morphology and testicular damage, as compared to no treatment, in rats

(Chinoy et al. 1993), mice (Chinoy and Sharma 2000), and rabbits (Chinoy et al. 1991). The combined

administration of ascorbic acid and calcium was the most effective treatment. Postexposure

administration of vitamins E and/or D was also effective in the recovery of sodium-fluoride induced

testicular effects in mice (Chinoy and Sharma 1998). Likewise, posttreatment administration of ascorbic


3. HEALTH EFFECTS

acid and/or calcium and vitamins E and/or D also aided in the recovery of ovarian effects in mice (Chinoy

and Patel 1998; Chinoy et al. 1994). It is believed that the antioxidant properties of ascorbic acid and

vitamin E aid in the recovery of fluoride damage. Vitamin D promotes the intestinal absorption of

calcium and phosphorus, thus maintaining the optimal blood concentration of these elements (Chinoy and

Patel 1998). The calcium may act by forming insoluble complexes with fluoride (Chinoy and Patel 1998;

Chinoy et al. 1994). Similarly, Guna Sherlin and Verma (2001) found that co-administration of

vitamin D reduced the maternal toxicity (decreased body weight gain and feed intake) and fetal toxicity

(increased percentage of fetuses with skeletal or visceral abnormalities) as compared to rats only

receiving sodium fluoride.

Hydrogen Fluoride/Hydrofluoric Acid. The primary focus of research on reducing the toxic effects

following dermal exposure to hydrogen fluoride or hydrofluoric acid is on methods for reducing

absorption and decreasing the amount of fluoride ions. The tissue damage associated with hydrogen

fluoride exposure is believed to be caused by the binding of fluoride ions with tissue calcium and

magnesium cations to form insoluble salts, which are believed to interfere with cellular metabolism,

inducing cellular death and necrosis. Thus, the most effective method for interfering with the mechanism

of action is removal of the fluoride ions; these methods are discussed in Section 3.11.2.

3.12 ADEQUACY OF THE DATABASE

Section 104(i)(5) of CERCLA, as amended, directs the Administrator of ATSDR (in consultation with the

Administrator of EPA and agencies and programs of the Public Health Service) to assess whether

adequate information on the health effects of fluorides, hydrogen fluoride, and fluorine is available.

Where adequate information is not available, ATSDR, in conjunction with the National Toxicology

Program (NTP), is required to assure the initiation of a program of research designed to determine the

health effects (and techniques for developing methods to determine such health effects) of fluorides,

hydrogen fluoride, and fluorine.

The following categories of possible data needs have been identified by a joint team of scientists from

ATSDR, NTP, and EPA. They are defined as substance-specific informational needs that if met would

reduce the uncertainties of human health assessment. This definition should not be interpreted to mean

that all data needs discussed in this section must be filled. In the future, the identified data needs will be

evaluated and prioritized, and a substance-specific research agenda will be proposed.


3. HEALTH EFFECTS

3.12.1 Existing Information on Health Effects of Fluorides, Hydrogen Fluoride, and Fluorine

The existing data on health effects of inhalation, oral, and dermal exposure of humans and animals to

fluorides, hydrogen fluoride, and fluorine are summarized in Figures 3-6, 3-7, and 3-8. The purpose of

these figures is to illustrate the existing information concerning the health effects of fluorides, hydrogen

fluoride, and fluorine. Each dot in the figure indicates that one or more studies provide information

associated with that particular effect. The dot does not necessarily imply anything about the quality of the

study or studies, nor should missing information in this figure be interpreted as a “data need”. A data

need, as defined in ATSDR’s Decision Guide for Identifying Substance-Specific Data Needs Related to

Toxicological Profiles (Agency for Toxic Substances and Disease Registry 1989), is substance-specific

information necessary to conduct comprehensive public health assessments. Generally, ATSDR defines a

data gap more broadly as any substance-specific information missing from the scientific literature.

There are many case reports and epidemiological studies investigating the health effects of hydrogen

fluoride in humans by the inhalation and dermal routes, and the health effects of fluoride compounds by

the inhalation and oral routes. There are also limited data from experimental human exposure to fluorine.

Most human studies of the health effects of oral exposure to fluoride are community-based studies of

populations ingesting drinking water with various levels of fluoride and case reports of acute and chronic

oral exposure to sodium fluoride. There are also some case reports of acute dermal exposure to

hydrofluoric acid.

Human fatalities have resulted from both oral exposure to sodium fluoride and dermal exposure to

hydrofluoric acid. Dermal exposure to hydrofluoric acid is often accompanied by inhalation of

hydrofluoric acid fumes. Human studies and case reports have investigated the effects of nonlethal oral

doses of sodium fluoride, although only after acute exposure. These exposures have resulted in mostly

gastrointestinal effects and consequences of hypocalcemia (e.g., nervous system and cardiovascular

effects). Exposure to fluorine gas causes respiratory, ocular, and dermal irritation in humans after acute

exposure. One study on chronic exposure to fluorine was located. Chronic human studies have generally

examined health effects in workers exposed to hydrogen fluoride or fluoride-containing dusts by

inhalation, and populations exposed to ionic fluoride through drinking water. These studies have

investigated the relationship between fluoride and neurological and reproductive effects and cancer.


3. HEALTH EFFECTS

Figure 3-6. Existing Information on Health Effects of Fluoride


3. HEALTH EFFECTS

Figure 3-7. Existing Information on Health Effects of Hydrogen Fluoride/Hydrofluoric Acid


3. HEALTH EFFECTS

Figure 3-8. Existing Information on Health Effects of Fluorine


3. HEALTH EFFECTS

Studies conducted on animals have been fairly extensive, and have focused on the health effects following

inhalation of hydrogen fluoride and oral exposure to fluoride. A few studies on inhalation exposure to

fluorine also exist. Dermal studies in animals are limited to those investigating dermal and ocular effects

from exposure to fluorine, hydrofluoric acid, and sodium fluoride. A number of studies on the

genotoxicity of fluoride were located.

3.12.2 Identification of Data Needs

Acute-Duration Exposure.

Fluoride. Information on the acute toxicity of inhaled fluoride dust is limited to two animal studies that

found respiratory tract damage and impaired immune response in mice exposed to sodium fluoride for

4 hours/day for 10–14 days (Chen et al. 1999; Yamamoto et al. 2001). These data were not considered

adequate for derivation of an acute-duration inhalation MRL because the upper respiratory tract, a

potentially sensitive target of toxicity, was not examined in either study. Studies examining a wide range

of end points, including the upper respiratory tract, and using a number of exposure concentrations would

be useful for establishing concentration-response relationships and deriving an acute-duration inhalation

MRL for fluorides. The acute toxicity of ingested fluorides has been investigated in human and animal

studies. Most of the available human (Eichler et al. 1982; Hodge and Smith 1965; Sharkey and Simpson

1933) and animal (DeLopez et al. 1976; Lim et al. 1978; Skare et al. 1986; Whitford et al. 1990) acute

studies reported lethal doses and effects resulting from exposure to a lethal dose of sodium fluoride. The

gastrointestinal tract (Hoffman et al. 1980; Kessabi et al. 1985; Spak et al. 1989, 1990; Spoerke et al.

1980) and bone (Guggenheim et al. 1976) have been identified as targets of toxicity following a nonlethal

exposure to fluorides in human and rat studies, respectively. The potential of sodium fluoride to induce

reproductive (Li et al. 1987a) and developmental (Guna Sherlin and Verma 2001; Heindel et al. 1996)

effects has also been investigated in laboratory animals. An acute-duration oral MRL was not derived for

fluoride; the available data suggest that gastric irritation is the most sensitive end point of acute fluoride

toxicity; however, additional studies are needed to establish a concentration-response curve and to assess

whether the gastric mucosa would adapt to repeated exposure to fluoride. These studies should also

examine other potentially sensitive targets. Data on the dermal toxicity of fluoride is limited to a study

that found epidermal necrosis and marked edema of the dermis following application of sodium fluoride

to the abraded skin of rats (Essman et al. 1981). Additional dermal exposure studies would be useful for

establishing concentration-response relationships for fluoride.


3. HEALTH EFFECTS

Hydrogen Fluoride/Hydrofluoric Acid. A number of studies have examined the acute toxicity of

hydrogen fluoride in humans under accidental exposure conditions (Dayal et al. 1992; Wing et al. 1991)

or experimental conditions (Lund et al. 1997, 1999, 2002; Machle et al. 1934) and in laboratory animals

(Dalbey et al. 1998a, 1998b; Rosenholtz et al. 1963; Stavert et al. 1991). These studies demonstrate that

the respiratory tract is the most sensitive target of toxicity; at slightly higher concentrations, skin and eye

irritation are also observed. Hematological (increased red blood cell and hemoglobin levels) and liver

(increased aspartate aminotransferase activity) alterations have also been observed in laboratory animals

exposed to much higher concentrations (Dalbey et al. 1998a, 1998b). An acute duration inhalation MRL

based on lower respiratory tract irritation in humans (Lund et al. 1997) was derived for hydrogen fluoride.

Data on the oral toxicity of hydrofluoric acid are limited to a report of six deaths following accidental

consumption of a rust remover containing hydrofluoric acid (Menchel and Dunn 1986). These data were

not considered adequate for derivation of an acute-duration oral MRL for hydrofluoric acid. It is likely

that the most sensitive target following acute oral exposure to hydrofluoric acid would be the

gastrointestinal tract; studies are needed to confirm this hypothesis and establish a concentration-response

curve. Dermal exposure studies demonstrate that hydrofluoric acid is very caustic, and severe tissue

damage can result from direct contact (Chela et al. 1989; Derelanko et al. 1985; Mayer and Gross 1985;

Roberts and Merigan 1989). Exposure to a high concentration or prolonged exposure can result in

systemic effects that are similar to fluoride (Braun et al. 1984; Mayer and Gross 1985; Mullett et al.

1987). There are limited concentration-response data and additional dermal exposure studies would be

useful.

Fluorine. A series of studies conducted by Keplinger and Suissa (1968) have investigated the acute

toxicity of fluorine in humans, rats, mice, rabbits, guinea pigs, and dogs. In all species tested, fluorine

was irritating to the respiratory tract, skin, and eyes. In addition to these direct contact effects, exposure

to fluorine also resulted in liver (necrosis and cloudy swelling) and kidney (necrosis) effects in the

laboratory animal species. An acute-duration MRL for fluorine was derived from the Keplinger and

Suissa (1968) human study, which identified a NOAEL and LOAEL for nasal irritation. Additional

studies are needed to evaluate the concentration-response relationship for skin effects as well as other end

points following dermal-only exposure.

Intermediate-Duration Exposure.

Fluoride. The toxicity of inhaled fluoride is limited to an animal study that found lung effects in mice

exposed to sodium fluoride for 4 hours/day for 20–30 days (Chen et al. 1999). With the exception of

direct contact effects, it is likely that the toxicity of inhaled fluoride would be similar to ingested fluoride.


3. HEALTH EFFECTS

Additional inhalation studies would be useful for establishing a concentration-response relationship and

deriving an intermediate-duration inhalation MRL for fluorides. A number of animal studies have

investigated the toxicity of fluoride following intermediate oral exposure; no intermediate-duration

human studies were located. These animal studies have reported a number of systemic effects, including

alterations in bone and tooth mineralization (Collins et al. 2001a; DenBesten and Crenshaw 1984;

Harrison et al. 1984; Marie and Hott 1986; Turner et al. 2001; Uslu 1983; Zhao et al. 1998), hyperplasia

of the glandular stomach (NTP 1990), alterations in thyroid function (Bobek et al. 1976; Zhao et al.

1998), and kidney damage (Greenberg 1986; NTP 1990). Additionally, neurological (Mullenix et al.

1995; Paul et al. 1998; Purohit et al. 1999), reproductive (Al-Hiyasat et al. 2000; Araibi et al. 1989;

Chinoy and Sequeira 1992; Chinoy et al. 1992, 1997; Krasowska and Wlostowski 1992; Messer et al.

1973; Narayana and Chinoy 1994), and developmental effects in the presence of maternal toxicity

(Collins et al. 1995) have been observed. The available studies identify the bones and possibly the

thyroid as the most sensitive targets of fluoride toxicity in rodents following intermediate-duration

exposure to fluoride. Chronic-duration studies in humans strongly support the identification of bone as a

sensitive target of fluoride toxicity. However, bone growth in rats differs from humans, and it is not

known whether it is appropriate to extrapolate an adverse effect level from rats to humans. The potential

of fluoride to induce thyroid effects in humans has not been adequately assessed; additional studies are

needed to determine whether this end point is relevant for humans. The intermediate-duration database

was considered inadequate for derivation of an MRL due to the uncertainties associated with the use of

rodent data, and derivation of an MRL using the Bobek et al. (1976) or Turner et al. (2001) animal studies

that identified the lowest LOAEL values would result in an MRL that is lower than the human-based

chronic-duration MRL. No intermediate-duration dermal toxicity studies were identified for fluorides;

based on the results of an acute-duration rat study (Essman et al. 1981), it is likely that fluoride exposure

would result in damage to the skin. Studies are needed to confirm that this would also be the most

sensitive target of toxicity following longer-duration exposure and to assess whether there are other

sensitive targets.

Hydrogen Fluoride/Hydrofluoric Acid. Nasal irritation was reported in the only human intermediate-

duration study identified for hydrogen fluoride (Largent 1960). A small number of animal studies are

available. These inhalation studies found respiratory tract irritation (Machle and Kitzmiller 1935;

Stokinger 1949), skin and eye irritation (Stokinger 1949), kidney damage (Machle and Kitzmiller 1935),

and neurobehavioral alterations (Sadilova et al. 1965) in laboratory animals. An intermediate-duration

inhalation MRL was not derived for hydrogen fluoride because an MRL based on the Largent (1960)

study is higher than the acute-duration inhalation MRL derived from the Lund et al. (1997, 1999) study.


3. HEALTH EFFECTS

Additional studies are needed to identify a NOAEL for respiratory tract effects. No intermediate-duration

oral or dermal exposure studies were identified; the gastrointestinal tract and skin, respectively, are the

likely targets of toxicity. Studies are needed for establishing concentration-response curves for these

exposure routes and identifying other possible targets of toxicity.

Fluorine. The database on the intermediate-duration toxicity of fluorine is limited to a multispecies study

that found eye, nose, and mouth irritation in rats and dogs and lung damage in rats, rabbits, and dogs

(Stokinger 1949). Because the measurements of exposure concentrations were questionable, this study

was not selected as the basis of an intermediate-duration inhalation MRL for fluorine. Additional studies

using multiple exposure concentrations are needed to establish the concentration-response relationship for

fluorine and derive an MRL. Studies involving dermal-only exposure to fluorine gas would be useful for

assessing the dermal toxicity of this element in humans wearing respirators without adequate protective

clothing.

Chronic-Duration Exposure and Cancer.

Fluoride. No studies have examined the chronic toxicity of inhaled fluorides; however, several

occupational exposure studies have examined workers exposed to hydrogen fluoride and fluoride dusts,

and these are discussed under hydrogen fluoride. Thus, a chronic-duration inhalation MRL was not

derived for fluorides. Shorter-term inhalation studies and chronic-duration oral studies suggest that the

respiratory tract, teeth, and bones are likely to be the principal targets of fluoride. Studies are needed to

confirm this hypothesis and to establish concentration-response data. A large number of human and

animal studies have investigated the chronic toxicity of ingested fluoride. Most of the human studies are

ecological studies examining communities with fluoridated water or naturally high levels of fluoride in

water. For the most part, these studies have focused on the occurrence of dental fluorosis (DHHS 1991;

Eklund et al. 1987; Heifetz et al. 1988; Ismail and Bandekar 1999; Jackson et al. 1995; McDonagh et al.

2000; Selwitz et al. 1995; Teotia and Teotia 1994; Warren and Levy 1999) and alterations in bone density

or increased bone fracture rates (Arnala et al. 1986; Cauley et al. 1995; Cooper et al. 1990, 1991;

Danielson et al. 1992; Goggin et al. 1965; Jacobsen et al. 1990, 1992, 1993; Haguenauer et al. 2000;

Hillier et al. 2000; Karagas et al. 1996; Kleerekoper et al. 1991; Kröger et al 1994; Kurttio et al. 1999;

Lehmann et al. 1998; Li et al. 2001; Phipps et al. 2000; Riggs et al. 1990, 1994; Simonen and Laittinen

1985; Suarez-Almazor et al. 1993). At typical fluoridation levels (0.9–1.0 ppm), increases, decreases, or

no effect on bone fracture rates have been found. At higher doses, fluoride has consistently increased

bone fracture rates. Other potential targets of toxicity that have been examined in humans include the

cardiovascular system (Hagan et al. 1954; Heasman and Martin 1962), gastrointestinal tract (Susheela et


3. HEALTH EFFECTS

al. 1992), kidneys (Lantz et al. 1987), intelligence and behavior (Li et al. 1995a; Lu et al. 2000; Morgan et

al. 1998), reproductive system (Freni 1994; Susheela and Jethanandani 1996), and developing organism

(Berry 1958; Erickson et al. 1976; Li et al. 1995a; Lu et al. 2000; Needleman et al. 1974; Rapaport 1956;

Takahashi 1998). These studies did not find positive and/or consistent results. Several animal studies

have examined the chronic toxicity; the observed effects included bone alterations in rats (NTP 1990),

mice (NTP 1990), and mink (Aulerich et al. 1987), intestinal damage in rabbits (Susheela and Das 1988),

hematological effects in rabbits (Susheela and Jain 1983), immunological effects in rabbits (Jain and

Susheela 1987), and male reproductive effects in rabbits (Kumar and Susheela 1994, 1995; Susheela and

Kumar 1991, 1997). One limitation of the animal studies is that the doses used were much higher

(>10 times higher) than doses that result in increased fracture rates in humans. Additional animal studies

that used lower doses would be useful in determining if there are additional sensitive targets of toxicity

following chronic-duration oral exposure to fluoride. A large community-based study by Li et al. (2001)

was used to derive a chronic-duration oral MRL for fluoride. No chronic-duration dermal studies were

identified. The toxicity of fluoride is not likely to be route-specific, with the exception of direct contact

effects. An acute toxicity study (Essman et al. 1981) found skin damage in animals exposed to sodium

fluoride; studies are needed to identify the threshold of toxicity of dermal irritation and other potentially

sensitive targets such as teeth and bone.

The carcinogenicity of fluoride has been assessed in a number of human studies of communities with

fluoridated water or naturally high levels of fluoride in the drinking water (Cohn 1992; Erickson 1978;

Freni and Gaylor 1992; Gelberg et al. 1995; Hoover et al. 1976, 1991a, 1991b; Kinlen and Doll 1981;

Mahoney et al. 1991; McGuire et al. 1991; Neuberger 1982; Oldham and Newell 1977; Rogot et al. 1978;

Takahashi et al. 2001; Taves 1977; Yiamouyiannis and Burk 1977) and chronic-duration oral exposure

studies of rats (Maurer et al. 1990; NTP 1990) and mice (NTP 1990). Although some human studies have

found positive results, particularly for bone cancer (Cohn 1992; Hoover et al. 1991b; Takahashi et al.

2001; Yiamouyiannis and Burk 1977), the majority of the studies have not found significant increases in

cancer risk. The NTP (1990) bioassay found a weak, equivocal fluoride-related increase in the

occurrence of osteosarcomas in male rats, and no evidence of carcinogenicity in female rats or male or

female mice. Significant increases in cancer risk were found in the Maurer et al. (1990) study.

Additional studies are needed to further evaluate the potential of fluoride to induce bone cancers

following chronic oral exposure.

Hydrogen Fluoride/Hydrofluoric Acid. The available data on the chronic toxicity are limited to several

occupational exposure studies of workers (Carnow and Conibear 1981; Chan-Yeung et al. 1983a, 1983b;


3. HEALTH EFFECTS

Czerwinski et al. 1988; Derryberry et al. 1963; Dinman et al. 1967c; Kaltreider et al. 1972; Macuch et al.

1963; Moller and Gudjonsson 1932) exposed to hydrogen fluoride and fluoride dusts and an inhalation

study in guinea pigs (Rioufol et al. 1982). The occupational exposure studies primarily focused on

respiratory tract and skeletal effects and the guinea pig study examined the kidneys. Although the

occupational exposure studies examined the primary targets of hydrogen fluoride and fluoride toxicity,

they are limited by co-exposure to a number of other chemicals and limited, if any, exposure data.

Additional chronic-duration studies are needed to derive a chronic-duration inhalation MRL for hydrogen

fluoride. No chronic-duration dermal exposure studies were located for hydrogen fluoride. At high

concentrations, the skin is the most sensitive target of toxicity; however, long-term exposure to lower

concentrations is likely to result in different targets of toxicity, possibly the same as chronic fluoride

toxicity. Additional chronic-duration studies are needed to establish the concentration-response

relationships for direct contact effects and other possible targets of toxicity.

Several studies have examined the carcinogenicity of hydrogen fluoride and fluoride dust exposures in

cryolite workers (Grandjean et al. 1985, 1992), aluminum industry workers (Andersen et al. 1982; Gibbs

and Horowitz 1979; Milham 1979; Rockette and Arena 1983), fluorspar miners (deVilliers and Windish

1964), and individuals residing near or working in the steel industry (Cecilioni 1972). Several studies

reported increases in respiratory tract cancer rates (Andersen et al. 1982; deVilliers and Windish 1964;

Gibbs and Horowitz 1979; Grandjean et al. 1985, 1992; Milham 1979); however, no adjustments for

occupational exposure to other carcinogenic compounds and smoking were made in most of these studies.

Well-controlled studies are needed to assess the carcinogenic potential of hydrogen fluoride and fluoride

dust exposure.

Fluorine. Data on the chronic toxicity of fluorine is limited to an occupational exposure study in which a

relatively insensitive measure of respiratory tract effects (visits to the medical department with respiratory

complaints and absences from work) was used and in which the controls and exposed workers were

exposed to uranium hexafluoride and hydrogen fluoride (Lyon 1962). This study was considered

inadequate for derivation of a chronic-duration inhalation MRL. Additional studies are needed to define

the concentration-response relationships following exposure to inhaled fluorine gas and following dermal-

only exposure to fluorine. There are no data on the carcinogenicity of fluorine; the carcinogenicity of

absorbed fluorine is expected to be similar to fluoride. However, additional studies are needed to assess

whether long-term exposure to fluorine would result in portal-of-entry cancers.


3. HEALTH EFFECTS

Genotoxicity. There is a significant database on the genotoxicity of fluoride compounds in several

species and several cell types. However, the results from well-characterized systems are much more

limited, and additional well-designed experiments would be useful in resolving contradictory data. The

results have been inconsistent in many instances, but a consensus is developing that at toxic levels

(>10 µg/mL, and usually seen at >40 µg/mL), there may be a general inhibition of enzymes, including the

DNA polymerases (Caspary et al. 1987, 1988).

Reproductive Toxicity. Hydrogen fluoride and fluorine animal inhalation exposure studies and

human and animal fluoride oral exposure studies have assessed reproductive toxicity. No data are

available on the reproductive toxicity following dermal exposure in humans or animals. Degenerative

testicular changes were observed in rats exposed to high concentrations of hydrogen fluoride (Stokinger

1949) or fluorine (Stokinger 1949); it is possible that these effects were due to direct contact with the gas

rather than a systemic effect. Several studies have investigated the reproductive toxicity of fluoride in

humans. One study found a significant association between decreasing total fertility rates and increasing

fluoride levels in drinking water (Freni 1994) and another study found decreases in serum testosterone

levels in men with skeletal fluorosis (Susheela and Jethanandani 1996). Both studies have several

limitations that preclude drawing firm conclusions from them about the potential of fluoride to induce

reproductive toxicity. Alterations in the male reproductive system have also been observed in rats and

rabbits orally exposed to sodium fluoride. The observed effects included alterations in serum testosterone

levels (Araibi et al. 1989; Narayana and Chinoy 1994), histological alterations in the testes (Krasowska

and Wlostowski 1992; Narayana and Chinoy 1994; Susheela and Kumar 1991), alterations in sperm

morphology or spermatogenesis (Chinoy et al. 1992, 1995, 1997; Kumar and Susheela 1994, 1995;

Susheela and Kumar 1991), and impaired fertility (Chinoy and Sequeira 1992; Chinoy et al. 1992).

However, other studies have not found any effects on male reproduction (Dunipace et al. 1989; Li et al.

1987a; Sprando et al. 1997, 1998). Additional studies are needed to address the conflicting results. As

with the male reproductive effects, conflicting results have been found for fluoride-induced female

reproductive effects. Infertility was observed in one study (Messer et al. 1973), but not in three others

(Collins et al. 2001a; Marks et al. 1984; Tao and Suttie 1973). A decrease in fetus viability and an

increase in resorption rate have also been reported at maternally toxic doses (Al-Hiyasat et al. 2000).

Developmental Toxicity. The potential of fluoride, hydrogen fluoride, or fluorine to induce

developmental effects following inhalation or dermal exposure has not been investigated in humans or

animals. Several community-based studies have examined the possible association between fluoridated

water consumption and developmental effects (Berry 1958; Erickson et al. 1976; Needleman et al. 1974;


3. HEALTH EFFECTS

Rapaport 1956; Takahashi 1998); the overall weight of evidence suggests that low levels of fluoride are

not associated with developmental effects. However, higher exposure levels (levels associated with

dental or skeletal fluorosis) have been associated with developmental effects in humans (Gupta et al.

1995; Li et al. 1995a; Lu et al. 2000); additional studies are needed to confirm the results of these studies,

which do not appear to adjust for potential confounders such as poor nutrition and exposure to other

chemicals. Studies in laboratory animals have not found adverse developmental effects in the offspring of

rats or rabbits exposed to sodium fluoride in drinking water (Collins et al. 1995, 2001b; Heindel et al.

1996); however, fetal mortality and abnormalities were observed at maternally toxic doses (Collins et al.

1995; Guna Sherlin and Verma 2001). Studies in wild or domestic animals (cattle and mink) (Aulerich et

al. 1987; Krook and Maylin 1979; Maylin and Krook 1982) have reported developmental effects; the

relevance to humans is not known.

Immunotoxicity. Information of the potential of fluoride, hydrogen fluoride, or fluorine to induce

immune effects is limited to an inhalation study in mice that found a decrease in bactericidal activity

following exposure to sodium fluoride (Yamamoto et al. 2001) and an oral exposure study in rabbits that

found a decrease in antibody titers following an 18-month exposure via gavage to sodium fluoride and

immunization with transferrin (Jain and Susheela 1987). These studies provide some suggestive evidence

that the immune system is a target of fluoride toxicity. A study utilizing an immune battery of tests

would be useful in assessing the immunotoxic potential of fluoride.

Neurotoxicity. Alterations in the light adaptive reflex were found in humans exposed to very low

concentrations of hydrogen fluoride (Sadilova et al. 1965). The investigators of this study also found

alterations in conditioned responses in rats exposed to relatively low concentrations. This finding has not

been supported by other human or animal studies. A decrease in IQ scores has also been observed in

children living in areas with high fluoride levels in the water (Li et al. 1995a; Lu et al. 2000; Zhao et al.

1996); however, the lack of control of potential confounding variables limits the interpretation of these

studies. Epidemiology studies examining this end point and controlling for potentially confounding

variables, such as poor nutrition and exposure to other chemicals, would provide confirming or refuting

data. Alterations in spontaneous behavior were found in rats orally exposed to sodium fluoride (Mullenix

et al. 1995a; Paul et al. 1998); however, another study did not find this effect (Whitford et al. 2003).

Studies utilizing a neurobehavioral test battery would provide valuable information on the neurotoxic

potential of fluoride, hydrogen fluoride, and fluorine.


3. HEALTH EFFECTS

Epidemiological and Human Dosimetry Studies. Available data on the toxicity of inhaled

hydrogen fluoride and fluorine come from case reports involving exposure to hydrogen fluoride (Bennion

and Franzblau 1997; Braun et al. 1984; Chan et al. 1987; Chela et al. 1989; Dieffenbacher and Thompson

1962; Kleinfeld 1965; Machle et al. 1934; Tepperman 1980; Waldbott and Lee 1978), accidental exposure

of a community to hydrogen fluoride (Dayal et al. 1992; Wing et al. 1991), experimental studies of

exposure to hydrogen fluoride (Largent 1960; Lund et al. 1997, 1999, 2002; Machle et al. 1934) and

fluorine (Keplinger and Suissa 1968), and occupational exposure to hydrogen fluoride and fluoride dusts

(Carnow and Conibear 1981; Chan-Yeung et al. 1983a; Czerwinski et al. 1988; Derryberry et al. 1963;

Dinman et al. 1976c; Kaltreider et al. 1972; Moller and Gudjonsson 1932), fluorides (McGarvey and

Ernstene 1947; Roholm 1937; Wolff and Kerr 1938), or fluorine (Lyon 1962). These studies identify the

respiratory tract as the most sensitive target of toxicity, and data are sufficient to derive acute-duration

inhalation MRLs for hydrogen fluoride and fluorine using these human data. However, the long-term

toxicity of fluorides, hydrogen fluoride, and fluorine has not been adequately investigated. The only

consistently reported effect is skeletal fluorosis (Czerwinski et al. 1988; Dinman et al. 1976c; Kaltreider

et al. 1972; Moller and Gudjonsson 1932); poor exposure characterization and difficulty assessing the

skeletal fluorosis limit these studies.

Many studies have examined the possible association between the long-term exposure to fluoridated

water and adverse health effects, particularly effects on bone and teeth. Most of the studies are

community-based studies examining the prevalence of dental fluorosis (DHHS 1991; Eklund et al. 1987;

Heifetz et al. 1988; Jackson et al. 1995; McDonagh et al. 2000; Selwitz et al. 1995; Teotia and Teotia

1994; Warren and Levy 1999) and bone fracture rates (Arnala et al. 1986; Cauley et al. 1995; Cooper et

al. 1990, 1991; Danielson et al. 1992; Goggin et al. 1965; Jacobsen et al. 1990, 1992, 1993; Karagas et al.

1996; Kröger et al 1994; Kurttio et al. 1999; Lehmann et al. 1998; Phipps et al. 2000; Simonen and

Laittinen 1985; Suarez-Almazor et al. 1993) in residents living in communities with fluoridated water or

water with naturally high levels of fluoride. Overall, the data on dental fluorosis provide strong evidence

of increased prevalence and severity of dental fluorosis with increasing fluoride exposure levels.

However, a dose-response relationship is difficult to establish because other sources of fluoride (e.g.,

dentrifices, bottled water) were typically not taken into consideration. The findings on the possible

association between exposure to approximately 1 ppm fluoride in water (typical level of fluoride in

communities with fluoridated water) and increases in hip fracture rates in the elderly are inconsistent,

with studies finding increases, decreases, or no effect. A common limitation of these community-based

studies is the lack of individual exposure data; fluoride levels in drinking water were used to estimate

intake and other sources of fluoride or water consumption levels were not taken into consideration.


3. HEALTH EFFECTS

Experimental studies (Haguenauer et al. 2000; Riggs et al. 1990, 1994) and a community study (Li et al.

2001) involving exposure to higher levels of fluoride have consistently found increases in bone fracture

rates. Human case reports (Hoffman et al. 1980; Rao et al. 1969; Spoerke et al. 1980) and experimental

studies (Spak et al. 1989, 1990) have also identified the gastrointestinal tract as a sensitive target

following bolus administration of fluoride; additional studies are needed to establish the dose-response

relationship for this end point.

In addition to these effects, human studies have examined reproductive (Freni et al. 1994), neurodevelop-

mental (Li et al. 1995a; Lu et al. 2000 Zhao et al. 1996), and developmental (Erickson et al. 1976; Gupta

et al. 1995) end points; inadequate exposure characterization and adjustments for potentially confounding

variables limit the interpretation of these studies. A number of studies have examined the carcinogenicity

of fluoride in communities with fluoridated water (or high levels of naturally occurring fluoride) (Cohn

1992; Erickson 1978; Freni and Gaylor 1992; Gelberg et al. 1995; Hoover et al. 1976, 1991a, 1991b;

Kinlen and Doll 1981; Mahoney et al. 1991; McGuire et al. 1991; Neuberger 1982; Oldham and Newell

1977; Rogot et al. 1978; Takahashi et al. 2001; Taves 1977; Yiamouyiannis and Burk 1977). Most of

these studies have not found a significant association, although some studies have found increased risks

(Takahashi et al. 2001; Yiamouyiannis and Burk 1977), particularly for bone cancer in young men (Cohn

1992; Hoover et al. 1991b). Additional studies that control for potentially confounding variables are

needed to adequately assess whether there is an increased risk of bone cancer in young males living in

communities with fluoridated water.

Biomarkers of Exposure and Effect.

Exposure. Fluoride can be readily detected in biological tissues such as urine (Ekstrand and Ehrnebo

1983; Ekstrand et al. 1983; Zipkin et al. 1956), plasma (Ekstrand et al. 1983), nails (Whitford et al.

1999a), saliva (Oliveby et al. 1990; Whitford et al. 1999b), and tooth enamel (McClure and Likins 1951).

Urinary fluoride is most commonly used to assess fluoride exposure and has been shown to be a good

predictor of total daily fluoride intake (Villa et al. 2000). Urine, plasma, and saliva can be used as

biomarkers for acute exposures; however, measurements should be taken shortly after exposure due to the

rapid elimination of fluoride. Bone (Baud et al. 1978; Boivin et al. 1988) and nail (Schamschula et al.

1985; Whitford et al. 1999a) fluoride levels can be used to quantitate long-term fluoride exposure.

Additional studies are needed to relate levels of fluoride in these biological tissues to exposure dose.

Effect. Fluoride accumulates in bone, with levels increasing with age. This accumulation of fluoride in

bone can lead to adverse effects such as alterations in bone density, which can be detected by radiographs.


3. HEALTH EFFECTS

However, these are nonspecific changes and other elements can sequester in the skeleton and produce

similar changes observed in radiographs. Exposure to elevated levels of fluoride can also result in dental

fluorosis in children (Den Besten and Thariani 1992; DHHS 1991; Eklund et al. 1987; Fejerskov et al.

1990; Heifetz et al. 1988; Ismail and Bandekar 1999; Jackson et al. 1995; McDonagh et al. 2000; Selwitz

et al. 1995; Teotia and Teotia 1994; Warren and Levy 1999). There is some evidence that dental fluorosis

can be used as a reliable biomarker in children younger than 7 years of age (Den Besten 1994). However,

additional studies are needed to quantify the effect of several variables including dose, duration of

exposure, and timing of exposure.

Absorption, Distribution, Metabolism, and Excretion. The absorption, distribution,

metabolism, and excretion of fluoride, hydrogen fluoride, and fluorine have been investigated in humans

and animals. Evidence for absorption of fluorine, hydrogen fluoride, and fluoride after exposure via the

inhalation and dermal routes is provided by the observation of elevated urine and plasma levels in

workers exposed to hydrogen fluoride and fluoride dusts (Collings et al. 1951; Ehrnebo and Ekstrand

1986; Rye 1961; Søyseth et al. 1994), in people accidentally exposured to hydrofluoric acid (Buckingham

1988; Burke et al. 1973), and in subjects experimental exposed to hydrogen fluoride (Lund et al. 1997).

A number of human experimental studies provide strong evidence that fluoride is rapidly and completely

absorbed following oral exposure to soluble fluoride compounds (Carlson et al. 1960a; Ekstrand et al.

1977, 1978; Shulman and Vallejo 1990; Trautner and Einwag 1987) and insoluble fluoride compounds

are poorly absorbed (Afseth et al. 1987; Trautner and Einwag 1987). The results of animal inhalation

(Keplinger and Suissa 1968; Morris and Smith 1982; Stokinger 1949), oral (McClure et al. 1945, 1950;

Zipkin and Likins 1957), and dermal (Keplinger and Suissa 1968; Watanabe et al. 1975) exposure studies

confirm the results of the human studies. Additional studies would be useful in characterizing the

absorption of fluoride, hydrogen fluoride, and fluorine following inhalation and dermal exposure.

The distribution of fluoride following oral exposure has been characterized in human (Ekstrand et al.

1977a, 1978, 1979, 1994a, 1994b; Guy et al. 1976; Rigalli et al. 1996) and animal (Ekstrand and Whitford

1984; Richards et al. 1982; Spak et al. 1986; Whitford and Johnson 2003; Whitford et al. 1979a, 1990)

studies. The limited available information on the distribution of inhaled fluoride (Baud et al. 1978;

Boivin et al. 1988; Chan-Yeung et al. 1983b; Czerwinski et al. 1988; Kaltreider et al. 1972), hydrogen

fluoride (Machle and Scott 1935; Morris and Smith 1983; Stokinger 1949), and fluorine (Stokinger 1949)

suggested that the long-term distribution is similar to fluoride following oral exposure. No information is

available on the distribution of fluoride following dermal exposure; it is likely that the distribution would

be similar to the oral route.


3. HEALTH EFFECTS

Occupational exposure studies provide some information on the excretion of hydrogen fluoride and

fluoride dusts (Collings et al. 1951; Ehrnebo and Ekstrand 1986; Rye 1961) and animal inhalation studies

provide excretion data for hydrogen fluoride (Stokinger 1949) and fluorine (Stokinger 1949). The

excretion of fluoride following ingestion has been extensively investigated in humans (Carlson et al.

1960a; Ekstrand 1977; Ekstrand et al. 1978, 1980a, 1982; Järnberg et al. 1980, 1981, 1983; Jeandel et al.

1992; Oliveby et al. 1989, 1990; Machle and Largent 1943; Schiffl and Binswanger 1982; Spak et al.

1985; Villa et al. 2000; Waterhouse et al. 1980; Whitford et al. 1976). No excretion data are available for

the dermal route of exposure. Because the excretion of fluoride, hydrogen fluoride, and fluorine

following inhalation or dermal exposure would be similar to that following ingestion of fluoride, no

additional excretion studies are needed at this time.

Comparative Toxicokinetics. A study by Whitford et al. (1991) provides evidence for differences

in the toxicokinetic properties of fluoride in dogs, cats, rabbits, rats, and hamsters. Plasma, renal, and

extrarenal clearance in the dog was most similar to humans. Although there are adequate data to assess

the toxicokinetics of fluoride in humans and the current MRLs are based on human data, additional

studies are needed to evaluate the relevance of other animal species to humans to allow for the assessment

of other potentially relevant end points of toxicity, such as reproductive toxicity and carcinogenicity.

Methods for Reducing Toxic Effects. Fluoride, hydrogen fluoride, and fluorine are rapidly

absorbed following inhalation, oral, or dermal exposure. For fluoride, gastric lavage administration of

calcium, magnesium, or aluminum compounds can decrease absorption by forming less soluble

complexes with the fluoride (Ellenhorn and Barceloux 1988; Goldfrank et al. 1990; Haddad and

Winchester 1990; Morgan 1989). For hydrogen fluoride and fluorine, the recommended methods for

decreasing absorption involve removal from the area, irrigation of skin and eyes (Bronstein and Curranc

1988; Dibbell et al. 1970), and application of magnesium, calcium, or quaternary ammonium compounds

to limit further dermal absorption (Browne 1974; Goldfrank et al. 1990; Haddad and Winchester 1990;

Stutz and Janusz 1988). There is some evidence that a diet high in calcium will reduce the fluoride body

burden (Susheela and Bhatnagar 2002; Whitford 1994); additional studies are needed to determine if this

is an effective method for reducing bone fluoride levels.

Children’s Susceptibility. The available human studies that examined the toxicity of fluoride in

children primarily focused on effects on teeth, particularly dental fluorosis. It should be noted that there

is also an extensive database on the beneficial effects of fluoride in preventing dental caries, which will


3. HEALTH EFFECTS

not be discussed in this section dealing with fluoride toxicity. Excess fluoride exposure has been shown

to cause dental fluorosis in young children; the severity is dependent on the amount of fluoride ingested,

the duration of exposure, and the stage of enamel development at the time of exposure (DHHS 1991;

Eklund et al. 1987; Heifetz et al. 1988; Jackson et al. 1995; Selwitz et al. 1995; Teotia and Teotia 1994;

Warren and Levy 1999). Although the severity of fluorosis is known to increase with dose, the exact

dose-response relationship is not known because very few studies measured individual fluoride intake;

additional studies are needed to better assess this relationship. Because more fluoride is deposited in

children’s bones than adults, there is a need for additional studies to assess whether children are more

susceptible to skeletal effects. Human studies have suggested that high doses of fluoride may result in

spina bifida (Gupta et al. 1995) or decreased intelligence (Li et al. 1995a; Lu et al. 2000; Zhao et al. 1996)

but, as noted previously, the Gupta et al. (1995), Li et al. (1995a), Lu et al. (2000), and Zhao et al. (1996)

studies appear to have major study design deficiencies. In general, animal studies have not found

developmental effects following oral exposure; however, these studies did not examine neurodevelop-

mental end points. Additional animal studies are needed to assess neurodevelopmental potential of

fluoride.

A number of studies have examined potential differences in the toxicokinetic properties of fluoride

between adults and children. These studies suggest that absorption (Ekstrand et al. 1978, 1983, 1994a,

1994b) and excretion (Whitford 1999) of ingested fluoride do not appear to be strongly influenced by age.

However, the uptake of fluoride into bone is strongly influenced by age; with a higher percentage of

ingested fluoride being sequestered in bone in very young children compared to adults (Ekstrand and

Whitford 1984; Ekstrand et al. 1979, 1994a, 1994b; Lawrenz et al. 1940; Miller and Phillips 1956; Suttie

and Phillips 1959; Whitford 1990; Zipkin and McClure 1952; Zipkin et al. 1956).

Child health data needs relating to exposure are discussed in Section 6.8.1 Identification of Data Needs:

Exposures of Children.

3.12.3 Ongoing Studies

Ongoing studies pertaining to fluoride, hydrogen fluoride, or fluorine have been identified and are shown

in Table 3-9.


3. HEALTH EFFECTS

Table 3-9. Ongoing Studies on the Health Effects of Fluoride, Hydrogen Fluoride, or Fluorine

Investigator Affiliation Research description Ziegler, EE University of Iowa Toxicokinetic properties in infants Levy, SM University of Iowa Bone development in children Boskey, AL Hospital for Special Therapies Osteoporosis therapy Source: FEDRIP 2002


4. CHEMICAL AND PHYSICAL INFORMATION

4.1 CHEMICAL IDENTITY

The common synonyms and other information for fluorine, hydrogen fluoride, sodium fluoride,

fluorosilicic acid, and sodium fluorosilicate are listed in Table 4-1. The terms “fluorine” and “fluoride”

are often used interchangeably in the literature as generic terms. In this document, we will use “fluoride”

as a general term to refer to all combined forms of fluorine unless the particular compound or form is

known and there is a reason for referring to it. The term “fluorine gas” will sometimes be used to

emphasize the fact that we are referring to the elemental form of fluorine rather than a combined form. In

general, the differentiation between different ionic and molecular or gaseous and particulate forms of

fluorine-containing substances is uncertain and may also be unnecessary.

4.2 PHYSICAL AND CHEMICAL PROPERTIES

Fluorine is the lightest member of Group 17 (VIIA) of the periodic table. This group, the halogens, also

includes chloride, bromine, and iodine. As with the other halogens, fluorine occurs as a diatomic

molecule, F2, in its elemental form. It has only one stable isotope and its valence in all compounds is -1.

Fluorine is the most reactive of all the elements, which may be attributed to its large electronegativity

(estimated standard potential +2.85 V). It reacts at room temperature or elevated temperatures with all

elements other than nitrogen, oxygen, and the lighter noble gases. Fluorine is also notable for its small

size; large numbers of fluorine atoms fit around atoms of another element. This, along with its

electronegativity, allows the formation of many simple and complex fluorides in which the other element

is in its highest oxidation date. Important physical and chemical properties of fluorine, hydrogen fluoride,

sodium fluoride, fluorosilicic acid, and sodium fluorosilicate are presented in Table 4-2. It should be

noted that fluorosilicic acid only exists in aqueous solution, and not in the anhydrous state. Its properties

will depend on its concentration and temperature (Aigueperse et al. 1988).



Table 4-1. Chemical Identity of Fluorine, Hydrogen Fluoride, Sodium Fluoride, Fluosilicic Acid, and Sodium Silicofluoridea

Characteristic Fluorine Hydrogen fluoride Sodium fluoride Synonym(s) Fluorine-19 Hydrofluoric acid; hydrofluoride Monosodium

flurorideb Registered trade name(s) No data No data Alcoa sodium

fluorideb Chemical formula F2 FH FNa Chemical structure F-F H-F Na-F Identification numbers: CAS registry 7782-41-4 7664-39-3 7681-49-4 NIOSH RTECS NIOSH/LM64750000 NIOSH/MW7890000 NIOSH/WB0350000 EPA hazardous waste P056 U134 No data OHM/TADS No data 7216750 7216897 DOT/UN/NA/IMO shipping

UN1045; fluorine UN1790; hydrofluoric acid solution UN1052; anhydrous hydrogen fluoride

UN1690; sodium fluoride

HSDB 541 546 1766 EINECS 231-954-8 231-634-8 231-667-8 NCI No data No data C55221



Table 4-1. Chemical Identity of Fluorine, Hydrogen Fluoride, Sodium Fluoride,

Fluosilicic Acid, and Sodium Silicofluoridea

Characteristic Fluorosilicic acid Sodium fluorosilicate Synonym(s)c Dihydrogen hexafluorosilicate;

hexafluorosilicic acid; fluosilicic acid; hexafluosilicic acid; hydro-fluorosilicic acid; hydrogen hexa-fluorosilicate; hydrosilicofluoric acid; silicofluoric acid; silicon hexa-fluoride dihydride

Disodium hexafluorosilicate; disodium silicofluoride; silicon sodium fluoride; sodium silicofluoride; sodium fluosilicate; sodium hexafluorosilicate; sodium hexafluosilicate; sodium silicon fluoride

Registered trade name(s)c FKS Prodan; Salufer Chemical formula H2SiF6 Na2SiF6 Chemical structure

FSi

F FF F

F

2 Na+

2-

Identification numbers: CAS registry 16961-83-4 16893-85-9 NIOSH RTECS NIOSH/VV8410000 NIOSH/VV8225000 EPA hazardous waste No data No data OHM/TADS No data No data DOT/UN/NA/IMO shipping

UN 2674; sodium silicofluoride UN 1778; fluosilicic acid

HSDB 770 2018 EINECS 241-034-8 240-934-8 NCI No data No data aAll information obtained from HSDB 2003 and ChemID 2001 except where noted. bSodium fluoride is an ingredient in many dental care products and rodenticides. Since it is not the only component in these products, they cannot properly be considered trade names or synonyms. Some of these products are: Floridine, Antibulit, Cavi-trol, Chemifluor, Credo, Duraphat, F1-tabs, Florocid, Flozenges, Fluoral, Fluorident, Fluorigard, Fluorineed, Fluorinse, Fluoritab, Fluorocid, Fluor-o-kote, Fluorol, Fluoros, Flura, Flura drops, Flura-gel, Flura-Loz, Flurcare, Flursol, Fungol B, Gel II, Gelution, Gleem, Iradicav, Karidium, Karigel, Kari-rinse, Lea-Cov, Lemoflur, Luride, Luride Lozi-tabs, Luride-SF, Nafeen, Nafpak, Na Frinse, Nufluor, Ossalin, Ossin, Osteofluor, Pediaflor, Pedident, Pennwhite, Pergantene, Phos-flur, Point Two, Predent, Rafluor, Rescue Squad, Roach salt, So-flo, Stay-flo, Studafluor, Super-dent, T-fluoride, Thera-flur, Thera-Flur-N, Villiaumite, and Zymafluor. Another compound of sodium and fluorine is sodium bifluoride (also called sodium hydrofluoride and sodium hydrofluoride), NaF-HF or NaHF2, which is not discussed here. cIARC 1982 CAS = Chemical Abstracts Services; DOT/UN/NA/IMCO = Department of Transportation/United Nations/North America/International Maritime Organization Code; EINECS = European INventory of Existing Chemical Substances; EPA = Environmental Protection Agency; HSDB = Hazardous Substances Data Bank; NCI = National Cancer Institute; NIOSH = National Institute for Occupational Safety and Health; OHM/TADS = Oil and Hazardous Materials/Technical Assistance Data System; RTECS = Registry of Toxic Effects of Chemical Substances

SiFF

FF

2HF



Table 4-2. Physical and Chemical Properties of Fluorine, Hydrogen Fluoride, Sodium Fluoride, Fluosilicic Acid, and Sodium Silicofluoridea

Property Fluorine Hydrogen fluoride Sodium fluoride Molecular weight 37.997 20.006 42.00 Color Pale yellow Colorless Colorless Physical state Gas Gas Cubic or tetragonal

crystals Molecular formula F2 FH FNa Melting point, °C -219.61 -83.36 993 Boiling point, °C -188.13 19.51b 1,704 Density, g/cm3 1.5127 at -188.13 °C 0.991 at 19.54 °C 2.78 Odor Pungent, irritating odor Strong, irritating odor Odorless Odor threshold: Water Not relevant No data No data Air 0.035 ppm 0.5–3 ppm No data Solubility: Water 1.69 mg/L Miscible 43 g/L at 25 °C Organic solvents No data Benzene (2.54); toluene (1.80);

ethanol (very soluble); m-xylene (1.28); tetraline (0.27)b

Very slightly soluble in ethanol

Partition coefficients: Log Kow Not relevant No data No data Log Koc Not relevant Not relevant No data Vapor pressure 0.4 kPa (3 mmHg) at

55 °Kc; 12.3 kPa (92.3 mmHg) at 70 °K

400 mmHg at 2.5 °C 1 mmHg at 1,077 °C

Henry’s Law constant at 20 °C

No data 0.104 at m-L/molee No data

Autoignition temperature No data No data No data Flashpoint Not flammable Not flammable Not flammable Flammability limits No data No data No data Conversion factors 1 mg/m3 = 1.554 ppmd

1 ppm = 0.64 mg/m3 1 mg/m3 = 1.223 ppmd 1 ppm = 0.82 mg/m3

Not applicable

Explosive limits No data No data No data



Table 4-2. Physical and Chemical Properties of Fluorine, Hydrogen Fluoride,

Sodium Fluoride, Fluosilicic Acid, and Sodium Silicofluoridea

Property Fluorosilicic Acid Sodium Fluorosilicate Molecular weight 144.1 188.1 Color Colorless, fuming liquid white Physical state liquid granular powder Molecular formula H2SiF6 Na2SiF6 Melting point, °C 60-70% solution solidifies at about

19 °C, forming a crystalline dihydratedecomposes at red heatb

Boiling point, °C decomposes decomposes at red heatb Density, g/cm3 1.4634 (60.97% solution) at 25 °C:

17.5/17.5 1.2742 (30% solution)f 2.679f

Odor Sour, pungent odorb No data Odor threshold: Water No data No data Air No data No data Solubility: Water No data 0.76 g/100 g water at 25 °Cg Organic solvents No data No data Partition coefficients: Log Kow No data No data Log Koc No data No data Vapor pressure No data No data Henry’s Law constant at 20 °C

No data No data

Autoignition temperature No data No data Flashpoint No data No data Flammability limits No data No data Conversion factors Not applicable Not applicable Explosive limits No data No data aAll information obtained from HSDB 2003 except where noted bBudavari 2001 cLide 1992 dNAS 1971a eBetterton 1992; apparent Henry’s law constant (ratio of the gas phase concentration to that of the total dissolved solute) fIARC 1982 gAigueperse et al. 1988


5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL

5.1 PRODUCTION

The most important natural starting material for the production of fluorine chemicals, including fluorine,

hydrogen fluoride, and sodium fluoride, is the mineral fluorite (calcium fluoride [CaF2]), commonly

called fluorspar. Other important fluorine minerals are fluorapatite (Ca5(PO4)3F) and cryolite (Na3AlF6).

There has been no fluorspar mine production in the United States since 1996; supplies were imported or

purchased from the National Defense Stockpile. In addition, some byproduct calcium fluoride was

recovered from industrial waste streams. An estimated 8,000–10,000 metric tons of fluorspar are

recovered each year from uranium enrichment, stainless steel pickling, and petroleum alkylation. To

supplement fluorspar supplies, fluorosilicic acid is recovered from phosphoric acid plants processing

phosphate rock. In 2001, the main fluorspar-producing countries, in order of importance, were China,

Mexico, South Africa, Russia, Spain, and France (USGS 2002b). The apparent consumption of fluorspar

(excluding fluorspar equivalents of fluorosilicic acid, hydrofluoric acid, and cryolite) in the United States

was 601,000 metric tons in 2000 and was estimated to be 636,000 metric tons in 2001 (USGS 2002a).

Approximately 60–65% of the fluorspar consumed goes into the production of hydrogen fluoride. Large

amounts are also used as a flux in steel production.

In 2001, 65,200 tons of byproduct fluorosilicic acid (equivalent to 104,000 tons of fluorspar) were

produced by 10 plants owned by 6 companies. Fluorosilicic acid was used primarily in water

fluoridation, either directly or after processing into sodium silicofluoride. Fluorosilicic acid is also used

to make aluminum fluoride for the aluminum industry. About 41,200, 4,700, and 13,200 tons of

byproduct fluorosilicic acid were sold for water fluoridation, AlF3 production for the aluminum industry,

and for other uses, such as sodium silicofluoride production, respectively. Domestic production data for

fluorosilicic acid for 2001 were developed by the U.S. Geological Survey from voluntary surveys of U.S.

operations. Of the 11 fluorosilicic acid operations surveyed, 10 respondents reported production and

1 respondent reported zero production (USGS 2002b).

Anhydrous hydrogen fluoride is manufactured by the action of sulfuric on calcium fluoride. Powdered

acid-grade fluorspar (≥97% CaF2) is distilled with concentrated sulfuric acid; the gaseous hydrogen

fluoride that leaves the reactor is condensed and purified by distillation (Smith 1994). The U.S. capacity

for hydrogen fluoride production was 208,000 metric tons in 2001 (SRI 2002). The demand for



hydrofluoric acid, which was 350,000 metric tons in 2001, is expected to increase to 364,000 metric tons

in 2005 (CMR 2002).

Sodium fluoride is manufactured by the reaction of hydrofluoric acid with sodium carbonate or sodium

hydroxide. The salt is centrifuged and dried (Mueller 1994). Information concerning the amount of

sodium fluoride produced is not available. Fluorosilicic acid is a byproduct of the action of sulfuric acid

on phosphate rock containing fluorides and silica or silicates. Hydrogen fluoride acts on silica to produce

silicon tetrafluoride, which reacts with water to form fluorosilicic acid (Lewis 1997).

Fluorine is produced commercially by electrolyzing anhydrous hydrogen fluoride containing dissolved

potassium fluoride to achieve adequate conductivity (Jaccaud and Faron 1988; Shia 1994). Potassium

fluoride and hydrogen fluoride form potassium bifluoride (KHF2 or KF·HF). Fluoride is oxidized at the

anode, producing fluorine, and the hydrogen ion is reduced at the cathode, producing hydrogen gas.

Information concerning the amount of fluorine produced is not available. The commercial fluorine

production capacity of the United States and Canada is over 5,000 tons/year (Shia 1994).

Current U.S. manufacturers of fluorine, hydrogen fluoride, sodium fluoride, fluorosilicic acid, and sodium

silicofluoride are given in Table 5-1. Tables 5-2 and 5-3 list the number of facilities in each state that

manufacture, process, or use hydrogen fluoride and fluorine, respectively, their intended uses, and the

range of maximum amounts of these substances that are stored on-site. In 2000, there were, respectively,

1,031 and 15 reporting facilities that produced, processed, or used hydrogen fluoride or fluorine in the

United States. The data listed in Tables 5-2 and 5-3 are derived from the Toxics Release Inventory

(TRI01 2003). Only certain types of facilities were required to report. Therefore, this is not an

exhaustive list. Sodium fluoride or other fluoride salts are not listed on TRI.

5.2 IMPORT/EXPORT

In 2000, the United States imported 484,000 metric tons of acid grade (>97%) fluorspar and

39,000 metric tons of metallurgical-grade (<97%) fluorspar (USGS 2002a). This importation was

supplemented by the fluorspar equivalent of 208,000 metric tons from hydrofluoric acid plus cryolite.

The estimated imports of fluorspar for 2001 were 530,000 metric tons of acid-grade, 33,000 of

metallurgical-grade, and 181,000 tons from hydrofluoric acid plus cryolite. Between 1997 and 2000, 63%

of fluorspar imports came from China, 26% from South Africa, and 11% from Mexico. Exports of



Table 5-1. U.S. Manufacturers of Hydrogen Fluoride, Fluorine, Sodium Fluoride, Fluosilicic Acid, and Sodium Silicofluoridea

Company Location Hydrogen Fluorideb,c Dupont La Porte, Texas Honeywelld Geismar, Louisiana Fluorine Honeywelld Metropolis, Illinois Sodium fluoride Mallinckrodt Baker, Inc. Phillipsburg, New Jersey Ozark Fluorine Specialties, Inc. Tulsa, Oklahoma Solvay Fluorides, Inc. Alorton, Illinois Sodium silicofluoride IMC Phosphates Company, IMC-Agrico Phosphates Faustina, Louisiana Kaiser Aluminum and Chemical Corporation Mulberry, Florida Solvay Fluorides, Inc. Alorton, Illinois Fluosilicic acid Cargill Fertilizer, Inc. Riverview, Florida Farmland Hydro, L.P. Bartow, Florida IMC Phosphates Company, IMC-Agrico Phosphates Faustina, Louisiana; Nichols, Florida; South

Pierce, Florida; Uncle Sam, Louisiana PCS Phosphate Co. Inc. Aurora, North Carolina Royster-Clark Inc. Americus, Georgia; Chesapeake, Virginia;

Florence, Alabama; Hartsville, South Carolina Solvay Fluorides, Inc. Alorton, Illinois U.S. Agri-Chemicals Corporation Fort Meade, Florida aDerived from SRI 2002 bPlant capacity was available only for hydrogen fluoride, and was reported as 80,000 and 120,000 metric tons for DuPont and Honeywell, respectively. cMerchant producers. Alcoa produces hydrogen fluoride as a nonisolatable product. dFormally General Electric



Table 5-2. Facilities that Produce, Process, or Use Hydrogen Fluoride

Statea Number of facilities

Minimum amount on site in poundsb

Maximum amount on site in poundsb Activities and usesc

AK 2 0 99,999 1, 5, 13 AL 28 0 9,999,999 1, 5, 6, 11, 12, 13 AR 13 0 9,999,999 1, 5, 6, 7, 8, 11, 12, 13 AZ 23 0 999,999 1, 4, 5, 6, 7, 9, 10, 11, 12, 13 CA 34 0 49,999,999 1, 3, 4, 5, 6, 7, 9, 10, 11, 12, 14 CO 16 0 999,999 1, 5, 7, 9, 11, 12 CT 5 100 99,999 1, 5, 10, 11, 12 DE 3 0 999,999 1, 5, 6 FL 24 0 999,999 1, 2, 3, 5, 6, 7, 9, 10, 11, 12, 13, 14 GA 26 0 999,999 1, 5, 7, 11, 12, 13 IA 15 0 99,999 1, 5, 7, 12 ID 5 100 99,999 1, 5, 10, 11, 12, 13, 14 IL 41 0 9,999,999 1, 2, 3, 4, 5, 6, 7, 9, 10, 11, 12, 13 IN 36 0 999,999 1, 5, 7, 10, 11, 12, 13, 14 KS 14 0 9,999,999 1, 2, 3, 5, 6, 7, 8, 9, 10, 13 KY 29 0 9,999,999 1, 2, 3, 5, 6, 9, 10, 11, 12 LA 19 0 9,999,999 1, 3, 4, 5, 6, 10, 12 MA 11 0 99,999 1, 5, 10, 11, 12 MD 12 0 9,999 1, 5, 11, 13 ME 3 0 9,999 1, 11, 13 MI 25 0 99,999 1, 2, 3, 5, 6, 7, 10, 11, 12, 13 MN 14 0 99,999 1, 5, 6, 10, 11, 12, 13 MO 27 0 99,999 1, 5, 7, 11, 12 MS 9 0 999,999 1, 5, 8, 11, 13 MT 6 0 999,999 1, 5, 10 NC 37 0 999,999 1, 5, 11, 12, 13 ND 8 0 999,999 1, 5, 10, 12, 13 NE 8 0 999,999 1, 3, 5, 9, 13 NH 4 0 99,999 1, 5, 12 NJ 15 0 9,999,999 1, 5, 6, 10, 12 NM 7 0 999,999 1, 5, 10, 11, 13 NV 2 0 999,999 1, 5 NY 29 0 99,999 1, 5, 6, 10, 11, 12 OH 62 0 999,999 1, 5, 6, 7, 8, 9, 10, 11, 12, 13 OK 17 0 999,999 1, 2, 3, 5, 6, 7, 8, 9, 10, 11, 12, 13 OR 20 0 999,999 1, 3, 4, 5, 7, 9, 10, 11, 12 PA 67 0 9,999,999 1, 2, 3, 5, 6, 7, 9, 10, 11, 12, 13 PR 1 100,000 999,999 6 RI 3 100 99,999 6, 10, 11 SC 30 0 999,999 1, 3, 5, 6, 10, 11, 12, 14



Table 5-2. Facilities that Produce, Process, or Use Hydrogen Fluoride




SD 1 0 99 1, 13 TN 19 0 999,999 1, 2, 5, 6, 10, 11, 13 TX 82 0 49,999,999 1, 2, 3, 4, 5, 6, 7, 9, 10, 11, 12, 13, 14UT 14 0 999,999 1, 5, 6, 10, 11, 12, 13 VA 23 0 99,999 1, 5, 10, 11, 12 VT 2 1,000 99,999 11 WA 18 0 999,999 1, 5, 10, 11, 12 WI 24 0 99,999 1, 5, 7, 10, 11, 12, 13 WV 20 0 999,999 1, 5, 10, 11, 12 WY 9 0 99,999 1, 2, 3, 5, 10, 13 Source: TRI01 2003 aPost office state abbreviations used bAmounts on site reported by facilities in each state cActivities/Uses: 1. Produce 2. Import 3. Onsite use/processing 4. Sale/Distribution 5. Byproduct

6. Impurity 7. Reactant 8. Formulation Component 9. Article Component 10. Repackaging

11. Chemical Processing Aid 12. Manufacturing Aid 13. Ancillary/Other Uses 14. Process Impurity



Table 5-3. Facilities that Produce, Process, or Use Fluorine




AL 1 0 99 1, 13 IL 1 10,000 99,999 1, 3, 6, 7 KS 1 0 99 1, 5, 12 LA 1 1,000 9,999 1, 3, 6, 12 OK 1 1,000 9,999 8 PA 2 1,000 999,999 1, 3, 4, 6, 9, 10 PR 1 1,000 9,999 10 TX 1 1,000 9,999 12 Source: TRI01 2003 aPost office state abbreviations used bAmounts on site reported by facilities in each state cActivities/Uses: 1. Produce 2. Import 3. Onsite use/processing 4. Sale/Distribution 5. Byproduct

6. Impurity 7. Reactant 8. Formulation Component 9. Article Component

10. Repackaging

11. Chemical Processing Aid 12. Manufacturing Aid 13. Ancillary/Other Uses 14. Process Impurity



fluorspar for 2000 were 40,000 metric tons and are estimated to be 21,000 in 2001 (USGS 2002a).

Exports consist of imported material that was reexported or material obtained from the National Defense

Stockpile. In 2001, no disposal of metalurgical-grade fluorspar from the stockpile was reported. In 2001,

most of the exports were to Canada and Taiwan (USGS 2002a, 2002b).

U.S. imports for consumption are available for three other fluorides: hydrofluoric acid, cryolite, and

aluminum fluoride. For 2001, these were 112,000, 6,750, and 17,400 metric tons, respectively. For

hydrofluoric acid, 74% of imports came from Mexico and 23% from Canada (USGS 2002b).

5.3 USE

Hydrogen fluoride is the most important compound of fluorine. Anhydrous hydrogen fluoride is used in

the production of most fluorine-containing chemicals. It is used in the production of refrigerants,

herbicides, pharmaceuticals, high-octane gasoline, aluminum, plastics, electrical components, and

fluorescent light bulbs. Aqueous hydrofluoric acid is used in stainless steel pickling, glass etching, metal

coatings, exotic metal extraction, and quartz purification (Hance et al. 1997). The most important use of

hydrogen fluoride is in the production of fluorocarbon chemicals, including hydrofluorocarbons, hydro-

fluorochlorocarbons, and fluoropolymers; 60% of production is used for this purpose. Demand for

hydrogen fluoride for fluorocarbons, broadly used as refrigerants, is increasing as a nonchlorinated

alternative to ozone-depleting chlorofluorocarbons. (Production of fluorocarbons uses more hydrogen

fluoride than production of chlorofluorocarbons.) The next most important uses of hydrogen fluoride are:

chemical derivatives, 18%; aluminum manufacturing, 6%; stainless steel pickling, 5%; petroleum

alkylation catalysts, 4%; and uranium chemicals production, 3%. Miscellaneous other uses include glass

etching, herbicides, and rare metals (CMR 2002). Generally, the aluminum industry consumes 10–40 kg

of fluoride per metric ton of aluminum produced. The AlF3 used in aluminum reduction cells may be

produced directly from acid-grade fluorspar or byproduct fluorosilicic acid, rather than from hydrogen

fluoride. Anhydrous hydrogen fluoride is used as a catalyst in the petroleum alkylation, a process that

increases the octane rating of petroleum. In uranium chemicals production, hydrogen fluoride is used to

convert uranium oxide (yellow cake, U3O8) to UF4 before further fluorination to UF6.

Fluorine gas is used captively for the production of various inorganic fluorides. The preparation of

fluorides of an element in its highest oxidation state makes use of fluorine’s oxidizing and fluorinating

ability. The most important product is uranium hexafluoride (UF6), which is used in the gaseous diffusion

process for producing enriched uranium-235 for the nuclear industry. This use consumes 70–80% of



fluorine production. The second most important product is sulfur hexafluoride (SF6), which is used as a

gaseous dielectric for electrical and electronic equipment and a tracer gas for determining ventilation rates

and air movements in buildings. Other uses of fluorine include: the treatment of polyolefin containers to

reduce their permeability to organic liquids; the treatment of a polymer surface for the application of an

adhesive or coating; and the production of some fluorinated organic compounds (Guo et al. 2001; Shia

1994).

The chemicals most commonly used by American waterworks for water fluoridation are fluorosilicic acid,

sodium silicofluoride, and sodium fluoride (Urbansky 2002). Generally, 1.5–2.2 mg of sodium fluoride is

added per liter of water (0.7–1.0 mg/L as fluoride) (Mueller 1994). Data from the Centers for Disease

Control’s (CDC) 1992 Fluoridation Census indicate that 25% of utilities reported using sodium fluoride;

however, this corresponds to 9.2% of the U.S. population drinking fluoride-supplemented tap water

(Urbansky 2002). Sodium fluoride may also be applied topically to teeth as a 2% solution to prevent

tooth decay. It is also used as a flux for deoxidizing rimmed steel, as a component of laundry sours

(removal of iron stains), and in the re-smelting of aluminum, manufacture of vitreous enamels, pickling of

stainless steel, wood preservative compounds, casein glues, manufacture of coated papers, and heat-

treating salts (Mueller 1994). Fluorosilicic acid, as a 1–2% solution, is used widely for sterilizing

equipment in brewing and bottling. Other concentrations of fluorosilicic acid solutions are used in

electrolytic refining of lead, in electroplating, for hardening cement, for crumbling lime or brick work, for

removal of lime from hides during the tanning process, for removals of molds, and as a preservative for

timber. Sodium fluorosilicate is also used in enamels for china and porcelain, in the manufacturing of

opal glass, as an insecticide, as a rodentcide, and for mothproofing of wool. It is also an intermediate in

the production of synthetic cryolite (Budavari 2001).

5.4 DISPOSAL

According to the TRI, in 2001, an estimated 2.5 million pounds of hydrogen fluoride were transferred off-

site, including to publicly owned-treatment works (POTWs), by 991 reporting facilities presumably for

disposal (TRI01 2003). In 2001, 240,196 pounds of fluorine were transferred off-site by 9 reporting

facilities. According to the TRI, in 2001, 77% of hydrogen fluoride that was recycled or treated was

performed on-site (TRI01 2003). Of the hydrogen fluoride recycled in 2001, 23.8 million pounds were

recycled on-site and 251,203 pounds were recycled off-site. Of the hydrogen fluoride that was treated,

234 million pounds were treated on-site and 2 million pounds were treated off-site (TRI01 2003). No

information was found concerning how hydrogen fluoride is generally treated for disposal.



Fluorine gas can be disposed of by conversion to perfluorocarbons or fluoride salts. Because of the long

atmospheric lifetimes of perfluorocarbons, conversion to fluoride salts is preferable. Industrially, the

waste stream is scrubbed with a caustic solution, KOH or NaOH, and for dilute streams, allowed to react

with limestone (Shia 1994). Adequate contact and residence time is essential in the scrubber to ensure

complete neutralization of the intermediate oxygen difluoride to prevent it from leaving the scrub tower.

According to the TRI, in 2001, 18,973 pounds of fluorine were treated on-site and 240,196 pounds were

treated off-site (TRI01 2003).

No information was found regarding the disposal of sodium fluoride. It would appear from its use that

most of it is disposed of in municipal landfills or POTWs.


6. POTENTIAL FOR HUMAN EXPOSURE

6.1 OVERVIEW

Fluorides, hydrogen fluoride, and fluorine have been identified in at least 188 of the 1,636 hazardous

waste sites that have been proposed for inclusion on the EPA National Priorities List (NPL) (HazDat

2003). However, the number of sites evaluated for fluorides, hydrogen fluoride, and fluorine is not

known. The frequency of these sites can be seen in Figure 6-1. Of these sites, all are located within the

United States.

Fluorides are naturally-occurring components of rocks and soil and are also found in air, water, plants,

and animals. They enter the atmosphere through volcanic emissions and the resuspension of soil by wind.

Volcanoes also emit hydrogen fluoride and some fluorine gas. Fluorine is a highly reactive element and

readily hydrolyzes to form hydrogen fluoride and oxygen. Hydrogen fluoride reacts with many materials

both in the vapor phase and in aerosols. The resultant fluorides are typically nonvolatile, stable

compounds. Marine aerosols also release small amounts of gaseous hydrogen fluoride and fluoride salts

into the air (Friend 1989). Anthropogenic fluoride emissions include the combustion of fluorine-

containing materials, which releases hydrogen fluoride, as well as particulate fluorides, into the air. Coal

contains small amounts of fluorine, and coal-fired power plants constitute the largest source of

anthropogenic hydrogen fluoride emissions. According to the Toxic Chemical Release Inventory (TRI),

in 2001, the largest contributing industrial sectors were electrical utilities (TRI01 2003). Total air

emissions of hydrogen fluoride by electrical utilities in 1998, 1999, 2000, and 2001 were reported as 64.1,

58.3, 58.3, and 55.8 million tons, respectively. Major sources of industrial fluoride emissions are

aluminum production plants and phosphate fertilizer plants; both emit hydrogen fluoride and particulate

fluorides (EPA 1998b). Other industries releasing hydrogen fluoride are: chemical production; steel;

magnesium; and brick and structural clay products. Hydrogen fluoride would also be released by

municipal incinerators as a consequence of the presence of fluoride-containing material in the waste

stream. Hydrogen fluoride is one of the 189 chemicals listed as a hazardous air pollutant (HAP) in

Title III, Section 112 of the Clean Air Act Amendments of 1990. Maximum achievable control

technology (MACT) emission standards are being developed by the EPA for each HAP. The goal of



Figure 6-1. Frequency of NPL Sites with Fluoride, Hydrogen Fluoride, and Fluorine Contamination

1-2

3-4

5-6

7-8

9-11

14-19

Frequency o fNPL S i tes

Derived from HazDat 2003



HAP emissions control is to reduce human health risks (Kelly et al. 1994). In addition to industrial

effluent and natural releases (e.g., weathering of rocks and runoff from soil), fluorides are released into

surface water in municipal waste water as a result of water fluoridation.

In the atmosphere, gaseous hydrogen fluoride will be absorbed by atmospheric water (rain, clouds, fog,

snow) forming an aerosol or fog of aqueous hydrofluoric acid. It will be removed from the atmosphere

primarily by wet deposition. Particulate fluorides are similarly removed from the atmosphere and

deposited on land or surface water by wet and dry deposition. Atmospheric precipitation weathers crustal

rocks and soil, but dissolves out very little fluoride; most of the fluoride mobilized during weathering is

bound to solids such as clays. Upon reaching bodies of water, fluorides gravitate to the sediment

(Carpenter 1969). Fluorides have been shown to accumulate in some marine aquatic organisms (Hemens

and Warwick 1972). When deposited on land, fluoride is strongly retained by soil, forming complexes

with soil components. Fluorides in soils are transported to surface waters through leaching or runoff of

particulate-bound fluorides. Leaching removes only a small amount of fluorides from soils. Fluorides

may be taken up from soil and accumulate in plants. The amount of fluorides accumulated depends on

the type of plant and soil and the concentration and form of fluoride in the soil. Fluorides may also be

deposited on above-ground surfaces of the plant. Tea plants are particularly known to accumulate

fluoride, 97% of which is accumulated in the leaves (Fung et al. 1999). Fluoride accumulates primarily in

the skeletal tissues of terrestrial animals that consume fluoride-containing foliage. However, milk and

edible tissue from animals fed high levels of fluorides do not appear to contain elevated fluoride

concentrations (NAS 1971a).

In natural water, fluoride forms strong complexes with aluminum in water, and fluorine chemistry in

water is largely regulated by aluminum concentration and pH (Skjelkvale 1994). Below pH 5, fluoride is

almost entirely complexed with aluminum and consequently, the concentration of free F- is low. As the

pH increases, Al-OH complexes dominate over Al-F complexes and the free F- levels increase. Fluoride

forms stable complexes with calcium and magnesium, which are present in sea water. Calcium carbonate

precipitation dominates the removal of dissolved fluoride from sea water (Carpenter 1969). Fluorine is

incorporated into the calcium salt structure and removed from solution when the latter precipitates.

Fluoride occurs in soil in a variety of minerals and complexes with aluminum, iron, and calcium.

Fluorides occur predominantly as aluminum fluorosilicate complexes in acidic soils and calcium fluoride

in alkaline soils. The availability of these soluble complexes increases with decreasing pH (Fung et al.

1999; Shacklette et al. 1974). This explains why acidic soils have both higher water-soluble fluoride and



higher extractable aluminum levels. The retention of fluoride in alkaline soils depends largely upon the

aluminum content of the soil.

The general population is exposed to fluoride through consumption of drinking water, foods, and

dentifrices. Fluorides used in dentifrices are sodium fluoride, sodium monofluorophosphate, and

stannous fluoride (Pader 1993). Populations living in areas with naturally high fluoride levels in water

and soil may be exposed to high levels of fluoride in water. This is especially true if drinking water is

derived from wells.

Fluoride intake in infants depends on whether or not the child is nursed. Fluoride intake by an infant who

is exclusively breast fed is generally <2 µg/kg-day(Fomon and Ekstrand 1999). Levy et al. (2001) found

that for most children, water fluoride intake was the predominant source of fluoride, especially through

age 12 months. This was due in large part to children receiving fluoridated water mixed with infant

formula concentrate (Levy et al. 1995b, 2001). Fluoride exposure was calculated to be 102, 105, and

167 µg/kg-day for infants consuming concentrated liquid milk-based formula, concentrated liquid isolated

soy protein-based formula, and powdered milk-based formula, respectively, which were diluted with

water that is 1 ppm in fluoride. Infants may be exposed to higher fluoride concentrations now than in the

past. In the 1960s, nearly 80% of infants were fed cow's milk by 6 months of age. In 1991, 80% of

6-month-old infants were fed formula (Fomon and Ekstrand 1999).

Some plants, most notably tea, accumulate fluorides, and people who drink large quantities of tea may be

exposed to high levels of fluoride in their diets. Populations living near industrial sources of fluoride may

be exposed to higher levels of fluorides in the air they breathe. Vegetables and fruits grown near such

sources may contain higher levels of fluorides particularly from fluoride-containing dust settling on the

plant. Populations exposed to relatively high concentrations of fluoride include workers in fluoride-

processing industries and individuals residing near such industries. Similarly, populations living near

hazardous waste sites may also be exposed to high levels of fluoride by analogous routes.

6.2 RELEASES TO THE ENVIRONMENT

According to the TRI, in 2001, total releases of hydrogen fluoride to the environment (including air,

water, soil, and underground injection) from 991 reporting facilities that produced, processed, or used

hydrogen fluoride were 72.1 million pounds (TRI01 2003). Table 6-1 lists amounts released from these



Table 6-1. Releases to the Environment from Facilities that Produce, Process, or Use Hydrogen Fluoride

Reported amounts released in pounds per yeara

Stateb Number of facilities Airc Water

Under-ground injection Land

Total on-site released

Total off-site releasee

Total on and off-site release

AK 2 73,027 No data 0 0 73,027 0 73,027 AL 28 3,304,387 0 0 12,000 3,316,387 18,596 3,334,983 AR 13 942,385 0 0 0 942,385 8 942,393 AZ 23 694,190 No data 0 3,405 697,595 1,062 698,657 CA 35 9,211 5 0 0 9,216 2,886 12,102 CO 17 795,831 No data 0 0 795,831 0 795,831 CT 5 107,388 0 0 0 107,388 10,732 118,120 DE 3 201,815 No data 0 0 201,815 0 201,815 FL 24 2,358,937 5 0 7,965 2,366,907 0 2,366,907 GA 28 3,286,300 0 0 0 3,286,300 2,944 3,289,244 IA 16 1,300,253 No data 0 0 1,300,253 0 1,300,253 ID 5 208,065 0 0 0 208,065 255 208,320 IL 41 2,255,380 1 0 5 2,255,386 1,510 2,256,896 IN 36 3,888,416 250 0 0 3,888,666 0 3,888,666 KS 16 775,771 0 0 0 775,771 930 776,701 KY 29 2,090,877 0 0 0 2,090,877 1,301 2,092,178 LA 19 613,860 250 0 11 614,121 0 614,121 MA 11 197,829 No data 0 0 197,829 237 198,066 MD 14 1,376,506 No data 0 0 1,376,506 15 1,376,521 ME 3 1,286 0 0 0 1,286 0 1,286 MI 27 2,139,731 0 0 0 2,139,731 39,376 2,179,107 MN 15 217,532 0 0 0 217,532 0 217,532 MO 29 2,464,416 0 0 158,300 2,622,716 0 2,622,716 MS 9 461,108 197 0 2,287 463,592 0 463,592 MT 7 167,298 0 0 0 167,298 0 167,298 NC 38 5,160,908 5 0 0 5,160,913 0 5,160,913 ND 8 490,133 0 0 0 490,133 260 490,393 NE 8 1,279,219 No data 0 0 1,279,219 0 1,279,219 NH 4 208,550 No data 0 0 208,550 391 208,941 NJ 15 249,406 0 0 0 249,406 2 249,408 NM 7 209,568 No data 0 0 209,568 420 209,988 NV 2 439,874 No data 0 0 439,874 0 439,874 NY 31 1,137,383 0 0 0 1,137,383 750 1,138,133 OH 64 6,147,565 1,601 4,400,000 0 10,549,166 34,884 10,584,050 OK 18 892,504 100 0 0 892,604 250 892,854 OR 21 67,943 0 0 18,398 86,341 0 86,341 PA 70 5,056,848 35 0 5 5,056,888 17,156 5,074,044



Table 6-1. Releases to the Environment from Facilities that Produce, Process, or Use Hydrogen Fluoride







PR 1 500 No data 0 0 500 0 500 RI 3 3,683 No data 0 0 3,683 0 3,683 SC 30 2,153,397 0 0 0 2,153,397 0 2,153,397 SD 2 89,000 No data 0 0 89,000 0 89,000 TN 19 2,069,004 0 0 0 2,069,004 0 2,069,004 TX 83 3,828,730 10 0 21 3,828,761 1,100 3,829,861 UT 14 467,778 0 0 24,930 492,708 0 492,708 VA 23 1,745,413 0 0 0 1,745,413 0 1,745,413 VT 2 4,141 0 0 0 4,141 0 4,141 WA 19 323,942 0 0 0 323,942 1,405 325,347 WI 24 1,231,556 0 0 0 1,231,556 0 1,231,556 WV 21 3,722,619 19,090 0 0 3,741,709 0 3,741,709 WY 9 337,011 No data 0 52,248 389,259 0 389,259 Total 991 67,248,474 21,549 4,400,000 279,575 71,949,598 136,470 72,086,068 Source: TRI01 2003 aData in TRI are maximum amounts released by each facility. bPost office state abbreviations are used. cThe sum of fugitive and stack releases are included in releases to air by a given facility. dThe sum of all releases of the chemical to air, land, water, and underground injection wells. eTotal amount of chemical transferred off-site, including to publicly owned treatment works (POTW).



facilities grouped by state. In addition, 136,470 pounds of hydrogen fluoride were transferred off-site by

these facilities (TRI01 2003). Starting in 1998, metal mining, coal mining, electric utilities and Resource

Conservation and Recovery Act (RCRA)/solvent recovery industries were required to report to the TRI,

industries with potentially large releases of hydrogen fluoride. The industrial sector producing,

processing, or using hydrogen fluoride that contributed the greatest environmental releases was electrical

utilities, which contributed 78% of the total environmental releases.

According to the TRI, in 2001, total releases of fluorine to the environment (including air, water, soil, and

underground injection) from 9 reporting facilities that produced, processed, or used fluorine were

165,938 pounds (TRI01 2003). Table 6-2 lists amounts of fluorine released from these facilities grouped

by state. The two largest contributing industrial sectors were electrical utilities and primary metals, which

respectively contributed 65 and 19% of the total environmental releases. Neither sodium fluoride nor any

other fluorides are listed on TRI. The TRI data should be used with caution because only certain types of

facilities are required to report. This is not an exhaustive list.

Hydrogen fluoride is one of the 189 chemicals listed as a HAP in Title III, Section 112 of the Clean Air

Act Amendments of 1990. MACT emission standards are being developed by the EPA for each HAP.

The goal of HAP emissions control is to reduce human health risks (Kelly et al. 1994). The Final Air

Toxic MACT Rule for fluoride emissions from primary aluminum reduction plants, published in 1997,

was projected to reduce fluoride emissions by 3,700 tons per year. The Final Air Toxic MACT Rule for

fluoride emissions from phosphoric acid manufacturing and phosphate fertilizer production, published in

1999, was projected to reduce fluoride emissions by 260 tons per year (EPA 2000).

Fluorides have been identified in a variety of environmental media (air, surface water, leachate,

groundwater, soil, and sediment) collected at 188 of 1,636 current or former NPL hazardous waste sites

(HazDat 2003).

6.2.1 Air

The major natural source of hydrogen fluoride emissions to the atmosphere is volcanoes. These

emissions are estimated to range from 0.6 to 6 million metric tons per year. On average, <10% of these

emissions are a result of large eruptions that are efficiently injected into the stratosphere (Symonds et al.

1988). Passive degassing of volcanoes is a major source of tropospheric hydrogen fluoride. In addition



Table 6-2. Releases to the Environment from Facilities that Produce, Process, or Use Fluorine







AL 1 0 31,328 0 0 31,328 0 31,328 IL 1 4,979 No data 0 0 4,979 0 4,979 KS 1 429 No data 0 107,282 107,711 0 107,711 LA 1 2,280 No data 0 0 2,280 0 2,280 OK 1 263 No data 0 0 263 0 263 PA 2 1,001 No data 0 0 1,001 0 1,001 PR 1 0 18,376 0 0 18,376 0 18,376 TX 1 0 No data 0 0 0 0 0 Total 9 8,952 49,704 0 107,282 165,938 0 165,938 Source: TRI01 2003 aData in TRI are maximum amounts released by each facility. bPost office state abbreviations are used. cThe sum of fugitive and stack releases are included in releases to air by a given facility. dThe sum of all releases of the chemical to air, land, water, and underground injection wells. eTotal amount of chemical transferred off-site, including to publicly owned treatment works (POTW).



to hydrogen fluoride, volcanic gases also contain other fluorine compounds, namely SiF4, H2SiF6, and F2.

Soil naturally contains fluoride, and resuspension of soil by wind also contributes to the atmospheric

burden of fluorides in the form of soil minerals (NAS 1971a). Another source is sea salt aerosol, which

releases small amounts of gaseous hydrogen fluoride and fluoride salts into the air. The marine aerosol is

potentially a major source of tropospheric hydrogen fluoride (Friend 1989). However, these releases

would be confined to the air over the oceans.

The largest anthropogenic source of hydrogen fluoride emissions to air in the United States is electrical

utilities. Coal naturally contains fluorides as impurities and this will be released primarily in the form of

hydrogen fluoride during combustion. Some of the fluoride in the coal may be absorbed onto fly ash or

bottom ash. A typical 650 megawatt coal-burning power plant running at 67% capacity (the average for

U.S. coal plants) would release 180,000 pounds of hydrogen fluoride per year (Rubin 1999). EPA

(1998a) reports an emission factor of 0.15 pounds/ton (0.075 kg/Mg) for coal combustion under a variety

of firing conditions. The Canadian Environmental Protection Act (CEPA) (1996) reports hydrogen

fluoride emission factors for bituminous and lignite coals of 0.12 and 0.01 kg/Mg coal, respectively.

Hydrogen fluoride is water soluble and emissions are readily controlled by acid gas scrubbers. Other

gaseous fluorides that may occur in the flue gas are SiF4 and H2SiF6. Emissions of fluorides from

aluminum reduction processes are primarily gaseous hydrogen fluoride and particulate fluorides,

principally aluminum fluoride and calcium fluoride. Emission factors for aluminum production are

0.03 pounds of total fluorides and 0.02 pounds of hydrogen fluoride per ton of aluminum produced (EPA

1998b). Fluorine-containing compounds are contained in the raw materials used to produce brick and

structural clay products and, therefore, hydrogen fluoride and other fluoride compounds are emitted from

kilns used to manufacture these products. In addition, coal may be used to fire the kilns and contribute to

the fluoride emissions. In the production of phosphate fertilizers, gaseous fluorides (hydrogen fluoride

and silicon tetrafluoride), as well as particulate fluorides, may be released. EPA’s Office of Air Quality

Planning and Standards has developed emission factors for hydrogen fluoride for these and other

hydrogen fluoride emitting industries. Hydrogen fluoride would be released by municipal incinerators as

a consequence of the presence of fluoride-containing material in the waste stream. The amount of

hydrogen fluoride released in flue gas would depend on the fluorine content of the waste stream and the

efficiency of pollution control devises used in the stack.

Anthropogenic hydrogen fluoride emissions to the atmosphere in Canada were estimated to be

5,400 metric tons per year, of which 75% was contributed by primary aluminum producers. Other

industries releasing hydrogen fluoride in Canada and their relative contributions were: coal-burning



utilities, 10%; chemical production, 6%; steel production, 4%; phosphate fertilizer production, 2%; and

magnesium production, 1% (CEPA 1996).

On a global scale, emissions of fluorides from coal combustion and other anthropogenic sources are

minor and of local concern compared with natural emissions, estimated as 2.5x1010 kg/year (Carpenter

1969). Anthropogenic releases of total fluorides into the atmosphere were 155,300 tons/year from the

major fluoride-processing industries measured between 1964 and 1970 (EPA 1980a). The major

contributors were steel, brick, tile, and aluminum manufacturing, combustion of coal, and production of

phosphorus and phosphate fertilizer (EPA 1980a; NAS 1971a). In 1977 and 1978, monthly atmospheric

emission factors for fluorides from the Kitimat aluminum plant in British Columbia, Canada ranged from

4.0 to 6.8 kg fluoride per ton of aluminum produced; production capacity was 300,000 tons of aluminum

per year (Sauriol and Gauthier 1984). Subsequently, regulations were established that set emissions

standards for aluminum manufacturing (EPA 1980b) and phosphate fertilizer plants (EPA 1975).

Fluorides can also enter the atmosphere in dusts and aerosols from the manufacture and use of pesticides

such as sodium fluoride, sodium fluorosilicate, barium fluorosilicate, and cryolite (NAS 1971a). In the

United States, fluoride emissions from coal-burning electric utilities are estimated to be around

37x106 kg/year (Bauer and Andren 1985).

There is evidence that emissions of fluorides have been declining. Fluoride in precipitation has declined

since 1967 (Ares 1990). A recent study from a forested area near Cologne, Germany registered a sharp

decline in the fluoride content of Roe deer antlers from peak levels in the 1950s and 1960s (Kierdorf and

Kierdorf 2000). In the 1990s, levels were almost an order of magnitude lower than the peak levels, which

are attributed to reduced emissions from stationary sources. Fluoride is a skeletally-deposited

contaminant, and it can be assumed that fluoride is mobilized during the annual antler growth period and

transported to the mineralizing antlers. Therefore, the fluorine content of antlers is a good indicator of

fluoride release.

According to the TRI, in 2001, releases of 67.2 million pounds of hydrogen fluoride to air from

991 reporting facilities accounted for 93% of the total environmental releases of hydrogen fluoride

(TRI01 2003). Table 6-1 lists amounts of hydrogen fluoride released to air from these facilities grouped

by state. The industrial sector contributing the largest release of hydrogen fluoride to air was electrical

utilities, which contributed 83% of releases to air.



According to the TRI, in 2001, releases of 8,952 pounds of fluorine to air from 9 reporting facilities

accounted for 5% of the total environmental releases of fluorine (TRI01 2003). Table 6-2 lists amounts of

fluorine released to air from these facilities grouped by state. The TRI data should be used with caution,

however, since only certain types of facilities are required to report. This is not an exhaustive list.

According to the TRI, total air emissions for hydrogen fluoride ranged from 15.9 million pounds in 1998

to 8.9 million pounds in 1994, during the period from 1988 to 2001. Total air emissions of fluorine have

decreased from 18,319 pounds in 1995 to 8,523 pounds in 2001 (TRI01 2003). This trend information

only includes emission data from the original industry subtotal, those industries with Standard Industrial

Classification (SIC) Codes 20–39. Starting in 1998, metal mining, coal mining, electric utilities,

Resource Conservation and Recovery Act (RCRA)/solvent recovery industries, and chemical wholesalers

were also required to report. Of these industries, electrical utilities contribute significantly to emissions

of hydrogen fluoride to air. Total air emissions of hydrogen fluoride by electrical utilities in 1998, 1999,

2000, and 2001 were reported as 64.1, 58.3, 58.3, and 55.8 million tons, respectively.

Fluorides were detected in the air at 8 of the 188 current or former NPL hazardous waste sites, where they

were detected in some environmental media (HazDat 2003).

6.2.2 Water

Natural sources of fluoride released to waters are primarily a result of runoff from the weathering of

fluoride-containing rocks and soils and the leaching of fluorides from the soil into groundwater. In the

western regions of the United States, rocks and soils have greater than average concentrations of fluoride;

as a result, greater amounts of fluorides leach into the groundwater. Leaching from alkaline igneous

rocks, dolomite, phosphorite, and volcanic glasses may result in water with high-fluoride levels (EPA

1980a; NAS 1971a).

Anthropogenic sources contributing to fluoride levels in water include atmospheric deposition of

emissions from coal-fired power plants and other industrial sources that are deposited directly into water

or that are first deposited on land and enter waterways in runoff. Most of this deposition is in the form of

precipitation. Waste water may enter surface water directly or as effluent of water treatment plants.

Since much of the nation’s water supplies are fluoridated to a level of 0.7–1.2 ppm to decrease the

incidence of tooth decay (DHHS 1991), this will contribute to fluoride in effluents from treatment plants.



According to the TRI, in 2001, releases of 21,549 pounds of hydrogen fluoride to water from

991 reporting facilities accounted for 0.030% of the total environmental releases of these substances

(TRI01 2003). Table 6-1 lists amounts of hydrogen fluoride released to water from these facilities

grouped by state. According to the TRI, in 2001, releases of 49,704 pounds of fluorine to water from

9 reporting facilities accounted for 30% of the total environmental releases of this substance (TRI01

2003). Table 6-2 lists amounts of fluorine released to water from these facilities grouped by state. As of

1998, TRI no longer separately collects data on substances released indirectly to POTWs, part of which

may ultimately be released to surface waters. The TRI data should be used with caution, however, since

only certain types of facilities are required to report. This is not an exhaustive list.

Fluorides were detected in groundwater and surface water at 135 and 53 sites, respectively, of the

188 NPL hazardous waste sites where they were detected in some environmental media (HazDat 2003).

6.2.3 Soil

Fluoride comprises about 0.09% of the earth’s crust, ranking 13th in order of abundance (Lindahl and

Mahmood 1994). Fluoride-containing minerals include biotite, muscovite, hornblende, apatite, and

fluorspar (NAS 1971a). Fluorides are released to soils from the weathering of crustal rock and minerals,

deposition of fluorides released to air from natural and anthropogenic sources, and plant and animal

residues. Man-made sources applied directly to soil include phosphate fertilizers, mine tailings, and

landfilled industrial and municipal waste (EPA 1980a; NAS 1971a). In a study by Oelschläger (1971),

fertilization with superphosphates added 8–20 kg fluoride/hectare to the soil. Soil contamination by

atmospheric fluorides near an industrial source reflected the gradient of fluoride deposition. In one study,

the total fluoride concentration was found to decrease over a distance of 8.8 km from 2,700 to 616 µg/g

fluoride and the water extractable fraction decreased from 292 to 10 µg fluoride/g (Polomski et al. 1982).

According to the TRI, in 2001, releases of 279,575 pounds and 4.4 million pounds of hydrogen fluoride

respectively to land and underground injection from 991 reporting facilities accounted for respectively

0.38 and 6.1% of total environmental releases of these substances (TRI01 2003). Table 6-1 lists amounts

of hydrogen fluoride released to land and underground injection from these facilities grouped by state.

According to the TRI, in 2001, 107,282 pounds of fluorine were released to land from 9 reporting

facilities accounted for 65% of the total environmental releases of this substance (TRI01 2003).

However, it is not clear how a gaseous substance can be released to land, and this figure is likely an error.

Table 6-2 lists amounts of fluorine released to air from these facilities grouped by state. The TRI data



should be used with caution, however, since only certain types of facilities are required to report. This is

not an exhaustive list.

Fluorides were detected in soil and sediment collected at 32 and 22 sites, respectively, of the 178 NPL

hazardous waste sites, where they were detected in some environmental media (HazDat 2003).

6.3 ENVIRONMENTAL FATE

6.3.1 Transport and Partitioning

In the atmosphere, gaseous hydrogen fluoride will be absorbed by atmospheric water (rain, clouds, fog,

snow) forming an aerosol or fog of aqueous hydrofluoric acid. It will be removed from the atmosphere

primarily by wet deposition (including rainout or in-cloud scavenging and washout or below-cloud

scavenging). Particulate fluorides are similarly removed from the atmosphere and deposited on land or

surface water by wet and dry deposition. Atmospheric precipitation weathers crustal rocks and soil, but

dissolves out very little fluoride; most of the fluoride mobilized during weathering is bound to solids such

as clays. Upon reaching bodies of water, fluorides gravitate to the sediment (Carpenter 1969).

Most of the fluorides in the oceans are received from rivers; a lesser amount comes from atmospheric

deposition. Losses occur in aerosols to the atmosphere and incorporation into the tissue of aquatic

organisms. Fluorides have been shown to accumulate in some marine aquatic organisms. In a study by

Hemens and Warwick (1972), toxic effects due to fluorosis were observed in species of mussel, mullet,

crab, and shrimp in an estuary where waste from an aluminum plant was released.

Fluoride is strongly retained by soil, forming complexes with soil components. Fluorides in soils are

transported to surface waters through leaching or runoff of particulate-bound fluorides. Leaching

removes only a small amount of fluorides from soils. Oelschläger (1971) reported that about 0.5–6.0% of

the yearly increment of fluoride added to forest and agricultural areas through the application of

phosphate fertilizer was lost in the leaching process. In this study, superphosphates added 8–20 kg

fluoride/hectare to the soil, while seepage water contained between 52 and 208 µg fluoride/L, depending

upon soil levels of clay, lime, and fluoride.

Fluorides may be taken up from soil and accumulate in plants. They may also be deposited on above-

ground surfaces of the plant. Tea plants are known to accumulate fluoride, 97% of which is accumulated



in the leaves and 3% in the other parts of the plant. Fung et al. (1999) observed that the fluoride contents

of tea leaves were 1,000 times the soluble fluoride content of the soil and 2–7 times the total fluoride

content. The amount of fluoride taken up by plants is more a function of the soil type, its pH, and calcium

and phosphorous content than of the total fluoride content of the soil (Brewer 1966). The addition of

soluble fluoride to unlimed soil will result in increased fluoride uptake. In studies of plants grown on

heavily polluted soil near aluminum smelters, uptake was via the roots and the stomata. Fluoride

concentrations were much lower in the leaves than in the roots of plants, and most of the fluoride

adsorbed by the roots was desorbed in water. Others have found that fluoride uptake is increased by the

presence of aluminum, probably due to the uptake of aluminum–fluoride complexes. The fluoride uptake

in ryegrass and clover from contaminated soil was strongly correlated with water and calcium chloride-

extractable fluoride in the soil (Arnesen 1997). In this study, the fluoride content of pasture ryegrass

exceeded the recommended fluoride limit only in grass grown in the most polluted soil, while that in

clover exceeded this limit even in moderately polluted soil.

Fluoride accumulates primarily in the skeletal tissues of terrestrial animals that consume fluoride-

containing foliage. However, milk and edible tissue from animals fed high levels of fluorides do not

appear to contain elevated fluoride concentrations (NAS 1971a). Fluoride is taken up by hens and

concentrated in the shell of their eggs. Hens living in the vicinity of two major coal-fired power plants

had fluoride levels in egg shells of 1.75 mg/kg compared with reference means of 0.07 mg/kg, indicating

significant uptake of anthropogenic fluoride (de Moraes Flores and Martins 1997).

6.3.2 Transformation and Degradation

6.3.2.1 Air

Hydrogen fluoride is the most abundant gaseous fluoride released into the atmosphere. It reacts with

many materials both in vapor and in aerosols. For example, hydrogen fluoride reacts with silica, forming

silicon tetrafluoride. However, no information was found on the reactions of hydrogen fluoride with

common atmospheric species or estimates of its overall atmospheric half-life. The predominant mode of

degradation of inorganic fluorides in the air is hydrolysis. Silicon tetrafluoride, a major industrial

pollutant, reacts with water vapor in air to form hydrated silica and fluorosilicic acid. Sulfur

hexafluoride, a gaseous dielectric for electrical and electronic equipment, reacts with water at elevated

temperatures (>850 °C) to form sulfuric acid and hydrogen fluoride (Guo et al. 2001). Molecular fluorine



hydrolyzes to form hydrogen fluoride and oxygen. Hydrolysis of uranium hexafluoride, which is used in

nuclear power applications, also produces hydrogen fluoride as well as nonvolatile uranyl fluoride. These

compounds are then removed from the atmosphere by condensation or nucleation processes (NAS 1971a).

Fluorides emitted by industries in particulate matter are stable compounds that do not readily hydrolyze.

6.3.2.2 Water

Contrary to traditional thought, hydrogen fluoride, a very weak acid in dilute solution, is dissociated in

solution, but forms tight ion pairs F-...H+–OH2, unique to F-, which reduce the thermodynamic activity

coefficient of H3O+ (Cotton et al. 1999). In natural water, fluoride ions form strong complexes with

aluminum, and fluorine chemistry in water is largely regulated by aluminum concentration and pH.

Below pH 5, fluorine is almost entirely complexed with aluminum and consequently, the concentration of

free F- is low. As the pH increases, Al-OH complexes dominate over Al-F complexes and the free F-

level increases. The dominant Al-F complex at pH <5 is AlF2+ (Skjelkvale 1994). In the absence of

aluminum, dissolved fluorides are usually present as free F- at neutral pH (Bell et al. 1970). As the pH

decreases, the proportion of F- decreases, while HF2- and undissociated hydrogen fluoride increase.

Levels of undissociated hydrogen fluoride also increase in concentrated solutions. Fluorine can form

stable complexes with calcium and magnesium, which are present in sea water. Using the stability

constants valid for sea water, 51.0% of fluorine will be present as free F-, 47.0% as MgF+, and 2.0% as

CaF+ (Stumm and Morgan 1981). Calcium carbonate precipitation dominates the removal of dissolved

fluoride from sea water. Fluoride is incorporated into the calcium salt structure and is removed from

solution when the latter precipitates. The next most important removal mechanism is incorporation into

calcium phosphates (Carpenter 1969). The residence time of dissolved fluoride in the oceans, as

calculated from its sedimentation rate, is 2–3 million years (Carpenter 1969).

In a recent review article, different models of the equilibria of the hexafluorosilicate anion in water

solution were compared. It was concluded that concentrations of any fluorosilicate species are extremely

small at drinking water pH (Urbansky 2002). The analysis presented reaffirms the conclusions made

earlier by Feldman et al. (1957), that in drinking water with a pH of ≥5, fluoridated with sodium

silicofluoride to a concentration of ≤16 ppm of fluoride ion or less, silicofluoride is completely

hydrolyzed to silicic acid, fluoride ion, and hydrogen fluoride. While the kinetics of dissociation and

hydrolysis of the hexafluorosilicate anion are not well understood from a mechanistic or fundamental

perspective, the rate data suggest that equilibrium should be achieved by the time drinking water reaches

the consumer (Urbansky 2002).



6.3.2.3 Sediment and Soil

Fluoride occurs in soil as a variety of minerals and complexes with aluminum, iron, and calcium. At low

pH, aluminum complexes, AlF3, AlF2+, and AlF2+, are the dominant dissolved species, and the availability

of these soluble complexes increases with decreasing pH (Fung et al. 1999; Shacklette et al. 1974). This

explains why more acidic soils have both higher water-soluble fluoride and higher extractable aluminum

levels. While aluminum may complex with organic ligands, this does not appear to alter aluminum-

fluoride complexation significantly (Ares 1990). In certain soils in which calcium is present mostly as

calcium fluoride and in which there is sufficient alumina, fluoride is fixed by the formation of relatively

insoluble aluminum fluorosilicate, Al2(SiF6)3 (Brewer 1966).

6.3.2.4 Other Media

Several species of plants have the capacity to convert fluoride obtained from soil or water into carbon-

fluorine compounds such as monofluoroacetic acid, ω-fluoro-oleic acid, ω-fluoropalmitic acid, and

ω-fluoromyristic acid (Marais 1944; NRC Canada 1971; Ward et al. 1964). These compounds have a

higher mammalian toxicity than inorganic fluoride salts.

6.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT

6.4.1 Air

The concentration of fluoride in ambient air depends on the presence of industrial sources of fluoride in

the area, the distance from the sources, meteorological conditions, and topography (Davis 1972).

Ambient concentrations of hydrogen fluoride measured in the United States (ca. 1985) ranged from 1.0 to

7.5 µg/m3 (Kelly et al. 1993). In a study by Thompson et al. (1971) of 9,175 urban air samples in the

United States in 1966, 1967, and 1968, 87% of all measurements at urban stations and 97% of all

measurements at non-urban stations showed fluoride concentrations below 0.05 µg/m3, the threshold of

detectability. Only 18 measurements (0.2%) exceeded 1.00 µg/m3; the maximum concentration was

1.89 µg/m3 at urban locations and 0.16 µg/m3 at non-urban locations (Yunghans and McMullen 1970).



The ambient air concentration of gaseous fluoride varies from 0.01 to 1.65 µg/m3 in Canada and the

United States, approximately 75% of which exists as hydrogen fluoride (CEPA 1996).

Atmospheric hydrogen fluoride concentrations were measured at nine sites in Southern California during

the last 8 months of 1986. Samples were collected every 6th day for a 24-hour sampling period. Average

hydrogen fluoride concentrations ranged between 0.13 µg/m3 (0.15 ppb) and 0.22 µg/m3 (0.25 ppb)

(Hance et al. 1997). The lowest concentration was at a remote off-shore location (San Nicolas Island).

The maximum hydrogen fluoride levels at the eight on-shore sites varied from 0.34 µg/m3 (0.38 ppb) to

1.91 µg/m3 (2.14 ppb). Ambient hydrogen fluoride levels were fairly constant throughout the year.

However, there were occasional isolated peaks in the hydrogen fluoride levels. These are thought to be

the result of accidental releases. Although there are major refineries and chemical plants in the area that

use hydrogen fluoride, it was not possible to correlate the spike in hydrogen fluoride levels with any

reported accidental releases.

Atmospheric fluoride levels are often elevated near fluorine-related industrial operations. A 1976 study

reported fluoride levels 1.5 km from an aluminum plant that emitted 34 kg fluoride/hour (Krook and

Maylin 1979). The average particulate fluoride level was 0.31 µg/m3 (5.53 µg/m3, 12-hour maximum),

and the average gaseous fluoride level was 0.36 µg/m3 (6.41 µg/m3, 12-hour maximum). An indicator of

atmospheric fluoride levels is the amount of fluoride dust deposited on foliage. After an aluminum plant

began operating in 1958 in Oregon, the average fluoride content of foliage in cherry and peach trees

jumped from 13 to 65 and 76 ppm, respectively. The highest average values occurred 2 years later,

measuring 196 and 186 ppm, respectively (NAS 1971a). Since then, the fluoride levels in foliage

dropped appreciably.

6.4.2 Water

Surface Water. Fluoride levels in water vary according to local geology and proximity to emission

sources. In rivers, fluoride concentrations range from <1 to 6,500 µg/L; the average fluoride

concentration is around 200 µg/L (Fleischer et al. 1974). Fluoride levels may be higher in lakes,

especially in saline lakes and lakes in closed basins in areas of high evaporation. The Great Salt Lake in

Utah has a fluoride content of 14,000 µg/L (Fleischer et al. 1974). Lakes in East Africa where fluoride

leaches from the alkalic rocks in the region contain 1,000–1,600 mg/L of fluoride. Fluoride levels in the

Norwegian ‘1,000 lake survey’ ranged from <5 to 560 µg/L with one outlier at 4,120 µg/L and a median

of 37 µg/L (Skjelkvale 1994). The highest levels were found in lakes in Southern Norway that receive the



greatest amounts of acid rain. Fluoride concentrations at these lakes are correlated with sulfate

concentrations, an indicator of acid rain. In studies of natural water in the Rift Valley of Kenya and

Tanzania, high fluoride levels in water and a high incidence of fluorosis were correlated with low levels

of calcium and magnesium in the water (Gaciri and Davies 1993). Calcium carbonate entraps fluorides

and removes it from solution. These results are consistent with researchers who maintain that waters low

in hardness and high in alkalinity present the highest risk of fluorosis. Other reasons for high fluoride

levels in some Kenyan waters are evaporative concentration resulting in much higher fluoride levels in

surface water than groundwater, fluoride-rich volcanic rocks in the region, and contamination by waste

water from fluorspar mining. Seawater contains more fluoride than fresh water, approximately 1,200–

1,500 µg/L (Bowen 1966; Carpenter 1969; Fleischer et al. 1974; Goldschmidt 1954).

Fluoride content of waters for Yellowstone National Park ranged from 0.5 mg/L in Yellowstone River to

24.0 mg/L in the Midway Geyser Basin. Fluoride concentrations in some selected thermal waters in

Idaho ranged from 9 to 30 mg/L. Data from more than 300 geothermal waters in the Western United

States indicate that at least 68% of these waters contain fluoride, with concentrations ranging from 2.1 to

30 mg/L. Fluoride concentrations from a regular well and a geothermal well from a ranch in Idaho were

0.8 and 14.2 mg/L, respectively. Use of geothermal well water for irrigation induces high fluoride levels

in alfalfa and pasture grasses consumed by cattle (Miller et al. 1999).

Groundwater. The fluoride content of groundwater generally ranges from 20 to 1,500 µg/L (EPA 1980a;

Fleischer 1962). Fleischer et al. (1974) contains a map of the fluoride content in groundwater in the

conterminous United States by county. Highest fluoride levels in groundwater are generally found in the

southwest, and maximum groundwater levels in Nevada, southern California, Utah, New Mexico, and

western Texas exceed 1,500 µg/L. In a survey of fluoride levels in Texas groundwater in which water

from nearly 7,000 wells in 237 counties were analyzed, Hudak (1999) identified four regions with high

fluoride levels. In one region in northwest Texas, at least 50% of the wells sampled in each of five

counties had fluoride levels exceeding the primary drinking water standard of 4,000 µg/L. County-

median fluoride concentrations ranged from 90 to 5,110 µg/L. Twenty-five counties had median fluoride

levels above the secondary standard of 2,000 µg/L and 84 counties had median concentrations higher than

1,000 µg/L, the target fluoride concentration for many water fluoridation programs. Factors responsible

for the elevated fluoride levels were the mineral constitution of the aquifers, seepage from nearby saline

formations, and low recharge and dilution rates in the aquifers. The results of this study suggest that

geology has an important influence on the distribution of fluoride in Texas groundwater. Groundwater

constitutes approximately 60% of the water consumed in Texas.



Fluoride levels in groundwater are higher than in surface water because they are more influenced by the

rocks in which they occur (EPA 1980a; Fleischer et al. 1974; NAS 1971a; WHO 1984). Groundwater

from granitic rock, basaltic rock, limestones and dolomites, and shales and clays average 1,200, 100, 300,

and 400 µg fluoride/L, respectively, while groundwater from alkalic rocks average 8,700 µg fluoride/L

(Fleischer et al. 1974). An example of the influence of geology on the concentration of fluorides in

groundwater is illustrated by a region in the Pampa in Argentina where groundwater is alkaline and

moderately saline (Nicolli et al. 1989). Forty-two percent of groundwater samples from this area had

fluoride levels exceeding 1,400 µg/L and the maximum level was 6,300 µg/L. The highest levels of

fluoride were found in waters with the highest sodium and potassium contents.

Drinking Water. The concentration of fluoride in 384 Norwegian waterworks sampled during the winter

of 1983 ranged from 13 to 1,210 µg/L with a mean and median of 87 and 58 µg/L, respectively (Flaten

1991). Fluoride is a naturally-occurring constituent of groundwater and the fluoride in the water was

mostly a consequence of local soil or rock formations. In addition, there was evidence that the fluoride

levels were influenced by local sources and long-range transport. In a random survey of farmstead wells

by the Kansas Department of Health and Environment, 2 of the 103 wells sampled contained fluoride

levels above EPA’s maximum contaminant level (MCL) that was reported at the time as 1,800 µg/L for

public water supplies (Steichen et al. 1988). The highest fluoride level found in this study was

2,300 µg/L.

Rain Water. Rain water sampling was conducted in eight arctic catchments in Northern Europe from

May to September in 1994 (Reimann et al. 1997). Some of the world’s largest industrial sources are in

this region. The median concentrations of fluoride in all of the 30-day composite rain water samples from

the eight catchments were <0.05 mg/L. In five of the catchments, all samples contained <0.05 mg/L of

fluoride. The maximum concentration of fluoride was 1.53 mg/L. Concentrations of fluoride in

precipitation in Norway ranged from 0 to 253 µg/L with volume-weighted averages from 13 to 25 µg/L

(Skjelkvale 1994). Correlations of fluoride content with other ions indicated that the fluoride is not of

marine origin and is mostly correlated with industrial sources of sulfur oxides. Higher fluoride levels in

some rain samples were due to nearby aluminum smelters.



6.4.3 Sediment and Soil

Fluorides are widely distributed in the earth's crust. The concentration of fluoride in soils and other

surficial materials in the conterminous United States ranges from <10 to 3,700 ppm with a mean of

430 ppm (Shacklette and Boerngen 1984). Other values for the mean fluoride content of mineral soils

ranges from 200 to 300 ppm (Bowen 1966; NAS 1971a; Worl et al. 1973). The fluoride content of

organic soils is usually lower. The chief fluorine-containing minerals are fluorspar, cryolite, and

fluorapatite. In soils with high concentrations of these minerals, the soil fluoride content is much higher

and may range from 7 to 38 g/kg (Smith and Hodge 1979). In most soils, fluorine is associated with

micas and other clay minerals. Robinson and Edgington (1946) reported the fluorine content of 137 soil

samples in 30 soil profiles as ranging from trace to 7.07% fluorine, with an average of 0.029%. While the

highest fluoride concentration was found in a Tennessee soil high in rock phosphate (apatite), the main

source of fluoride in the soil were micaceous clays. In general, silt and clay loam soils had higher

fluoride content than sandy soils. Average fluoride soil concentrations differ between the eastern and

western United States. The average concentrations are 340 ppm in the east and 410 ppm in the west

(EPA 1980a). Fluoride concentrations also tend to increase with soil depth. Of 30 domestic soil samples,

the mean fluoride concentration at a depth of 0–3 inches was 190 ppm, whereas the mean concentration at

a depth of 3–12 inches averaged 292 ppm (NAS 1971a).

The fluoride content of soil may be increased by the addition of fluoride-containing phosphate fertilizers

(WHO 1984). Soils near industrialized sources show elevated concentrations that decrease with distance

from the source and depth below the surface. Concentrations of fluoride in the top 0.5 inches of soil

located near a phosphorus extraction facility near Silver Bow, Montana, were reported to range from

265 to 1,840 ppm (Van Hook 1974). Humus near an elementary phosphorus plant in Newfoundland,

Canada, where 80–95% of balsam fir trees were dead because of the pollution, contained average fluoride

levels of 58 ppm dry weight in 1973 and 24.2 ppm in 1974 (Sauriol and Gautier 1984). In 1975, when the

plant was not in operation during the growing season, the humus fluoride content was 8.1 ppm. Humus

fluoride levels in an uncontaminated zone were 2.0 ppm.

The fluoride concentrations in recent oceanic sediments appear to vary between 450 and 1,100 ppm

(Carpenter 1969). Similar levels have been reported for fresh water lakes.



6.4.4 Other Environmental Media

Several factors influence the level of fluorides in food. These include the locality in which the food is

grown and whether there were sources of fluoride emissions in the area, the amount of fertilizer and

pesticides applied, the type of processing the food receives, and whether fluoridated water is used in food

preparation (McClure 1949; Myers 1978; Waldbott 1963b). Foods characteristically high in fluoride

content are certain types of fish and seafood (1.9–28.5 mg/kg), especially those types in which the bones

are consumed, bone products such as bone meal and gelatin, and tea, which contains approximately

0.52 mg fluoride/cup (Cook 1969; Kumpulainen and Koivistoinen 1977).

During a comprehensive total diet study, foods were collected in Winnipeg, Canada in 1987 and were

processed into 148 composite food samples (Dabeka and McKenzie 1995). The mean, median, and range

of fluoride in all samples were 325, 99, and <11–4,970 ng/g, respectively. Food categories with the

highest mean fluoride levels were fish (2,118 ng/g), beverages (1,148 ng/g), and soups (606 ng/g).

Individual samples with the highest fluoride levels were tea (4,970 ng/g), canned fish (4,570 ng/g),

shellfish (3,360 ng/g), cooked veal (1,230 ng/g), and cooked wheat cereal (1,020 ng/g). The drinking

water used to prepare the food came from a single source containing the optimal fluoride concentration of

1 mg/L. This fluoride would contribute substantially to the fluoride levels in the food. The fluoride level

in 68 samples of cows’ milk purchased in retail stores throughout Canada ranged from 7 to 86 ng/g, with

a mean and median concentration of 41 and 40 ng/g, respectively (Dabeka and McKenzie 1987).

Provincial mean levels varied from 25 to 74 ng/g. Other studies of fluoride levels in cows from

uncontaminated areas reported similar fluoride levels in milk (Dabeka and McKenzie 1987). A study

compared fluoride content in foods and beverages from a negligibly fluoridated community

(Connersville, Indiana) and an optimally fluoridated community (Richmond, Indiana). The fluoride

concentrations in Connersville and Richmond are 0.16±0.01 and 0.90±0.05 µg F/g. It was found that

fluoride content in non-cooked and non-reconstituted foods and beverages ranged from 0.12 to

0.55 µg F/g and that there was no significant difference between the two communities. The difference in

fluoride content of foods prepared and/or cooked with water from the two study sites were statistically

different, except in the case of cooked vegetables (Jackson et al. 2002).

Beverages may contain fluoride from the fluoride content of the water used in their production, as well as

the base ingredients (e.g., fruit, flavoring) in the product. In a North Carolina study, beverages purchased

from six regions of the state showed considerable differences in the fluoride content of the product. This

was especially true for carbonated beverages. The ranges (means) of fluoride concentrations in various

beverage types were: sodas, 0.07–1.37 ppm (0.28 ppm); juices, 0.01–1.70 ppm (0.36 ppm); punches,



0.00–1.44 ppm (0.33 ppm); tea, 0.61–6.68 ppm (2.56 ppm); and Gatorade, 0.02–1.04 ppm (0.85 ppm)

(Pang et al. 1992). Fluoride concentrations were measured in 332 carbonated soft drinks, manufactured

by 10 companies, which are available in Iowa grocery stores. Fluoride concentrations were found to

range from 0.02 to 1.28 ppm, with a mean of 0.72 ppm. For 71% of the drinks analyzed, fluoride

concentrations exceeded 0.60 ppm. Concentrations were found to vary substantially by production site,

even within the same company and for the same product (Heilman et al. 1999).

The fluoride content of most plant foliage growing in areas removed from sources of fluoride pollution

ranges from 2 to 20 ppm dry weight (Brewer 1966). A notable exception is tea plants. The highest

fluoride concentration reported in vegetation was over 8,000 ppm in tea leaves. Tea plants take up

fluoride from soil and accumulate it in the leaves. A large percentage of the total fluoride, 25–84%, is

released during infusion, and tea is considered to be a major source of fluoride. The older tea leaves

contain more fluoride and brick tea, which is prepared from older leaves, may be very high in fluoride

content, 4.73–7.34 mg/L, compared with quality green and black tea, which is prepared from younger

leaves and may contain 1.2–1.7 and 0.9–1.9 mg/L, respectively (Fung et al. 1999).

Fruits and vegetables grown in industrial areas where fluoride emissions are high contain elevated

fluoride levels compared with those grown in control areas. The highest levels are found in the leafy

parts of the plants rather than the roots. In a Polish study, vegetables grown 1.5 and 5 km from a steel

plant contained average fluoride levels of 0.54–8.82 and 0.39–4.95 mg/kg, respectively, compared with

0.02–0.41 mg/kg for controls (Krelowska-Kulas 1994). Fruits grown 1.5 and 5 km from the steel plant

contained average fluoride levels of 1.42–5.44 and 1.24–2.75 mg/kg, respectively, compared with 0.40–

1.05 mg/kg for controls. Vegetables from the Saint-Régis Mohawk Indian reservation contained an

average of 1.54–45.17 ppm fluoride dry weight compared with 0.63–11.3 ppm fluoride for vegetables

from an uncontaminated site (Sauriol and Gauthier 1984). The reservation is located along the

St. Lawrence River, straddling territory in New York State, Québec, and Ontario, where there are three

potential sources of industrial fluoride emissions, namely two aluminum plants and a phosphate fertilizer

plant.

Fluoride concentrations in vegetation form Yellowstone National Park varies over a wide range from 3 to

430 ppm. Studies where plants were watered by spray treatments containing 4 ppm fluoride showed that

plants accumulated up to 36 ppm fluoride (dry weight), but a significant amount of this could be removed

by washing the leaves in distilled water. In another experiment using 6 ppm fluoride solution, leaf

analysis contained up to 55 ppm fluoride in the unwashed leaves and 35 ppm in washed leaves. Fluoride



content in vegetation around a phosphate plant was found to range from 4 to 718 ppm. Fluoride was

present in the air in the form of particulate fluorides and hydrogen fluoride gas (Miller et al. 1999).

Fluoride levels in various marine crustaceans were found to range from not detected to 2,500 (whole-

body), not detected to 5,977 (exoskeleton), and not detected to 257 (muscle) µg/g, dry weight. Fluoride

levels in saltwater fish were found to range from 45 to 1,207 (skeletal bone) and from 1.3 to 26 (muscle)

mg/kg, wet weight (Camargo 2003).

The fluoride concentration in most dental products available in the United States ranges from 230 ppm

(0.05% NaF mouth rinse) to 12,300 ppm (1.23% acidulated phosphate fluoride gel) (NRC 1993). The

most commonly used dental products, toothpastes, contain 900–1,100 ppm fluoride (ca. 0.10%), most

often as sodium fluoride, but also as disodium monofluorophosphate.

The fluoride concentration of a bituminous coal used in power generation is around 65.0 ppm dry weight

and may contain up to 200 mg fluoride/kg (Rubin 1999; Skjelkvale 1994). The fluoride in the coal occurs

predominantly as fluorapatite and fluorspar. Hydrogen fluoride and other fluorides are released from the

coal during combustion. Bauer and Andren (1985) studied fluoride emissions from an electricity-

generating plant in Portage, Wisconsin that consisted of two nearly-identical 527-MW pulverized-coal

units, differing only in the type of coal burned and the operating conditions. In one unit, emissions

contained a median of 1.9 mg fluoride/scm (86% of available fluoride in coal) and the other contained a

median of 0.22 mg fluoride/scm (4.2% of available fluoride in coal). The first unit burned a bituminous

coal from Colstrip, Montana containing 9% ash and 46 ppm fluoride and the second unit burned a

bituminous coal from Gillette, Wyoming containing 5% ash and 45 ppm fluoride. It was thought that the

greater mineral matter in the coal feeding the first unit may have played a role in the greater release of

fluoride in the vapor phase from this unit. The concentration of hydrogen fluoride reported in emissions

from a modern municipal waste incinerator in Germany was 0.2–0.3 mg/m3 (Greim 1990). Fluoride

concentrations in waste water from a coal-fired power plant in Utah ranged from 2.4 to 3.8 ppm (Miller et

al. 1999).

6.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE

The major sources of fluoride intake by the general population are water, beverages, food, and fluoride-

containing dental products. Since levels in ambient air are, in most cases, below detectable limits, the

levels inhaled are generally very low except for in areas immediately surrounding industries that emit



fluorides into the air. Hodge and Smith (1977) estimated air intake of fluoride of about 0.01 mg/day. In

occupational settings where airborne concentrations are frequently at the exposure limit of 2.5 mg/m3

(OSHA 1985), fluoride intake via inhalation can be 16.8 mg/day, assuming an 8-hour shift and that a

person inhales 20 m3 air/day. The daily intake of fluoride from drinking water fluoridated at the optimal

levels (0.7–1.2 mg/L) would be 1.4–2.4 mg.

The chemicals most commonly used by American waterworks are fluorosilicic acid, sodium

silicofluoride, and sodium fluoride. Data from the CDC's 1992 Fluoridation Census indicate that 25% of

utilities reported using sodium fluoride; however, this corresponds to 9.2% of the U.S. population

drinking fluoride-supplemented tap water (Urbansky 2002). Concerns over the purity of water

fluoridation agents have been raised as well as possible links between fluoridation agents and lead levels

in the bloodstream (Masters et al. 2000). Analyses of available grades of fluorosilicic acid, sodium

fluoride, and sodium fluorosilicate show the presence of arsenic and lead, but at levels far below that

which would necessitate recommended maximum impurity content (RMIC) values based on the

maximum dosage of 1.2 mg of fluoride ion per liter (NRC 1982).

Based on a comprehensive total diet study conducted in Winnipeg, Canada in 1987, the estimated daily

dietary intake of fluoride by the average Canadian was 1,763 µg and varied from 353 µg for the 1–4-year-

old-age group to 3,032 µg for 40–64-year-old males (Dabeka and McKenzie 1995). The results for all

age groups are shown in Table 6-3. The drinking water used to prepare the food came from a single

source containing the optimal fluoride concentration of 1 µg/mL (1 mg/L). This fluoride would

contribute substantially to the fluoride intake in the food. In an earlier study in which the dietary intake of

24 adult Canadians was assessed, Dabeka et al. (1987) compared the intake of half of the participants who

lived in communities with 1 µg/g (1 mg/L) fluoride in their drinking water with those who lived in

communities with <0.2 µg/g (<0.2 mg/L) of fluoride in water. The respective median intakes of fluoride

were 2,090 or 30.3 µg/kg/day and 414 or 7.0 µg/kg/day. For the cities with fluoridated water, the

majority of fluoride was contributed by beverages (68%) and water (13%); for the nonfluoridated cites,

beverages contributed 58% of the fluoride intake. These results can be compared with earlier estimates of

fluoride intake by U.S. adults. San Filippo and Battistone (1971) estimated the average daily adult

fluoride intake from food ranged from 0.8 to 0.9 mg, while the daily intake from food and water was 2.1–

2.4 mg. Spencer et al. (1970) estimated the fluoride intakes as 1.2–2.7 mg/day from food and 2.82–

5.9 mg/day from food and water. Kumpulainen and Koivistoinen (1977) reported the average total

dietary intake in 12 fluoridated U.S. cities as 2.7 mg/day. In areas where fluoride is not added to water,



Table 6-3. Mean Daily Dietary Intake of Fluoride for Selected Canadian Population Groupsa

Population Mean daily intake (µg/day) 1–4 years, males and females 353 5–11 years, males and females 530 12–19 years, males and females 1,025 12–19 years, females 905 20–39 years, males 2,544 20–39 years, females 2,172 40–65 years, males 3,032 40–65 years, females 2,615 65+ years, males 2,588 65+ years, females 2,405 All ages male and female 1,763 aDabeka and McKenzie 1995



the total intake from food and water does not usually exceed 1.0 mg/day (WHO 1984). However, there

are exceptions, such as an area in China where the fluoride content of the water is low, but the intake from

food and tea is high enough that the rate of dental fluorosis exceeds 80% (Han et al. 1995). In England,

where much more tea is consumed, a study found daily average intakes of fluoride from tea to be

1.26 mg/day in children and 2.55 mg/day in adults (Cook 1969). In areas near sources of fluoride

emissions, oral intake may also be increased from dust contamination of food (WHO 1984). Fluoridated

dentifrices and mouth rinses are additional sources of fluoride (Barnhart et al. 1974; Ericsson and

Forsman 1969). Fluorides approved by the FDA for use in dentifrices are sodium fluoride (0.22%),

sodium monofluorophosphate (0.76%), and stannous fluoride (0.41%) (Pader 1993). The concentration

of fluoride in each of these formulations is 0.1% (equivalent to 1,000 mg/kg or 1,000 ppm). Fluoride

tablets or drops are ingested in some areas where water fluoride levels are low, providing 0.25, 0.50, or

1.00 mg/day depending on the age of the child and the drinking water fluoride concentration. In his

analysis of systemic fluoride intake, Burt (1992) found that there is no evidence from dietary surveys to

show that fluoride intake in adults has increased since the 1970s.

In considering dietary intake, it is important to take bioavailability into account, and not simply the

fluoride content of the consumed substance. As discussed in Sections 2.3.1.2 and 2.8, absorption is

affected by factors such as whether the material was eaten with a meal, the chemical and physical form of

the fluoride, and the current health status of the individual (Rao 1984). The bioavailability of fluoride as

sodium fluoride is high. In contrast, absorption of calcium fluoride is rather inefficient, but is enhanced

when administered with food. Thus, the actual absorbed dose could be smaller than the intake levels

reported above. NRC (1993) reports that approximately 75–90% of ingested fluoride is absorbed from

the alimentary tract.

The fluoride content of urine and plasma are useful as short-term indicators of fluoride exposure; hair,

fingernails, and tooth enamel are indicators of longer-term response. The mean and median serum

fluoride levels of 168 representative Danish adults were 470±270 and 400 nmol/L (0.00893±0.00513 and

0.00760 mg/L), respectively (Poulsen et al. 1994). Levels were significantly higher in urban inhabitants

than rural inhabitants and increased significantly with age. Shida et al. (1986) measured fluoride

concentrations in five different layers of enamel of incisors that had been extracted due to periodontal

disease. Half of the teeth were treated with 0.9% acidified fluorophosphate for 4 minutes. In the

fluoride-treated group, the outer layer of enamel contained 1,660–5,910 ppm fluoride compared with

147–698 ppm in the untreated group. A similar method was employed by Schamschula et al. (1982) on



enamel of children. They found that the fluoride content of enamel did reflect environmental fluoride

exposure of the group, but variations occurred among individuals.

The NIOSH National Occupational Exposure Survey (NOES) conducted in 1981–1983 estimated that

about 182,589 workers were potentially exposed to hydrogen fluoride (NIOSH 1989). The NOES was

based on field surveys of 4,490 facilities that included virtually all workplace environments, except

mining and agriculture, where eight or more persons are employed. The principal exposure pathway

would be inhalation.

Workers in the electronics industry in Japan who used hydrogen fluoride for glass etching (e.g., TV

picture tubes) and as a silicon cleaner (e.g., semiconductors) are exposed daily to mean air hydrogen

fluoride concentrations of up to 5 ppm (Kono et al. 1987). The mean urinary fluoride levels were linearly

related to the hydrogen fluoride concentration in the air and there were also significant differences in pre-

and postshift urinary fluoride level of the workers. The workers in this study were only exposed to

gaseous hydrogen fluoride. The wide variation of fluoride levels in serum and urine in the workers and

controls has been ascribed to dietary differences, particularly the consumption of tea and seafood (water

fluoridation is not practiced in Japan). In a follow-up study Kono et al. (1993) found a linear correlation

between urine fluoride levels and hair fluoride levels.

A study evaluated the use of urinary fluoride as an exposure index for a prospective study of asthma in an

aluminum smelter. In the first part of the study, 32 subjects wore personal air sampling pumps. The

12-hour time weighted average results show that overall mean levels were 15.7, 4.07, and 0.74 mg/m3 for

particulate mass, total fluoride, and hydrogen fluoride, respectively. Urinary fluoride concentrations were

considered reasonably low, 1.3 and 3.0 mg/g creatinine in pre- and post-shift collections. Carbon

smelters had the highest exposure levels as compared to workers working as potmen and trappers (Seixas

et al. 2000). An average total fluoride exposure of 0.91 mg/m3, of which 34% was gaseous fluoride, was

measured for 41 workers in an aluminum plant in Sweden. Mean fluoride plasma concentrations were

determined to be 23 and 48 ng/mL pre- and post-shift, respectively. Use of a safety mask during the shift

led to a reduction in exposure of inhaled fluoride. Workers wearing a safety-mask throughout the whole

shift reduced inhalation of fluoride to 30–40% of those workers not wearing masks (Ehrnebo and

Ekstrand 1986).

Certain populations, such as patients with kidney disease, may be especially sensitive to fluoride

exposure. In 1993, 20 patients became ill due to acute fluoride intoxication after receiving hemodialysis



treatment for end-stage renal failure. This outbreak was found to be caused by errors in the maintenance

of the deionization system used to treat the water used for dialysis. In this case, the deionization units

continued to be used after the ion exchange resins were exhausted, resulting in the release of the resin-

bound fluoride into the treated water (Arnow et al. 1994).

6.6 EXPOSURES OF CHILDREN

This section focuses on exposures from conception to maturity at 18 years in humans. Differences from

adults in susceptibility to hazardous substances are discussed in Section 3.7 Children’s Susceptibility.

Children are not small adults. A child’s exposure may differ from an adult’s exposure in many ways.

Children drink more fluids, eat more food, breathe more air per kilogram of body weight, and have a

larger skin surface in proportion to their body volume. A child’s diet often differs from that of adults.

The developing human’s source of nutrition changes with age: from placental nourishment to breast milk

or formula to the diet of older children who eat more of certain types of foods than adults. A child’s

behavior and lifestyle also influence exposure. Children crawl on the floor, put things in their mouths,

sometimes eat inappropriate things (such as dirt or paint chips), and spend more time outdoors. Children

also are closer to the ground, and they do not use the judgment of adults to avoid hazards (NRC 1993).

Children are exposed to fluorides primarily through their diets and dental products. Normal dietary

sources of fluorides are augmented by fluoridation of water supplies. Based on data obtained from a 1987

total diet study in Winnipeg, Canada, the average 1–4 and 5–11 year olds consume 353 and 530 µg

fluoride/day, respectively, compared with 1,763 µg/day for all age groups combined (Dabeka and

McKenzie 1995). The mean daily dietary intakes of fluoride by 6-month-old infants and 2-year-old

children in four regions of the United States were 0.21–0.54 and 0.32–0.61 mg/day, respectively (NRC

1993; Ophaug et al. 1985). The mean intake of 2-year-old children, but not 6-month-old infants, was

directly related to the fluoride concentration in the drinking water. Dietary intake may increase in areas

where there are industrial emissions containing fluorides. Increased incidences of mottled teeth were

observed in children living within 3 km of a superphosphate fertilizer plant in Port Maitland, Ontario

(Sauriol and Gauthier 1984). The most plausible reason for the increased fluoride intake is higher

fluoride levels in vegetables and fruits from dust deposited on the plants.

It has been assumed that children in communities without fluoridated water consume a negligible amount

of fluoride other than from food. Because of the marked increase in dental fluorosis in nonfluoridated



populations and the increased consumption of beverages that may have been prepared with fluoridated

water, a study was conducted to estimate the average daily amount of fluoride ingested by a sample of

North Carolinian children aged 2–10 from these beverages (Pang et al. 1992). The study found that

children of ages 2–3, 4–6, and 7–10 consumed daily means of 0.36, 0.54, and 0.6 mg fluoride,

respectively, from beverages. This is a significant source of fluoride intake. Beverages contributed about

60% of the children’s total liquid consumption. While fluoride consumption increased with age, little

difference was found between males and females. Children in a high fluoride area of Kenya consume

high levels of fluoride from the water (9 ppm) and from the practice of giving tea to young children. In

this area, children aged 0–1 and 1–4 years old had mean daily fluoride intakes of 0.62 and 1.23 mg/kg

body weight, respectively. Tea accounted for nearly half of the fluoride intake of 1–2-year-old children.

The daily fluoride consumption from breast milk supplements and substitutes averaged 7.6 mg,

>250 times the amount of fluoride provided by 800 mL of breast milk (Opinya et al. 1991a).

Fluoride intake in infants depends on whether the child is nursed or not. Human breast milk contains very

little fluoride (about 0.5 µmol/L or 0.01 mg/L) and provides <0.01 mg fluoride/day (NRC 1993).

Fluoride intake by an infant who is exclusively breast fed and consuming 170 mL/kg-day is generally

<2 µg/kg-day (Fomon and Ekstrand 1999). Levy et al. (2001) found that for most children, water fluoride

intake was the predominant source of fluoride, especially through age 12 months. This was due in large

part to children receiving fluoridated water mixed with infant formula concentrate (Levy et al. 1995b,

2001).

The results of a survey of fluoride levels in 68 samples of cows’ milk and 115 samples of infant formulas

and oral electrolytes are shown in Table 6-4. Mean fluoride levels in cows’ milk, evaporated milk, and

ready-to-use formula were 0.041, 0.23, and 0.79 µg/g, respectively. Mean levels in concentrated liquid

and powder formula were 0.60 and 1.13 µg/g, respectively (Dabeka and McKenzie 1987). A major

source of fluoride in the infant formulas appears to be the processing water used in its manufacture. In

the United States where manufacturers remove fluoride from the processing water, mean levels of

fluoride were much lower than in the Canadian products. All U.S. products were well within the upper

guideline of 0.40 µg/g for ready-to-use formula proposed by the Committee on Nutrition of the American

Academy of Pediatrics. Fluoride exposure was calculated to be 102, 105, and 167 µg/kg-day for infants

consuming 170 mL/kg-day of concentrated liquid milk-based formula, concentrated liquid isolated soy

protein-based formula, and powdered milk-based formula, respectively, which were diluted with water

that is 1 ppm in fluoride. Infants may be exposed to higher fluoride concentrations now than in the past.



Table 6-4. Comparison of Fluoride Levels (µg/g) in Cow Milk and Infant Formulasa

Number Mean Median Rangea Cow milk 64 0.041 0.040 0.007–0.086 Evaporated milk 9 0.23 0.12 0.06–0.55 Ready-to-use formula, all Canadian 34 0.90 0.86 0.35–2.31 U.S. 7 0.23 0.26 0.15–0.28 Ready-to-use formula, glassb Canadian 20 0.82 0.83 0.46–1.13 U.S. 3 0.28 0.28 0.28–0.28 Ready-to-use formula, canned Canadian 14 1.02 0.95 0.35–2.31 U.S. 4 0.19 0.17 0.15–0.26 Concentrated liquid formula, canned 33 0.60 0.60 0.15–1.47 Formula, powdered concentrate 18 1.13 0.80 0.14–5.53 Electrolytes (water), glassb 12 0.066 0.04 0.01–0.15 aDabeka and McKenzie 1995 bProduct not available on retail market, obtained from hospitals.



In the 1960s, nearly 80% of infants were fed cow's milk by 6 months of age. In 1991, 80% of 6-month-

old infants were fed formula (Fomon and Ekstrand 1999). Fluorinated organic chemicals are widely used

and may accumulate in breast milk due to their high fat solubility and slow rate of metabolism and

excretion. The breast milk fluoride concentration from a German study was 25 ppb (Broomhall and

Kovar 1986). Fluoride may be an important mineral for babies born prematurely, since prematurity is

associated with an increased incidence of dental caries; however, recommendations for fluoride intake are

only available for full-term infants (Zlotkin et al. 1995).

Fluoridated dentifrices and mouth rinses are additional sources of fluoride, particularly in small children

who do not have complete control of the swallowing reflex. Dentifrice ingestion was inversely correlated

with age; average ingested levels per brushing for children aged 2–4, 5–7, and 11–13 were 0.30, 0.13, and

0.07 g (Barnhart et al. 1974). Average fluoride intake from these sources in children younger than 7 years

old ranged from 0.3 to 0.4 mg/use for mouth rinses, depending on the child's age, and was about

0.1 mg/brushing for fluoridated toothpaste use (Ericsson and Forsman 1969). Other studies indicated that

an average of 25% (range, 10–100%) of the toothpaste introduced into the mouth was swallowed. The

average amount of fluoride in toothpaste used in one brushing is about 1.0 mg. From these studies, it has

been estimated that the amount of fluoride ingested in toothpaste by children who live in communities

with fluoridated water, who have good control of swallowing, and brush their teeth twice a day is

approximately equal to dietary fluoride intakes. For younger children who have poor control of

swallowing, intakes from dental products could exceed dietary intakes.

Although Burt (1992) concludes that data on fluoride intake by children from food and beverages, infant

foods included, are not strong enough to conclude that an increase in fluoride ingestion has occurred since

the 1970s, he warns that the suggested upper limit of fluoride intake is substantially being reached by

many children by ingestion of fluoride from food and drink (0.2–0.3 mg/day) and from fluoride

toothpaste (0.2–0.3 mg/day). Levy (1994) also found substantial variation in ingestion among

individuals; 10–20% of individuals received up to several times as much exposure as the mean. Some

children appeared to ingest enough fluoride from one source to exceed the total recommended fluoride

intake, and are therefore at increased risk of dental fluorosis. Levy et al. (1995a) made the following

recommendations concerning use of fluoride by children:

“(1) the fluoride content of foods and beverages, particularly infant formulas and water used in their

reconstitution, should continue to be monitored closely in an effort to limit excessive fluoride intake;

(2) ingestion of fluoride from dentifrice by young children should be controlled, and the use of only small



quantities of dentifrice by young children should be emphasized; and (3) dietary fluoride supplements

should be considered a targeted preventive regimen only for those children at higher risk for dental caries

and with low levels of ingested fluoride from other sources (Levy et al. 1995a).”

Schamschula et al. (1985) analyzed various body fluids and tissue from a group of Hungarian children

exposed to low, intermediate, and high levels of fluoride in their drinking water. These tissue levels,

included in Table 6-5, are indicators of exposure over the short and long term. Fluoride dentifrices were

not in general use in the villages from which the sample populations were drawn. Mean fluoride

concentrations of 1.85, 5.28, and 7.52 mg/kg were found in fingernails of Brazilian children, 6–7 years

old, living in communities where fluoride concentrations were 0.1, 1.6, and 2.3 ppm, respectively.

Analysis of these data indicated a direct relationship between fluoride concentrations in drinking water

and fingernails. The 95% confidence intervals for the 0.1 and 1.6–2.3 ppm areas showed no overlap; a

small overlap was noted for the 1.6 and 2.3 ppm areas (Whitford et al. 1999a).

6.7 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES

Populations living in areas with high fluoride levels in groundwater may be exposed to higher levels of

fluorides in their drinking water or in beverages prepared with the water. Among these populations,

outdoor laborers, people living in hot climates, and people with polydipsia will generally have the greatest

daily intake of fluorides because they consume greater amounts of water. Groundwater fluoride levels are

especially high in the southwest; maximum groundwater levels in Nevada, southern California, Utah,

New Mexico, and western Texas exceed 1,500 µg/L. In one region of northwest Texas, the median level

in well water exceeded 4,000 µg/L. People who drink large amounts of tea or consume large quantities of

seafood may also have high intakes of fluoride.

Populations living downwind of facilities emitting high levels of fluorides (e.g., phosphate fertilizer

plants, aluminum plants, or coal-fired power plants) may be exposed to higher fluoride levels in the air

(Ernst et al. 1986). Emissions from these plants may contaminate vegetables and fruit with fluorides from

industrial emissions, exposing people eating local produce to potentially high levels of fluorides in their

diets. Workers in industries where fluoride-containing substances are used, most notably the aluminum

and phosphate fertilizer plants, may be occupationally exposed to high levels of both gaseous and

particulate fluorides. Workers using sulfur hexafluoride as a tracer gas for determining ventilation rates



Table 6-5. Levels of Fluoride in Human Tissue and Urine—Selected Studies

Site Population Sample Concentration Type Units Reference Human plasma from blood banks in five U.S. cites with different fluoride levels in drinking water

Guy et al. 1976

Albany, NY (n=30) <0.1 ppm fluoride

Blood plasma 0.38 (0.14-1.1) Mean (Range)

µmol/L

Rochester, NY (n=30) 1 ppm fluoride

0.89 (0.35-4.2)

Corpus Christi, TX (n=12) 0.9 ppm fluoride

1.0 (0.60-1.7)

Hillsboro, TX (n=4) 2.1 ppm fluoride

1.9 (0.60-2.6)

Andrews, TX (n=30) 5.6 ppm fluoride

4.3 (1.4-8.7)

Poland (1980) Miszke et al. 1984 Employee of electrolysis

shop of aluminum plant Urine, random 1.87 mg/dm3

HF workers in the electronics industry, Japan Kono et al. 1987 Unexposed controls (n=82) Urine, random 0.58 (0.23) Geometric

mean (GSD)

ppm

All workers (n=142) 2.34 (1.40) Hydrogen fluoride exposure

level

0.3 ppm (n=16) 0.91 (0.26) 0.5 ppm (n=20) 1.04 (0.34) 0.6 ppm (n=12) 1.07 (0.41) 1.2 ppm (n=14) 2.02 (0.57) 1.6 ppm (n=17) 2.40 (0.68) 2.8 ppm (n=21) 3.94 (1.07) 4.2 ppm (n=32) 5.05 (1.30) 5.0 ppm (n=10) 6.50 (1.98) HF workers in the electronics industry, Japan Kono et al. 1993 All hydrogen fluoride

workers (n=142) Hair 61.1 (101.6) Geometric

mean (GSD)

µg/g

Controls (n=237) 13.4 (6.4) HF workers, Japan Kono et al. 1984 Hydrogen fluoride workers

(n=120) Serum 40.10 (23.72) Mean (SD) µg/L

Controls (n=320) 24.50 (12.10) Hydrogen fluoride workers

(n=120) Urine, 24 hour 0.98 (0.75) Mean (SD) mg/L

Controls (n=320) 0.54 (0.30)



Table 6-5. Levels of Fluoride in Human Tissue and Urine—Selected Studies

Site Population Sample Concentration Type Units Reference Danish adults Poulsen et al. 1994 Representative population

(n=168) Serum 470 (270) Mean (SD) nmol/L

Brazilian children (6-7 years old) exposed to different water fluoride concentrations Whitford et al. 1999a Fluoride concentration in

drinking water:

0.1 ppm (n=19) fingernail 1.85 (0.75-3.53) Mean (range)

mg/kg

1.6 ppm (n=12) 5.28 (2.28-7.53) 2.3 ppm (n=15) 7.52 (4.00-13.18) Hungarian children exposed to three levels of fluoride in drinking water Schamschula et al.

1985 Low exposurea (n=45) Urine 0.15 (0.07) Mean (SD) ppm Medium exposureb (n=53) 0.62 (0.26) High exposurec (n=41) 1.24 (0.52) Low exposurea (n=45) Nails 0.79 (0.26) Mean (SD) ppm Medium exposureb (n=53) 1.31 (0.49) High exposurec (n=41) 2.31 (1.14) Low exposurea (n=45) Hair 0.18 (0.07) Mean (SD) ppm Medium exposureb (n=53) 0.23 (0.11) High exposurec (n=41) 0.40 (0.25) Low exposurea (n=45) Saliva 6.25 (2.44) Mean (SD) ppb Medium exposureb (n=53) 11.23 (4.29) High exposurec (n=41) 15.87 (6.01) Low exposurea (n=45) Enamel (0.44–

0.48 µm depth)

1,549 (728) Mean (SD) ppm

Medium exposureb (n=53) 2,511 (1,044) High exposurec (n=41) 3,792 (1,362) Low exposurea (n=45) Enamel (2.44–

2.55 µm depth)

641 (336) Mean (SD) ppm

Medium exposureb (n=53) 1,435 (502) High exposurec (n=41) 2,107 (741) aLow exposure: concentration of fluoride in water 0.06–0.11 ppm, 0.09 ppm, mean. bMedium exposure: concentration of fluoride in water 0.5–1.1 ppm, 0.82 ppm, mean. cHigh exposure: concentration of fluoride in water 1.6–3.1 ppm, 1.91 ppm, mean. GSD = geometric standard deviation; SD = standard deviation



and air flow in buildings may be exposed to hydrogen fluoride when unvented combustion sources are

present in the building because SF6 reacts with water vapor at high temperatures, forming hydrogen

fluoride (Guo et al. 2001).

Populations living in the vicinity of hazardous waste sites may be exposed to fluorides through contact

with contaminated air, water, and soil. Food grown near the source may also be contaminated. Data on

the concentrations of fluorides in waste site media are quite limited, and no information was located

regarding daily intake of fluorides from these sources.




adequate information on the health effects of fluorine, hydrogen fluoride, and fluorides is available.



health effects (and techniques for developing methods to determine such health effects) of fluorine,

hydrogen fluoride, and fluorides.







Physical and Chemical Properties. The physical/chemical properties of fluorine, hydrogen

fluoride, and sodium fluoride are sufficiently well characterized to enable assessment of the

environmental fate of these compounds.

Production, Import/Export, Use, Release, and Disposal. Information on the production and

importation of fluorspar and hydrogen fluoride are available (CMR 2002; USGS 2001). Information on

exports is only available for fluorspar. No data are available on the production, import, or export of



fluorine, sodium fluoride, and other fluorides. Information is readily available on the uses of fluorine,

hydrogen fluoride, and other fluorides (Mueller 1994). Because of its high reactivity, fluorine is disposed

of by conversion to fluoride salts in a scrubber (Shia 1994). The TRI contains information on the

amounts of hydrogen fluoride transferred off-site, presumably for disposal, and the amount recycled. No

information was found regarding the disposal of sodium fluoride. Additional quantitative information on

production, import, and export of fluorides, as well as common disposal practices, would be useful in

assessing the release of, and potential exposure to, these compounds.

According to the Emergency Planning and Community Right-to-Know Act of 1986, 42 U.S.C.

Section 11023, industries are required to submit chemical release and off-site transfer information to

EPA. The TRI, which contains this information for 2001, is currently available. This database will be

updated yearly and should provide a list of industrial production facilities and emissions.

Environmental Fate. Upon release to the atmosphere, fluorine gas will readily react to form

hydrogen fluoride. Both hydrogen fluoride and particulate fluorides will be transported in the atmosphere

and deposited on land or water by wet and dry deposition. Fluorides undergo transformations in soil and

water, forming complexes and binding strongly to soil and sediment (NAS 1971a; WHO 1984).

Information on the environmental fate of fluorides is sufficient to permit a general understanding of the

widespread transport and transformation of fluorides in the environment.

A recent review (Urbansky 2002) looked at the fate of fluorosilicate drinking water additives. Various

fluorosilicates and aquo/hydroxo/oxo/fluorosilicates may exist in fluoridated water systems and these

species may occur, regardless of the fluoridating agent used, since water may contain natural silica. The

author states that it would be desirable to be able to identify and measure or calculate concentrations of

those species that do exist and rule out those that do not exist (Urbansky 2002).

Bioavailability from Environmental Media. Fluorides are absorbed by humans following

inhalation of workplace and ambient air that has been contaminated (Chan-Yeung et al. 1983a; Waldbott

1979), ingestion of drinking water and foods (Carlson et al. 1960a; Spencer et al. 1970), and dermal

contact (Browne 1974; Buckingham 1988). Information is available on factors that influence

bioavailability of ingested fluoride (Rao 1984). However, this information is rarely coupled with the

available information on total ingested fluoride to determine actual bioavailable dose. Additional

information on absorption following ingestion of contaminated soils (i.e., by children) would be useful in



determining the bioavailability of fluorides from these routes of exposure, which may be of particular

importance for populations living in the vicinity of hazardous waste sites.

Food Chain Bioaccumulation. Fluorides have been shown to accumulate in animals that consume

fluoride-containing foliage (Hemens and Warwick 1972). However, accumulation is primarily in skeletal

tissue and therefore, it is unlikely that fluoride will biomagnify up the food chain.

Exposure Levels in Environmental Media. Fluorides have been detected in ambient air, surface

water, groundwater, drinking water, and foods (Barnhart et al. 1974; Davis 1972; EPA 1980a; Hudak

1999; Waldbott 1963b). However, the existing monitoring data are not current. Air concentrations are

expected to be different today in view of changes in industries and the wider use of pollution control

devises. Recent serial measurements of fluorides in air are needed. Groundwater contains higher fluoride

levels than surface water. Although Fleischer (1962) mapped the levels of fluoride in groundwater in the

United States and these levels would not be expected to change, it would be useful to survey the

concentration of fluoride in groundwater used for drinking. This is particularly important in areas where

groundwater has high fluoride content, as in northwest Texas where 50% of the well water in some

counties exceed 4 µg/L (Hudak 1999). The fluoride level in food depends on the locality in which the

food is grown, including the geology, potential sources of fluorine emissions in the area, the amount of

fertilizer and pesticides applied, the type of processing the food receives, and whether fluoridated water is

used in food preparation (McClure 1949; Myers 1978; Waldbott 1963b). Foods characteristically high in

fluoride content include tea, seafood, and bone products such as bone meal and gelatin (Cook 1969;

Kumpulainen and Koivistoinen 1977). Old estimates of intake via ingestion have been made for members

of the general population (Kumpulainen and Koivistoinen 1977; NAS 1971a; Spencer et al. 1970; WHO

1984). Recent data are available on the concentration of fluoride in different foods in Canada and the

daily dietary intakes for different Canadian age groups (Dabeka and McKenzie 1995). However, recent

analogous information is not available for the United States. Up-to-date data on concentrations of

fluoride in food items and the dietary intake of fluorides in the United States is important in view of the

changes in fluoride emissions and the effect that the use of fluoridated water or water with a high natural

fluoride content may have on the fluoride levels in processed food and beverages (Pang et al. 1992).

Fluorides have also been detected in a limited number of surface water, groundwater, and soil samples

taken at hazardous waste sites (HazDat 2003; Van Hook 1974). Additional information is needed on

concentrations in ambient air, surface water, groundwater, and soils at these waste sites. This information



will be helpful in estimating exposures of populations living near these sites through contact with

contaminated media.

Exposure Levels in Humans. Fluorides can be measured in urine, plasma, saliva, tooth enamel,

nails, bone, and other tissues. Detection of fluoride in biological tissues, particularly urine, has been used

as an indicator of human exposure to fluorides in the workplace and through consumption of fluoridated

drinking water (Chan-Yeung et al. 1983a; Kaltreider et al. 1972; Spencer et al. 1970). Additional data on

fluoride levels in urine and other fluids and tissues are needed for populations living near hazardous waste

sites. This information will be helpful in establishing exposure profiles for waste site populations that

may be exposed to higher than background levels of fluorides through contact with contaminated media.

The total human intake is of interest, since multiple sources, all of which are generally considered safe by

themselves, could, under some circumstances, provide total intake that is considered to be above the

"safe" level.

Exposures of Children. Children are exposed to fluorides primarily through their diets and the use

of dental products, particularly toothpaste. Normal dietary sources of fluorides are augmented by

fluoridation of water supplies. Human breast milk contains very little fluoride (NRC 1993). Information

is available on the levels of fluoride in infant formula in Canada and results show that major source of

fluoride appears to be the processing water used in its manufacture (Dabeka and McKenzie 1987). In the

United States, manufacturers remove fluoride from the processing water and thus, fluoride levels in infant

formulas are much lower. The mean dietary intake of fluoride by infants and children is available for

Winnipeg, Canada and four regions of the United States (Dabeka and McKenzie 1995; Fomon and

Ekstrand 1999; NRC 1993). The mean daily dietary intakes of fluoride by 6-month-old infants and

2-year-old children in four regions of the United States were 0.21–0.54 and 0.32–0.61 mg/day,

respectively. The mean intakes of 2 year olds, but not 6 month olds, were directly related to the fluoride

concentration in the drinking water. Pang et al. (1992) noted that children obtain a sizeable amount of

fluoride from beverages. Infants may be exposed to higher fluoride concentrations now than in the past.

While nearly 80% of infants were fed cow's milk by 6 months of age in the 1960s, in 1991, 80% of

6-month-old infants were fed formula, which contains higher fluoride concentrations than either human or

cow's milk (Fomon and Ekstrand 1999). Since beverages may not be prepared with water from the local

community and beverages constitute 60% of children’s total liquid consumption, more information on the

fluoride content of beverages would be useful in estimating children’s dietary intake of fluoride. Intake

of fluoride by children from fluoridated dentifrices and mouth rinses have been estimated (Barnhart et al.

1974; Ericsson and Forsman 1969). For younger children who have poor control of swallowing, intakes



from dental products could exceed dietary intakes. Fluoride may be an important mineral for babies born

prematurely, since prematurity is associated with an increased incidence of dental caries; however,

recommendations for fluoride intake are only available for full-term infants (Zlotkin et al 1995).

Fluoride exposure in communities near mining and other industrial facilities where fluoride-containing

rock or minerals are processed are a public health concern, especially for infants and children. The same

is true for hazardous waste sites containing fluoride waste. Since fluoride remains in the surface soil

indefinitely and long past land uses may be forgotten, people may not realize that they are living in areas

where high levels of fluoride may occur in soil. Contaminated soils pose a particular hazard to children

because of both hand-to-mouth behavior and intentional ingestion of soil (pica) that contains fluorides and

other contaminants. In these communities, fluorides may have been tracked in from outdoors and

contaminate carpeting. Fluoride-containing dust may be brought home in the clothing of parents working

in industries where they are exposed to fluoride. Children may be exposed to this fluoride while crawling

around or playing on contaminated carpeting. Exposure may also result from dermal contact with soil, or

by inhaling dust and then swallowing it after mucociliary transport up out of the lungs. Because much of

the fluoride in soil is embedded in or strongly adsorbed to soil particles or insoluble, it may not be in a

form accessible for uptake by the body.

Child health data needs relating to susceptibility are discussed in Section 3.12.2 Identification of Data

Needs: Children’s Susceptibility.

Exposure Registries. No exposure registries for fluorides were located. This compound is not

currently one of the compounds for which a subregistry has been established in the National Exposure

Registry. The compound will be considered in the future when chemical selection is made for

subregistries to be established. The information that is amassed in the National Exposure Registry

facilitates the epidemiological research needed to assess adverse health outcomes that may be related to

the exposure to this compound.


The Federal Research in Progress (FEDRIP 2002) database provides additional information obtainable

from a few ongoing studies that may fill in some of the data needs identified in Section 6.8.1.



Remedial investigations and feasibility studies conducted at the 188 NPL sites known to be contaminated

with fluorine, hydrogen fluoride, or fluorides may add to the existing database on exposure levels in

environmental media at hazardous waste sites, exposure levels in humans, and exposure registries.

J.G. Schumacher of USGS, Water Resources Division, Weldon Spring, Missouri, is doing research

sponsored by USGS to determine the geochemical controls on contaminant migration from the raffinate

pits, Weldon Spring chemical plant, St. Charles County, Missouri. The former U.S. army facility

processed uranium ore-concentrates and scrap into uranium trioxide, uranium tetrafluoride, and uranium

metal. Waste from these operations (referred to as raffinate) was pumped into four large pits that contain

various quantities of uranium, thorium, nitrate, sulfate, fluoride, magnesium, and other elements. The

raffinate pits have been determined to be leaking and Li, U, NO3, and SO4, and various trace elements

have been found in groundwater and surface water both on and off site.

No other ongoing studies pertaining to the environmental fate of fluorine, hydrogen fluoride, or fluorides

were identified.


7. ANALYTICAL METHODS

The purpose of this chapter is to describe the analytical methods that are available for detecting,

measuring, and/or monitoring fluorides, hydrogen fluoride, and fluorine, its metabolites, and other

biomarkers of exposure and effect to fluorides, hydrogen fluoride, and fluorine. The intent is not to

provide an exhaustive list of analytical methods. Rather, the intention is to identify well-established

methods that are used as the standard methods of analysis. Many of the analytical methods used for

environmental samples are the methods approved by federal agencies and organizations such as EPA and

the National Institute for Occupational Safety and Health (NIOSH). Other methods presented in this

chapter are those that are approved by groups such as the Association of Official Analytical Chemists

(AOAC) and the American Public Health Association (APHA). Additionally, analytical methods are

included that modify previously used methods to obtain lower detection limits and/or to improve accuracy

and precision.

Fluorine gas is too reactive to exist in biological or environmental samples. Indeed, fluorine is too

reactive to be analyzed directly by conventional methods, but rather is quantitatively converted to

chlorine gas and the latter is analyzed (Shia 1994). The methods discussed below are for the analysis of

the fluoride ion, or in the case of gaseous acid fluorides, hydrogen fluoride. The particular fluorine

molecule is rarely identified.

7.1 BIOLOGICAL MATERIALS

Trace levels of fluoride in biological media are determined primarily by potentiometric (ion selective

electrode [ISE]) and gas chromatographic (GC) methods. Colorimetric methods are available, but are

more time consuming and lack the sensitivity of the other methods (Kakabadse et al. 1971;

Venkateswarlu et al. 1971). Other methods that have been used include fluorometric, enzymatic, and

proton activation analysis (Rudolph et al. 1973). The latter technique is sensitive to trace amounts of

sample and requires minimal sample preparation. Urine and blood and other bodily fluids can be

analyzed with a minimum of sample preparation. Tissue will require ashing, digestion with acid, or even

fusion with alkali to free the fluoride from its matrix. The most accurate method of sample preparation is

microdiffusion techniques, such as the acid-hexamethyldisiloxane (HMDS) diffusion method by Taves

(1968). These methods allows for the liberation of fluoride from organic or inorganic matrices (WHO

2002). During sample preparation, the analyst must be careful to avoid sample contamination, incomplete



release from matrices, and losses due to volatilization (NRC Canada 1971). Vogel et al. (1990) reported

methodologies for sample manipulation and fluoride analysis on very small sample volumes. Techniques

included micropipette procedures for transferring samples, preparation of micro fluoride-selective

electrodes, and methods for adapting standard electrodes for micro- and semi-micro volumes (0.005–

5 µL). These techniques have been used for fluoride analysis of various biological samples, such as

salvia, plaque, and tooth enamel (Vogel et al. 1990, 1992a, 1992b). Table 7-1 describes some analytical

methods for determining fluorides in biological materials.

There is extensive literature on the ISE methodology because it is the most frequently used method for

fluoride measurement in biological media. The fluoride ion selective membrane utilizes a membrane

consisting of a slice of a single crystal of lanthanum fluoride that has been doped with europium (II)

fluoride to improve its conductivity (Skoog et al. 1990). It has a theoretical response to changes in

fluoride ion activity in the range of 100–10-6 M. It is selective to fluoride over other common anions by

several orders of magnitude; only hydroxide ion causes serious interference. The pH of the solution

analyzed is adjusted to approximately 5 to eliminate interference. ISE is the methodology recommended

by NIOSH in Method 8308 for the determination of fluoride in urine (NIOSH 1994). Fluoride analyses

using the ion selective electrode are simple, sensitive, and rapid. Recoveries are usually >90%, but this is

dependent on the type of sample and the sample preparation required. Sample for ISE analysis must be

prepared to solubilize the fluoride in the sample. For some samples, ashing or NaOH fusion is required.

A total-ionic strength adjustment buffer (TISAB) is used to adjust samples and standards to the same

ionic strength and pH; this allows the concentration, rather than the activity, to be measured directly and

often read directly off a meter. The pH of the buffer is about 5, a level at which F- is the predominant

fluorine-containing species. The buffer contains cyclo-hexylene-dinitrilotetraacetic acid, which forms

stable complexes with Fe(III) and Al(III), thus removing interferences by freeing fluoride ions from

complexes with these ions (NIOSH 1994; Schamschula et al. 1985; Tusl 1970). Bone fluoride levels can

be measured using the ISE technique after ashing of the sample (Boivin et al. 1988). Fingernail fluoride

levels can be measured using the ISE technique after nail clippings were prepared by HMDS-facilitated

diffusion overnight. This sample preparation was found to quantitatively remove fluoride from the nail

material (Whitford et al. 1999a). Whitford et al. (1999a) also reported that soaking the fingernail samples

in deionized water for 6 hours or in a solution of 1.0 ppm fluoride for 2 hours did not change the

concentration of fluoride found in the nail.

Recent studies have employed GC to measure fluoride concentrations in human urine and plasma (Chiba

et al. 1982; Ikenishi and Kitagawa 1988; Ikenishi et al. 1988). In this method, derivatization and



Table 7-1. Analytical Methods for Determining Fluoride in Biological Materials

Sample matrix Preparation method Analytical method

Sample detection limit

Percent recovery Reference

Urine Extract with TMCS; inject organic phase (microwave induced plasma emission detector)

GC 4 µg/L 935 Chiba et al. 1982

Add equal volume TISAB solution ISE, NIOSH 8308

0.1 mg/L 95% NIOSH 1994

Add TMCS toluene solution; centrifuge; inject toluene layer

GC >5 ng/mL No data Ikenishi et al. 1988

Biological fluids and tissue ex-tracts (ionic and ionizable fluoride)

Absorb with calcium phosphate; centrifuge; analyze

ISE 10 µg/L 92–102% Venkateswarlu et al. 1971

Saliva Resuspend in TISAB buffer; analyze ISE No data 99.8% Petersson et al. 1987; Schamschula et al. 1985

Biological fluids Add TMCS toluene solution; centri-fuge; inject toluene layer and analyze by measuring TMFS peak height

GC 5 ng/L 88.1–97.2%

Ikenishi et al. 1988

Biological tissues and fluids

Extraction from acidified sample as fluorosilane; reverse extraction as fluoride ion into alkaline solution

ISE with hanging drop assembly

>0.04 ng/sample

No data Venkateswarlu 1974

Biological tissues

Sample pulverized to fine powder; irradiate with energetic beam of protons; detect gamma rays emitted

PAA <10 ng/sample

No data Rudolph et al. 1973

Decomposition of sample at 700–1,000 °C (pyrohydrolytic technique)

Colori-metry

1 µg/sample

No data Kakabadse et al. 1971

Tooth enamel Soak teeth; decalcify in HClO4; add TISAB; analyze

ISE No data No data Schamschula et al. 1982; Shida et al. 1986

Plaque Dried; microdiffusion; analyze ISE No data 97% Schamschula et al. 1985

Bone Ash sample; dissolve in perchloric acid; add 1,2-cyclohexylenedinitro-tetraacetic acid

ISE No data No data Boivin et al. 1988

Hair/fingernail Wash in diethylether; dry; de-compose in NaOH

ISE No data 94–96% Schamschula et al. 1985

Fingernail HMDS-facilitated diffusion overnight ISE No data No data Whitford et al. 1999a

GC = gas chromatography; HClO4 = perchloric acid; HMDS = hexamethyldisiloxane; ISE = ion selective electrode; NaOH = sodium hydroxide; NIOSH = National Institute for Occupational Safety and Health; PAA = proton activation analysis; TISAB = total ionic strength activity buffer; TMCS = trimethylchlorosilane; TMFS = trimethylfluorosilane



extraction is achieved using trimethylchlorosilane (TMCS) in toluene to produce trimethylfluorosilane

(TMFS). The organic layer is injected into the GC system and the TMFS peak height is compared with

those of standard solutions. The GC method has the advantage of high sensitivity—nanogram quantities

of fluoride are detectable in a milliliter of urine or plasma. This method is also useful for assessing the

fluoride released from fluorine-containing drugs in biological fluids. The detection of bound fluorine

provides an advantage over the ISE technique, which is not suitable for bound or organic fluoride

measurements. It should also be noted that the aluminum ion may cause interference under the operating

conditions of the GC, as it does with the ISE method.

7.2 ENVIRONMENTAL SAMPLES

The ISE method is the most widely used method for determining fluoride levels in the environmental

media. Table 7-2 describes this and other methods for determining fluoride in environmental samples.

Table 7-3 describes methods for determining hydrogen fluoride in air. ISE methods are simple to perform

and have good precision and sensitivity. Fluoride-specific electrodes are commercially available. The

method detects only free fluoride ions in solution. Because of the inherent restriction of this technique,

several approaches have been recommended to prepare the sample for analysis. Lopez and Navia (1988)

assayed total fluoride (bound and free) in food and beverages by initially acid hydrolyzing samples at

100 °C in borosilicate vials. This closed-system approach decreases contamination, eliminates dry

ashing, and yields high recoveries. Dabeka and McKenzie (1981) employed microdiffusion with 40%

perchloric acid to food samples in Petri dishes at 60 °C for 24–48 hours. Difficulties arose in controlling

contamination and fluoride loss in the Petri dishes, and low recoveries were reported. Preparation of total

fluoride in dry plant material (i.e., hay, barley, straw, corn, grass) was described by Eyde (1982); samples

were fused in nickel crucibles with sodium hydroxide at 350–475 °C. The ash was diluted and filtered for

analysis. This method is more tedious than the others, and fluoride loss is expected from the high fusion

temperatures. All of these preparatory techniques can liberate bound fluoride from the sample matrices.

It is important to prevent interference of other ions and to avoid fluoride loss at high decomposition

temperatures before potentiometric analyses. Kakabadse et al. (1971) described a pyrohydrolytic

technique for tea, coca, or tobacco samples that could be employed prior to colorimetric or ISE analysis.

Decomposition of the sample at 700–1,000 °C is mediated by a current of air or pure oxygen to evolve

hydrogen fluoride. An advantage of this approach is that fluoride is collected from inorganic and organic

fluorides in one operation. Ashing, which may produce loss of organic fluorine, is eliminated.



Table 7-2. Analytical Methods for Determining Fluoride in Environmental Samples

Sample matrix Preparation method

Analytical method



Air Ambient air collected using teflon tubing; detect with continuous flow analyzer

ISE 0.1 µg/L No data Danchik et al. 1980

Sample at 1–2 L/minute using cellulose ester membrane filter and alkaline-impregnated backup pad to collect particulate and gaseous fluorides. Extract hydrogen fluoride and soluble fluorides with water; insoluble fluorides require NaOH fusion

IC/conductivity detector; NIOSH 7906

3 µg/sample (gas); 120 µg/sample (particulate)

No data NIOSH 1994

Sample at 1–2 L/minute using cellulose ester membrane filter and alkaline-impregnated backup pad to collect particulate and gaseous fluorides; extract hydrogen fluoride and soluble fluorides with 50 mL 1:1 TISAB: water; insoluble fluorides require NaOH fusion

ISE, NIOSH 7902

3 µg/sample No data NIOSH 1994

Syringe-sampling; dilute with 50% (v/v) 1,2-dioxane containing Amadec-F

Colorimetry 0.3 ppm No data Bethea 1974

Water Dilute sample; add barium chloride; complex with zirconium-xylenol orange for color development

Colorimetry 2,000 µg/L No data Macejunas 1969

Sample added to sulfuric acid and distilled to remove inter-ferences; distilled sample treated with SPADNS reagent; color loss resulting from reaction of reagent with fluoride is determined at 570 nm and concentration read off standard curve

Colorimetry; EMSLC Method 340.1

0.10 mg/L No data EPA 1998c

Mix sample and standard 1:1 with TISAB (for soluble fluorides)

ISE, OSW Method 9214

0.500 mg/L No data EPA 1996

No sample treatment required ISE, EMSLC Method 340.2


Bellack distillationa, after which fluoride ion reacts with the red cerous chelate of alizarin complexone in an autoanalyzer

Colorimetry, EMSLC Method 340.3




Table 7-2. Analytical Methods for Determining Fluoride in Environmental Samples


Analytical method



Extract with TMCS; analyze organic phase (microwave induced plasma emission detector)

GC 4 µg/L 93–100% Chiba et al. 1982

Waste water

Centrifuge sample to settle solids; filter and dilute

Anion exclusion chromatography

200 µg/L No data Hannah 1986

Water, rain Dilute sample with TISAB buffer; analyze in flow injection system

ISE 2 µg/L No data Fucsko et al. 1987

Food, beverage

Homogenize sample; acid hydrolysis in a closed system

ISE 0.1 µg/g 97% Lopez and Navia 1988

Sample pulverized to powder PAA 1 µg/g dry weight

No data Shroy et al. 1982

Tea, cocoa, tobacco

Decomposition at 700–1,000 °C in moist current of oxygen or air; collect hydrogen fluoride; react to form Ce(III)alizarin-complexan

Colorimetry >1 µg No data Kakabadse et al. 1971

Milk, peas, pears

Sample is dried and ground to powder; microdiffusion in Petri dish; analyze

ISE 0.2–5 µg/g 54–109% Dabeka and McKenzie 1981

Vegetation Fluorine-19 sample activation INAA 14 µg/sample No data Knight et al. 1988

Extraction of sample ISE >0.05 µg/g >95% Jacobson and Heller 1971

Fusion with NaOH; dissolve in tiron buffer

ISE 10 µg/g No data Sager 1987

Feed Sample is dried and acidified ISE 15 µg/g 90–108% Melton et al. 1974

Household products

Dilute sample, add buffer; addition procedure

ISE No data 98–104% Schick 1973

Plants Sample dried and fused in nickel crucibles; filter

ISE >0.3 µg/g 87–102% Eyde 1982

aBellack distillation uses HClO4/AgClO4 to remove chloride. Ce III = cesium ion (+3 oxidation state); EMSLC = EPA Environmental Monitoring Systems Laboratory in Cincinnati; GC = gas chromatography; HPLC = high pressure liquid chromatography; IC = ion chromatography; INAA = instrumental neutron activation analysis; ISE = ion selective electrode; NaOH = sodium hydroxide; NIOSH = National Institute for Occupational Safety and Health; OSW = Office of Soild Waste; PAA = proton activation analysis; SPADNS = sodium 2-(parasulfophenylazo)-1,8-dihydroxy-3,6-naphthalene disulfonate; TISAB = total ionic strength activity buffer; TMCS = trimethylchlorosilane; (v/v) = volume/volume



Table 7-3. Analytical Methods for Determining Hydrogen Fluoride in Environmental Samplesa


Analytical method



Air Personal air sampled at 1–2 L/minute for total sample of 12–800 L onto treated pad; soak pad in 25 mL water and 25 mL TISAB; collect using teflon tubing and analyze with continuous flow analyzer.

ISE, NIOSH 7902

0.7 µg fluoride/sample

No data NIOSH 1994

Personal air sampled at 0.2–0.3 L/min for total sample size of 3–100 L using silica gel sample tube; boil sorbent from sample tube in bicarbonate/carbonate buffer for 10 minutes.

IC/conductivity detector, NIOSH 7903

0.7 µg/sample No data NIOSH 1994

Personal air sampled at 1–2 L/minute using cellulose ester membrane filter and alkaline-impregnated backup pad to collect particulate and gaseous fluorides; extract hydrogen fluoride and soluble fluorides with water; insoluble fluorides requires NaOH fusion.

IC/conductivity detector, NIOSH 7906

3 µg/sample (gas); 120 µg/sample (particulate)

No data NIOSH 1994

Hydrogen fluoride vapor collected with dosimeter containing poly-propylene element.

ISE 100 µg/L No data Young and Monat 1982

Dual cellulose filter to separate particulate and gaseous fluoride; heat filters at 75 °C; extract; dilute with TISAB buffer.

ISE 1.2 µg/filter No data Einfeld and Horstman 1979

aSome methods measure both gaseous (HF) and particulate fluorides. IC = ion chromatography; ISE = ion selective electrode; NIOSH = National Institute for Occupational Safety and Health; TISAB = total ionic strength activity buffer, v/v = volume/volume



Fluoride ions form stable, colorless complexes with certain multivalent ions, such as (AlF6)3-, (FeF6)3-,

and (ZrF6)3-. Most colorimetric methods for the determination of fluoride are based on the bleaching of

colored complexes of these metals with organic dyes when fluoride is added (WHO 1984). The degree of

bleaching is determined with a spectrophotometer, and the concentration of fluoride ions is assessed by

comparison with standard solutions. In EPA Method 340.1, the sodium 2-(parasulfophenylazo)-1,8-di-

hydroxy-3,6-naphthalenedisulfonate (SPADNS) reagent is used, and the color loss is measured at 570 nm

(EPA 1998c). In EPA Method 340.3, the red cerium complex with alizarin complex one turns blue on the

addition of fluoride (EPA 1998c).

Ion chromatography (IC) utilizes anion exchange resins as a stationary phase to separate fluoride ions

from other species. In most cases, conductivity detectors are used to detect the ions in the eluent. Both

the stationary phase and the eluent must be chosen to separate fluoride from overlapping ions. Hannah

(1986) used a variant of ion exchange chromatography, namely anion exclusion chromatography, to

analyze fluoride in waste water. This method is generally applied to the separation of weak organic acids

and its use for fluoride determinations is based on the fact that fluoride is an anion of a weak acid,

hydrogen fluoride, with a pKa of 3.19, similar to that of weak organic acids. The acids elute in order of

increasing pKa. At low pH, anions of strong acids remain disassociated and are excluded from the resin

and are rapidly eluted. Hydrogen fluoride exists primarily in the molecular form, and interacts with the

resin, delaying its elution. In this way, fluoride is sufficiently separated from ionic interferences to be

reliably quantified. Interfering anions, such as chloride, emerge as one peak before the fluoride elutes.

Resolution can be controlled by adjusting the pH.

Fluorides in air may be present in the gas phase (generally hydrogen fluoride) or in the particulate phase.

Sampling may involve trapping the particulate phase on a membrane filter and the hydrogen fluoride on

an alkaline impregnated backup pad as in NIOSH Method 7906 (NIOSH 1994). Several modifications

have been suggested for the air sample collection. Einfeld and Horstman (1979) found that gaseous

fluoride, to some extent, may get trapped in the filter for particulate fluoride. They suggest that

postsampling heat treatment promotes desorption of the gaseous fluoride from the particulate phase. The

use of Teflon® tubing and materials in the analyzer is indicated for controlling loss of sample ions

(Candreva and Dams 1981; Danchik et al. 1980).

For the analysis of pollutants in the environment, EPA has approved the ISE (Method 340.2) and

colorimetric methods (Methods 340.1 and 340.3) for determining inorganic fluoride in water (EPA 1998).



NIOSH recommends the use of ISE (Method 7902) and IC methods (Methods 7903 and 7906) for the

determination of fluoride and hydrogen fluoride in air (NIOSH 1994).

Fluoride gas or vapors in ambient air are measured primarily with the ISE method. NIOSH Method 7902

uses this technique for the determination of hydrogen fluoride and particulate fluorides in air (NIOSH

1994). The hydrogen fluoride gas and particulate fluorides are collected on separate filters before

determination. Several modifications have been suggested for the air sample collection. Einfeld and

Horstman (1979) found that gaseous fluoride may get trapped in the filter for particulate fluoride to some

extent. They utilized postsampling heat treatment to desorb hydrogen fluoride from particulates. The use

of Teflon® tubing and materials in the analyzer is indicated for controlling fluoride loss (Candreva and

Dams 1981; Danchik et al. 1980).

Young and Monat (1982) developed a dosimeter to be worn on the lapel in the workplace for monitoring

airborne fluoride vapor. A replaceable collection element adsorbs the fluoride vapors. Samples are

desorbed with TISAB solution and analyzed on the ISE. The study authors noted its convenience,

stability, retentivity, and insensitivity to moisture at 5–88% humidity and competing sulfur dioxide

vapors. Interference may occur from reactive volatile fluorine compounds. Wind, temperature, and

atmospheric pressure can affect results. The dosimeter yields a sample detection range of 0.1–387 ppm

fluoride in air.

Two analytical methods for fluorine determination have been developed based on neutron or proton

activation of fluorine-9 (Knight et al. 1988; Shroy et al. 1982). Instruments measure the emitted gamma

rays or x-rays using lithium-drifted germanium detectors. This approach has wide application, since it

does not depend on a specific sample matrix or chemical form. However, the need for a special facility

with a source of neutrons or protons limits its use.




adequate information on the health effects of fluorides, hydrogen fluoride, and fluorine is available.





health effects (and techniques for developing methods to determine such health effects) of fluorides,

hydrogen fluoride, and fluorine.







Methods for Determining Biomarkers of Exposure and Effect.

Exposure. Sensitive, reproducible analytical methods are available for detecting fluorides in biological

materials following short-term exposure (such as plasma and urine) and long-term exposure (i.e., bone).

The most common technique is the ISE method because it is reliable, simple, and sensitive, and has good

recoveries (NIOSH 1994; Venkateswarlu et al. 1971). GC is also useful for detection of trace levels of

fluoride in plasma and urine (Chiba et al. 1982; Ikenishi and Kitagawa 1988; Ikenishi et al. 1988). Both

methods can measure samples at concentrations at which health effects may occur.

Urinary fluoride is a widely accepted biomarker of recent fluoride exposure and has frequently been used

as an indicator of fluoride exposure in occupational studies (Chan-Yeung et al. 1983a; Kaltreider et al.

1972) and to determine exposure from drinking water (Spak et al. 1985). A minimum fluoride level of

4 mg/L in the urine using the ISE technique has been recommended as an indicator of recent fluoride

exposure in workers (Derryberry et al. 1963). Other possible biomarkers of fluoride exposure include

fluoride concentrations in tooth enamel (Shida et al. 1986), hair (Schamschula et al. 1982), nails

(Schamschula et al. 1982; Whitford et al. 1999a), saliva (Petersson et al. 1987), blood (Jackson and

Hammersley 1981), and bone (Baud et al. 1978; Bruns and Tytle 1988; Fisher 1981; Sauerbrunn et al.

1965) for which analytical methods are available.

Effect. For biomarkers of effect following chronic exposure, investigators have looked for skeletal

fluorosis using radiographs. Bone density is a common index used for evaluation (Kaltreider et al. 1972).

Guminska and Sterkowicz (1975) found an increase in erythrocyte enzyme activity (i.e., enolase, pyruvate

kinase, ATPase) that may reflect altered glucose metabolism during prolonged fluoride exposure. These



biochemical alterations are suggested for possible diagnostic purposes, but they represent a response that

may be induced in the body by a physiological change or other chemical agents. Therefore, more specific

analytical methods are needed for measuring biomarkers of effect.

Methods for Determining Parent Compounds and Degradation Products in Environmental Media. Methods are available for determining fluoride levels in environmental samples. Methods

determine the fluoride concentration and not the particular fluorine-containing compound. Therefore,

analytical methods do not distinguish between parent compound and degradation product. The ISE

method is the most common method for measuring fluoride in environmental samples. It is a convenient,

sensitive, and reliable method, but fluoride ions must first be released from any matrix and rendered free

in solution. Methods are available for preparing various types of environmental samples for analysis

(Dabeka and McKenzie 1981; EPA 1998c; Eyde 1982; Kakabadse et al. 1971; Lopez and Navia 1988;

NIOSH 1994; NRC Canada 1971; WHO 1984).


One ongoing study regarding techniques for measuring and determining fluoride in biological and

environmental samples was located. Noah Seixas of the University of Washington proposes to adapt real-

time instruments for monitoring HF and SO2 and a nonspecific particulate, integrating currently available,

electrochemical sensor, and light scattering technology and, using these instruments, to monitor exposure

in four aluminum smelting operations (FEDRIP 2002).


8. REGULATIONS AND ADVISORIES

No international regulations pertaining to fluorides were found. The national and state regulations and

guidelines regarding fluorides, hydrogen fluoride, and fluorine in air, water, and other media are

summarized in Table 8-1.

A chronic-duration oral MRL of 0.05 mg fluoride/kg/day has been derived for fluoride. This MRL is

based on a NOAEL of 0.15 mg fluoride/kg/day and a LOAEL of 0.25 mg fluoride/kg/day for skeletal

effects (increased fracture rate) (Li et al. 2001). The MRL was derived by dividing the NOAEL by an

uncertainty factor of 3 to account for human variability.

An acute-duration inhalation MRL of 0.02 ppm fluoride has been derived for hydrogen fluoride. This

MRL is based on a minimal LOAEL of 0.5 ppm for upper respiratory tract inflammation in humans

exposed to hydrogen fluoride for 1 hour (Lund et al. 1997, 1999). The MRL was derived by dividing the

unadjusted LOAEL by an uncertainty factor of 30 (3 for a use of a minimal LOAEL and 10 to account for

human variability).

An acute-duration inhalation MRL of 0.01 ppm has been derived for fluorine. This MRL is based on a

NOAEL of 10 ppm for respiratory irritation in humans exposed to fluorine for 15 minutes (Keplinger and

Suissa 1968). The MRL was derived by dividing the 24-hour adjusted NOAEL of 0.1 ppm by an

uncertainty factor of 10 to account for human variability.

EPA (IRIS 2003) derived an oral reference dose (RfD) of 0.06 mg/kg/day for fluorine (soluble fluoride).

The RfD was based on a NOAEL of 0.06 mg/kg/day and a LOAEL of 0.12 mg/kg/day for the cosmetic

effect of dental fluorosis in children (Hodge 1950). The NOAEL was divided by an uncertainty factor

of 1 to derive the RfD.



Table 8-1. Regulations and Guidelines Applicable to Fluoride, Sodium Fluoride, Hydrogen Fluoride, and Fluorine

Agency Description Information Reference INTERNATIONAL Guidelines:

IARC Carcinogenicity classification Fluoride and sodium fluoride

Group 3a

IARC 1987

WHO Drinking water guideline Fluoride

1.5 mg/L

WHO 2001

NATIONAL Regulations and Guidelines:

a. Air ACGIH TLV-TWA

Fluoride Fluorine STEL (ceiling) Fluorine Hydrogen fluoride

2.5 mg/m3 1.0 ppm 2.0 ppm 3.0 ppm

ACGIH 2000

EPA Accidental release prevention Threshold quantity Fluorine Hydrogen fluoride

1,000 pounds 1,000 pounds

EPA 2001b 40CFR68.130 Table 1

Accidental release prevention Toxic end point Fluorine Hydrogen fluoride

0.0039 mg/L 0.0160 mg/L

EPA 2001a 40CFR68 Appendix A

OSHA PEL (8-hour TWA) General industry Fluoride Fluorine Hydrogen fluoride

2.5 mg/m3 0.2 mg/m3 2.0 mg/m3

OSHA 2001c 29CFR1910.1000 Table Z-1

PEL (8-hour TWA) Construction industry Fluoride Fluorine Hydrogen fluoride

2.5 mg/m3 0.2 mg/m3 2.0 mg/m3

OSHA 2001f 29CFR1926.55 Appendix A

PEL (8-hour TWA) Shipyards Fluoride Fluorine Hydrogen fluoride

2.5 mg/m3 0.2 mg/m3 2.0 mg/m3

OSHA 2001a 29CFR1915.1000 Table Z

Highly hazardous chemicals Threshold quantity Fluorine

1,000 pounds

OSHA 2001d 29CFR1910.119 Appendix A

Highly hazardous chemicals Threshold quantity Hydrogen fluoride

1,000 pounds

OSHA 2001e 29CFR1926.64 Appendix A




Agency Description Information Reference NATIONAL (cont.) OSHA Brazing and gas welding fluxes

shall have a cautionary wording to indicate that they contain fluorine compounds

OSHA 2001b 29CFR1910.252(c)(1)

NIOSH REL (TWA) Fluorine Hydrogen fluoride Sodium fluoride

0.2 mg/m3 2.5 mg/m3 2.5 mg/m3

NIOSH 2001a NIOSH 2001b NIOSH 2001c

IDLH Fluorine Hydrogen fluoride Sodium fluoride

25 ppm 30 ppm 250 ppm

NIOSH 2001a NIOSH 2001b NIOSH 2001c

USC HAP USC 2001 42USC7412

b. Water EPA BPT effluent limitationCfluoride

Maximum for 1 day Average of daily values for 30 consecutive days

6.1 kg/kkg 2.9 kg/kkg

EPA 2001c 40CFR415.82

Effluent limitationCfluoride Maximum for 1 day Average of daily values for 30 consecutive days

75 mg/L 25 mg/L

EPA 2001e 40CFR422.42

Groundwater protection standards at inactive uranium processing sitesClisted constituents include fluorine and hydrogen fluoride

EPA 2001f 40CFR192 Appendix I

MCLGCfluoride 4.0 mg/L EPA 2001j 40CFR141.51(b)

MCLCfluoride 4.0 mg/L EPA 2001k 40CFR141.62(b)

Secondary MCLCfluoride 2.0 mg/L EPA 2001l 40CFR143.3

Water pollutionChazardous substance designation

Hydrogen fluoride Sodium fluoride

EPA 2001r 40CFR116.4

c. Food EPA PesticidesCfluorine compounds;

residue tolerances Apricots, beets, blackberries, blueberries, boysenberries, broccoli, brussels sprouts, cabbage, cauliflower, citrus fruits, collards, cranberries

7 ppm

EPA 2001n 40CFR180.145




Agency Description Information Reference NATIONAL (cont.) EPA PesticidesCfluorine compounds;

residue tolerances Cucumbers, dewberries, eggplant, grapes, kale, kohlrabi, lettuce, loganberries, melons, nectarines, peaches, peppers, plums, pumpkins, radish, raspberries, rutabaga, squash, strawberries, tomatoes, turnip, youngberries Potatoes Potatoes, processing waste Kiwifruit

7 ppm 2 ppm 22 ppm 15 ppm

EPA 2001n 40CFR180.145

FDA Adhesive component, indirect food additiveCfor use only as bonding agent for aluminum foil, stabilizer, or preservative Hydrogen fluoride Sodium fluoride

Total fluoride from all sources not to exceed 1% by weight of the finished adhesive

FDA 2000e 21CFR175.105(c)(5)

Bottled waterCno fluoride added Temperatureb mg/L 53.7Bbelow 2.4 53.8B58.3 2.2 58.4B63.8 2.0 63.9B70.6 1.8 70.7B79.2 1.6 79.3B90.5 1.4

FDA 2000g 21CFR165.110

Bottled waterCfluoride added Temperatureb mg/L 53.7Bbelow 1.7 53.8B58.3 1.5 58.4B63.8 1.3 63.9B70.6 1.2 70.7B79.2 1.0 79.3B90.5 0.8

Over-the-counter drug products LabelingCfluoride, fluorine, and sodium fluoride

FDA 2000b 21CFR355.50 FDA 2000c 21CFR355.60

Over-the-counter drug products TestingCfluoride

FDA 2000d 21CFR355.70

Over-the-counter drug products Active ingredientCfluorine, hydrogen fluoride, and sodium fluoride

FDA 2000a 21CFR355.10 FDA 2000f 21CFR310.545(a)(2)




Agency Description Information Reference NATIONAL (cont.) FDA Surface component, food

contactCsodium fluoride for use as preservative only

FDA 2000h 21CFR177.2800 (d)(5)

d. Other ACGIH Carcinogenicity classification

Fluoride BEI Fluorides in urine Prior to shift End of shift

A4c 3 mg/g creatinine 10 mg/g creatinine

ACGIH 2000

CPSC Requirements for child-resistant packaging for household products containing elemental fluoride

More than 50 mg and more than 0.5%

CPSC 2001 16CFR1700

DOT Hazardous materials Reportable quantity Fluorine Hydrogen fluoride Sodium fluoride

10 pounds 100 pounds 1,000 pounds

DOT 2001 40CFR172.101 Appendix A

EPA RfDCfluorine 6x10-2 mg/kg/day IRIS 2003 Toxic chemical release reporting;

Community Right-to-KnowCeffective date Fluorine Hydrogen fluoride

01/01/95 01/01/87

EPA 2001q 40CFR372.65

Contaminated soilCfluoride Concentrations greater than 10 times UTS

EPA 2001d 40CFR268.49(f)

Hazardous wasteChealth based limits for exclusion of waste-derived-residue Fluorine residue concentration limit

4.0 mg/kg

EPA 2001g 40CFR266 Appendix VII

Hazardous wasteCidentification and listing Fluorine Hydrogen fluoride

P056 U134

EPA 2001h 40CFR261.33(e) EPA 2001i 40CFR261.33(f)

PesticidesCresidue tolerances Sodium fluoride

Not more than 25% of pesticide formulation

EPA 2001m 40CFR180.1001(d)

SuperfundCreportable quantity Fluorine Hydrogen fluoride Sodium fluoride

1 pound 5,000 pounds 5,000 pounds

EPA 2001o 40CFR302.4 Appendix A




Agency Description Information Reference NATIONAL (cont.) EPA SuperfundCextremely hazardous

Reportable quantity Fluorine Hydrogen fluoride Threshold planning quantity Fluorine Hydrogen fluoride

10 pounds 100 pounds 500 pounds 100 pounds

EPA 2001p 40CFR355 Appendix A

STATE a. Air Connecticut HAPCfluoride, fluorine, and

hydrogen fluoride BNA 2001

Hawaii Air contaminantChydrogen fluoride

BNA 2001

Idaho Toxic air pollutants Fluoride OEL EL AAC Fluorine OEL EL AAC

2.5 mg/m3 0.167 pounds/hour 0.125 mg/m3 2.0 mg/m3 0.133 pounds/hour 0.1 mg/m3

BNA 2001

Michigan PEL (TWA) Fluoride Fluorine Hydrogen fluoride

2.5 mg/m3 0.2 mg/m3 3.0 ppm

BNA 2001

Montana Air contaminant (TWA) Fluoride Fluorine Hydrogen fluoride

2.5 mg/m3 0.2 mg/m3 2.0 mg/m3

BNA 2001

New Mexico Toxic air pollutant Fluorides OEL Emissions Fluorine OEL Emissions

2.5 mg/m3 0.167 pounds/hour 2.0 mg/m3 0.133 pounds/hour

BNA 2001

New York Air contaminant (TLV) Fluoride Fluorine Hydrogen fluoride

2.5 mg/m3 0.2 mg/m3 2.0 mg/m3

BNA 2001




Agency Description Information Reference STATE (cont.) Washington Toxic air pollutantCASIL

Fluoride Fluorine Hydrogen fluoride

8.3 µg/m3 5.3 µg/m3 8.7 µg/m3

BNA 2001

PEL Fluoride Fluorine Hydrogen fluoride (STEL)

2.5 mg/m3 0.2 mg/m3 3.0 ppm

BNA 2001

Wisconsin Emission rate (pounds/hour) Fluoride Fluorine Hydrogen fluoride

<25 feet 0.2088 0.1656 0.1272

>25 feet 0.8640 0.6720 0.4800

BNA 2001

b. Water Alaska MCLCfluoride

Secondary MCLCfluoride 4.0 mg/L 2.0 mg/L

BNA 2001

Arizona Drinking water guidelineCfluoride 4.0 mg/L HSDB 2003 Reporting limitCfluoride 2.0 mg/L BNA 2001 California Drinking water standardsC

fluoride 2.0 mg/L HSDB 2003

Connecticut MCLCfluoride 4.0 mg/L BNA 2001 Delaware Drinking water standardsC


Georgia MCLCfluoride 4.0 mg/L BNA 2001 Hawaii Drinking water standardsC

fluoride 1.4B2.4 mg/L HSDB 2003

Idaho Groundwater quality standardsC fluoride

4.0 mg/L BNA 2001

Kansas AgricultureCfluoride Livestock Irrigation Public health foodCfluoride Domestic water supply

2.0 mg/L 1.0 mg/L 2.0 mg/L

BNA 2001

Maine Drinking water guidelineCfluoride 2.4 mg/L HSDB 2003 Maximum exposure guideline

Action level 2.4 mg/L 1.2 mg/L

BNA 2001

Mississippi Groundwater standardsCfluoride 4.0 ppm BNA 2001 Nebraska MCLCfluoride 4.0 mg/L BNA 2001




Agency Description Information Reference STATE (cont.) New Jersey Groundwater quality criteriaC

fluoride PQLCfluoride

2.0 mg/L 0.5 mg/L

BNA 2001

New York Groundwater effluent limitationsC fluoride

3.0 mg/L BNA 2001

MCLCfluoride 2.2 mg/L BNA 2001 North Carolina Drinking water standardsC


North Dakota MCLCfluoride 4.0 mg/L BNA 2001 Oklahoma MCLCfluoride 4.0 mg/L BNA 2001 Pennsylvania Drinking water standardsC


Rhode Island MCLGCfluoride MCLCfluoride

4.0 ppm 4.0 ppm

BNA 2001

South Dakota Groundwater quality standardsC fluoride

2.4 mg/L BNA 2001

Tennessee MCLCfluoride 4.0 ppm BNA 2001 Texas MCLCfluoride 4.0 mg/L BNA 2001 Utah Groundwater standards 4.0 mg/L BNA 2001 MCLCfluoride 4.0 mg/L BNA 2001 Vermont Groundwater quality standardsC

fluoride Enforcement standard Preventive action level

4.0 mg/L 2.0 mg/L

BNA 2001

MCLCfluoride 4.0 mg/L BNA 2001 Washington MCLCfluoride 4.0 mg/L BNA 2001 West Virginia Groundwater standards Not to exceed 4.0 mg/L BNA 2001 Wisconsin MCLGCfluoride

MCLCfluoride 4.0 mg/L 4.0 mg/L

BNA 2001

Groundwater standardsCfluoride Enforcement standard Preventive action limit

4.0 mg/L 0.8 mg/L

BNA 2001

c. Food No data d. Other Connecticut Use of pesticides; control of

registrations and usesCsodium fluoride

For use as a wood preservative

BNA 2001




Agency Description Information Reference STATE (cont.) Minnesota Hazardous substanceCfluoride

(as F, as dust), fluorides (inorganic), fluorine, and hydrogen fluorine

BNA 2001

New Jersey Hazardous substanceCfluorine and hydrogen fluoride

BNA 2001

aGroup 3: not classifiable as to its carcinogenicity to humans bTemperature: annual average of maximum daily air temperatures (EF) cA4: not classifiable as a human carcinogen AAC = acceptable ambient concentrations; ACGIH = American Conference of Governmental Industrial Hygienists; ASIL = acceptable source impact levels; BEI = biological exposure indices; BNA = Bureau of National Affairs; BPT = best practicable control technology; CFR = Code of Federal Regulations; CPSC = Consumer Product Safety Commission; DOT = Department of Transportation; EL = emissions levels; EPA = Environmental Protection Agency; FDA = Food and Drug Administration; HAP = hazardous air pollutant; HSDB = Hazardous Substances Data Bank; IARC = International Agency for Research on Cancer; IDLH = immediately dangerous to life and health; IRIS = Integrated Risk Information System; MCL = maximum contaminant level; MCLG = maximum contaminant level goal; NIOSH = National Institute for Occupational Safety and Health; OEL = occupational exposure limit; OSHA = Occupational Safety and Health Administration; PEL = permissible exposure limit; PQL = practical quantitation level; REL = recommended exposure limit; RfD = reference dose; STEL = short term exposure limit; TLV = threshold limit values; TWA = time-weighted average; USC = United States Code; UTS = universal treatment standards; WHO = World Health Organization


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*Ward PFV, Hall RJ, Peters RA. 1964. Fluoro-fatty acids in the seeds of Dichapetabum toxicarium. Nature 201:611-612. Warneke G, Setnikar I. 1993. Effects of meal on the pharmacokinetics of fluoride from oral monofluorophosphate. Arzneim Forsch 43(1):590-595. *Warren JJ, Levy SM. 1999. A review of the fluoride dentifrice related to dental fluorosis. Pediatric Dent 21(4):265-271. *Watanabe M, Yoshida Y, Watanabe M, et al. 1975. Effect of hydrofluoric acid on glucose metabolism of the mouse studied by whole-body autoradiography. Br J Ind Med 32:316-320. *Waterhouse C, Taves D, Munzer A. 1980. Serum inorganic fluoride: Changes related to previous fluoride intake renal function and bone resorption. Clin Sci 58:145-152. Watson AP, Griffin GD. 1992. Toxicity of vesicant agents scheduled for destruction by the chemical stockpile disposal program. Environ Health Perspect 98:259-280. Weast RC, Lide DR, Astle MJ, et al. 1989. CRC handbook of chemistry and physics. 70th ed. Boca Raton, FL: CRC Press, Inc. Weatherell JA, Strong M, Robinson C, et al. 1986. Fluoride distribution in the mouth after fluoride rinsing. Caries Res 20:111-119. Weber CW, Reid BL. 1973. Effect of low fluoride diets fed to mice for six generations. Proceedings of the 2nd International Symposium on Trace Element Metabolism in Animals 2:707-709. *Weddle DA, Muhler JC. 1954. The effects of inorganic salts on fluoride storage in the rat. J Nutr 54:437-444. Wei SH, Connor CW Jr. 1983. Fluoride uptake and retention in vitro following topical fluoride application. J Dent Res 62:830-832. Weiss G, ed. 1986. Hazard chemicals data book. 2nd ed. Park Ridge, NJ: Noyes Data Corporation, 16-18. *West JR, Smith HW, Chasis H. 1948. Glomerular filtration rate, effective renal blood flow, and maximal tubular excretory capacity in infancy. J Pediatr 32:10-18. West PW, Lyles GR, Miller JL. 1970. Spectrophotometric determination of atmospheric fluorides. Environ Sci Technol 4:487-491. Wheeler SM, Turner AD, Brock TB, et al. 1988. The effect of 30 mg/L fluoride in drinking water on ewes and their lambs and current bone levels of sheep in New South Wales, Australia. Fluoride 21:60-68. White DA. 1980. Hydrofluoric acid. J Soc Occup Med 30:12-14. White DJ, Nancollas GH. 1990. Physical and chemical considerations of the role of firmly and loosely bound fluoride in caries prevention. J Dent Res 69(special issue):587-594.


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Whitford GM. 1983. Fluorides: Metabolism, mechanisms of action and safety. Dent Hyg 57:16-18, 20-22, 24-29. Whitford GM. 1989. Plasma ion concentrations associated with acute fluoride toxicity [Abstract]. J Dent Res 68:335. *Whitford GM. 1990. The physiological and toxicological characteristics of fluoride. J Dent Res 69(Special Issue):539-549. *Whitford GM. 1994. Effects of plasma fluoride and dietary calcium concentrations on GI absorption and secretion of fluoride in the rat. Calcif Tissue Int 54:421-425. *Whitford GM. 1997. Determinants and mechanisms of enamel fluorosis. Ciba Found Symp 205:226-245. *Whitford GM. 1999. Fluoride metabolism and excretion in children. J Public Health Dent 59(4):224-228. *Whitford GM, Johnson NA. 2003. Comparison of fluoride metabolism when administered as NaF or silicofluorides to rats. J Dent Res 82 (Special Issue A):Abst 81. *Whitford GM, Pashley DH. 1984. Fluoride absorption: The influence of gastric acidity. Calcif Tissue Int 36:302-307. Whitford GM, Taves DR. 1973. Fluoride induced diuresis: Renal-tissue solute concentrations, functional, hemodynamic, and histological correlates in the rat. Anesthesiology 39:416-427. *Whitford GM, Williams JL. 1986. Fluoride absorption: Independence from plasma fluoride levels. Proc Soc Exper Biol Med 181:550-554. Whitford GM, Allmann DW, Shahed AR. 1987a. Topical fluorides: Effects on physiologic and biochemical processes. J Dent Res 66:1072-1078. Whitford GM, Biles ED, Birdsong-Whitford NL. 1991. A comparative study of fluoride pharmacokinetics in five species. J Dent Res 70:948-951. *Whitford GM, Birdsong-Whitford NL, Finidori C. 1990. Acute oral toxicity of sodium fluoride and monofluorophosphate separately or in combination in rats. Caries Res 24:121-126. Whitford GM, Finidori C, Birdsong-Whitform NL. 1987b. Acute LD50 values of fluorine given as sodium fluoride and/or MFP in the rat. Caries Res 21:166. *Whitford GM, Hobbs SH, Stoddard JL, et al. 2003. Failure to find fluoride-induced learning deficits in rats. J Dent Res 82 (Special Issue A):Abst 80. Whitford GM, Pashley DH, Reynolds KE. 1977a. Fluoride absorption from the rat urinary bladder: A pH-dependent event. Am J Physiol 232:F10-15. *Whitford GM, Pashley DH, Reynolds KE. 1979a. Fluoride tissue distribution: Short-term kinetics. Am J Physiol 236:F141-148.


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Zipkin I, Leone NC. 1957. Rate of urinary fluoride output in normal adults. Am J Public Health 47:848-851. Zipkin I, Likins RC. 1957. Absorption of various fluorine compounds from the gastrointestinal tract of the rat. Am J Physiol 191:549-550. *Zipkin I, McClure FJ. 1952. Deposition of fluorine in the bones and teeth of the growing rat. J Nutr 47:611-620. *Zipkin I, Likins RC, McClure FJ, et al. 1956. Urinary fluoride levels associated with use of fluoridated waters. Public Health Rep 71:767-772. Zipkin I, McClure FJ, Leone KC, et al. 1958. Fluoride deposition in human bones after prolonged ingestion of fluoride in drinking water. Public Health Rep 73:732-740. *Zipkin I, Zucas SM, Lavender DR, et al. 1970. Fluoride and calcification of the aorta. Calcif Tiss Res 6:173-182. *Zlotkin SH, Atkinson S, Lockitch G. 1995. Trace elements in nutrition for premature infants. Clin Perinatol 22(1):223-240. Zong-Chen L, En-Huei W. 1986. Osteoporosis - an early radiographic sign of endemic fluorosis. Skeletal Radiology 15:350-353.


10. GLOSSARY Absorption—The taking up of liquids by solids, or of gases by solids or liquids. Acute Exposure—Exposure to a chemical for a duration of 14 days or less, as specified in the Toxicological Profiles. Adsorption—The adhesion in an extremely thin layer of molecules (as of gases, solutes, or liquids) to the surfaces of solid bodies or liquids with which they are in contact. Adsorption Coefficient (Koc)—The ratio of the amount of a chemical adsorbed per unit weight of organic carbon in the soil or sediment to the concentration of the chemical in solution at equilibrium. Adsorption Ratio (Kd)—The amount of a chemical adsorbed by sediment or soil (i.e., the solid phase) divided by the amount of chemical in the solution phase, which is in equilibrium with the solid phase, at a fixed solid/solution ratio. It is generally expressed in micrograms of chemical sorbed per gram of soil or sediment. Benchmark Dose (BMD)—Usually defined as the lower confidence limit on the dose that produces a specified magnitude of changes in a specified adverse response. For example, a BMD10 would be the dose at the 95% lower confidence limit on a 10% response, and the benchmark response (BMR) would be 10%. The BMD is determined by modeling the dose response curve in the region of the dose response relationship where biologically observable data are feasible. Benchmark Dose Model—A statistical dose-response model applied to either experimental toxicological or epidemiological data to calculate a BMD. Bioconcentration Factor (BCF)—The quotient of the concentration of a chemical in aquatic organisms at a specific time or during a discrete time period of exposure divided by the concentration in the surrounding water at the same time or during the same period. Biomarkers—Broadly defined as indicators signaling events in biologic systems or samples. They have been classified as markers of exposure, markers of effect, and markers of susceptibility. Cancer Effect Level (CEL)—The lowest dose of chemical in a study, or group of studies, that produces significant increases in the incidence of cancer (or tumors) between the exposed population and its appropriate control. Carcinogen—A chemical capable of inducing cancer. Case-Control Study—A type of epidemiological study that examines the relationship between a particular outcome (disease or condition) and a variety of potential causative agents (such as toxic chemicals). In a case-controlled study, a group of people with a specified and well-defined outcome is identified and compared to a similar group of people without outcome. Case Report—Describes a single individual with a particular disease or exposure. These may suggest some potential topics for scientific research, but are not actual research studies. Case Series—Describes the experience of a small number of individuals with the same disease or exposure. These may suggest potential topics for scientific research, but are not actual research studies.


10. GLOSSARY

Ceiling Value—A concentration of a substance that should not be exceeded, even instantaneously. Chronic Exposure—Exposure to a chemical for 365 days or more, as specified in the Toxicological Profiles. Cohort Study—A type of epidemiological study of a specific group or groups of people who have had a common insult (e.g., exposure to an agent suspected of causing disease or a common disease) and are followed forward from exposure to outcome. At least one exposed group is compared to one unexposed group. Cross-sectional Study—A type of epidemiological study of a group or groups of people that examines the relationship between exposure and outcome to a chemical or to chemicals at one point in time. Data Needs—Substance-specific informational needs that if met would reduce the uncertainties of human health assessment. Developmental Toxicity—The occurrence of adverse effects on the developing organism that may result from exposure to a chemical prior to conception (either parent), during prenatal development, or postnatally to the time of sexual maturation. Adverse developmental effects may be detected at any point in the life span of the organism. Dose-Response Relationship—The quantitative relationship between the amount of exposure to a toxicant and the incidence of the adverse effects. Embryotoxicity and Fetotoxicity—Any toxic effect on the conceptus as a result of prenatal exposure to a chemical; the distinguishing feature between the two terms is the stage of development during which the insult occurs. The terms, as used here, include malformations and variations, altered growth, and in utero death. Environmental Protection Agency (EPA) Health Advisory—An estimate of acceptable drinking water levels for a chemical substance based on health effects information. A health advisory is not a legally enforceable federal standard, but serves as technical guidance to assist federal, state, and local officials. Epidemiology—Refers to the investigation of factors that determine the frequency and distribution of disease or other health-related conditions within a defined human population during a specified period. Genotoxicity—A specific adverse effect on the genome of living cells that, upon the duplication of affected cells, can be expressed as a mutagenic, clastogenic, or carcinogenic event because of specific alteration of the molecular structure of the genome. Half-life—A measure of rate for the time required to eliminate one half of a quantity of a chemical from the body or environmental media. Immediately Dangerous to Life or Health (IDLH)—The maximum environmental concentration of a contaminant from which one could escape within 30 minutes without any escape-impairing symptoms or irreversible health effects. Incidence—The ratio of individuals in a population who develop a specified condition to the total number of individuals in that population who could have developed that condition in a specified time period.


10. GLOSSARY

Intermediate Exposure—Exposure to a chemical for a duration of 15–364 days, as specified in the Toxicological Profiles. Immunologic Toxicity—The occurrence of adverse effects on the immune system that may result from exposure to environmental agents such as chemicals. Immunological Effects—Functional changes in the immune response. In Vitro—Isolated from the living organism and artificially maintained, as in a test tube. In Vivo—Occurring within the living organism. Lethal Concentration(LO) (LCLO)—The lowest concentration of a chemical in air that has been reported to have caused death in humans or animals. Lethal Concentration(50) (LC50)—A calculated concentration of a chemical in air to which exposure for a specific length of time is expected to cause death in 50% of a defined experimental animal population. Lethal Dose(LO) (LDLO)—The lowest dose of a chemical introduced by a route other than inhalation that has been reported to have caused death in humans or animals. Lethal Dose(50) (LD50)—The dose of a chemical that has been calculated to cause death in 50% of a defined experimental animal population. Lethal Time(50) (LT50)—A calculated period of time within which a specific concentration of a chemical is expected to cause death in 50% of a defined experimental animal population. Lowest-Observed-Adverse-Effect Level (LOAEL)—The lowest exposure level of chemical in a study, or group of studies, that produces statistically or biologically significant increases in frequency or severity of adverse effects between the exposed population and its appropriate control. Lymphoreticular Effects—Represent morphological effects involving lymphatic tissues such as the lymph nodes, spleen, and thymus. Malformations—Permanent structural changes that may adversely affect survival, development, or function. Minimal Risk Level (MRL)—An estimate of daily human exposure to a hazardous substance that is likely to be without an appreciable risk of adverse noncancer health effects over a specified route and duration of exposure. Modifying Factor (MF)—A value (greater than zero) that is applied to the derivation of a Minimal Risk Level (MRL) to reflect additional concerns about the database that are not covered by the uncertainty factors. The default value for a MF is 1. Morbidity—State of being diseased; morbidity rate is the incidence or prevalence of disease in a specific population. Mortality—Death; mortality rate is a measure of the number of deaths in a population during a specified interval of time.


10. GLOSSARY

Mutagen—A substance that causes mutations. A mutation is a change in the DNA sequence of a cell’s DNA. Mutations can lead to birth defects, miscarriages, or cancer. Necropsy—The gross examination of the organs and tissues of a dead body to determine the cause of death or pathological conditions. Neurotoxicity—The occurrence of adverse effects on the nervous system following exposure to a chemical. No-Observed-Adverse-Effect Level (NOAEL)—The dose of a chemical at which there were no statistically or biologically significant increases in frequency or severity of adverse effects seen between the exposed population and its appropriate control. Effects may be produced at this dose, but they are not considered to be adverse. Octanol-Water Partition Coefficient (Kow)—The equilibrium ratio of the concentrations of a chemical in n-octanol and water, in dilute solution. Odds Ratio (OR)—A means of measuring the association between an exposure (such as toxic substances and a disease or condition) which represents the best estimate of relative risk (risk as a ratio of the incidence among subjects exposed to a particular risk factor divided by the incidence among subjects who were not exposed to the risk factor). An odds ratio of greater than 1 is considered to indicate greater risk of disease in the exposed group compared to the unexposed group. Organophosphate or Organophosphorus Compound—A phosphorus-containing organic compound and especially a pesticide that acts by inhibiting cholinesterase. Permissible Exposure Limit (PEL)—An Occupational Safety and Health Administration (OSHA) allowable exposure level in workplace air averaged over an 8-hour shift of a 40-hour workweek. Pesticide—General classification of chemicals specifically developed and produced for use in the control of agricultural and public health pests. Pharmacokinetics—The science of quantitatively predicting the fate (disposition) of an exogenous substance in an organism. Utilizing computational techniques, it provides the means of studying the absorption, distribution, metabolism, and excretion of chemicals by the body. Pharmacokinetic Model—A set of equations that can be used to describe the time course of a parent chemical or metabolite in an animal system. There are two types of pharmacokinetic models: data-based and physiologically-based. A data-based model divides the animal system into a series of compartments, which, in general, do not represent real, identifiable anatomic regions of the body, whereas the physiologically-based model compartments represent real anatomic regions of the body. Physiologically Based Pharmacodynamic (PBPD) Model—A type of physiologically based dose-response model that quantitatively describes the relationship between target tissue dose and toxic end points. These models advance the importance of physiologically based models in that they clearly describe the biological effect (response) produced by the system following exposure to an exogenous substance. Physiologically Based Pharmacokinetic (PBPK) Model—Comprised of a series of compartments representing organs or tissue groups with realistic weights and blood flows. These models require a


10. GLOSSARY

variety of physiological information: tissue volumes, blood flow rates to tissues, cardiac output, alveolar ventilation rates, and possibly membrane permeabilities. The models also utilize biochemical information such as air/blood partition coefficients, and metabolic parameters. PBPK models are also called biologically based tissue dosimetry models. Prevalence—The number of cases of a disease or condition in a population at one point in time. Prospective Study—A type of cohort study in which the pertinent observations are made on events occurring after the start of the study. A group is followed over time. q1*—The upper-bound estimate of the low-dose slope of the dose-response curve as determined by the multistage procedure. The q1* can be used to calculate an estimate of carcinogenic potency, the incremental excess cancer risk per unit of exposure (usually µg/L for water, mg/kg/day for food, and µg/m3 for air). Recommended Exposure Limit (REL)—A National Institute for Occupational Safety and Health (NIOSH) time-weighted average (TWA) concentrations for up to a 10-hour workday during a 40-hour workweek. Reference Concentration (RfC)—An estimate (with uncertainty spanning perhaps an order of magnitude) of a continuous inhalation exposure to the human population (including sensitive subgroups) that is likely to be without an appreciable risk of deleterious noncancer health effects during a lifetime. The inhalation reference concentration is for continuous inhalation exposures and is appropriately expressed in units of mg/m3 or ppm. Reference Dose (RfD)—An estimate (with uncertainty spanning perhaps an order of magnitude) of the daily exposure of the human population to a potential hazard that is likely to be without risk of deleterious effects during a lifetime. The RfD is operationally derived from the no-observed-adverse-effect level (NOAEL-from animal and human studies) by a consistent application of uncertainty factors that reflect various types of data used to estimate RfDs and an additional modifying factor, which is based on a professional judgment of the entire database on the chemical. The RfDs are not applicable to nonthreshold effects such as cancer. Reportable Quantity (RQ)—The quantity of a hazardous substance that is considered reportable under the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA). Reportable quantities are (1) 1 pound or greater or (2) for selected substances, an amount established by regulation either under CERCLA or under Section 311 of the Clean Water Act. Quantities are measured over a 24-hour period. Reproductive Toxicity—The occurrence of adverse effects on the reproductive system that may result from exposure to a chemical. The toxicity may be directed to the reproductive organs and/or the related endocrine system. The manifestation of such toxicity may be noted as alterations in sexual behavior, fertility, pregnancy outcomes, or modifications in other functions that are dependent on the integrity of this system. Retrospective Study—A type of cohort study based on a group of persons known to have been exposed at some time in the past. Data are collected from routinely recorded events, up to the time the study is undertaken. Retrospective studies are limited to causal factors that can be ascertained from existing records and/or examining survivors of the cohort. Risk—The possibility or chance that some adverse effect will result from a given exposure to a chemical.


10. GLOSSARY

Risk Factor—An aspect of personal behavior or lifestyle, an environmental exposure, or an inborn or inherited characteristic that is associated with an increased occurrence of disease or other health-related event or condition. Risk Ratio—The ratio of the risk among persons with specific risk factors compared to the risk among persons without risk factors. A risk ratio greater than 1 indicates greater risk of disease in the exposed group compared to the unexposed. Short-Term Exposure Limit (STEL)—The American Conference of Governmental Industrial Hygienists (ACGIH) maximum concentration to which workers can be exposed for up to 15 minutes continually. No more than four excursions are allowed per day, and there must be at least 60 minutes between exposure periods. The daily Threshold Limit Value - Time Weighted Average (TLV-TWA) may not be exceeded. Standardized Mortality Ratio (SMR)—A ratio of the observed number of deaths and the expected number of deaths in a specific standard population. Target Organ Toxicity—This term covers a broad range of adverse effects on target organs or physiological systems (e.g., renal, cardiovascular) extending from those arising through a single limited exposure to those assumed over a lifetime of exposure to a chemical. Teratogen—A chemical that causes structural defects that affect the development of an organism. Threshold Limit Value (TLV)—An American Conference of Governmental Industrial Hygienists (ACGIH) concentration of a substance to which most workers can be exposed without adverse effect. The TLV may be expressed as a Time Weighted Average (TWA), as a Short-Term Exposure Limit (STEL), or as a ceiling limit (CL). Time-Weighted Average (TWA)—An allowable exposure concentration averaged over a normal 8-hour workday or 40-hour workweek. Toxic Dose(50) (TD50)—A calculated dose of a chemical, introduced by a route other than inhalation, which is expected to cause a specific toxic effect in 50% of a defined experimental animal population. Toxicokinetic—The study of the absorption, distribution, and elimination of toxic compounds in the living organism. Uncertainty Factor (UF)—A factor used in operationally deriving the Minimal Risk Level (MRL) or Reference Dose (RfD) or Reference Concentration (RfC) from experimental data. UFs are intended to account for (1) the variation in sensitivity among the members of the human population, (2) the uncertainty in extrapolating animal data to the case of human, (3) the uncertainty in extrapolating from data obtained in a study that is of less than lifetime exposure, and (4) the uncertainty in using lowest-observed-adverse-effect level (LOAEL) data rather than no-observed-adverse-effect level (NOAEL) data. A default for each individual UF is 10; if complete certainty in data exists, a value of 1 can be used; however, a reduced UF of 3 may be used on a case-by-case basis, 3 being the approximate logarithmic average of 10 and 1. Xenobiotic—Any chemical that is foreign to the biological system.

FLUORIDES, HYDROGEN FLUORIDE, AND FLUORINE

A-1

APPENDIX A. ATSDR MINIMAL RISK LEVEL AND WORKSHEETS The Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) [42 U.S.C.

9601 et seq.], as amended by the Superfund Amendments and Reauthorization Act (SARA) [Pub. L. 99–

499], requires that the Agency for Toxic Substances and Disease Registry (ATSDR) develop jointly with

the U.S. Environmental Protection Agency (EPA), in order of priority, a list of hazardous substances most

commonly found at facilities on the CERCLA National Priorities List (NPL); prepare toxicological

profiles for each substance included on the priority list of hazardous substances; and assure the initiation

of a research program to fill identified data needs associated with the substances.

The toxicological profiles include an examination, summary, and interpretation of available toxicological

information and epidemiologic evaluations of a hazardous substance. During the development of

toxicological profiles, Minimal Risk Levels (MRLs) are derived when reliable and sufficient data exist to

identify the target organ(s) of effect or the most sensitive health effect(s) for a specific duration for a

given route of exposure. An MRL is an estimate of the daily human exposure to a hazardous substance

that is likely to be without appreciable risk of adverse noncancer health effects over a specified duration

of exposure. MRLs are based on noncancer health effects only and are not based on a consideration of

cancer effects. These substance-specific estimates, which are intended to serve as screening levels, are

used by ATSDR health assessors to identify contaminants and potential health effects that may be of

concern at hazardous waste sites. It is important to note that MRLs are not intended to define clean-up or

action levels.

MRLs are derived for hazardous substances using the no-observed-adverse-effect level/uncertainty factor

approach. They are below levels that might cause adverse health effects in the people most sensitive to

such chemical-induced effects. MRLs are derived for acute (1–14 days), intermediate (15–364 days), and

chronic (365 days and longer) durations and for the oral and inhalation routes of exposure. Currently,

MRLs for the dermal route of exposure are not derived because ATSDR has not yet identified a method

suitable for this route of exposure. MRLs are generally based on the most sensitive chemical-induced end

point considered to be of relevance to humans. Serious health effects (such as irreparable damage to the

liver or kidneys, or birth defects) are not used as a basis for establishing MRLs. Exposure to a level

above the MRL does not mean that adverse health effects will occur.

MRLs are intended only to serve as a screening tool to help public health professionals decide where to

look more closely. They may also be viewed as a mechanism to identify those hazardous waste sites that

FLUORIDES, HYDROGEN FLUORIDE, AND FLUORINE A-2

APPENDIX A

are not expected to cause adverse health effects. Most MRLs contain a degree of uncertainty because of

the lack of precise toxicological information on the people who might be most sensitive (e.g., infants,

elderly, nutritionally or immunologically compromised) to the effects of hazardous substances. ATSDR

uses a conservative (i.e., protective) approach to address this uncertainty consistent with the public health

principle of prevention. Although human data are preferred, MRLs often must be based on animal studies

because relevant human studies are lacking. In the absence of evidence to the contrary, ATSDR assumes

that humans are more sensitive to the effects of hazardous substance than animals and that certain persons

may be particularly sensitive. Thus, the resulting MRL may be as much as a hundredfold below levels

that have been shown to be nontoxic in laboratory animals.

Proposed MRLs undergo a rigorous review process: Health Effects/MRL Workgroup reviews within the

Division of Toxicology, expert panel peer reviews, and agencywide MRL Workgroup reviews, with

participation from other federal agencies and comments from the public. They are subject to change as

new information becomes available concomitant with updating the toxicological profiles. Thus, MRLs in

the most recent toxicological profiles supersede previously published levels. For additional information

regarding MRLs, please contact the Division of Toxicology, Agency for Toxic Substances and Disease

Registry, 1600 Clifton Road, Mailstop E-29, Atlanta, Georgia 30333.


APPENDIX A

MINIMAL RISK LEVEL (MRL) WORKSHEET Chemical Name: Fluoride CAS Number: NA Date: December 1, 2003 Profile Status: Final Route: [ ] Inhalation [X] Oral Duration: [ ] Acute [ ] Intermediate [X] Chronic Key to Figure: 53 Species: Humans Minimal Risk Level: 0.05 [X] mg/kg/day [ ] mg/m3 Reference: Li Y, Liang C, Slemenda CW, et al. 2001. Effect of long-term exposure to fluoride in drinking water on risks of bone fractures. J Bone Miner Res 16:932-939. Experimental design (human study details or strain, number of animals per exposure/control groups, sex, dose administration details): Six communities in rural China with different levels of naturally occurring fluoride in the water were examined. The subjects were 50 years and older; the mean ages ranged from 62.6 to 64.0 years. The majority of the subjects had been living in the same community since birth. There was a higher percentage of males in the highest fluoride group (52.4%) than in the other groups (41.8–47.0%). The water fluoride concentrations were 0.25–0.34, 0.58–0.73, 1.00–1.06, 1.45–2.19, 2.62–3.56, and 4.32–7.97 ppm. Three-day dietary surveys were collected for 10% of randomly selected subjects; estimated nutrition levels were adequate for all six populations. None of the subjects used fluoride-containing toothpaste or mouthwashes and there was a minimal use of packaged beverages and canned foods; fluoride levels in brewed tea samples were largely determined by the levels of fluoride in the water. The authors calculated total daily fluoride intakes of 0.7, 2, 3, 7, 8, and 14 mg/day. The subjects self-reported bone fractures. If the fracture received medical attention, then original x-rays were obtained; for other fractures, x-rays were taken to verify self-reported fractures. The reliability of the reported fracture was 99.1%. Effects noted in study and corresponding concentrations: Age, gender, alcohol consumption, and level of physical activity were significant factors for the risk of overall bone fractures since age 20 years; cigarette smoking and BMI did not significantly alter bone fracture prevalence. The trend for overall bone fracture prevalence (adjusted for age and gender) had a U-shaped pattern. As compared to the 1.00–1.06 ppm group, significantly higher prevalences of bone fracture were found in the lowest (0.25–0.34 ppm fluoride) and highest (4.32–7.97 ppm) groups. The prevalences were 7.41, 6.40, 5.11, 6.04, 6.09, and 7.40%, respectively. When only hip fractures since age 20 were examined, significantly higher prevalences (adjusted for age and BMI) were found in the highest fluoride group, as compared to the 1.00–1.06 ppm group. The prevalences of hip fractures were 0.37, 0.43, 0.37, 0.89, 0.76, and 1.20%, respectively. A similar pattern was observed when overall fractures since age 50 were examined; the prevalences were 4.33, 3.20, 3.28, 3.30, 3.62, and 4.80 (p=0.02), respectively. Only a small number of subjects reported spine fractures (49); none of the fluoride groups significantly differed from the 1.00–1.06 ppm group.


APPENDIX A

Concentration and end point used for MRL derivation: The MRL is based on a NOAEL of 0.15 mg fluoride/kg/day for increased fracture rate. [X] NOAEL [ ] LOAEL Uncertainty Factors used in MRL derivation: [ ] 10 for use of a LOAEL in a sensitive subpopulation [ ] 10 for extrapolation from animals to humans

[X] 3 for human variability; a value less than 10 was used because the most sensitive population, elderly men and women, were examined.

Was a conversion factor used from ppm in food or water to a mg/body weight dose? Yes. Doses were calculated using the reported daily fluoride intakes of 0.7, 2, 3, 7, 8, and 14 mg/day and a reference body weight of 55 kg. If an inhalation study in animals, list conversion factors used in determining human equivalent concentration: NA Was a conversion used from intermittent to continuous exposure? NA Other additional studies or pertinent information that lend support to this MRL: A number of studies have examined the possible association between exposure to fluoridated water and the risk of increased bone fractures, in particular, hip fractures. In general, the studies involved comparing the incidence of hip fractures among residents aged 55 years and older living in a community with fluoridated water (around 1 ppm) with the incidence in a comparable community with low levels of fluoride in the water. Inconsistent results have been found, with studies finding decreases (Lehmann et al. 1998; Phipps et al. 2000; Simonen and Laittinen 1985), increases (Cooper et al. 1990, 1991; Danielson et al. 1992; Jacobsen et al. 1990, 1992; Kurttio et al. 1999), or no effect (Arnala et al. 1986; Cauley et al. 1995; Goggin et al. 1965; Jacobsen et al. 1993; Karagas et al. 1996; Kröger et al 1994; Suarez-Almazor et al. 1993) on hip fracture risk. Studies by Li et al. (2001) and Sowers et al. (1986) have examined communities with higher levels of naturally occurring fluoride in the water. Both studies found increases in the incidence of hip fractures in residents exposed to 4 ppm fluoride and higher (Li et al. 2001; Sowers et al. 1986, 1991); the hip fracture incidence in the highly exposed community was compared to the rates in communities with approximately 1 ppm fluoride in the water. Significant increases in the occurrence of nonvertebral fractures were also observed in postmenopausal women ingesting sodium fluoride (34 mg fluoride/kg/day) for the treatment of osteoporosis (Riggs et al. 1990, 1994). This result was not found in another study of postmenopausal women with spinal osteoporosis treated with 34 mg fluoride/kg/day as sodium fluoride (Kleerekoper et al. 1991). A meta-analysis of these data, as well as other clinical studies, found a significant correlation between exposure to high levels of fluoride and an increased relative risk of nonvertebral fractures (Haguenauer et al. 2000). Agency Contact (Chemical Manager): Carolyn A. Tylenda, D.M.D., Ph.D., Dennis Jones, D.V.M..


APPENDIX A

MINIMAL RISK LEVEL (MRL) WORKSHEET Chemical Name: Hydrogen Fluoride CAS Number: 7664-39-3 Date: December 1, 2003 Profile Status: Final Route: [X] Inhalation [ ] Oral Duration: [X] Acute [ ] Intermediate [ ] Chronic Key to Figure: 6 Species: Humans Minimal Risk Level: 0.02 [ ] mg/kg/day [X] ppm Reference: Lund K, Ekstrand J, Poe J, et al. 1997. Exposure to hydrogen fluoride: an experimental study in humans of concentrations of fluoride in plasma, symptoms, and lung function. Occup Environ Med 54:32-37. Lund K, Refsnes M, Sandstrøm T, et al. 1999. Increased CD3 positive cells in bronchoalveolar lavage fluid after hydrogen fluoride inhalation. Scand J Work Environ Health 25:326-334. Experimental design (human study details or strain, number of animals per exposure/control groups, sex, dose administration details): Groups of 7-9 healthy, nonsmoking males (21–44 years of age) were exposed to 0.2-0.6, 0.7–2.4, or 2.5–5.2 mg/m³ hydrogen fluoride for 1 hour. For the last 15 minutes of the exposure, the subjects performed an ergometric test at a fixed work load of 75W. Bronchoalveolar lavage (BAL) was performed 3 weeks prior to exposure and 24 hours after exposure. Lung function tests were performed immediately before exposure, every 15 minutes during exposure, at exposure termination, 30 minutes after exposure, and 1, 2, 3, and 4 hours after exposure. Symptom surveys were completed before exposure initiation, after 30 minutes of exposure, at exposure termination, and 4 and 24 hours after exposure. Eye, upper airway (nose and throat), and lower airway symptoms were scored based on a 5 point scale with 5 being the most severe. The midpoint of the range of concentrations was used to calculate ppm levels: 0.4 mg hydrogen fluoride/m³ x 24.45/20 x 19/20 = 0.5 ppm fluoride; 1.7 mg/m³ = 1.9 ppm, 3.9 mg/m³ = 4.5 ppm Effects noted in study and corresponding concentrations: No significant exposure-related alterations in lung function (FEV1 or FVC) were observed and no significant correlations between plasma fluoride concentrations and FVC or FEV1 were found. Increases (as compared to scores prior to exposure) in upper airway symptom scores were observed in the low (p=0.06) and high (p=0.02) concentration groups and for all concentrations combined (p<0.001); similarly, total symptom scores were significantly (p<0.04) increased in the low and high concentration groups and all groups combined. The severity of the upper airway score was low (scores of 1–3) in the low exposure group. All subjects reported a change in the upper airway symptom score in the high concentration group; four subjects scored the symptoms as low and three scored them as high. A significant increase in eye symptom score was also observed in all groups combined, but not for individual exposure level groups. The effect of hydrogen fluoride exposure was assessed by comparing the before and after exposure BAL fluid. Significant increases in the percentage of CD3-positive cells were found in the bronchial portion of the mid- and high-dose group and in the bronchoalveolar portion of the high-dose group. A significant increase in the percentage of lymphocytes in the bronchial and bronchoalveolar portions in the mid-concentration group was observed. A significant correlation between the individual changes in the percentage of CD3-positive cells and the


APPENDIX A

changes in the percentage of lymphocytes from the bronchoalveolar portion was also observed. Significant increases in myeloperoxidase and interkeukin-6 levels were found in the high dose group. Concentration and end point used for MRL derivation: The MRL is based on a minimal LOAEL of 0.5 ppm fluoride as hydrogen fluoride for upper respiratory tract irritation. [ ] NOAEL [X] LOAEL Uncertainty Factors used in MRL derivation: [X] 3 for use of a minimal LOAEL [ ] 3 for extrapolation from animals to humans with dosimetric adjustments [X] 10 for human variability Was a conversion factor used from ppm in food or water to a mg/body weight dose? No If an inhalation study in animals, list conversion factors used in determining human equivalent concentration: Was a conversion used from intermittent to continuous exposure? No. Data on nasal irritation from the Largent (1960) report, the Lund et al. (2002) study, and the intermediate-duration study by Largent (1960) provide suggestive evidence that the severity of nasal irritation does not increase with increasing exposure duration. These three studies identified similar LOAEL values for different exposure durations: 3.22 ppm 6 hours/day for 10 days (Largent 1960), 3.8 ppm 1 hour/day for 1 day (Lund et al. 2002), and 2.98 ppm 6 hours/day, 6 days/week for 15–50 days. Thus, time scaling was not used to derive the acute MRL. Other additional studies or pertinent information that lend support to this MRL: The respiratory tract appears to be the primary target of hydrogen fluoride toxicity. Upper respiratory tract irritation and inflammation and lower respiratory tract inflammation have been observed in several human studies. Nasal irritation was reported by one subject exposed to 3.22 ppm fluoride as hydrogen fluoride 6 hours/day for 10 days (Largent 1960). Very mild to moderate upper respiratory symptoms were reported by healthy men exposed to 0.5 ppm fluoride as hydrogen fluoride for 1 hour (Lund et al. 1997). At higher concentrations, 4.2–4.5 ppm fluoride as hydrogen fluoride for 1 hour, more severe symptoms of upper respiratory irritation were noted (Lund et al. 1997, 2002). In subjects exposed to 4.2 ppm for 1 hour, analysis of nasal lavage fluid provided suggestive evidence that hydrogen fluoride induces an inflammatory response in the nasal cavity (Lund et al. 2002). Similarly, bronchoalveolar lavage fluid analysis revealed suggestive evidence of bronchial inflammation in another study of subjects exposed to 1.9 ppm fluoride as hydrogen fluoride for 1 hour (Lund et al. 1999); no alterations were observed at 0.5 ppm. Respiratory effects have also been reported in rats acutely exposed to hydrogen fluoride. Mild nasal irritation was observed during 60-minute exposure to 120 ppm fluoride (Rosenholtz et al. 1963), and respiratory distress was observed at 2,310, 1,339, 1,308, and 465 ppm fluoride for 5, 15, 30, or 60 minutes, respectively (Rosenholtz et al. 1963). Midtracheal necrosis was reported in rats exposed to 902 or 1,509 ppm fluoride as hydrogen fluoride for 2 or 10 minutes using a mouth breathing model with a tracheal cannula (Dalbey et al. 1998a, 1998b). These effects were not observed when the tracheal cannula was not used. The Lund et al. (1997, 1999) study was selected as the basis of the acute-duration inhalation MRL for hydrogen fluoride. As reported in the 1997 publication, a trend (p=0.06) toward increased upper respiratory tract symptom score, as compared to pre-exposure symptom scores, was observed at the lowest concentration tested (0.5 ppm). A significant increase in the total symptom score was also


APPENDIX A

observed at this concentration. No significant alterations in symptom scores were observed at the mid concentration (1.9 ppm), and increases in upper respiratory and total symptom scores were observed at the high concentration (4.5 ppm). Suggestive evidence of bronchial inflammation was also observed at ≥1.9 ppm fluoride (Lund et al. 1999), although no alterations in lower respiratory tract symptoms (Lund et al. 1997) or lung function (Lund et al. 1997) were observed at any of the tested concentrations. Agency Contact (Chemical Manager): Carolyn A. Tylenda, D.M.D., Ph.D., Dennis Jones, D.V.M.


APPENDIX A

MINIMAL RISK LEVEL (MRL) WORKSHEET Chemical Name: Fluorine CAS Number: 7782-41-4 Date: December 1, 2003 Profile Status: Final Route: [X] Inhalation [ ] Oral Duration: [X] Acute [ ] Intermediate [ ] Chronic Key to Figure: 6 Species: Humans Minimal Risk Level: 0.01 [ ] mg/kg/day [X] ppm Reference: Keplinger ML, Suissa LW. 1968. Toxicity of fluorine short-term inhalation. Am Ind Hyg Assoc J 29(1):10-18. Experimental design (human study details or strain, number of animals per exposure/control groups, sex, dose administration details): Five volunteers (aged 19–50 years; gender not specified) were exposed to various concentrations of fluorine: 10 ppm for 3, 5, or 15 minutes; 23 ppm for 5 minutes, 50 ppm for 3 minutes, 67 ppm for 1 minute, 78 ppm for 1 minute, and 100 ppm for 0.5 or 1 minute. The fluorine was administered via a mask that covered the eyes and nose; the subjects could remove the mask from their face and could breathe fresh air via their mouth. No information was provided on the amount of time between exposures or whether all subjects were exposed to all concentrations. Effects noted in study and corresponding concentrations: No nasal or eye irritation was noted by subjects exposed to 10 ppm for 3, 5, or 15 minutes; it was also noted that the 15-minute exposure did not result in respiratory tract irritation. Eye irritation was observed at ≥23 ppm; nose irritation at ≥50 ppm, and skin irritation at ≥78 ppm. The severity of the irritation was concentration related. Exposure to 100 ppm was considered very irritating and the subjects did not inhale during the exposure period. No incidence data were reported. Concentration and end point used for MRL derivation: The MRL is based on a NOAEL of 10 ppm and LOAEL of 23 ppm fluorine for irritation in humans. [X] NOAEL [] LOAEL Uncertainty Factors used in MRL derivation: [ ] 10 for use of a LOAEL [ ] 10 for extrapolation from animals to humans [X] 10 for human variability Was a conversion factor used from ppm in food or water to a mg/body weight dose? No

If an inhalation study in animals, list conversion factors used in determining human equivalent concentration: NA


APPENDIX A

Was a conversion used from intermittent to continuous exposure? Yes. The 15-minute exposure duration was adjusted for a continuous 24-hour exposure using the following equation: 10 ppm x 0.25 hours/24 hours = 0.1 ppm The study authors noted that exposure to 10 ppm for 3–5 minutes every 15 minutes over a 2- or 3-day period resulted slight irritation to the eyes and skin, but no other subjective effects (no additional details on this study were provided). These data are suggestive that the toxicity of fluorine may be dependent on concentration and duration of exposure. Thus, it is appropriate to adjust for continuous exposure. Other additional studies or pertinent information that lend support to this MRL: Respiratory effects have also been observed in, rats, mice, guinea pigs, rabbits, and dogs exposed to fluorine for 1–60 minutes (Keplinger and Suissa 1968). The observed effects include diffuse lung congestion, dyspnea, irritation, and alveolar necrosis and hemorrhage. The severity of the lung congestion was concentration-related and no species differences were found. Agency Contact (Chemical Manager): Carolyn A. Tylenda, D.M.D., Ph.D., Dennis Jones, D.V.M.


APPENDIX A

FLUORIDES, HYDROGEN FLUORIDE, AND FLUORINE B-1

APPENDIX B. USER'S GUIDE Chapter 1 Public Health Statement This chapter of the profile is a health effects summary written in non-technical language. Its intended audience is the general public, especially people living in the vicinity of a hazardous waste site or chemical release. If the Public Health Statement were removed from the rest of the document, it would still communicate to the lay public essential information about the chemical. The major headings in the Public Health Statement are useful to find specific topics of concern. The topics are written in a question and answer format. The answer to each question includes a sentence that will direct the reader to chapters in the profile that will provide more information on the given topic. Chapter 2 Relevance to Public Health This chapter provides a health effects summary based on evaluations of existing toxicologic, epidemiologic, and toxicokinetic information. This summary is designed to present interpretive, weight-of-evidence discussions for human health end points by addressing the following questions.

1. What effects are known to occur in humans?

2. What effects observed in animals are likely to be of concern to humans?

3. What exposure conditions are likely to be of concern to humans, especially around hazardous waste sites?

The chapter covers end points in the same order that they appear within the Discussion of Health Effects by Route of Exposure section, by route (inhalation, oral, and dermal) and within route by effect. Human data are presented first, then animal data. Both are organized by duration (acute, intermediate, chronic). In vitro data and data from parenteral routes (intramuscular, intravenous, subcutaneous, etc.) are also considered in this chapter. The carcinogenic potential of the profiled substance is qualitatively evaluated, when appropriate, using existing toxicokinetic, genotoxic, and carcinogenic data. ATSDR does not currently assess cancer potency or perform cancer risk assessments. Minimal Risk Levels (MRLs) for noncancer end points (if derived) and the end points from which they were derived are indicated and discussed. Limitations to existing scientific literature that prevent a satisfactory evaluation of the relevance to public health are identified in the Chapter 3 Data Needs section. Interpretation of Minimal Risk Levels Where sufficient toxicologic information is available, ATSDR has derived MRLs for inhalation and oral routes of entry at each duration of exposure (acute, intermediate, and chronic). These MRLs are not meant to support regulatory action, but to acquaint health professionals with exposure levels at which adverse health effects are not expected to occur in humans.


APPENDIX B

MRLs should help physicians and public health officials determine the safety of a community living near a chemical emission, given the concentration of a contaminant in air or the estimated daily dose in water. MRLs are based largely on toxicological studies in animals and on reports of human occupational exposure. MRL users should be familiar with the toxicologic information on which the number is based. Chapter 2, "Relevance to Public Health," contains basic information known about the substance. Other sections such as Chapter 3 Section 3.9, "Interactions with Other Substances,” and Section 3.10, "Populations that are Unusually Susceptible" provide important supplemental information. MRL users should also understand the MRL derivation methodology. MRLs are derived using a modified version of the risk assessment methodology that the Environmental Protection Agency (EPA) provides (Barnes and Dourson 1988) to determine reference doses (RfDs) for lifetime exposure. To derive an MRL, ATSDR generally selects the most sensitive end point which, in its best judgement, represents the most sensitive human health effect for a given exposure route and duration. ATSDR cannot make this judgement or derive an MRL unless information (quantitative or qualitative) is available for all potential systemic, neurological, and developmental effects. If this information and reliable quantitative data on the chosen end point are available, ATSDR derives an MRL using the most sensitive species (when information from multiple species is available) with the highest no-observed-adverse-effect level (NOAEL) that does not exceed any adverse effect levels. When a NOAEL is not available, a lowest-observed-adverse-effect level (LOAEL) can be used to derive an MRL, and an uncertainty factor (UF) of 10 must be employed. Additional uncertainty factors of 10 must be used both for human variability to protect sensitive subpopulations (people who are most susceptible to the health effects caused by the substance) and for interspecies variability (extrapolation from animals to humans). In deriving an MRL, these individual uncertainty factors are multiplied together. The product is then divided into the inhalation concentration or oral dosage selected from the study. Uncertainty factors used in developing a substance-specific MRL are provided in the footnotes of the levels of significant exposure (LSE) Tables. Chapter 3 Health Effects Tables and Figures for Levels of Significant Exposure (LSE) Tables and figures are used to summarize health effects and illustrate graphically levels of exposure associated with those effects. These levels cover health effects observed at increasing dose concentrations and durations, differences in response by species, MRLs to humans for noncancer end points, and EPA's estimated range associated with an upper- bound individual lifetime cancer risk of 1 in 10,000 to 1 in 10,000,000. Use the LSE tables and figures for a quick review of the health effects and to locate data for a specific exposure scenario. The LSE tables and figures should always be used in conjunction with the text. All entries in these tables and figures represent studies that provide reliable, quantitative estimates of NOAELs, LOAELs, or Cancer Effect Levels (CELs). The legends presented below demonstrate the application of these tables and figures. Representative examples of LSE Table 3-1 and Figure 3-1 are shown. The numbers in the left column of the legends correspond to the numbers in the example table and figure. LEGEND


APPENDIX B

See Sample LSE Table 3-1 (page B-6)

(1) Route of Exposure. One of the first considerations when reviewing the toxicity of a substance using these tables and figures should be the relevant and appropriate route of exposure. Typically when sufficient data exists, three LSE tables and two LSE figures are presented in the document. The three LSE tables present data on the three principal routes of exposure, i.e., inhalation, oral, and dermal (LSE Table 3-1, 3-2, and 3-3, respectively). LSE figures are limited to the inhalation (LSE Figure 3-1) and oral (LSE Figure 3-2) routes. Not all substances will have data on each route of exposure and will not, therefore, have all five of the tables and figures.

(2) Exposure Period. Three exposure periods—acute (less than 15 days), intermediate (15–364

days), and chronic (365 days or more)—are presented within each relevant route of exposure. In this example, an inhalation study of intermediate exposure duration is reported. For quick reference to health effects occurring from a known length of exposure, locate the applicable exposure period within the LSE table and figure.

(3) Health Effect. The major categories of health effects included in LSE tables and figures are

death, systemic, immunological, neurological, developmental, reproductive, and cancer. NOAELs and LOAELs can be reported in the tables and figures for all effects but cancer. Systemic effects are further defined in the "System" column of the LSE table (see key number 18).

(4) Key to Figure. Each key number in the LSE table links study information to one or more data

points using the same key number in the corresponding LSE figure. In this example, the study represented by key number 18 has been used to derive a NOAEL and a Less Serious LOAEL (also see the two "18r" data points in sample Figure 3-1).

(5) Species. The test species, whether animal or human, are identified in this column. Chapter 2,

"Relevance to Public Health," covers the relevance of animal data to human toxicity and Section 3.4, "Toxicokinetics," contains any available information on comparative toxicokinetics. Although NOAELs and LOAELs are species specific, the levels are extrapolated to equivalent human doses to derive an MRL.

(6) Exposure Frequency/Duration. The duration of the study and the weekly and daily exposure

regimen are provided in this column. This permits comparison of NOAELs and LOAELs from different studies. In this case (key number 18), rats were exposed to 1,1,2,2-tetrachloroethane via inhalation for 6 hours/day, 5 days/week, for 3 weeks. For a more complete review of the dosing regimen refer to the appropriate sections of the text or the original reference paper (i.e., Nitschke et al. 1981).

(7) System. This column further defines the systemic effects. These systems include respiratory,

cardiovascular, gastrointestinal, hematological, musculoskeletal, hepatic, renal, and dermal/ocular. "Other" refers to any systemic effect (e.g., a decrease in body weight) not covered in these systems. In the example of key number 18, one systemic effect (respiratory) was investigated.

(8) NOAEL. A NOAEL is the highest exposure level at which no harmful effects were seen in the

organ system studied. Key number 18 reports a NOAEL of 3 ppm for the respiratory system, which was used to derive an intermediate exposure, inhalation MRL of 0.005 ppm (see footnote "b").


APPENDIX B

(9) LOAEL. A LOAEL is the lowest dose used in the study that caused a harmful health effect. LOAELs have been classified into "Less Serious" and "Serious" effects. These distinctions help readers identify the levels of exposure at which adverse health effects first appear and the gradation of effects with increasing dose. A brief description of the specific end point used to quantify the adverse effect accompanies the LOAEL. The respiratory effect reported in key number 18 (hyperplasia) is a Less Serious LOAEL of 10 ppm. MRLs are not derived from Serious LOAELs.

(10) Reference. The complete reference citation is given in Chapter 9 of the profile. (11) CEL. A CEL is the lowest exposure level associated with the onset of carcinogenesis in

experimental or epidemiologic studies. CELs are always considered serious effects. The LSE tables and figures do not contain NOAELs for cancer, but the text may report doses not causing measurable cancer increases.

(12) Footnotes. Explanations of abbreviations or reference notes for data in the LSE tables are found

in the footnotes. Footnote "b" indicates that the NOAEL of 3 ppm in key number 18 was used to derive an MRL of 0.005 ppm.

LEGEND

See Sample Figure 3-1 (page B-7) LSE figures graphically illustrate the data presented in the corresponding LSE tables. Figures help the reader quickly compare health effects according to exposure concentrations for particular exposure periods.

(13) Exposure Period. The same exposure periods appear as in the LSE table. In this example, health effects observed within the intermediate and chronic exposure periods are illustrated.

(14) Health Effect. These are the categories of health effects for which reliable quantitative data

exists. The same health effects appear in the LSE table.

(15) Levels of Exposure. Concentrations or doses for each health effect in the LSE tables are graphically displayed in the LSE figures. Exposure concentration or dose is measured on the log scale "y" axis. Inhalation exposure is reported in mg/m3 or ppm and oral exposure is reported in mg/kg/day.

(16) NOAEL. In this example, the open circle designated 18r identifies a NOAEL critical end point in

the rat upon which an intermediate inhalation exposure MRL is based. The key number 18 corresponds to the entry in the LSE table. The dashed descending arrow indicates the extrapolation from the exposure level of 3 ppm (see entry 18 in the Table) to the MRL of 0.005 ppm (see footnote "b" in the LSE table).

(17) CEL. Key number 38r is one of three studies for which CELs were derived. The diamond

symbol refers to a CEL for the test species-mouse. The number 38 corresponds to the entry in the LSE table.

(18) Estimated Upper-Bound Human Cancer Risk Levels. This is the range associated with the upper-

bound for lifetime cancer risk of 1 in 10,000 to 1 in 10,000,000. These risk levels are derived from the EPA's Human Health Assessment Group's upper-bound estimates of the slope of the cancer dose response curve at low dose levels (q1*).


APPENDIX B

(19) Key to LSE Figure. The Key explains the abbreviations and symbols used in the figure.

FLUO

RID

ES, HYD

RO

GEN

FLUO

RID

E, AND

FLUO

RIN

E

B-6

APPEND

IX B

Reference

10

↓

Nitschke et al. 1981

Wong et al. 1982

NTP 1982

NTP 1982

Serious (ppm)

(CEL, multiple organs)

(CEL, lung tumors, nasal tumors)

(CEL, lung tumors, hemangiosarcomas)

11

↓

20

10

10

LOAEL (effect) Less serious (ppm)

9

↓

10 (hyperplasia)

SAMPLE

NOAEL (ppm)

8

↓

3b

System

7

↓

Resp

Exposure frequency/ duration

6

↓

13 wk 5 d/wk 6 hr/d

18 mo 5 d/wk 7 hr/d

89-104 wk 5 d/wk 6 hr/d

79-103 wk 5 d/wk 6 hr/d

Species

5

↓

Rat

Rat

Rat

Mouse

TABLE 3-1. Levels of Significant Exposure to [Chemical x] – Inhalation

Key to figurea INTERMEDIATE EXPOSURE

Systemic

18 CHRONIC EXPOSURE

Cancer

38

39

40

a The number corresponds to entries in Figure 3-1. b Used to derive an intermediate inhalation Minimal Risk Level (MRL) of 5x10-3 ppm; dose adjusted for intermittent exposure and divided by an uncertainty factor of 100 (10 for extrapolation from animal to humans, 10 for human variability).

→

→

→

→

→

1

2

3

4

12

FLUO

RID

ES, HYD

RO

GEN

FLUO

RID

E, AND

FLUO

RIN

E

B-7

APPEND

IX B

FLUORIDES, HYDROGEN FLUORIDE, AND FLUORINE C-1

APPENDIX C. ACRONYMS, ABBREVIATIONS, AND SYMBOLS ACGIH American Conference of Governmental Industrial Hygienists ACOEM American College of Occupational and Environmental Medicine ADI acceptable daily intake ADME absorption, distribution, metabolism, and excretion AED atomic emission detection AFID alkali flame ionization detector AFOSH Air Force Office of Safety and Health ALT alanine aminotransferase AML acute myeloid leukemia AOAC Association of Official Analytical Chemists AOEC Association of Occupational and Environmental Clinics AP alkaline phosphatase APHA American Public Health Association AST aspartate aminotransferase atm atmosphere ATSDR Agency for Toxic Substances and Disease Registry AWQC Ambient Water Quality Criteria BAT best available technology BCF bioconcentration factor BEI Biological Exposure Index BMD benchmark dose BMR benchmark response BSC Board of Scientific Counselors C centigrade CAA Clean Air Act CAG Cancer Assessment Group of the U.S. Environmental Protection Agency CAS Chemical Abstract Services CDC Centers for Disease Control and Prevention CEL cancer effect level CELDS Computer-Environmental Legislative Data System CERCLA Comprehensive Environmental Response, Compensation, and Liability Act CFR Code of Federal Regulations Ci curie CI confidence interval CL ceiling limit value CLP Contract Laboratory Program cm centimeter CML chronic myeloid leukemia CPSC Consumer Products Safety Commission CWA Clean Water Act DHEW Department of Health, Education, and Welfare DHHS Department of Health and Human Services DNA deoxyribonucleic acid DOD Department of Defense DOE Department of Energy DOL Department of Labor DOT Department of Transportation


APPENDIX C

DOT/UN/ Department of Transportation/United Nations/ NA/IMCO North America/International Maritime Dangerous Goods Code DWEL drinking water exposure level ECD electron capture detection ECG/EKG electrocardiogram EEG electroencephalogram EEGL Emergency Exposure Guidance Level EPA Environmental Protection Agency F Fahrenheit F1 first-filial generation FAO Food and Agricultural Organization of the United Nations FDA Food and Drug Administration FEMA Federal Emergency Management Agency FIFRA Federal Insecticide, Fungicide, and Rodenticide Act FPD flame photometric detection fpm feet per minute FR Federal Register FSH follicle stimulating hormone g gram GC gas chromatography gd gestational day GLC gas liquid chromatography GPC gel permeation chromatography HPLC high-performance liquid chromatography HRGC high resolution gas chromatography HSDB Hazardous Substance Data Bank IARC International Agency for Research on Cancer IDLH immediately dangerous to life and health ILO International Labor Organization IRIS Integrated Risk Information System Kd adsorption ratio kg kilogram Koc organic carbon partition coefficient Kow octanol-water partition coefficient L liter LC liquid chromatography LC50 lethal concentration, 50% kill LCLo lethal concentration, low LD50 lethal dose, 50% kill LDLo lethal dose, low LDH lactic dehydrogenase LH luteinizing hormone LOAEL lowest-observed-adverse-effect level LSE Levels of Significant Exposure LT50 lethal time, 50% kill m meter MA trans,trans-muconic acid MAL maximum allowable level mCi millicurie MCL maximum contaminant level MCLG maximum contaminant level goal


APPENDIX C

MF modifying factor MFO mixed function oxidase mg milligram mL milliliter mm millimeter mmHg millimeters of mercury mmol millimole mppcf millions of particles per cubic foot MRL Minimal Risk Level MS mass spectrometry NAAQS National Ambient Air Quality Standard NAS National Academy of Science NATICH National Air Toxics Information Clearinghouse NATO North Atlantic Treaty Organization NCE normochromatic erythrocytes NCEH National Center for Environmental Health NCI National Cancer Institute ND not detected NFPA National Fire Protection Association ng nanogram NHANES National Health and Nutrition Examination Survey NIEHS National Institute of Environmental Health Sciences NIOSH National Institute for Occupational Safety and Health NIOSHTIC NIOSH's Computerized Information Retrieval System NLM National Library of Medicine nm nanometer nmol nanomole NOAEL no-observed-adverse-effect level NOES National Occupational Exposure Survey NOHS National Occupational Hazard Survey NPD nitrogen phosphorus detection NPDES National Pollutant Discharge Elimination System NPL National Priorities List NR not reported NRC National Research Council NS not specified NSPS New Source Performance Standards NTIS National Technical Information Service NTP National Toxicology Program ODW Office of Drinking Water, EPA OERR Office of Emergency and Remedial Response, EPA OHM/TADS Oil and Hazardous Materials/Technical Assistance Data System OPP Office of Pesticide Programs, EPA OPPT Office of Pollution Prevention and Toxics, EPA OPPTS Office of Prevention, Pesticides and Toxic Substances, EPA OR odds ratio OSHA Occupational Safety and Health Administration OSW Office of Solid Waste, EPA OW Office of Water OWRS Office of Water Regulations and Standards, EPA PAH polycyclic aromatic hydrocarbon


APPENDIX C

PBPD physiologically based pharmacodynamic PBPK physiologically based pharmacokinetic PCE polychromatic erythrocytes PEL permissible exposure limit pg picogram PHS Public Health Service PID photo ionization detector pmol picomole PMR proportionate mortality ratio ppb parts per billion ppm parts per million ppt parts per trillion PSNS pretreatment standards for new sources RBC red blood cell REL recommended exposure level/limit RfC reference concentration RfD reference dose RNA ribonucleic acid RQ reportable quantity RTECS Registry of Toxic Effects of Chemical Substances SARA Superfund Amendments and Reauthorization Act SCE sister chromatid exchange SGOT serum glutamic oxaloacetic transaminase SGPT serum glutamic pyruvic transaminase SIC standard industrial classification SIM selected ion monitoring SMCL secondary maximum contaminant level SMR standardized mortality ratio SNARL suggested no adverse response level SPEGL Short-Term Public Emergency Guidance Level STEL short term exposure limit STORET Storage and Retrieval TD50 toxic dose, 50% specific toxic effect TLV threshold limit value TOC total organic carbon TPQ threshold planning quantity TRI Toxics Release Inventory TSCA Toxic Substances Control Act TWA time-weighted average UF uncertainty factor U.S. United States USDA United States Department of Agriculture USGS United States Geological Survey VOC volatile organic compound WBC white blood cell WHO World Health Organization


APPENDIX C

> greater than ≥ greater than or equal to = equal to < less than ≤ less than or equal to % percent α alpha β beta γ gamma δ delta µm micrometer µg microgram q1

* cancer slope factor – negative + positive (+) weakly positive result (–) weakly negative result

FLUORIDES, HYDROGEN FLUORIDE, AND FLUORINE D-1

APPENDIX D. FLUORIDE AND DENTAL CARIES

Dental caries or tooth decay is a progressively destructive disease of the tooth caused by cariogenic

bacteria. These bacteria, which reside in dental plaque, colonize on tooth surfaces and produce

polysaccharides that enhance adherence of the plaque to the tooth enamel. Once plaque is formed, the

bacteria on the teeth produce an enzyme that promotes erosion of the enamel by converting sugars and

other fermentable carbohydrates into acids. The acids dissolve the minerals (calcium and phosphorus) in

the tooth enamel in a process known as demineralization (DHHS 2001b).

Several studies conducted by Dean and associates in the 1930s and 1940s demonstrated a relationship

between the levels of naturally-occurring fluoride in drinking water and the prevalence of dental caries

(Dean 1938; Dean et al. 1939, 1941, 1942). Children living in communities with high levels of fluoride

in the drinking water had lower occurrences of dental caries. This relationship between fluoride and

dental caries prompted the city of Grand Rapids, Michigan to implement a water fluoridation program in

1945. Studies conducted in some of the earliest cities to adopt a fluoridation program reported dramatic

decreases in the occurrence of dental caries (Ast et al. 1951; Dean et al. 1950; Hill et al. 1951; Hutton et

al. 1951). The prevalence of dental caries in children living in communities with fluoridated water was

50–70% lower than in children living in areas without fluoridated water. Surveys conducted after the late

1980s found smaller differences; the occurrence of dental caries was 9–25% lower in communities with

fluoridated water as compared to communities without fluoridated water (Brunelle and Carlos 1990;

DeLiefde 1998; Eklund et al. 1987; Englander and DePaola 1979; Jackson et al. 1995; Selwitz et al.

1995). In one study, no significant differences in the occurrence of dental caries was found in school-

aged children 5–17 years old (Yiamouyiannis 1990); however, when just 5 year olds were examined, the

incidence of dental caries was 42% lower in children with lifetime exposure to fluoridated water and 24%

lower in children exposed to fluoridated water for only a portion of their lifetime. Several studies have

also examined the impact of termination of a water fluoridation program on the incidence of dental caries.

Conflicting results have been reported. Some studies found increases in dental caries occurrence

(Attwood and Blinkhorn 1991; Stephen et al. 1987; Thomas et al. 1995), some found no change in the

occurrence of dental caries (Burt et al. 2000; Kalsbeek et al. 1993; Künzel and Fischer 1997; Seppä et al.

2000; Stephen et al. 1987), and other studies found decreases in dental caries occurrence (Künzel and

Fischer 2000; Künzel et al. 2000; Maupomé et al. 2001). A meta-analysis of 26 studies examined the

relationship between water fluoridation and prevalence of dental caries or the change in decayed, missing,

and filled teeth (DMFT) (McDonagh et al. 2000). In 19 of the 30 analyses conducted, a significant

increase in the prevalence of children without dental caries was found in the fluoridated areas compared


APPENDIX D

to non-fluoridated areas. Additionally, 15 of the 16 analyses found a significant increase in the mean

change in DMFT in fluoridated water areas (levels of DMFT declined in response to fluoridation).

The decline or stabilization of the occurrence of dental caries in the absence of water fluoridation has

been attributed to a number of factors (Horowitz 1996), including diffusion of effects of fluoridated

drinking water, dilution effects from other sources of fluoride on the measurement of effectiveness of

community water fluoridation, and improved dental care. The diffusion effect occurs when residents of

communities without fluoridated water consume products manufactured or bottled in areas with

fluoridated water (thus fluoride enters the foodstuff) or attend schools in areas with fluoridated water. An

often cited example of the diffusion effect is the 1986–1987 NIDR survey of dental health status of U.S.

school children (Brunelle and Carlos 1990). In the Pacific region, which has a low percentage of

communities with fluoridated water (19%), children living in area with nonfluoridated water have 61%

higher dental caries score as compared to children living in areas with fluoridated water. In contrast, in

the Midwest region with a high percentage of communities with fluoridated water (74%), there is no

difference in dental caries scores between fluoridated and nonfluoridated areas. The dilution effect is due

to the development and use of other fluoride agents, including fluoride supplements, fluoride solutions,

gels, and varnishes used by dental professionals, fluoridated toothpaste, and fluoride mouthwash. The use

of the fluoride products that provide protection from dental decay diminishes the difference in the levels

of dental decay between fluoridated and nonfluoridated communities (Ripa 1993).

The primary mechanism by which fluoride prevents the occurrence of dental caries is through its

influence on the demineralization and remineralization process (Featherstone 1999; Koulourides 1990;

Ten Cate 1999). The acid produced from the metabolism of sugars and fermentable carbohydrates by

cariogenic bacteria in plaque begins to dissolve or demineralize the enamel crystal surface of the tooth

resulting in the loss of calcium, phosphate, and carbonate from the tooth enamel. The increased acid

production results in a decrease in plaque pH and the release of fluoride from the dental plaque. This

fluoride, along with calcium and phosphate, is incorporated into the apatite molecule to form

fluor(hydroxyl)apatite. In the presence of fluoride, cycles of partial demineralization and then

remineralization will create apatite, which has less carbonate, more fluoride, and is less soluble.

Fluor(hydroxyl)apatite, which has high levels of fluoride and low levels of carbonate, is more acid

resistant (Chow 1990; Ericsson 1977; Featherstone 1999; Kidd et al. 1980; Ten Cate 1999; Thylstrup

1990; Thylstrup et al. 1979). When the beneficial effects of fluoride on caries prevention was first

discovered, it was believed that the incorporation of the fluoride into developing enamel resulted in

improved enamel and dental caries prevention (Dean et al. 1935; McClure and Likins 1951). However,


APPENDIX D

more recent data suggest that fluoride works primarily after teeth have erupted (Clarkson et al. 1996). In

a fluoride-rich environment, demineralization and remineralization cycling, which occurs throughout the

lifetime of the tooth, will result in teeth that are more resistant to cariogenic bacterial damage. Another

mechanism in which fluoride prevents dental caries is via a direct effect on cariogenic bacterial

metabolism. There are in vitro data that demonstrate that fluoride can inhibit bacterial metabolism of

carbohydrates, which results in a decreased production of acids (Bowden 1990; Bowden et al. 1982;

Marquis 1990; Rosen et al. 1978). However, it is likely that this would occur at fluoride levels that far

exceed those present in the mouth (Geddes and Bowen 1990).

Based on this relationship between fluoride and dental caries prevention, the Institute of Medicine (IOM

1997) and the World Health Organization (WHO 2002) consider fluoride to be an essential dietary

element. The Institute of Medicine has derived adequate intake levels (AIs) ranging from 0.01 to

4 mg/day (IOM 1997). The AIs for each age group are presented below:

Age Range Adequate Intake Level (mg/day) 0–6 months 0.01 6–12 months 0.5 1–3 years 0.7 4–8 years 1 9–13 years (males and females) 2 14–18 years (males and females) 3 >18 years (males) 4 >18 years (females) 3

Expert panels convened by the U.S. Department of Health and Human Services (DHHS 1991, 2000,

2001b) and the World Health Organization (WHO 1994) support optimal fluoridation of drinking water.

A work group assembled by the Centers for Disease Control and Prevention (DHHS 2001b) made the

following recommendation:

“Because frequent exposure to small amounts of fluoride each day will best reduce the risk for dental caries in all age groups, the work group recommends that all persons drink water with an optimal fluoride concentration and brush their teeth twice daily with fluoride toothpaste. For persons at high risk of dental caries, additional fluoride measures might be needed. Measured use of fluoride modalities is particularly appropriate during the time of anterior tooth enamel development (i.e., age <6 years).”

SUBSTANCE PROFILES

REPORT ON CARCINOGENS, ELEVENTH EDITION

Tris(2,3-Dibromopropyl) PhosphateCAS No. 126-72-7Reasonably anticipated to be a human carcinogenFirst Listed in the Second Annual Report on Carcinogens (1981)

Carcinogenicity

Tris(2,3-dibromopropyl) phosphate is reasonably anticipated to be ahuman carcinogen based on sufficient evidence of carcinogenicity inexperimental animals (NCI 1978, IARC 1979, 1987, 1999). Whenadministered in the diet, tris(2,3-dibromopropyl) phosphate increasedthe incidences of kidney tubular cell adenomas or adenocarcinomas inrats of both sexes and male mice, hepatocellular carcinomas oradenomas in female mice, and forestomach squamous cell papillomasor carcinomas and bronchiolar/alveolar adenomas or carcinomas inmice of both sexes (NCI 1978). When administered topically,tris(2,3-dibromopropyl) phosphate increased the incidences of tumorsof the skin, lung, forestomach, and oral cavity in female mice (IARC1979, 1999).

No adequate human studies of the relationship between exposureto tris(2,3-dibromopropyl) phosphate and human cancer have beenreported (IARC 1987, 1999).

Properties

Tris(2,3-dibromopropyl) phosphate is a viscous, pale yellow or a densenearly colorless liquid. It is insoluble in water and miscible withcarbon tetrachloride, chloroform, and methylene chloride. Thecompound is hydrolyzed by acids and bases. Tris(2,3-dibromopropyl)phosphate is available in the United States in at least two grades.Typical impurities include 2,3-dibromopropanol, 1,2,3-tribromopropane, and 1,2-dibromo-3-chloropropane (HSDB 2001).

Use

Tris(2,3-dibromopropyl) phosphate is no longer used in the UnitedStates. Previously, it was used primarily as a flame retardant additive forsynthetic textiles and plastics. It was also recommended for use inphenolic resins, paints, paper coatings, and rubber. In 1977, theConsumer Product Safety Commission (CPSC) banned the use oftris(2,3-dibromopropyl) phosphate in children’s clothing and in fabric,yarn, and fiber when intended for use in such clothing. The ban,however, was not fully enforced. In 1978, the Commission identified22 products containing the compound that were commerciallyavailable, including children’s clothing, industrial uniforms, draperies,tent fabric, automobile headliners, epoxy resins for the electronicsindustry, Christmas decorations, and polyester thread (IARC 1979).

Production

There were no reports that tris(2,3-dibromopropyl) phosphate is currentlyproduced in the United States (WHO 1995). Chem Sources identifiedfive U.S. distributors of the compound in 2001 (Chem Sources 2001).The 1979 TSCA Inventory reported that three manufacturers produced605,000 lb in 1977 (TSCA 1979). In 1975, domestic production was

estimated to be between 9 million and 12 million lb (IARC 1979, 1999).No data on imports or exports were available. Commercial productionwas first reported in the United States in 1959 (IARC 1979, 1999).

Exposure

The primary routes of potential human exposure to tris(2,3-dibromopropyl) phosphate are inhalation, dermal contact, andingestion. When released to soil, it leaches slowly to ground water, andunder basic conditions it will hydrolyze. In water, it will rapidlyhydrolyze. In the atmosphere, it will sorb to particulate matter andreact with photochemically produced hydroxyl radicals (half-life = 3.74days). Since the compound is no longer produced in the United States,the potential for exposure should be small; however, since CPSC hasdetermined that it is present in some consumer products, the risk ofexposure to tris(2,3-dibromopropyl) phosphate has not beeneliminated. The compound persists in fabric and plastics, makingoccupational and consumer exposure possible. The chemical waswidely used in children’s sleepwear and mattresses, which presents acontinuing risk if the items are “handed down” or reused (EPA 1983).CPSC estimated that over a 6-year period, a child wearing clothingtreated with tris(2,3-dibromopropyl) phosphate could absorb from 2 to77 mg of the compound/kg body weight. Approximately 180 µg/day isabsorbed through the skin of children wearing treated polyesterpajamas (IARC 1979); more recently, the Commission indicated thatconcentrations may be higher. Since the compound is still available inthe United States, it is likely that workers involved in its use arepotentially exposed to the compound. The National OccupationalHazard Survey, conducted by NIOSH from 1972 to 1974, estimatedthat 29,000 workers were potentially exposed to tris(2,3-dibromopropyl) phosphate by dermal contact in the workplace,primarily in the telephone communication industry (NIOSH 1976).This figure has probably decreased substantially since production wasbanned. Tris(2,3-dibromopropyl) phosphate does not occur naturally,but it has been detected in food and water. EPA estimated that asmuch as 10% of U.S. production entered the environment from textilefinishing plants and laundries and that the remainder would have beendisposed as solid waste (IARC 1979).

RegulationsEPAComprehensive Environmental Response, Compensation, and Liability Act

Reportable Quantity (RQ) = 10 lbEmergency Planning and Community Right-to-Know Act

Toxics Release Inventory: Listed substance subject to reporting requirementsResource Conservation and Recovery Act

Listed Hazardous Waste: Waste codes in which listing is based wholly or partly onsubstance - U235

Listed as a Hazardous Constituent of Waste

REFERENCES

ChemSources. 2001. Chemical Sources International, Inc. http://www.chemsources.com.EPA. 1983. Draft Report: An Overview of the Exposure Potential of Commercial Flame Retardants. EPA Contract

No. 68-01-6239. Washington, D.C.: U.S. Environmental Protection Agency, Assessment Division.HSDB. 2001. Hazardous Substances Data Base. National Library of Medicine. http://toxnet.nlm.nih.gov/

cgi-bin/sis/htmlgen?HSDB.IARC. 1979. Some Halogenated Hydrocarbons. IARC Monographs on the Evaluation of Carcinogenic Risk of

Chemicals to Humans, vol. 20. Lyon, France: International Agency for Research on Cancer. 609 pp.IARC. 1987. Overall Evaluations of Carcinogenicity. IARC Monographs on the Evaluation of Carcinogenic Risk of

Chemicals to Humans, Supplement 7. Lyon, France: International Agency for Research on Cancer. 440 pp.IARC. 1999. Re-evaluation of Some Organic Chemicals, Hydrazine, and Hydrogen Peroxide. IARC

Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Humans, vol. 71. Lyon, France:International Agency for Research on Cancer. 1589 pp.

NCI. 1978. Bioassay of tris(2,3-Dibromopropyl) Phosphate for Possible Carcinogenicity (CAS No. 126-72-7).Technical Report Series No76. DHEW (NIH) Publication No. 78-1326. Bethesda, MD: NationalInstitute of Health. 62 pp.

NIOSH. 1976. National Occupational Hazard Survey (1972-74). Cincinnati, OH: Department of Health,Education and Welfare.

TSCA. 1979. Toxic Substances Control Act, Chemical Substances Inventory.

POO

O OH2C

CH2

CH2

CH

CH

CH

H2C

Br

H2C

Br

CH2

Br

BrBr

Br

http://www.chemsources.com

http://toxnet.nlm.nih.gov/

SUBSTANCE PROFILES

WHO. 1995. tris(2,3-Dibromopropyl) Phosphate and bis(2,3-dibromopropyl) phosphate. EnvironmentalHealth Criteria 173. Geneva: World Health Organization.

REPORT ON CARCINOGENS, ELEVENTH EDITION

Carnegie Mellon psychologist receives NIH grant http://news.bio-medicine.org/medicine-news-3/Carnegie-Mellon-psychologist-receives-NIH-grant-9110-1/ PITTSBURGH--Sheldon Cohen, the Robert E. Doherty Professor of Psychology at Carnegie Mellon University, has received a $3 million

grant from the National Institutes of Health to continue his cutting-edge research into the connection between physical health and social factors, such as relationships and family upbringing.

Cohen is one of the world's leading health psychologists and one of the

architects of Carnegie Mellon's highly regarded health psychology program. In 1997, he published a groundbreaking article in the Journal of the american medical association demonstrating that people with diverse social networks and greater sociability have better health

practices and increased resistance to disease.

The NIH grant will help Cohen and his colleagues to build on this work by exploring two major questions. One, what is the impact of a

person's social environment on their health and well-being? The

researchers will take into account study participants' childhood experiences, including the safety of their home and neighborhood, their activities as children and their parents' social networks as well as the nature of their current social activities and relationships. Next, the

researchers will try to determine which biological factors are influenced by social well-being to impact health. Cohen already has established, for example, that people with numerous and diverse relationships are less susceptible to infection than others.

"What we don't know is how our social environment gets 'under the

skin' to influence our health," Cohen said.

Cohen's co-investigators on the grant are Margaretha L. Casselbrant,

William J. Doyle and Eillie Mandel at Children's Hospital of Pittsburgh; Anna Marsland and Bruce S. Rabin at the University of Pittsburgh; and Ronald B. Turner at the University of Virginia.

Contact: Jonathan Potts [email protected] 412-268-6094 Carnegie Mellon University 6-Jul-2005

Carnegie Mellon University http://www.absoluteastronomy.com/topics/Carnegie_Mellon_University

Carnegie Mellon University (also known as CMU) is a private Private

university research Research university University in

Pittsburgh Pittsburgh, Pennsylvania Summary ,

Pennsylvania Pennsylvania , United States United States . It began as the

Carnegie Technical Schools, founded by Andrew Carne gie Andrew

Carnegie in 1900. In 1912, the school became Carne gie Institute of

Technology Carnegie Institute of Technology and began grantin g four-

year degrees. In 1967, the Carnegie Institute of Te chnology Carnegie

Institute of Technology merged with the Mellon Ins titute of Industrial

Research Mellon Institute of Industrial Research to form Ca rnegie Mellon University. The University’s 140-acre main campus i s three miles from Downtown Pittsburgh Downtown Pittsburgh, Pennsylvania and abuts the

campus of the University of Pittsburgh University of Pittsburgh in the

city's Oakland Oakland (Pittsburgh) neighborhood. The University has seven colleges and schools: the Carnegie Institute of Technology Carnegie Institute of Technology (engineering), th e College of

Fine Arts Carnegie Mellon College of Fine Arts , the College of Humanities

and Social Sciences Carnegie Mellon College of Humanities and Social

Sciences , the Mellon College of Science Mellon College of Science , the

Tepper School of Business Facts About Tepper School of Business , the

School of Computer Science Carnegie Mellon School of Computer Science

, and the H. John Heinz III School of Public Policy and Management Heinz

School . Since its inception, Carnegie Mellon has grown into a world-renowned institution, with numerous programs that are freque ntly ranked College

and university rankings among the best in the worl d. In the most recent release of the Top 200 World Universities by Times Higher Education, Carnegie Mellon was ranked 20th overall and 7th in technology. In the 2008 edition, U.S. News & World Report U.S. News & World Report ranked

Carnegie Mellon's undergraduate program 22nd in the nation amongst national research universities, and in the 2009 edi tion its graduate programs in Computer Science 4th, Engineering 7th, Business 17th, Public Affairs 10th, Fine Arts 7th and Psychology 9th. The university attracts students from all 50 U.S. states and 93 countries a nd was named one of the "New Ivies Ivy League " by Newsweek Facts About Newsweek in 2006. Peer

institutions of Carnegie Mellon include Caltech Facts About California

Institute of Technology , Cornell Cornell University , Duke Duke University

, Emory Emory University , Georgia Tech Facts About Georgia Institute of

Technology , MIT Massachusetts Institute of Technology ,

Northwestern Northwestern University , Penn University of Pennsylvania ,

Princeton Princeton University , Rice Rice University , and

Stanford Stanford University .

History Post-Civil War American Civil War industrialists accumulated unprecedented wealth and were eager to found instit utions in their names. Washington Duke Facts About Washington Duke at Duke University Facts

About Duke University , Leland Stanford Leland Stanford at Stanford

University Facts About Stanford University (for his late son), John D.

Rockefeller John D. Rockefeller at the University of Chicago University of

Chicago , Cornelius Vanderbilt Cornelius Vanderbilt at Vanderbilt

University Vanderbilt University , and Phoebe Hearst Phoebe Hearst at the

University of California, Berkeley Facts About University of California,

Berkeley were just a few. Carnegie Mellon Universit y was one of such schools. Carnegie Technical Schools was founded in 1900 in P ittsburgh Pittsburgh,

Pennsylvania by the Scottish American Scottish American industrialist

and philanthropist Andrew Carnegie Andrew Carnegie , who wrote the time-honored words "My heart is in the work" when h e donated the funds to create the institution. Carnegie's vision was to open a vocational training school for the sons and daughters of working-class Pittsburghers. The name was changed to the Carnegie Institute of Techn ology Carnegie

Institute of Technology in 1912, and the school be gan offering four-year degrees. In 1967, it merged with the Mellon Institu te of Industrial

Research Mellon Institute of Industrial Research to become Carnegie Mellon University. In addition, Carnegie founded Ca rnegie Mellon's coordinate women's college Women's colleges in the United States ,

Margaret Morrison Carnegie College Margaret Morrison Carnegie College in 1903 (the college closed in 1973). There was little change to the campus during the pe riod of the two World Wars and the Great Depression Facts About Great Depression . A 1938 master plan by Githens and Keally suggested acquisi tion of new land along Forbes Avenue, but the plan was not fully implement ed. The period starting with the construction of GSIA (1952) and ending wit h Wean Hall (1971) saw the institutional change from Carnegie Institute of Technology to Carnegie Mellon University. New facilities were needed to re spond to the University's growing national reputation in artificial intellige nce Artificial intelligence , business, robotics, and the arts. In addition, an e xpanding student population resulted in a need for improved faciliti es for student life, athletics, and libraries. The campus finally expand ed to Forbes Avenue Forbes Avenue from its original land along Schenle y

Park Schenley Park . A ravine long known as "the cut" wa s gradually filled in to campus level, joining "the Mall" as a major c ampus open space.

The buildings of this era reflect current attitudes toward architectural style. The International Style International style (architecture) , with its rejec tion of historical tradition and its emphases on functio nalism and expression of structure, had been in vogue in urban settings sinc e the 1930s. It came late to the Carnegie campus because of the hiatus in bui lding activity and a general reluctance among all institutions of higher education to abandon historical styles. By the 1960s, it was seen as a w ay to accomplish the needed expansion and at the same time give the camp us a new image. Each building was a unique architectural statement that may have acknowledged the existing campus in its placement, but not in its form or materials. During the 1970s and 1980s, the tenure of Universit y President Richard M. Cyert (1972–1990) witnessed a period of unparallele d growth and development. The research budget soared from roughl y $12 million annually in the early 1970s to more than $110 milli on in the late 1980s. The work of researchers in new fields like robotics Robotics and software

engineering Software engineering helped the university build o n its reputation for innovation and practical problem sol ving. President Cyert stressed strategic planning and comparative advanta ge, pursuing

opportunities in areas where Carnegie Mellon could outdistance its competitors. One example of this approach was the i ntroduction of the university's "Andrew" computing network in the mid- 1980s. This pioneering project, which linked all computers and workstations on campus, set the standard for educational computing and established Carnegie Mellon as a leader in the use of technolog y in education and research.

Carnegie Mellon today In the 1990s and into the 2000s, Carnegie Mellon so lidified its status among elite American universities, consistently ranking i n the top 25 in US News and World Report rankings. Carnegie Mellon is disti nct in its interdisciplinary approach to research and educatio n and through the establishment of programs and centers that are outs ide the limitations of departments or colleges has established leadership in fields such as computational finance Computational finance , information systems management, arts management, product design, behavi oral economics, human-computer interaction, entertainment technolog y Entertainment

technology Overview , and decision science. Within t he past two decades, the university has built a new University Center, t heater and drama building (Purnell Center), business school building (Posner Hall), and several dormitories. Baker Hall was renovated in the early 2000s, and new chemistry labs were established in Doherty Hall soo n after. Several computer-science buildings, such as Newell Simon Ha ll, also were established, renovated, or renamed in the early 200 0s. The university is in the process of building the Gates Center for Comput er Science and renovating historic academic and residence halls. The Gates Center for Computer Science will sit on a 5.6-acre site on the university's West Campus, surrounded by Cyert Hall, the Purnell Center for the Arts, Doherty Hall, Newell-Simon Hall, Smith an d Hamburg halls and the Collaborative Innovation Center. It will contain 31 8 offices as well as labs, computer clusters, lecture halls, classrooms and a 250-seat auditorium. The Gates Center for Computer Science was made poss ible by a $20 million lead gift from the Bill & Melinda Gates Fou ndation Bill & Melinda

Gates Foundation . The building is anticipated to b e completed within 2 years. The Gates Center for Computer Science and th e Purnell Center for the Arts will be connected by the Randy Pausch Randy Pausch Memorial Footbridge. On April 15, 1997, Jared L. Cohon Jared Cohon , former dean of Yale

University Yale University 's School of Forestry and Environme ntal Studies, was elected president by Carnegie Mellon's Board of Trustees.

During Cohon's presidency, Carnegie Mellon has cont inued its trajectory of innovation and growth. He leads a strategic plan th at aims to leverage the University's strengths to benefit society in the ar eas of biotechnology Biotechnology Overview and life sciences, informati on and

security technology, environmental science Environmental science and

practices, the fine arts and humanities Humanities , and

business Business and public policy Public policy .

Campus Carnegie Mellon's 140-acre main campus is three mil es (5 km) from downtown Pittsburgh Pittsburgh, Pennsylvania Overview , between

Schenley Park Schenley Park and the Squirrel Hill Squirrel Hill ,

Shadyside Shadyside (Pittsburgh) Overview , and Oakland Oakland

(Pittsburgh) neighborhoods. Carnegie Mellon is bor dered to the west by

the campus of the University of Pittsburgh University of Pittsburgh . Carnegie Mellon owns 81 buildings in the Oakland an d Squirrel Hill Squirrel Hill neighborhoods of Pittsburgh. A large grassy area known as "the Cut" forms the ba ckbone of the campus, with a separate grassy area known as "the Mall" run ning perpendicular. The Cut was formed by filling in a ravine (hence th e name) with soil from a nearby hill that was leveled to build the College o f Fine Arts building. The northwestern part of the campus (home to Hambur g Hall, Newell-Simon Hall, Smith Hall, and the site of the future Gates Center for Computer Science) was acquired from the U.S. Bureau of Mines in the 1980s.

Beyond Pittsburgh In addition to its Pittsburgh campus, Carnegie Mell on has extension campuses in Mountain View, California in the heart of Silicon Valley Silicon

Valley (offering masters programs in Software Engi neering Software

engineering and Software Management); Education Ci ty Education City

in Qatar Carnegie Mellon University (Qatar) Summary ; and a n ew campus in . The Adelaide campus, opened in May 2006, deliv ers masters programs from both the H. John Heinz III School of Public Po licy and Management and the Entertainment Technology Center. The Tepper School of Business Tepper School of Business maintains a satellite ce nter in

downtown Manhattan Manhattan and the Heinz School maintains one in Washington, DC. Carnegie Mellon also maintains the Carnegie Mellon Los Angeles Center in where students in the Master of E ntertainment Industry Management program are required to relocate to Los Angeles in their second year and attend classes at this facility. Ca rnegie Mellon's Information Networking Institute offers graduate pr ograms in and , in collaboration with Athens Information Technology an d the Hyogo Institute of Information Education Foundation, respectively. Starting in the fall of 2007, the cities of Aveiro Aveiro and will be added to the Information Networking Institute's remote locations, and starti ng in 2008 the Entertainment Technology Center will offer a gradua te program in and Singapore Singapore .

In media, entertainment & culture The Carnegie Mellon University campus in Pittsburgh served as the locale for many of the on-campus scenes in the 2000 film Wonder Boys Wonder

Boys (film) , starring Michael Douglas Michael Douglas and Tobey

Maguire Tobey Maguire . Other movies filmed at Carnegie Mel lon include

The Mothman Prophecies Facts About The Mothman Prophecies (film) ,

Dogma Dogma (film) , Lorenzo's Oil , and Flashdance Flashdance . The

university is also featured prominently in the film Smart People Smart

People , starring Sarah Jessica Parker Sarah Jessica Parker and Dennis

Quaid Dennis Quaid Summary .

Schools and divisions

• The Carnegie Institute of Technology Carnegie Institute of

Technology includes seven engineering departments: Biomedical

Engineering Biomedical engineering , Chemical

Engineering Chemical engineering , Civil Civil engineering and

Environmental Engineering Environmental engineering ,

Electrical Electrical engineering and Computer

Engineering Computer engineering , Engineering and Public

Policy Public policy , Mechanical Engineering Mechanical

engineering , and Materials Science Materials science and Engineering, and two institutes, the Information Ne tworking Institute and the Institute for Complex Engineered Systems.

• The College of Fine Arts Carnegie Mellon College of Fine Arts was founded in 1905, and today is a federation of schoo ls with professional training programs in the visual and pe rforming arts Performing arts : Architecture Architecture , Art Art Overview ,

Design Design (ranked #1 MFA program in Multimedia and Vi sual

Communication), Drama Drama and Music Music . The college shares research projects, interdisciplinary centers and educational programs with other units across the university.

• The H. John Heinz III School of Public Policy and M anagement offers masters degrees in Public Policy Public policy and

Management Management Summary , Health Care Policy and

Management, Medical Management, Public Management Public

management Overview , Arts Management, Entertainment Industry Management, and Information Security Policy and Man agement. The school leads the Universitywide Master of Informati on Systems Management and Master of Science in Information Tec hnology programs. It also offers a Ph.D. in Public Policy a nd Management as well as executive education programs.

• The College of Humanities and Social Sciences Carnegie Mellon

College of Humanities and Social Sciences departmen ts include

Economics Economics , English English studies , History HIStory ,

Modern Languages, Philosophy Philosophy ,

Psychology Psychology , Social and Decision Sciences Social and

Decision Sciences and Statistics Statistics Overview . The college also offers an undergraduate degree program in Info rmation Systems Information systems Overview .

• The Mellon College of Science Mellon College of Science includes

four departments: Biological Sciences, Chemistry Chemistry ,

Mathematical Sciences and Physics Physics . In addition, the

college is expanding efforts in green chemistry Green chemistry ,

bioinformatics Bioinformatics , computational

biology Computational biology , nanotechnology Nanotechnology ,

computational finance Computational finance , sensor research and biological physics.

• The School of Computer Science Carnegie Mellon School of

Computer Science : Carnegie Mellon University helpe d define, and

continually redefines, the field of computer scienc e Computer

science . The School of Computer Science is recogni zed internationally as one of the top schools for compu ter science.

• The Tepper School of Business Tepper School of Business offers undergraduate programs in Business Administration a nd Economics Economics . The Tepper School offers masters degree s in Business Administration and joint degrees in Com putational Finance Computational finance (MSCF) with the College of Humanities and Social Sciences, the Mellon College of Science and the School of Computer Science. In addition, joint degrees are offered with Civil and Environmental Engineering. T he Tepper School offers doctoral degrees in several areas and presen ts a number of executive education Executive Education programs.

In addition to the research and academic institutio ns, the University hosts the Pennsylvania Governor's School for the Sciences Pennsylvania

Governor's School for the Sciences , a state-funded summer program that aims to foster interest in science amongst gifted h igh school students. The Cyert Center for Early Education is a child care ce nter for Carnegie Mellon faculty and staff, as well as an observational sett ing for students in child development courses.

Undergraduate profile For the undergraduate class of 2011, the admission rate was 28.0%. In 2007, the University received a record 22,356 under graduate applicants, an increase of 18.5% from 2006, and admitted 6,259. Th e 2006 class had an average SAT verbal score of 657 and math score of 7 28. Also, 71% of the admitted students for the class of 2010 were in the top 10% of their graduating high school classes. In 2006, the most selective undergraduate college w as the Tepper School of Business, which admitted only 13.9% of total app licants. The largest college, in terms of enrollment, is the Carnegie In stitute of Technology with 423 students in the class of 2011, followed by the College of Fine Arts (with 265 students) and the College of Humanities & Socia l Sciences (with 260). The smallest college in terms of total undergraduat e students is the Tepper School of Business, with 93 undergraduate students enrolled for the class of 2011. Carnegie Mellon enrolls students from all 50 states, and 13% of the students are citizens of countries other than the U nited States. About 94% of first-year students return for their second year , and 69.3% graduate within four years (86.2% within six). Undergraduate tuition is $36,950 for the class of 2011 and room and board is $9,660. For the class of 2010, Carnegie Mellon had the high est overlap in applications with Cornell University Cornell University , the Massachusetts

Institute of Technology Facts About Massachusetts Institute of

Technology , and the University of Pennsylvania University of

Pennsylvania . The class of 2010 had the highest ov erlap in acceptances

with the University of Michigan University of Michigan , Johns Hopkins

University Johns Hopkins University Overview , and Washington U niversity

in St. Louis Washington University in St. Louis Summary .

Research For the 2006 fiscal year, the University spent $315 million on research. The primary recipients of this funding were the School of Computer Science ($100.3 million), the Software Engineering Institut e Software Engineering

Institute ($71.7 million), the Carnegie Institute of Technology ($48.5 million), and the Mellon College of Science ($47.7 million). The research money comes largely from federal sources, with fede ral investment of $277.6 million. The federal agencies that invest th e most money are the National Science Foundation National Science Foundation and the

Department of Defense United States Department of Defense , which contribute 26% and 23.4% of the total university re search budget

respectively. The Pittsburgh Supercomputing Center Pittsburgh Supercomputing Center (PSC) is a joint effort between Carnegie Mellon Uni versity, University of Pittsburgh University of Pittsburgh , and Westinghouse Electri c

Company Westinghouse Electric Company . PSC was founded in 1986 by its two scientific directors, Dr. Ralph Roskies of the University of Pittsburgh and Dr. Michael Levine of Carnegie Mello n University. PSC is a leading partner in the TeraGrid TeraGrid , the National Science Foundation’s cyberinfrastructure program. The Robotics Institute Robotics Institute (RI) is a division of the School of Computer Science and considered to be one of the le ading centers of robotics research in the world. The Field Robotics Center (FRC) has developed a number of significant robots, including Sandstorm Sandstorm

(vehicle) Summary and H1ghlander H1ghlander , which finished second

and third in the DARPA Grand Challenge DARPA Grand Challenge , and Boss, which won the DARPA Urban Challenge. The RI i s primarily sited at Carnegie Mellon's main campus in Newell-Simon hall. The Software Engineering Institute Software Engineering Institute (SEI) is a

federally funded research and development center Federally funded

research and development center sponsored by the U .S. Department of Defense and operated by Carnegie Mellon University, with offices in Pittsburgh, Pennsylvania, USA; Arlington, Virginia, and Frankfurt, Germany. The SEI publishes books on software engine ering Software

engineering for industry, government and military applications and practices. The organization is known for its Capabi lity Maturity Model Capability Maturity Model (CMM) and Capability Mat urity Model

Integration Capability Maturity Model Integration (CMMI), whic h identify essential elements of effective system and software engineering processes and can be used to rate the level of an organizatio n's capability for producing quality systems. The SEI is also the home of CERT/CC CERT

Coordination Center , the federally-funded computer security organization. The CERT Program's primary goals are to ensure that appropriate technology and systems management pract ices are used to resist attacks on networked systems and to limit da mage and ensure continuity of critical services subsequent to attac ks, accidents, or failures.

The Human-Computer Interaction Institute (HCII) is a division of the School of Computer Science and is considered one of the le ading centers of human-computer interaction research, integrating co mputer science, design, social science, and learning science. Such interdisciplinary collaboration is the hallmark of research done thro ughout the university. Carnegie Mellon is also home to the Carnegie School Carnegie School of management and economics. This intellectual school grew out of the Tepper School of Business Facts About Tepper School of Business in the 1950s and 1960s and focused on the intesection of b ehavioralism and management. Several management theories, most notab ly bounded rationality Bounded rationality and the behavioral theory of t he

firm Theory of the firm , were established by Carnegie S chool management scientists and economists.

Alumni and faculty There are more than 70,000 Carnegie Mellon alumni w orldwide. Famous alumni include former General Motors General Motors CEO and Secretary

of Defense, Charles Erwin Wilson Charles Erwin Wilson ; billionaire hedge

fund Hedge fund Summary investor David Tepper David Tepper Overview ;

James Gosling James Gosling , creator of the Java Java (programming

language) programming language; Andy Bechtolsheim Andy

Bechtolsheim , co-founder of Sun Microsystems Sun Microsystems ;

Vinod Khosla Vinod Khosla , billionaire venture capitalist and c o-founder

of Sun Microsystems Sun Microsystems ; pop artist Andy Warhol Andy

Warhol Summary ; and astronaut Astronaut Judith Resnik Judith Resnik ,

who perished in the Space Shuttle Challenger Space Shuttle Challenger disaster. Carnegie Mellon alumni have won Nobel prizes, Turin g awards, Academy awards, Emmy awards, and Tony awards. John Forbes N ash Facts About

John Forbes Nash , a 1948 graduate and winner of the 1994 Nobel Prize in

Economics Nobel Prize in Economics , was the subject of the b ook and

subsequent film A Beautiful Mind A Beautiful Mind . Alan Perlis Alan Perlis , a 1943 graduate was a pioneer in programming lang uages and recipient of the first ever Turing award Turing Award . Overall, Carnegie Mellon is

affiliated with 15 Nobel laureates, ten Turing Awar d Turing Award winners,

seven Emmy Award Emmy Award recipients, three Academy

Award recipients, and four Tony Award Tony Award recipients (including Andrew Omondi). Carnegie Mellon also has produced several alumni wh o have had success in Hollywood, Broadway Broadway theatre and the music industry. They

include Best Actress Academy award winner Holly Hun ter Holly Hunter ,

actor James Cromwell James Cromwell , Get Smart Get Smart

Overview actress Barbara Feldon Barbara Feldon , actor Ted Danson Ted

Danson , director George Romero, actor Zachary Quin to Zachary Quinto

and actor Blair Underwood Blair Underwood , among many others.

Rankings and reputation

Carnegie Mellon's offerings in computer science Carnegie Mellon School

of Computer Science , engineering Carnegie Institute of Technology ,

business Tepper School of Business , public policy Heinz School ,

psychology, and the arts Carnegie Mellon College of Fine Arts are considered among the best in their fields. Carnegie Mellon is ranked 22nd amongst national research universities in the most recent US News and World Report rankings. In the Times Higher Educatio n Supplement (THES) ranking of world universities, Carnegie Mellon rank s 12th overall in the United States (20th in the world), fifth in the Uni ted States (7th in the world) in the Technology category and 15th in the United S tates (28th in the world) in the social sciences category. In 2007, Webometri cs ranks Carnegie Mellon 12th/13th in the World. The university is on e of 60 elected members of the Association of American Universities Association of American

Universities and its academic reputation has led i t to be included in Newsweek’s list of “New Ivies”. Carnegie Mellon is ranked 4th for graduate studies in computer science in 2008, in rankings released by the US News and World Report. Carnegie Mellon is also ranked #15 in the social sciences an d #7 in Engineering/Technology and Computer Sciences among Shanghai Jiao Tong University's world's top 100 universities. Det ailed information on the rankings of undergraduate and graduate programs at Carnegie Mellon is available on the University website.

Student life

Traditions

• The Fence - In the early days of Carnegie Tech, the re was a single bridge, which connected Margaret Morrison Women's C ollege with the Carnegie Institute of Technology. The bridge wa s a meeting place for students. In 1916, the bridge was taken down an d the university filled in the area. The senior class of 1923 put up a wooden fence to be the new meeting place. The administration tried to tear it down, but some fraternity brothers painted it as a prank to advertise a fraternity party. Ever since, painting the Fence ha s been a Carnegie Mellon tradition. The Fence at Carnegie Mellon lies at the center of campus, in the area known as “the cut." Students “g uard” the fence 24 hours a day, and, as long as this vigil is maint ained, no other students may “take” the fence. Once the fence is ta ken, however, the painting traditionally happens between midnight and 6am.

• Mobot - "Mobot,' a general term resulting from shor tening "mobile robot," is an annual competition at Carnegie Mellon that made its debut in 1994. In this event, robots try (autonomou sly) to pass through gates, in order, and reach the finish line. There is a white line on the pavement connecting the gates, and the line is normally used to find the gates, though it is not mandated b y the rules that the robots follow the line.

• Spring Carnival - Usually held in April, Spring Car nival is the biggest event of the school year. In addition to classic ca rnival attractions, the Spring Carnival features the “Buggy Sweepstakes ” and "Booth" (a competition between various organizations to bui ld small, elaborate booths based around a theme chosen each y ear).

• Buggy Races - Buggy , officially called Sweepstakes, is a race around Schenley Park Schenley Park . It can be thought of as a relay race with five runners, using the buggy vehicle as the baton. Entrants submit a small, usually torpedo-shaped, ve hicle that is

pushed uphill and then allowed to roll downhill. Th e vehicles are unpowered, including the prohibition of such energy -storing devices as flywheels. They are, however, steered by a drive r who is usually a petite female student lying prone, arms stretched f orward to steer via a turning mechanism. Space is so tight inside the b uggies that the drivers usually cannot change position beyond turni ng their heads.

• Bagpipers - As the only College offering a degree i n bagpipe music, Carnegie Mellon's Pipe Band features the sounds of Scottish bagpipes and performs at University events. Head of the Pipe Band is world champion piper Alasdair Gillies, formerly a highly decorated pipe major in the British Army.

• Autographing the Green Room - Seniors in the Colleg e of Fine Arts Carnegie Mellon College of Fine Arts sign the Gree n Room's walls and ceilings before leaving the university. S upposedly, Oscar-winning actress Holly Hunter broke university tradi tion by signing the Green Room during her freshman year.

• The Kiltie Band- Carnegie Mellon's Kiltie Band, dre ssed in full Scottish regalia including kilts and knee socks, pe rforms during every home football game.

Fraternities and sororities The Greek tradition at Carnegie Mellon University b egan nearly 100 years ago with the founding of the first fraternity on ca mpus, Theta Xi Theta Xi , in 1912. The Panhellenic sorority community was fou nded in 1945, by Chi Omega Chi Omega , Delta Delta Delta Delta Delta Delta , Delta

Gamma Delta Gamma , Kappa Alpha Theta Kappa Alpha Theta , and Kappa

Kappa Gamma Kappa Kappa Gamma . During the spring semester of 2 006, the Greek community consisted of 26 active fraterni ties and sororities: 5 Panhellenic sororities; 12 Interfraternity Council fraternities; 4 Asian American groups, 2 fraternities and 2 sororities; a nd 4 National Pan-Hellenic (historically African American) chapters r epresented on campus (3 fraternities and 1 sorority). Of Carnegie Mellon’s undergraduates, 965 were members of social Greek-letter organizations. This number reflected 18.4% of the campus population.

Current Interfraternity Council fraternities:

• Alpha Epsilon Pi Alpha Epsilon Pi

• Beta Theta Pi Beta Theta Pi

• Kappa Delta Rho Kappa Delta Rho

• Kappa Sigma Kappa Sigma

• Phi Kappa Theta Phi Kappa Theta

• Pi Kappa Alpha Pi Kappa Alpha

• Sigma Alpha Epsilon Sigma Alpha Epsilon

• Sigma Nu Sigma Nu

• Sigma Phi Epsilon Sigma Phi Epsilon

• Sigma Tau Gamma Sigma Tau Gamma

• Theta Xi Theta Xi

• Zeta Beta Tau Zeta Beta Tau Overview

Current Panhellenic sororities:

• Alpha Chi Omega Alpha Chi Omega

• Delta Delta Delta Delta Delta Delta

• Delta Gamma Delta Gamma Overview

• Kappa Alpha Theta Kappa Alpha Theta

• Kappa Kappa Gamma Kappa Kappa Gamma

Current Pan-Hellenic Chapters (Historically Black):

• Alpha Kappa Alpha Alpha Kappa Alpha

• Alpha Phi Alpha Alpha Phi Alpha

• Kappa Alpha Psi Kappa Alpha Psi

• Omega Psi Phi Omega Psi Phi Overview

Current Asian-American fraternities and sororities:

• alpha Kappa Delta Phi Alpha Kappa Delta Phi

• Kappa Phi Lambda Kappa Phi Lambda

• Lambda Phi Epsilon Lambda Phi Epsilon

• Pi Delta Psi Pi Delta Psi Overview

Athletics The Carnegie Mellon Tartans were a founding member of the University Athletic Association University Athletic Association of the NCAA Divisi on III. Prior to World War II Carnegie Mellon (as Carn egie Tech) played with NCAA Division I teams and in 1939 the Tartan footba ll team earned a trip to the Sugar Bowl Facts About Sugar Bowl . That same year, Robert Dohe rty, university president at the time, banned the footba ll team from competing in postseason bowl games. Currently, varsity teams are fielded in basketball, track, cross country, football, golf, s occer, swimming, volleyball, tennis, and cheerleading. In addition, club teams exist in Ultimate Frisbee, rowing, rugby Carnegie Mellon Rugby Football Club , lacrosse, hockey,, baseball, softball, and cycling. Carnegie Mellon Athletics runs a comprehensive and popular intramural system, maintains facilities (primarily Skibo Gymnasium, University Center, and Gesling Stadium), and offers courses to students in fitness and sports. C arnegie Mellon's primary athletic rivals are fellow UAA University Athletic Association schools Case

Western Reserve University Case Western Reserve University and

Washington University in St. Louis Washington University in St. Louis . The Tartans have an especially intense rivalry with the Washington University in St. Louis Football Washington University in St. Louis football team.

Football In 1926, Carnegie Tech's football team beat Knute R ockne Knute Rockne

Overview 's Notre Dame Fighting Irish Notre Dame Fighting Irish football .

The game was ranked the fourth-greatest upset in co llege football College

football history by ESPN ESPN . In 2006, the varsity football team was offered a bi d to the NCAA Division III playoffs, and became one of the first teams in scho ol history (the first team to win a Division III playoff game was in 1977, whe n Carnegie Mellon beat

Dayton) and University Athletic Association confere nce history to win an NCAA playoff game with a 21-0 shutout of Millsaps C ollege Millsaps

College of the SCAC conference. In addition to win ning a playoff game, several team members were elected to the All Americ an and All Region Squads. The 2006 team won more games in a single se ason than any other team in school history. The current coach is Rich L ackner Rich Lackner , who is also a graduate of Carnegie Mellon and who h as been the head coach since 1986. Coach Erydl has been the offensiv e coordinator since the dawn of time, and coached Dan Marino in high sc hool. Him and Dan Marino used to have titty size competions until the invention of Nutri System. Eryd is still fat. Eryd also starred in the film, Happy Feet. Eryd has his third chin pierced. He hangs out with Doug Hill ing.

Crew The Carnegie Mellon University Rowing Club is a clu b-sponsored crew team organized by students of the university. They participate in several regattas across the northeast, including th e Dad Vail Regatta Dad

Vail Regatta in Philadelphia.

Track and cross country In recent years, the varsity track Athletics (track and field) and cross

country Cross country running programs have seen outstandi ng success

on the Division III Division III national level. The men's cross count ry team has finished in the top 15 in the nation each of th e last three years, and has boasted several individual All-America All-America ns. The men's track team has also boasted several individual All-Americ ans spanning sprinting, distance, and field disciplines. Recent All-America ns from the track team are Brian Harvey (2007, 2008), Davey Quinn (2007), Nik Bonaddio (2004, 2005), Mark Davis (2004, 2005), Russel Verbofsky (2 004, 2005) and Kiley Williams (2005).

January 14, 2004 The Honorable Philip S. English U.S. House of Representatives 1410 Longworth House Office Building Washington, DC 20515 Dear Representative English: The undersigned groups representing both health care providers, health professions education institutions and health benefit providers enthusiastically support tax relief provisions that are contained in the Higher Education Affordability and Equity Act of 2003 (H.R. 3412). We write to thank you for your sustained leadership on education tax issues and pledge to work with you to pass this important legislation. In particular, we are writing to support those sections of the Higher Education Affordability and Equity Act of 2003 that would improve current law by:

?? Expanding student loan interest deduction to allow borrowers to deduct interest payments on their student loans and increasing the income eligibility to claim the full deduction up to $100,000 adjusted gross income (with a phase-out deduction between $100,000-$115,000) for single taxpayers and up to $200,000 adjusted gross income (with a phase-out deduction between $200,000-$230,000) for joint return tax filers.

?? Excluding amounts received as part of a scholarship, fellowship or grant from

taxable income if used for qualified higher education expenses for undergraduate and graduate recipients.

Please accept our enthusiastic endorsement for these critical provisions that would help students finance their education and help health care professionals fulfill their dreams of practicing to benefit all Americans. On behalf of the following organizations: Academy of General Dentistry American Academy of Neurology American Academy of Ophthalmology American Academy of Oral and Maxillofacial Pathology American Academy of Pediatric Dentistry American Academy of Periodontology American Association for Dental Research American Association of Clinical Endocrinologists American Association of Clinical Urologists American Association of Colleges of Osteopathic Medicine American Association of Colleges of Pharmacy American Association of Colleges of Podiatric Medicine American Association of Critical-Care Nurses American Association of Public Health Dentistry American College of Nuclear Physicians American College of Nurse-Midwives American College of Osteopathic Family Physicians

American College of Physicians American College of Surgeons American Geriatrics Society American Dental Association American Dental Education Association American Medical Association American Organization of Nurse Executives American Osteopathic Association American Podiatric Medical Association American Psychological Association American Student Dental Association Arizona Dental Association Association of Academic Health Centers Association of American Medical Colleges Association of American Veterinary Medical Colleges Association of Chiropractic Colleges Association of State and Territorial Dental Directors Child Neurology Society Delta Dental Plans Association Hispanic Dental Association Infectious Diseases Society of America Iowa Dental Association Missouri Dental Association National League for Nursing National Medical Association Nebraska Dental Association Oklahoma State Medical Association Society of Critical Care Medicine Society of Nuclear Medicine Special Care Dentistry Virginia Dental Association Washington State Dental Association

Coalition for an Affordable and Accessible Graduate Education

The Coalition is a group of graduate and professional student organizations, along with individual universities and higher education groups, working together to make graduate and professional education in the United States available to anyone with the desire and skills to pursue it. We originally came together to address the question of tax exemptions on graduate scholarships, and this page is a resource for information about that campaign.

Most Recent News

Legislative Action Day, September 22-23

We held yet another Legislative Action Day in September 2005, asking members to support the HEAEA. This latest effort resulted in 11 more cosponsors, including another member of the critical Ways & Means Committee. This is the most members of Congress we have ever had signed on to our proposal, and represents major progress.

It is unclear when we will do another Washington-based day; our current plan is to pursue a state-by-state strategy focused on Ways & Means members. However, you can still write to your members of Congress using this action alert and ask them to support the HEAEA!

We're On Television!

HEAEA gets local news exposure in Youngstown, Ohio. Rep. Phil English discusses his plan, HR 1380 with students at Penn. State - Shenango and others. Click here to view the newscast from this event.

Contact Your Legislators!

Our friends at the American Medical Student Association have put up a new action alert at http://www.capwiz.com/ams/mail/oneclick_compose/?alertid=7207321 that will allow you to write to your Senators and Congressperson with only one click! Please take action now, even if you sent a letter through our old alert -- this is a new version that contacts new people.

Join our mailing list for regular biweekly updates!

Bill Introduced in House

On March 17th, 2005, Representative Phil English of Pennsylvania introduced H.R. 1380, the Higher Education Affordability and Equity Act (HEAEA). The HEAEA includes language that implements expanded tax exemptions for graduate scholarships, as well as a number of highly important tax incentives for education. We have a number of information documents about this bill, including a one-page summary, Phil English's longer summary or the full text. When you're done, please send a letter to your Representatives and ask them to support this bill! If you want to write your own letter, we've even put together some talking points for you.

Legislative Action Day, February 17-18, 2005

On February 17-18, 2005, graduate and professional students once again traveled to Washington, DC to talk to their legislators about the Higher Education Affordability & Equity Act and other issues facing students. Graduate and professional students from more than 30 Universities and Colleges from over 20 states met with nearly 100 members of the House of Representatives urging their representatives to cosponsor H.R. 1380 when Phil English introduces the bill. On March 17th, 2005, Representative Phil English introduced H.R. 1380 to the House where it has been referred to the Ways and Means committee and the Committee on Education and the Workforce. Graduate and professional students will once again convene in Washington D.C. over the summer to ask their representatives to cosponsor H.R. 1380.

About The Campaign In the News Resources for Local and National Action Our Supporters

About Our Campaign

Our goal is to broaden the tax exemptions on graduate and professional scholarships and restore a functional status equivalent to what existed prior to the 1986 Internal Revenue Code overhaul. Graduate scholarships generally include both direct tuition reimbursement and a stipend for books, supplies, and living expenses. Although the Code provides an exemption for scholarships (see 26 USC 117), this exemption only covers tuition and required fees and books.

Because graduate education is preparation to be an advanced scholar in a particular field, it does not follow as standardized a curriculum as undergraduate education. As such, most books and supplies needed by graduate students (including personal computers) are not considered "qualified educational expenses". Additionally, most graduate students are

older (meaning that they often have child care expenses) and cannot count on their parents for financial support. The net result, as shown by the US Department of Education's 2000 National Postsecondary Student Aid Survey is that while the average aid received yearly by a graduate student is roughly $19,500, the average yearly cost of education for that same student is $26,300. In an era where we are moving into a knowledege-based economy, we cannot afford to drive people away from advanced degrees by adding on this kind of debt.

Based on this clear need, we propose an expansion of the existing exemption for scholarship aid. We initially suggested that the definition of "qualified educational expenses" found in 26 USC 117 should be changed to be equivalent to the "cost of education" defined in the Higher Education Act (20 USC 1087LL). Since then, Congressional legislative counsel has found a better way -- linking graduate scholarships to education savings accounts defined in 26 USC 529 where room and board are treated as "qualified educational expenses". This achieves the same thing, but also makes the tax code simpler, which is nice. You can see the exact language in the text of the HEAEA.

For more information on this proposal and the reasons behind it, we have prepared a fact sheet and a PowerPoint presentation that give more details. You are also welcome to contact Jim Masterson ([email protected]) , who coordinates this campaign.

Current Status On March 17, 2005, Representative Phil English of Pennsylvania introduced H.R. 1380, the Higher Education Affordability and Equity Act. The HEAEA contains a provision to expand the tax-exempt treatment of all scholarships (graduate and undergraduate) by expanding the definition of "qualified educational expenses" to include room, board, and special needs services. It also includes provisions to make student loan interest more tax-deductible, increase contributions to education savings accounts, and generally make higher education more affordable at all levels. You can read a summary of the bill or the bill itself, plus Mr. English's letter describing it.

We are currently working to build cosponsors for this bill. You can check the list of cosponsors, and if your state's Represenatives aren't on it, send them a letter!

Resources

If you're interested in being part of the campaign or just want to know even more, we've compiled a list of resources to help you.

• Since the focus of this campaign is now on the Higher Education Affordability & Equity Act, the primary materials are our fact sheet on HEAEA, the longer bill summary, talking points for students, and a sample support letter for the bill. We

also have available the full text of the bill and Rep. English's "Dear Colleague" letter to Congress.

• If you'd like a quick way to contact your legislators, try the legislative center provided for us by AMSA.

• We originally developed a fact sheet about the graduate tax exemption which is still valid. It was last updated on November 6, 2003.

• For deeper analysis, we have prepared a statistical report which, using the state of California as an example, explains more about the high cost of attending graduate school and demonstrates the need for our proposed exemptions.

• If you're talking to a group about our work, you may want to use a version of our PowerPoint presentation, which contains a lot more detail about policy history and our lobbying efforts.

• We maintain several email distribution lists for people interested in receiving regular updates. There are currently lists for graduate students, governmental affairs professionals, and university administrators and deans. Click on any of the links above to subscribe to that list.

• If you're trying to get your university on board, we have an example letter that you can modify and send to your deans, provost, Chancellor, or other administrators.<BR

Our Supporters

Groups that support the Coalition include:

• Student Associations o National Association of Graduate-Professional Students (support letter) o American Medical Student Association (action alert)

o Individual graduate and progessional student organizations, most notably the University of California Student Association and the Graduate Student Assembly at Carnegie Mellon University.

• University Associations o Association of American Universities (House support letter, Senate

support letter) o Council of Graduate Schools (support letter) o American Council on Education (support letter), representing:

� American Council on Education � Association of American Universities

� Association of Jesuit Colleges and Universities � National Association of College and University Business Officers � National Association of Independent Colleges and Universities � National Association of State Universities and Land-Grant

Colleges

• Health Professions Associations (support letter)

Although their status prevents them from directly assisting our lobbying efforts, we have also received expressions of support from foundations and institutes that fund scientific and scholarly endeavors. For an example, see this letter from National Science Foundation Director Rita Colwell.

If you represent a group that's interested in working on this campaign and helping to make graduate education more affordable, please contact Jim ([email protected])!

Jim Masterson, NAGPS Legislative Concerns Chair Last modified: Mon Jan 30 17:54:01 EST 2006

Cut Fluoridation to Preserve Teeth, Yet Another Study Shows

http://www.holisticmed.com/fluoride/nyscof030905.html

Tooth decay declined substantially in prevalence and severity when Hong Kong children consumed less fluoride, indicative of a world-wide scientific trend revealing, with fluoride, less is best; none is better. In 1988, Hong Kong reduced water fluoride levels from 0.7 parts per million (ppm) to 0.5 ppm. By 1995, 31% fewer 11-year-olds had cavities with a 42% reduction in average cavity rates, according to the Hong Kong Public Health Bulletin (1). Similar reductions occurred in 1978 when Hong Kong's fluoridation rates were first cut from 1 ppm to 0.7 ppm (2). Hong Kong's dental health is superior to the United States' (3), even though U.S. children consume 1 ppm fluoridated water and brush with 1,000 ppm fluoridated toothpaste. And Hong Kong children use lower concentrated (500 ppm) fluoridated toothpaste (4). Evidence that eliminating fluoridation lessens decay:

• Seven years after fluoridation ended in LaSalud, Cuba, cavities remained low in 6- to 9-year-olds, decreased in 10- to 11-year-olds, and significantly decreased in 12- to 13-year-olds, while caries-free children increased dramatically, according to Caries Research (5).

• East German scientists report, "following the cessation of water fluoridation in the cities Chemnitz . . . and Plauen, a significant fall in caries prevalence was observed," according to Community Dentistry and Oral Epidemiology (6) . . . Surveys in the formerly-fluoridated towns of Spremberg and Zittau found "caries levels for the 12-year-olds of both towns significantly decreased... following the cessation of water fluoridation."

• In British Columbia, Canada, "the prevalence of caries decreased over time in the fluoridation-ended community while remaining unchanged in the fluoridated community," reported in Community Dentistry and Oral Epidemiology (7).

• In 1973, the Dutch town of Tiel stopped fluoridation. Researchers counted decayed, missing, and filled permanent tooth surfaces (DMFS) of Tiel's 15-year olds, then collected identical data from never-fluoridated Culemborg. DMFS rates initially increased in Tiel then dipped to 11% of baseline from 1968/69 to 1987/88 while never-fluoridated Culemborg's 15-year-olds had 72% less cavities over the same period, reports Caries Research (8).

In New York State, cavities and tooth loss are greater in fluoridated rather than in non-fluoridated counties (9). In fact, tooth decay crises exist in most, if not all, large fluoridated U.S. cities (10).

Sometimes stopping fluoridation has no effect as in Kuopio, Finland (11), and Durham, North Carolina (12). Some countries show lower decay rates in less fluoridated villages when compared to higher fluoridated villages such as in Uganda (13, 14), the Sudan (15) and Ethiopia (15a). In South Australia, dental examinations of 4800 ten- to fifteen-year-olds' permanent teeth reveal unexpected results - similar cavity rates whether they drink fluoridated water or not (16). In the United States, despite living without fluoridated water, rural children's cavity rates equal those of urban children, who are more likely to drink fluoridated water, according to a large national government study of over 24,000 U.S. children (17). And, to add insult to injury, cavity rates doubled (18) after water fluoridation began in Kentucky (19). References: (1) Hong Kong Government, Public Health and Epidemiiology Bulletin 1998 - http://www.info.gov.hk/dh/diseases/9802.htm (2) Chart showing decline cavity rate - http://www.info.gov.hk/tooth_club/prevent/flouride_water_e.htm (3) Section 8 - http://www.info.gov.hk/dh/publicat/english/ohse8.pdf (4) http://www.info.gov.hk/tooth_club/prevent/flouride_product_e.htm (5) "Caries prevalence after cessation of water fluoridation in LaSalud, Cuba," Caries Research Jan-Feb. 2000 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10601780&dopt=Abstract (6) "Decline of caries prevalence after the cessation of water fluoridation in the former East Germany," Community Dentistry and Oral Epidemiology, October 2000 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11014515&dopt=Abstract (7) "Patterns of dental caries following the cessation of water fluoridation," Community Dentistry and Oral Epidemiology, February 2001 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11153562&dopt=Abstract (8) "Caries experience of 15-year-old children in The Netherlands after discontinuation of water fluoridation," Caries Research, 1993 -

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8519058&dopt=Abstract (9) "Fluoridation Fails to Reduce New York State's Dental Decay or Expenses as Dentists' Promise," by Sally Stride, published February 1, 2005 - http://www.suite101.com/article.cfm/11749/113458 (10) "Cavity Crises in Fluoridated Cities" - http://www.orgsites.com/ny/nyscof2/_pgg6.php3 (11) "Caries trends 1992-1998 in two low-fluoride Finnish towns formerly with and without fluoridation," Caries Research, Nov-Dec 2000 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11093019&dopt=Abstract (12) "The effects of a break in water fluoridation on the development of dental caries and fluorosis," Journal of Dental Research, Feb. 2000 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10728978&dopt=Abstract (13) http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11355098&dopt=Abstract (14) http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11000321&dopt=Abstract (15) Clin Oral Investig. 2005 Jan 6; "Severity of dental caries among 12-year-old Sudanese children with different fluoride exposure," Birkeland JM, Ibrahim YE, Ghandour IA, Haugejorden O. - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15635473 (15a) Community Dent Oral Epidemiol. 2004 Oct, "The relationship between dental caries and dental fluorosis in areas with moderate- and high-fluoride drinking water in Ethiopia," by Wondwossen F, Astrom AN, Bjorvatn K, Bardsen A. - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15341618 (16) Community Dentistry and Oral Epidemiology, August 2004 Consumption of nonpublic water: implications for children's caries experience, byArmfield JM, Spencer AJ. - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15239780

(17) Journal of Rural Health, Summer 2003, "Oral Health Status of Children and Adolescents by Rural Residence, United States." by Clemencia M. Vargas, DDS, PhD; Cynthia R. Ronzio, PhD; and Kathy L. Hayes, DMD, MPH - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12839134&dopt=Abstract (18) "The 2001 Kentucky Childrens Oral Health Survey: findings for children ages 24 to 59 months and their caregivers," Pediatr Dent. 2003 Jul-Aug; 25(4):365-72 by Hardison JD, Cecil JC, White JA, Manz M, Mullins MR, Ferretti GA. - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=13678102&dopt=Abstract (19) Oral Health Program, Kentucky Department of Public Health, May 2002 - http://www.astdd.org/bestpractices/pdf/DES20001KYfluoridationsurveillance.pdf For more information, contact: Paul S. Beeber President & General Counsel New York State Coalition Opposed to Fluoridation PO Box 263 Old Bethpage, NY 11804 [email protected] http://www.orgsites.com/ny/nyscof

e-CFR Data is current as of December 4, 2008

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Title 21: Food and Drugs PART 101—FOOD LABELING Subpart E—Specific Requirements for Health Claims

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§ 101.80 Health claims: dietary noncariogenic car bohydrate sweeteners and dental caries.

(a) Relationship between dietary carbohydrates and dental caries. (1) Dental caries, or tooth decay, is a disease caused by many factors. Both environmental and genetic factors can affect the de velopment of dental caries. Risk factors include tooth enamel crystal s tructure and mineral content, plaque quantity and quality, saliva quanti ty and quality, individual immune response, types and physical characteristics of foods consumed, eating behaviors, presence of acid producing oral b acteria, and cultural influences.

(2) The relationship between consumption of ferment able carbohydrates, i.e., dietary sugars and starches, and tooth decay is well established. Sucrose, also known as sugar, is one of the most, b ut not the only, cariogenic sugars in the diet. Bacteria found in th e mouth are able to metabolize most dietary carbohydrates, producing ac id and forming dental plaque. The more frequent and longer the exposure o f teeth to dietary sugars and starches, the greater the risk for tooth decay.

(3) Dental caries continues to affect a large propo rtion of Americans. Although there has been a decline in the prevalence of dental caries among children in the United States, the disease remains widespread throughout the population, imposing a substantial burden on Am ericans. Recent Federal government dietary guidelines recommend tha t Americans choose diets that are moderate in sugars and avoid excessi ve snacking. Frequent between-meal snacks that are high in sugars and sta rches may be more harmful to teeth than eating such foods at meals an d then brushing.

(4) Noncariogenic carbohydrate sweeteners, such as sugar alcohols, can be used to replace dietary sugars, such as sucrose and corn sweeteners, in foods such as chewing gums and certain confectioner ies. Noncariogenic carbohydrate sweeteners are significantly less cari ogenic than dietary sugars and other fermentable carbohydrates.

(b) Significance of the relationship between noncariogenic carbohydrate sweeteners and dental caries. Noncariogenic carbohydrate sweeteners do not promote dental caries. The noncariogenic carboh ydrate sweeteners listed in paragraph (c)(2)(ii) of this section are slowly metabolized by bacteria to form some acid. The rate and amount of acid production is significantly less than that from sucrose and other fermentable carbohydrates and does not cause the loss of import ant minerals from tooth enamel.

(c) Requirements. (1) All requirements set forth in §101.14 shall be met, except that noncariogenic carbohydrate sweetener-co ntaining foods listed in paragraph (c)(2)(ii) of this section are exempt from §101.14(e)(6).

(2) Specific requirements —(i) Nature of the claim. A health claim relating noncariogenic carbohydrate sweeteners, compared to other carbohydrates, and the nonpromotion of dental caries may be made o n the label or labeling of a food described in paragraph (c)(2)(ii i) of this section, provided that:

(A) The claim shall state that frequent between-mea l consumption of foods high in sugars and starches can promote tooth decay .

(B) The claim shall state that the noncariogenic ca rbohydrate sweetener present in the food “does not promote,” “may reduce the risk of,” “useful [or is useful] in not promoting,” or “expressly [or is expressly] for not promoting” dental caries.

(C) In specifying the nutrient, the claim shall sta te “sugar alcohol,” “sugar alcohols,” or the name or names of the substances l isted in paragraph (c)(2)(ii) of this section, e.g., “sorbitol.” D-tag atose may be identified as “tagatose.”

(D) In specifying the disease, the claim uses the f ollowing terms: “dental caries” or “tooth decay.”

(E) The claim shall not attribute any degree of the reduction in risk of dental caries to the use of the noncariogenic carbohydrate sweetener-containing food.

(F) The claim shall not imply that consuming noncar iogenic carbohydrate sweetener-containing foods is the only recognized m eans of achieving a reduced risk of dental caries.

(G) Packages with less than 15 square inches of sur face area available for labeling are exempt from paragraphs (A) and (C) of this section.

(H) When the substance that is the subject of the c laim is a noncariogenic sugar, the claim shall identify the substance as a sugar that, unlike other sugars, does not promote the development of dental caries.

(ii) Nature of the substance. Eligible noncariogenic carbohydrate sweeteners are:

(A) The sugar alcohols xylitol, sorbitol, mannitol, maltitol, isomalt, lactitol, hydrogenated starch hydrolysates, hydrogenated gluc ose syrups, and erythritol, or a combination of these.

(B) The sugars D-tagatose and isomaltulose.

(C) Sucralose.

(iii) Nature of the food. (A) The food shall meet the requirement in §101.60(c)(1)(i) with respect to sugars content, ex cept that the food may contain D-tagatose or isomaltulose.

(B) A food whose labeling includes a health claim u nder this section shall contain one or more of the noncariogenic carbohydra te sweeteners listed in paragraph (c)(2)(ii) of this section.

(C) When carbohydrates other than those listed in p aragraph (c)(2)(ii) of this section are present in the food, the food shal l not lower plaque pH below 5.7 by bacterial fermentation either during c onsumption or up to 30 minutes after consumption, as measured by the indwe lling plaque pH test found in “Identification of Low Caries Risk Dietary Components,” dated 1983, by T. N. Imfeld, in Volume 11, Monographs in Oral Science, 1983. The Director of the Office of the Federal Register has approved the incorporation by reference of this material in acco rdance with 5 U.S.C. 552(a) and 1 CFR part 51. You may obtain copies fro m Karger AG Publishing Co., P.O. Box, Ch–4009 Basel, Switzerlan d, or you may examine a copy at the Center for Food Safety and Applied Nu trition's Library, Harvey W. Wiley Federal Building, 5100 Paint Branch Pkwy., College Park, MD, or at the National Archives and Records Administration (NARA). For information on the availability of this material at NARA, call 202–741–6030, or go to: http://www.archives.gov/federal_register/code_of_federal_regulations/ibr_locations.html.

(d) Optional information. (1) The claim may include information from paragraphs (a) and (b) of this section, which descr ibe the relationship between diets containing noncariogenic carbohydrate sweeteners and dental caries.

(2) The claim may indicate that development of dent al caries depends on many factors and may identify one or more of the fo llowing risk factors for dental caries: Frequent consumption of fermentable carbohydrates, such as dietary sugars and starches; presence of oral ba cteria capable of fermenting carbohydrates; length of time fermentabl e carbohydrates are in contact with the teeth; lack of exposure to fluorid e; individual susceptibility; socioeconomic and cultural factors; and characteristics of tooth enamel, saliva, and plaque.

(3) The claim may indicate that oral hygiene and pr oper dental care may help to reduce the risk of dental disease.

(4) The claim may indicate that a substance listed in paragraph (c)(2)(ii) of this section serves as a sweetener.

(e) Model health claim. The following model health claims may be used in food labeling to describe the relationship between noncariogenic carbohydrate sweetener-containing foods and dental caries.

(1) Examples of the full claim:

(i) Frequent eating of foods high in sugars and sta rches as between-meal snacks can promote tooth decay. The sugar alcohol [ name, optional] used to sweeten this food may reduce the risk of dental caries.

(ii) Frequent between-meal consumption of foods hig h in sugars and starches promotes tooth decay. The sugar alcohols i n [name of food] do not promote tooth decay.

(iii) Frequent eating of foods high in sugars and s tarches as between-meal snacks can promote tooth decay. [Name of sugar from paragraph (c)(2)(ii)(B) of this section], the sugar used to s weeten this food, unlike other sugars, may reduce the risk of dental caries.

(iv) Frequent between-meal consumption of foods hig h in sugars and starches promotes tooth decay. [Name of sugar from paragraph (c)(2)(ii)(B) of this section], the sugar in [name of food], unli ke other sugars, does not promote tooth decay.

(v) Frequent eating of foods high in sugars and sta rches as between-meal snacks can promote tooth decay. Sucralose, the swee tening ingredient used to sweeten this food, unlike sugars, does not promote tooth decay.

(2) Example of the shortened claim for small packag es:

(i) Does not promote tooth decay.

(ii) May reduce the risk of tooth decay.

(iii) [Name of sugar from paragraph (c)(2)(ii)(B) o f this section] sugar does not promote tooth decay.

(iv) [Name of sugar from paragraph (c)(2)(ii)(B) of this section] sugar may reduce the risk of tooth decay.

[61 FR 43446, Aug. 23, 1996, as amended at 62 FR 63 655, Dec. 2, 1997; 66 FR 66742, Dec. 27, 2001; 67 FR 71470, Dec. 2, 2002; 71 FR 15563, Mar. 29, 2006; 72 FR 52789, Sept. 17, 2007]

Environmental, Health, and Safety Guidelines PHOSPHATE FERTILIZER PLANTSMANUFACTURING

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Environmental, Health and Safety Guidelines for Phosphate Fertilizer Manufacturing

Introduction

The Environmental, Health, and Safety (EHS) Guidelines are

technical reference documents with general and industry-

specific examples of Good International Industry Practice

(GIIP)1. When one or more members of the World Bank Group

are involved in a project, these EHS Guidelines are applied as

required by their respective policies and standards. These

industry sector EHS guidelines are designed to be used

together with the General EHS Guidelines document, which

provides guidance to users on common EHS issues potentially

applicable to all industry sectors. For complex projects, use of

multiple industry-sector guidelines may be necessary. A

complete list of industry-sector guidelines can be found at:

www.ifc.org/ifcext/enviro.nsf/Content/EnvironmentalGuidelines

The EHS Guidelines contain the performance levels and

measures that are generally considered to be achievable in new

facilities by existing technology at reasonable costs. Application

of the EHS Guidelines to existing facilities may involve the

establishment of site-specific targets, with an appropriate

timetable for achieving them.

The applicability of the EHS Guidelines should be tailored to

the hazards and risks established for each project on the basis

of the results of an environmental assessment in which site-

specific variables, such as host country context, assimilative

1 Defined as the exercise of professional skill, diligence, prudence and foresight that would be reasonably expected from skilled and experienced professionals engaged in the same type of undertaking under the same or similar circumstances globally. The circumstances that skilled and experienced professionals may find when evaluating the range of pollution prevention and control techniques available to a project may include, but are not limited to, varying levels of environmental degradation and environmental assimilative capacity as well as varying levels of financial and technical feasibility.

capacity of the environment, and other project factors, are

taken into account. The applicability of specific technical

recommendations should be based on the professional opinion

of qualified and experienced persons.

When host country regulations differ from the levels and

measures presented in the EHS Guidelines, projects are

expected to achieve whichever is more stringent. If less

stringent levels or measures than those provided in these EHS

Guidelines are appropriate, in view of specific project

circumstances, a full and detailed justification for any proposed

alternatives is needed as part of the site-specific environmental

assessment. This justification should demonstrate that the

choice for any alternate performance levels is protective of

human health and the environment.

Applicability

The EHS Guidelines for Phosphate Fertilizer Manufacturing

includes information relevant to facilities that produce

phosphoric acid, single superphosphate (SSP),

triplesuperphosphate (TSP), and compound fertilizers (NPK).

Annex A contains a description of industry sector activities. This

document is organized according to the following sections:

Section 1.0 — Industry-Specific Impacts and Management Section 2.0 — Performance Indicators and Monitoring Section 3.0 — References and Additional Sources Annex A — General Description of Industry Activities


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1.0 Industry-Specific Impacts and Management

The following section provides a summary of EHS issues

associated with phosphate fertilizer plants, which occur during

the operational phase, along with recommendations for their

management. Recommendations for the management of EHS

issues common to most large industrial facilities during the

construction and decommissioning phases are provided in the

General EHS Guidelines.

1.1 Environment

Environmental issues associated with phosphate fertilizer plants

include the following:

• Air emissions

• Wastewater

• Hazardous materials

• Wastes

• Noise

Air Emissions

Combustion Source Emissions Exhaust gas emissions produced by the combustion of gas or

diesel in turbines, boilers, compressors, pumps and other

engines for power and heat generation, are a source of air

emissions from phosphate fertilizer manufacturing facilities.

Guidance for the management of small combustion source

emissions with a capacity of up to 50 megawatts thermal

(MWth), including air emission standards for exhaust emissions,

is provided in the General EHS Guidelines. Guidance for the

management of energy conservation, which can significantly

contribute to the reduction of emissions related to energy

production, is also presented in the General EHS Guidelines.

Production of phosphate fertilizers is an energy intensive

process typically requiring significant use of energy from fossil

fuels and resulting in significant generation of greenhouse

gases. The nitrophosphate production route requires the use of

CO2. Recommendations for the management of GHGs, in

addition to energy efficiency and conservation, are addressed in

the General EHS Guidelines.

Process Emissions – Phosphoric Acid Production Two different production processes can be used in the

manufacture of phosphoric acid:

• The wet process, which is the most commonly used in

fertilizer plants, where phosphate rocks are digested with

an acid (e.g. sulfuric, nitric or hydrochloric acid). The tri-

calcium phosphate from the phosphate rock reacts with

concentrated sulfuric acid to produce phosphoric acid and

calcium sulfate (an insoluble salt); and

• The thermal process, where elemental phosphorous is

produced from phosphate rock, coke, and silica in an

electrical resistance furnace and is then oxidized and

hydrated to form the acid. Thermal-generated acid is highly

purified, but also expensive, and hence produced in small

quantities, mainly for the manufacture of industrial

phosphates;

Process emissions include gaseous fluorides in the form of

hydrofluoric acid (HF) and silicon tetrafluoride (SiF4), released

during the digestion of phosphate rock, which typically contains

2-4 percent fluorine.

The emissions typically associated with the thermal production

process of phosphoric acid include phosphate, fluoride, dust,

cadmium (Cd), lead (Pb), zinc (Zn), and radionuclides (Po-210

and Pb-210). Dust emissions, containing water-insoluble

fluoride, may occur during the unloading, storage, handling and


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grinding of the phosphate rock, which is transferred to storage

and grinding sections by conveyor belts or trucks2.

Recommended emission prevention and control measures


• Properly select the phosphate rock (in terms of P2O5-

content, F-content, CaO/ P2O5 ratio, and physical quality)

to minimize the amount of acid required in the wet

production process, reduce emissions into the environment

and increase the possibility of phosphogypsum reuse;

• Select proper size of screens and mills (e.g. roller or chain

mills);

• Use covered conveyor belts and indoor storage;

• Apply good housekeeping measures (e.g. frequently

cleaning / sweeping facility surfaces and the quay);

• Recover dust from phosphate rock grinding through use of

properly operated and maintained fabric filters, ceramic

filters, and / or cyclones;

• Treat gaseous fluoride emissions using scrubbing systems

(e.g. void spray towers, packed beds, cross-flow venture,

and cyclonic column scrubbers). Fluorine is recovered as

fluosilicic acid, from which silica is removed through

filtration. A diluted solution of fluosilicic acid (H2SiF6) may

be used as the scrubbing liquid. Recovering of H2SiF6 is

an additional possibility for fluoride emission reduction.

Process Emissions – Superphosphate Phosphate Fertilizer Production Dust emissions may be generated during unloading, handling,

grinding, and curing of phosphate rock, in addition to granulation

and crushing of superphosphates. Emissions of gaseous

hydrofluoric acid (HF), silicon tetrafluoride (SiF4), and chlorides

may also generated from acidulation, granulation and drying.

Ammonia (NH3) and nitrogen oxides (NOx) may be generated

2 IPPC BREF (2006) and EFMA (2000a)

during the drying and neutralization phases of ammonium nitrate

fertilizers. In addition, during the reaction of phosphate rock with

acid, limited amounts of organic compounds (including

mercaptans), present in the phosphate rock, are released and

may cause odor.3

Phosphate rock dust emissions should be prevented and

controlled through similar measures to those discussed in the

phosphoric acid production section. Additional emission

prevention and control measures include the following:

• Use of direct granulation may reduce the levels of fugitive

emissions compared with curing emissions from indirect

granulation. If indirect granulation is used, the curing

section should be an indoor system with vents connected

to a scrubbing system or to the granulation section;

• Use of plate bank product cooling systems to reduce air

flow requirements (e.g. instead of rotary drums or fluid bed

coolers);

• Consider use of fabric filters or high efficiency cyclones

and/or fabric filters rather than a wet scrubbing system to

treat exhaust air from neutralization, granulation, drying,

coating and product coolers and equipment vents, in order

to avoid creation of additional wastewater. Filtered air

should be recycled as dilution air to the dryer combustion

system;

• Emissions from granulation should be minimized through

application of surge hoppers to product size distribution

measurement systems for granulation recycle control.

Process Emissions – Compound Fertilizer Production NPK fertilizers are typically produced from mixed acids or

nitrophosphate. Air emissions from NPK produced using the

mixed acids route include ammonia emissions from the

ammonization reactors; nitrogen oxides (NOX), mainly NO and

3 IPPC BREF. October 2006


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NO2 with some nitric acid, from phosphate rock digestion in nitric

acid; fluorides from the phosphate rock reactions; aerosol

emissions, including ammonium nitrate (NH4NO3), ammonium

fluoride (NH4F), and ammonium chloride (NH4Cl), formed in the

gas-phase neutralization reaction between ammonia and acidic

components, as well as by sublimation from the boiling reaction

mixture; and fertilizer dust originating from drying and cooling

drums, and from other sources (e.g. screens, crushers, and

conveyors).

Air emissions from NPK produced using the nitrophosphate

route are similar to those discussed for the mixed acids route,

however they also include aerosol emissions (e.g. from the

dryer and granulator) of ammonium chloride (NH4Cl), originating

from the reaction of ammonia and hydrogen chloride (HCl) when

potassium chloride (KCl) is added to the powder.4 Other

significant air emissions include ammonia from the

neutralization of nitrophosphoric acid. Ammonia emissions may

also be generated from the calcium nitrate tetrahydrate (CNTH,

empirical formula: Ca(NO3)2*4H2O) conversion section, the

ammonium nitrate (AN, empirical formula: NH4NO3) evaporation

section, and the granulation or prilling sections. Aerosols of

ammonium nitrate may also be formed during the different

production steps, and emissions of hydrogen chloride (HCl) may

be present in the exhaust gases from drum granulators,

cyclones, and scrubber systems.5

Recommended measures to prevent and control air emissions


• Reduce NOX emission from nitric acid use in phosphate

rock digestion by controlling the reactor temperature,6

optimizing the rock / acid ratio, and adding urea solution;

4 These emissions can cause the so-called “Tyndall-effect” creating a blue mist at the stack. 5 EIPPCB BREF (2006) and EFMA (2000b,c) 6 High temperature leads to excessive NOX formation.

• Treat gases from the digestion reactor in a spray tower

scrubber to recover NOX and fluorine compounds. The pH

may be adjusted by the addition of ammonia;

• Reduce NOx and odor emissions by selecting high grade

phosphate rock with low contents of organic compounds

and ferrous salts;

• Control particulate matter emissions, as discussed in the

phosphoric acid production section;

• Prevent and / or control emissions from granulation and

product cooling include:

o Scrubbing of gases from the granulator and the dryer

in venturi scrubbers with recirculating ammonium

phosphate or ammonium sulfo-phosphate solution;

o Discharge of scrubbed gases through cyclonic

columns irrigated with an acidic solution;

o Use of high efficiency cyclones to remove particulates

from dryer gases prior to scrubbing;

o Recycling of the air coming from the cooling

equipment as secondary air to the dryer after de-

dusting;

o Treating ammonia emissions by scrubbing with acidic

solutions;

• Fluoride emissions should be controlled through scrubbing

systems, as discussed for phosphoric acid production;

• Emissions to air from phosphate rock digestion, sand

washing and CNTH filtration should be reduced by applying

appropriate controls (e.g. multistage scrubbing, conversion

into cyanides);

• Ammonia in off-gases from the nitrophosphoric

neutralization steps should be removed through counter-

current scrubbers, with pH adjustment to most efficient

scrubbing condition (pH 3-4), with a mixture of HNO3

and/or H2SO4;

• Ammonia emissions from the granulation / drying sections

should be treated by scrubbing with acidic solutions;


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• Minimize contact between wastes containing NOX and NH3

to prevent aerosol formation in NPK nitrophosphate route;

• Reduce aerosol emission by installing cyclones and

scrubbers;

• Reduce fluorides emissions by recycling of warm air.

Fugitive Emissions

Fugitive emissions are primarily associated with operational

leaks from tubing, valves, connections, flanges, packings, open-

ended lines, floating roof storage tank and pump seals, gas

conveyance systems, compressor seals, pressure relief valves,

tanks or open pits/containments, and loading and unloading

operations of products.

Recommended measures for reducing the generation of fugitve

emissions include:

• Selection of appropriate valves, flanges, fittings during

design, operation, and maintenance;

• Implementation of monitoring, maintenance, and repair

programs, particularly in stuffing boxes on valve stems and

seats on relief valves, to reduce or eliminate accidental

releases;

• Installation of leak detection and continuous monitoring in

all sensitive areas;

• Use of open vents in tank roofs should be avoided by

installing pressure relief valves. All storages and unloading

stations should be provided with vapor recovery units.

Vapor processing systems may consist of different

methods, such as carbon adsorption, refrigeration,

recycling collecting and burning.

Wastewater

Effluents – Phosphoric Acid Production Effluents from phosphoric acid plants consist of discharges from

the vacuum cooler condensers and the gas scrubbing systems

used for condensation and cleaning of vapors from process

operations. Condensed acidic vapors may contain fluorine and

small amounts of phosphoric acid. Water from the slurry used to

transport phosphogypsum, the by-product from wet phosphoric

acid production, may be released as effluent if it is not

recirculated back into the process. Emissions to water for the

disposal of gypsum may contain a considerable amount of

impurities, such as phosphorus and fluorine compounds,

cadmium and other heavy metals, and radionuclides. Drainage

from material stockpiles may contain heavy metals (e.g. Cd,

mercury [Hg], and Pb),fluorides, and phosphoric acid. Specific

emissions to water from the thermal process of phosphoric acid

production may include phosphorus and fluorine compounds,

dust, heavy metals, and radionuclides (e.g., Po-210 and Pb-

210). Recommended effluents management measures include

the following:7

• Select phosphate rock with low levels of impurities to

produce clean gypsum and reduce potential impacts from

disposal of gypsum;

• Consider dry systems for air pollution abatement (versus

wet scrubbing) to reduce wastewater generation. To

reduce fluoride emissions, the installation of scrubbers with

suitable scrubber liquids may be necessary;

• Recover fluorine released from the reactor and evaporators

as a commercial by-product (fluosilicic acid);

• Scrubber liquors should be disposed of after neutralization

with lime or limestone to precipitate fluorine as solid

calcium fluoride, if the fluorine is not to be recovered;

• Recycle water used for the transport of phosphogypsum

back into the process following a settling step;

• Where available, consideration should be given to use

seawater as scrubbing liquid, to facilitate reaction of

fluorine to harmless calcium fluoride;

7 IPPC BREF (2006) and EFMA (2000a)


APRIL 30, 2007 6

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• Minimize contamination of the scrubber effluent with

phosphorus pentoxide (P2O5) by conveying vapors from

vacuum flash coolers and vacuum evaporators to a

separator to remove phosphoric acid droplets;

• Minimize contamination of the scrubber effluent with

phosphorus pentoxide P2O5 using entrainment separators.

Additional phosphate removal can be achieved by applying

magnesium ammonium phosphate (struvite) or by calcium

phosphate precipitation;

• Consider decadmation of H3PO4 up to 95% by reactive

extraction with an organic solvent.

Effluents - Superphosphate Fertilizer Production The main source of wastewater in phosphate fertilizer

production is the wet scrubbing systems to treat off-gases.

Contaminants may include filterable solids, total phosphorus,

ammonia, fluorides, heavy metals (e.g. Cd, Hg, Pb), and

chemical oxygen demand (COD). Recycling of scrubber liquids

back into the process should be maximized. Production of

acidulated phosphate rock (PAPR), a fertilizer product

consisting of a mixture of superphosphate and phosphate rock,

in addition to superphosphate (SSP), and triplesuperphosphate

(TSP) products can reduce wastewater volumes8.

Effluents - Compound Fertilizer Production Effluents are usually limited from NPK mixed acids route

facilities, mainly consisting of wastewater from granulation and

exhaust gas scrubbing.

Effluent from NPK facilities employing the nitrophosphate route

may contain ammonia, nitrate, fluoride and phosphate.

Ammonia is found in the effluents of the condensates of the

ammonium nitrate evaporation or the neutralization of the nitro

phosphoric acid solution. Solutions containing ammonium nitrate

8 IPPC BREF (2006)

must be pumped with care to limit the risks of explosions. The

main sources of nitrate and fluoride levels in effluent are the

scrubber liquors from phosphate digestion and sand (removed

from the process slurry) washing. Washing of sand also

generates phosphate content in the effluent.

Recommended effluent management measures include the

following9:

• Recycle the sand washing liquor to reduce phosphate

levels in wastewater effluents;

• Avoid co-condensation of vapors from ammonium nitrate

evaporation;

• Recycle NOX scrubber liquor to reduce ammonia, nitrate,

fluoride and phosphate levels;

• Recycle liquors resulting from scrubbing of exhaust gases

from neutralization;

• Consider reusing effluents as scrubber medium;

• Treat multi-stage scrubbing liquors, after circulation,

through settling (separation of solids), and recycle the

thickened portion back to the reactors.

• Consider combined treatment of exhaust gases from

neutralization, evaporation and granulation. This enables a

recycling of all scrubber liquids to the production process

and reduce waste water generation;

• Treat waste water through a biological treatment with

nitrification/denitrification and precipitation of phosphorous

compounds.

Process Wastewater Treatment

Techniques for treating industrial process wastewater in this

sector include filtration for separation of filterable solids; flow

and load equalization; sedimentation for suspended solids

reduction using clarifiers; phosphate removal using physical-

chemical treatment methods; ammonia and nitrogen removal 9 IPPC BREF (2006) and EFMA (2000b,c)


APRIL 30, 2007 7

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using physical-chemical treatment methods; dewatering and

disposal of residuals in designated waste landfills. Additional

engineering controls may be required for (i) fluoride removal and

(ii) advanced metals removal using membrane filtration or other

physical/chemical treatment technologies

Management of industrial wastewater and examples of

treatment approaches are discussed in the General EHS

Guidelines. Through use of these technologies and good

practice techniques for wastewater management, facilities

should meet the Guideline Values for wastewater discharge as

indicated in the relevant table of Section 2 of this industry sector

document.

Other Wastewater Streams & Water Consumption Guidance on the management of non-contaminated wastewater

from utility operations, non-contaminated stormwater, and

sanitary sewage is provided in the General EHS Guidelines.

Contaminated streams should be routed to the treatment system

for industrial process wastewater. Recommendations to reduce

water consumption, especially where it may be a limited natural

resource, are provided in the General EHS Guidelines.

Hazardous Materials

Phosphate fertilizer manufacturing plants use, store, and

distribute significant amounts of hazardous materials (e.g. acids

and ammonia). Recommended practices for hazardous material

management, including handling, storage, and transport, are

presented in the General EHS Guidelines. Manufacture and

distribution of materials should be conducted according to

applicable international requirements where applicable.10

Wastes Non-hazardous solid wastes may be generated from some

phosphate fertilizer manufacturing processes, including

10 For example, the Rotterdam Convention on the Prior Informed Consent (PIC) Procedure for Certain Hazardous Chemicals and Pesticides.

phosphogypsum from wet phosphoric acid production, and

quartz sand from NPK production using the nitrophosphate

route. Quartz sand should be separated, washed, and recycled

as a building material. There is limited hazardous waste

generated from the phosphate fertilizer manufacturing

processes. In addition to the industry specific information

provided below, guidance on the management of hazardous and

non-hazardous wastes is provided in the General EHS

Guidelines.

Phosphogypsum Phosphogypsum is the most significant by-product in wet

phosphoric acid production (approximately 4 - 5 tons of

phosphogypsum is produced for every ton of phosphoric acid,

as P2O5, produced11). Phosphogypsum contains a wide range of

impurities (residual acidity, fluorine compounds, trace elements

such as mercury, lead and radioactive components12). These

impurities and considerable amounts of phosphate might be

released to the environment (soil, groundwater and surface

water).Industry-specific pollution prevention and control

practices include13:

• Depending on its potential hazardousness (e.g. whether it

emits radon) phosphogypsum may be processed to

improve its quality and reused (e.g. as building material).

Possible options include:

o Production of cleaner phosphogypsum from raw

materials (phosphate rock) with low levels of

impurities

o Use of repulping

11 Gypsum contains a wide range of impurities (residual acidity, fluorine compounds, trace elements such as mercury, lead and radioactive components). IPPC BREF (2006) 12 Phosphate rock, phosphogypsum and the effluents produced from a phosphoric acid plant have generally a lower radioac-tivity than the exemption values given in the relevant international regulations and guidelines (for example, EU Directive 96/26/EURATOM) 13 IPPC BREF (2006) and EFMA (2000a,b,c)


APRIL 30, 2007 8

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• Use of di-hemihydrate recrystallization process with double

stage filtration;

• If phosphogypsum can not be recycled due to the

unavailability of commercially and technically viable

alternatives, it should be managed as a hazardous or non-

hazardous industrial waste, depending on its

characteristics, according to the guidance in the General

EHS Guidelines.14 Additional management alternatives

may include backfilling in mine pits, dry stacking15, and wet

stacking.

Noise

Noise is generated from large rotating machines, including

compressors and turbines, pumps, electric motors, air coolers,

rotating drums, spherodizers, conveyors belts, cranes, fired

heaters, and from emergency depressurization. Guidance on

noise management is provided in the General EHS Guidelines.

1.2 Occupational Health and Safety

The occupational health and safety issues that may occur during

the construction and decommissioning of phosphate fertilizer

manufacturing facilities are similar to those of other industrial

facilities, and their management is discussed in the General

EHS Guidelines.

Facility-specific occupational health and safety issues should be

identified based on job safety analysis or comprehensive hazard

or risk assessment, using established methodologies such as a

hazard identification study [HAZID], hazard and operability study

[HAZOP], or a quantitative risk assessment [QRA]. As a general

approach, health and safety management planning should

include the adoption of a systematic and structured approach for

14 The classification of phosphogypsum as a hazardous or non-hazardous waste may depend on the level of radon emissions of the material. Removal of this material from stack and subsequent disposal may be subject to specific regulatory requirements depending on the jurisdiction. 15 It should be noted that dry stacking does not eliminate acid water seepage except in very arid climates.

prevention and control of physical, chemical, biological, and

radiological health and safety hazards described in the General

EHS Guidelines.

The most significant occupational health and safety hazards

occur during the operational phase of phosphate fertilizer

manufacturing facilities and primarily include:

• Process Safety

• Chemical hazards

• Decomposition, fires and explosions

Process Safety Process safety programs should be implemented, due to

industry-specific characteristics, including complex chemical

reactions, use of hazardous materials (e.g. toxic, reactive,

flammable or explosive compounds), and multi-step reactions.

Process safety management includes the following actions:

• Physical hazard testing of materials and reactions;

• Hazard analysis studies to review the process chemistry

and engineering practices, including thermodynamics and

kinetics;

• Examination of preventive maintenance and mechanical

integrity of the process equipment and utilities;

• Worker training;

• Development of operating instructions and emergency

response procedures.

Chemical Hazards

Ammonia and acids vapors, especially HF, are common toxic

chemicals in phosphate fertilizer plants. Threshold values

associated with specific health effects can be found in

internationally published exposure guidelines (see Monitoring

below). In addition to guidance on chemical exposure provided

in the General EHS Guidelines, the following are


APRIL 30, 2007 9

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recommendations to prevent and control chemical exposure in

this sector:

• Avoid contact of acids with strong caustic substances. The

resulting reaction is exothermic and may cause splashes;

• Control fluoride gas build up in phosphoric acid storage

tanks;

• Install gas detectors in hazard areas;

• Provide adequate ventilation (e.g. air extraction and

filtration systems) in all areas where products are

produced, stored, and handled;

• Provide training and personal protection equipment for

personnel as described in the General EHS Guidelines.

Decomposition, Fire and Explosions

Decomposition16, fire and explosion hazards may be generated

from slurry pump explosions due to insufficient flow through the

pump or incorrect design; slurry decompositions due to low pH,

high temperature and contaminated raw materials; and

hydrogen gas generation due to phosphoric acid contact with

ferrous metals.

The risk of decomposition, fire and explosion can be minimized

by adopting measures such the following17:

• Inventory of ammonia, nitric and sulfuric acids should be

kept as low as possible. Supply by pipeline is

recommended in integrated chemical complexes;

• NPK fertilizer decomposition hazard should be prevented

through temperature control during production, adjustment

of formulations, and reduction of impurities. Compound

build–up on the inlet vanes in the dryer should be avoided

16 The manufacture, storage and transport of NPK fertilizers may generate a hazard related to self-sustaining decomposition of fertilizer compounds with ammonium nitrate at temperatures in excess of 130°C16. Decomposition is dependant on product grades and formulations, and may release significant amounts of toxic fumes. 17 EFMA. 2000b,c

and uniform temperature profile of the air inlet should be

ensured;

• Segregating process areas, storage areas, utility areas,

and safe areas, and adopting of safety distances.

• Implementing well controlled operation and procedures in

avoiding hazardous gas and slurry mixtures;

• NPK storage should be designed according to

internationally recognized guidance and requirements18.

Adequate fire detection and fighting system should be

installed.

• Storage areas should be cleaned before any fertilizer is

introduced. Spillage should be cleared up as soon as

practicable. Fertilizer contamination with organic

substances during storage should be prevented; and

• Fertilizers should not be stored in proximity of sources of

heat, or in direct sunlight or in conditions where

temperature cycling can occur.

• Contact of phosphoric acid with ferrous metal component

should be prevented. Stainless steel should be used for

components possibly in contact with the acid.

1.3 Community Health and Safety

Guidance on the management of community health and safety

impacts during the construction and decommissioning phases

common to those of other large industrial facilities are discussed

in the General EHS Guidelines.

The most significant community health and safety hazards

during the operation of phosphate fertilizers facilities relate to

the management, storage and shipping of hazardous materials

and products, with potential for accidental leaks / releases of

toxic and flammable gases, and the disposal of wastes (e.g.

phosphogypsum, off-spec products, sludge). Plant design and

18 See for example the EC Fertilizer Directives EC 76/116 and EC 80/876 and the COMAH Directive 96/82/EC.


APRIL 30, 2007 10

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operations should include safeguards to minimize and control

hazards to the community, including the following measures:

• Identify reasonable design leak scenarios;

• Assess the effects of potential leaks on surrounding areas,

including groundwater and soil pollution;

• Assess potential risks arising from hazardous material

transportation and select the most appropriate transport

routes to minimize risks to communities and third parties;

• Select plant location with respect to the inhabited areas,

meteorological conditions (e.g. prevailing wind directions),

and water resources (e.g., groundwater vulnerability).

Identify safe distances between the plant area, especially

the storage tank farms, and the community areas;

• Identify prevention and mitigation measures required to

avoid or minimize community hazards;

• Develop an Emergency Management Plan with the

participation of local authorities and potentially affected

communities.

Guidance on the transport of hazardous materials, the

development of emergency preparedness and response plans,

and other issues related to community health and safety is

discussed in the General EHS Guidelines.

2.0 Performance Indicators and Monitoring

2.1 Environment

Emissions and Effluent Guidelines Tables 1 and 2 present emission and effluent guidelines for this

sector. Guideline values for process emissions and effluents in

this sector are indicative of good international industry practice

as reflected in relevant standards of countries with recognized

regulatory frameworks. The guidelines are assumed to be

achievable under normal operating conditions in appropriately

designed and operated facilities through the application of

pollution prevention and control techniques discussed in the

preceding sections of this document.

Effluent guidelines are applicable for direct discharges of treated

effluents to surface waters for general use. Site-specific

discharge levels may be established based on the availability

and conditions in use of publicly operated sewage collection and

treatment systems or, if discharged directly to surface waters,

on the receiving water use classification as described in the

General EHS Guidelines. These levels should be achieved,

without dilution, at least 95 percent of the time that the plant or

unit is operating, to be calculated as a proportion of annual

operating hours. Deviation from these levels in consideration of

specific, local project conditions should be justified in the

environmental assessment.

Combustion source emissions guidelines associated with

steam- and power-generation activities from sources with a

capacity equal to or lower than 50 MWth are addressed in the

General EHS Guidelines with larger power source emissions

addressed in the Thermal Power EHS Guidelines. Guidance

on ambient considerations based on the total load of emissions

is provided in the General EHS Guidelines.

Environmental Monitoring Environmental monitoring programs for this sector should be

implemented to address all activities that have been identified to

have potentially significant impacts on the environment, during

normal operations and upset conditions. Environmental

monitoring activities should be based on direct or indirect

indicators of emissions, effluents, and resource use applicable

to the particular project. Monitoring frequency should be

sufficient to provide representative data for the parameter being

monitored. Monitoring should be conducted by trained

individuals following monitoring and record-keeping procedures

and using properly calibrated and maintained equipment.


APRIL 30, 2007 11

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Monitoring data should be analyzed and reviewed at regular

intervals and compared with the operating standards so that any

necessary corrective actions can be taken. Additional guidance

on applicable sampling and analytical methods for emissions

and effluents is provided in the General EHS Guidelines.

Table 1. Air Emissions Guidelines for Phosphate Fertilizers Plants

Pollutant Units Guideline Value

Phosphoric Acid Plants

Fluorides (gaseous) as HF mg/Nm3 5 Particulate Matter mg/Nm3 50

Phosphate Fertilizer Plants

Fluorides (gaseous) as HF mg/Nm3 5 Particulate Matter mg/Nm3 50 Ammonia mg/Nm3 50 HCl mg/Nm3 30

NOX mg/Nm3 500 nitrophosphate unit 70 mix acid unit

Table 2. Effluents Guidelines for Phosphate Fertilizer Plants

Pollutant Units Guideline Value

pH S.U. 6-9 Total Phosphorus mg/L 5

mg/L 20 kg/ton NPK 0.03

Fluorides kg/ton Phosphorus oxide

(P2O5) 2

TSS mg/L 50 Cadmium mg/L 0.1 Total Nitrogen mg/L 15 Ammonia mg/L 10 Total Metals mg/L 10

Resource Use and Energy Consumption, Emission and Waste Generation Table 3 provides examples of resource consumption indicators

for energy and water in this sector. Table 4 provides examples

of emission and waste generation indicators in this sector.

Industry benchmark values are provided for comparative

purposes only and individual projects should target continual

improvement in these areas.

Table 3. Resource and Energy Consumption

Product Unit Industry

Benchmark

Ton phosphate rock/ton P2O5

2.6-3.5 (1)

Ton H2SO4/ton P2O5 2.1-2.3 (1)

KWh/ton P2O5 120-180 (1)

Phosphoric Acid

m3 cooling water/ton P2O5

100-150 (1)

KWh/ton NPK 30-33 (1)(2) NPK A

Total energy for drying MJ/ton NPK

300-320 (1)(2)

KWh/ton NPK 50 (1)(2) NPK B

Total energy for drying MJ/ton NPK

450 (1)(2)

NPK C KWh/ton NPK 50-109 (2)

NPK C m3 cooling water/ton NPK

17 (2)

NPK C Ton CO2 required/ton P2O5

1(1)(2)

SSP KWh/ton SSP 19-34 (2)

SSP m3 water/ton SSP 0.1-2 (2)

Notes: NPK PLANTS A Granulation with a Pipe Reactor and Drum with ammoniation NPK PLANTS B Mixed Acids Process NPK PLANTS C Nitrophosphate Process 1. European Fertilizer Manufacturers Association (EFMA). 2000. 2. EU IPPC - Reference Document on Best Available Tec hniques in Large Volume

Inorganic Chemicals – Ammonia, Acids and Fertilizers Industries. December 2006


APRIL 30, 2007 12

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Table 4. Emissions, Effluents and Waste Generation

Parameter Unit Industry

Benchmark

Phosphoric acid p lants

Fluoride SO2 mg/Nm3kg/ton HF 5–300.001 – 0.01

Solid Waste Generation (phosphogypsum) (thermal/wet process)

ton/ton P2O5 3.2/4-5 (1)

NPK Production – Nitrophosphate Process

NH3 air emissions kg/ton P2O5 0.2

NOX (as NO2) air emissions

kg/ton P2O5 1.0

Fluoride airFluorides air emissions

kg/ton P2O5 0.01

Total nitrogen effluents kg/ton P2O5 0.001 – 0.01

P2O5 effluents kg/ton P2O5 1.2

Fluorides effluents kg/ton P2O5 0.7

NPK Production – Mixed Acids Process

NH3 emissions kg/ton NPK 0.2

NOX (as NO2) emissions kg/ton NPK 0.3

Fluorides emissions kg/ton NPK 0.02

Dust emissions kg/ton NPK 0.2

Total nitrogen effluents kg/ton NPK 0.2

Fluorides effluents kg/ton NPK 0.03

Fluorides air emissions mg/Nm3 0.4-4

Dust air emissions mg/Nm3 30-50

Chloride air emissions mg/Nm3 19-20

2.2 Occupational Health and Safety Performance

Occupational Health and Safety Guidelines

Occupational health and safety performance should be

evaluated against internationally published exposure guidelines,

of which examples include the Threshold Limit Value (TLV®)

occupational exposure guidelines and Biological Exposure

Indices (BEIs®) published by American Conference of

Governmental Industrial Hygienists (ACGIH),19 the Pocket

Guide to Chemical Hazards published by the United States

National Institute for Occupational Health and Safety (NIOSH),20

Permissible Exposure Limits (PELs) published by the

Occupational Safety and Health Administration of the United

States (OSHA),21 Indicative Occupational Exposure Limit Values

published by European Union member states,22 or other similar

sources.

Accident and Fatality Rates Projects should try to reduce the number of accidents among

project workers (whether directly employed or subcontracted) to

a rate of zero, especially accidents that could result in lost work

time, different levels of disability, or even fatalities. Facility rates

may be benchmarked against the performance of facilities in this

sector in developed countries through consultation with

published sources (e.g. US Bureau of Labor Statistics and UK

Health and Safety Executive)23.

Occupational Health and Safety Monitoring The working environment should be monitored for occupational

hazards relevant to the specific project. Monitoring should be

designed and implemented by accredited professionals24 as part

of an occupational health and safety monitoring program.

Facilities should also maintain a record of occupational

accidents and diseases and dangerous occurrences and

accidents. Additional guidance on occupational health and

safety monitoring programs is provided in the General EHS

Guidelines.

19 Available at: http://www.acgih.org/TLV/ and http://www.acgih.org/store/ 20 Available at: http://www.cdc.gov/niosh/npg/ 21 Available at: http://www.osha.gov/pls/oshaweb/owadisp.show_document?p_table=STANDARDS&p_id=9992 22 Available at: http://europe.osha.eu.int/good_practice/risks/ds/oel/ 23 Available at: http://www.bls.gov/iif/ and http://www.hse.gov.uk/statistics/index.htm 24 Accredited professionals may include Certified Industrial Hygienists, Registered Occupational Hygienists, or Certified Safety Professionals or their equivalent.

Environmental, Health, and Safety Guidelines PHOSPHATE FERTILIZER PLANTS

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3.0 References and Additional SourcesEuropean Commission. 2006. European Integrated Pollution Prevention and Control Bureau (EIPPCB). Reference Document on Best Available Techniques in Large Volume Inorganic Chemicals – Ammonia, Acids and Fertilizers. Seville: EIPPCB. Available at http://eippcb.jrc.es/pages/FActivities.htm

European Fertilizer Manufacturer’s Association (EFMA). 2000a. Best Available Techniques (BAT) Production of Phosphoric Acid (Booklet No. 4). Brussels: EFMA. Available at http://www.efma.org/Publications/

EFMA. 2000b. BAT Production of NPK Fertilizers by the Nitrophosphate Route (Booklet No. 7). Brussels: EFMA. Available at http://www.efma.org/Publications/

EFMA. 2000c. BAT Production of NPK Fertilizers by the Mixed Acid Route (Booklet No. 8). Brussels: EFMA. Available at http://www.efma.org/Publications/

EFMA and International Fertilizer Industry Association (IFA). 1992. Handbook for the Safe Storage of Ammonium Nitrate Based Fertilizers. Zurich/Paris: EFMA/IFA. Available at http://www.efma.org/publications/

German Federal Ministry for the Environment, Nature Conservation and Nuclear Safety (BMU). 2004. Waste Water Ordinance – AbwV. (Ordinance on Requirements for the Discharge of Waste Water into Waters). Promulgation of the New Version of the Waste Water Ordinance of 17 June 2004. Berlin: BMU. Available at http://www.bmu.de/english/water_management/downloads/doc/3381.php

German Federal Ministry for the Environment, Nature Conservation and Nuclear Safety (BMU). 2002. First General Administrative Regulation Pertaining to the Federal Emission Control Act (Technical Instructions on Air Quality Control – TA Luft). Berlin: BMU. Available at http://www.bmu.de/english/air_pollution_control/ta_luft/doc/36958.php

United Kingdom (UK) Environmental Agency. 2002. Sector Guidance Note Integrated Pollution Prevention and Control (IIPC) S4.03. Guidance for the Inorganic Chemicals Sector. Bristol: Environment Agency. Available at http://www.environment-agency.gov.uk/business/444304/1290036/1290086/1290209/1308462/1245952/

International Fertilizer Industry Association (IFA) / United Nations Environment Programmme (UNEP) / United Nations Industrial Development Organization (UNIDO). 1998. The Fertilizer Industry's Manufacturing Processes and Environmental Issues. (Technical Report No. 26, Part 1). Paris: IFA/UNEP/UNIDO.

United States (US) Environmental Protection Agency (EPA). 1995. Office of Compliance. Sector Notebook Project. Profile of the Inorganic Chemical Industry. Washington, DC: US EPA. Available at http://www.epa.gov/compliance/resources/publications/assistance/sectors/notebooks/inorganic.html

US EPA. 40 CFR Part 60, Standards of Performance for New and Existing Stationary Sources: Subpart T—Standards of Performance for the Phosphate Fertilizer Industry: Wet-Process Phosphoric Acid Plants. Washington, DC: US EPA. Available at http://www.epa.gov/epacfr40/chapt-I.info/

US EPA. 40 CFR Part 60, Standards of Performance for New and Existing Stationary Sources: Subpart W—Standards of Performance for the Phosphate Fertilizer Industry: Triple Superphosphate Plants. Washington, DC: US EPA. Available at http://www.epa.gov/epacfr40/chapt-I.info/

US EPA. 40 CFR Part 63, National Emission Standards for Hazardous Air Pollutants for Source Categories: Subpart AA—National Emission Standards for Hazardous Air Pollutants from Phosphoric Acid Manufacturing Plants. Washington, DC: US EPA. Available at http://www.epa.gov/epacfr40/chapt-I.info/

US EPA. 40 CFR Part 418 Fertilizer Manufacturing Point Source Category. Subpart A—Phosphate Subcategory. Washington, DC: US EPA. Available at http://www.epa.gov/epacfr40/chapt-I.info/

US EPA. 40 CFR Part 418 Fertilizer Manufacturing Point Source Category. Subpart G—Mixed and Blend Fertilizer Production Subcategory. Washington, DC: US EPA. Available at http://www.epa.gov/epacfr40/chapt-I.info/

US EPA. 40 CFR Part 422 Phosphate Manufacturing Point Source Category. Washington, DC: US EPA. Available at http://www.epa.gov/epacfr40/chapt-I.info/


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Annex A: General Description of Industry Activities A modern phosphate fertilizer manufacturing complex is

characterized by large volume productions and is normally

highly integrated with upstream (e.g. ammonia, and acids such

as nitric, sulfuric, and phosphoric) and downstream (e.g.

ammonium nitrate and calcium ammonium nitrate) production

with the aim at optimizing production cost, logistics, safety and

environmental protection (Figure A.1). Phosphate fertilizer

plants may produce single (or normal) superphosphate (SSP)

and triple superphosphate (TSP); mixed fertilizers such as

Mono-Ammonium Phosphate (MAP) and Di-Ammonium

Phosphate (DAP); and all grades of compound fertilizers (NPK)

using the nitrophosphate / nitric acid route and the mixed acid /

sulfuric acid route. Facilities are usually equipped with an

integrated steam and electric power distribution grid servicing all

the plants and supplied by a central steam boiler and power

station. A waste water treatment plant is usually present.

Sulfuric Acid Sulfuric acid (H2SO4) is used in the phosphate fertilizer industry

for the production of phosphoric acid. Sulfuric acid is

manufactured mainly from sulfur dioxide (SO2), produced

through the combustion of elemental sulfur. The exothermic

oxidation of sulfur dioxide over several layers of a suitable

catalyst (e.g. vanadium pentoxide) to produce sulfur trioxide

(SO3) is the most common process in sulfuric acid

manufacturing plants.25

Sulfuric acid is obtained from the absorption of SO3 and water

into H2SO4 (with a concentration of at least 98 percent) in

absorbers installed after multiple catalyst layers. The warm acid

produced is sparged with air in a column or in a tower to collect

25 IPPC BREF (2006)

the remaining SO2 in the acid. The SO2 laden air is returned to

the process.

Phosphoric Acid Phosphoric acid (H3PO4) is primarily used in the manufacture of

phosphate salts (e.g. for fertilizers and animal feed

supplements). Two different processes can be used in the

manufacture of phosphoric acid. In the first process, known as

the thermal process, elemental phosphorous is produced from

phosphate rock, coke, and silica in an electrical resistance

furnace and is then oxidized and hydrated to form the acid.

Thermal-generated acid is highly purified, but also expensive,

and hence produced in small quantities, mainly for the

manufacture of industrial phosphates.

The second type of process, known as the wet process, involves

digesting phosphate rocks with an acid (e.g. sulfuric, nitric or

hydrochloric acid). The tri-calcium phosphate from the

phosphate rock reacts with concentrated sulfuric acid to produce

phosphoric acid and calcium sulfate, which is an insoluble salt.

The operating conditions are generally designed so that the

calcium sulfate is precipitated as anhydrite, hemihydrate (HH)

and dihydrate (DH).

Different processes are needed because of different rocks and

gypsum disposal systems.26 The main production steps include

grinding of phosphate rock (if necessary); reaction with sulfuric

acid in a series of separate agitated reactors at a temperature of

70-80°C, filtration to separate the phosphoric acid from the

calcium sulfate; and concentration up to commercial phosphoric

acid with a concentration of 52-54 percent phosphorus

pentoxide (P2O5).

26 EIPPCB BREF (2006) and EFMA (2000a)


APRIL 30, 2007 15

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When the phosphoric acid plant is linked to a sulfuric acid plant,

the high-pressure steam produced in the waste heat recovery

boiler from the sulfuric acid is normally used to produce electric

power, and the low-pressure exhaust steam is used for

phosphoric acid vacuum concentration. The steam consumption

needed for the concentration can be reduced by using waste

heat originating in the sulfuric acid plant. This may be recovered

as heated water and used in the process of concentrating weak

acid to intermediate concentration. Phosphoric acid is most

commonly stored in rubber-lined steel tanks, although stainless

steel, polyester and polyethylene-lined concrete are also used.

Storage tanks are normally equipped to keep the solids in

suspension to avoid costly cleaning of the tank27.

Phosphate Fertilizers (SSP / TSP) Phosphate fertilizers are produced by adding acid to ground or

pulverized phosphate rock. If sulfuric acid is used, single or

normal, superphosphate (SSP) is produced, with a phosphorus

content of 16–21 percent as phosphorous pentoxide (P2O5).

SSP production involves mixing the sulfuric acid and the rock in

a reactor. The reaction mixture is discharged onto a slow-

moving conveyor belt. If the reaction The mixture is directly fed

to a granulator, the process is the so called “direct” granulation.

In “indirect” granulation, the reaction mixture is stored for

“curing” for 4 to 6 weeks before bagging and then granulated.28

If phosphoric acid is used to acidulate the phosphate rock, triple

superphosphate (TSP) is produced with a phosphorus content

of 43–48 percent as P2O5. Two processes are used to produce

TSP fertilizers: run-of-pile and granulation. The run-of-pile

process is similar to the SSP process. Granular TSP uses

lower-strength phosphoric acid (40 percent, compared with 50

percent for run-of-pile method). The reaction mixture, a slurry, is

27 EFMA (2000a) 28 EIPPCB BREF (2006)

sprayed onto recycled fertilizer fines in a granulator. Granules

grow and are then discharged to a dryer, screened, and sent to

storage.29

Compound Fertilizers (NPK) Compound fertilizers are a large group of products, varying

based on the particular nitrogen / phosphorus / potassium

(N/P/K) ratios. Production processes are also numerous and

product types include PK, NP (e.g. DAP), NK and NPK. This

can be achieved by using two different routes, namely

production by the nitrophosphate route, and production by the

mixed acid route.

Nitrophosphate Route The integrated nitrophosphate (NP) process produces

compound fertilizers (NPK) containing ammonium nitrate,

phosphate, and potassium salts (Figure A.2). The integrated

process starts with the dissolution of the phosphate rock in nitric

acid. Varying amounts of volatile compounds, such as carbon

dioxide (CO2), nitrogen oxides (NOX) and hydrogen fluoride

(HF), may be emitted, depending on the phosphate rock

characteristics. The resulting digestion solution contains

different amounts of suspended solids (e.g. quartz sand) that

are removed by centrifuges, hydrocyclones or, lamella

separators.30 After washing, the solids can be reused in the

building industry.

The liquor obtained from the process contains calcium ions in a

proportion that too high to guarantee the production of plant

available P2O5. The solution is therefore cooled so that calcium

nitrate tetrahydrate (CNTH) crystallizes out. The solution of

phosphoric acid, remaining calcium nitrate, and nitric acid,

called nitrophosphoric acid, can be separated from the CNTH

29 EIPPCB BREF (2006) 30 EFMA (2000b)


APRIL 30, 2007 16

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crystals by filtration. The nitrophosphoric acid is then neutralized

with ammonia, mixed with potassium / magnesium salts, sulfate

and/or micro-nutrients, and converted to NPK in a rotary

granulation drum, fluidized bed, prilling tower, or pug-mill to

obtain solid compound fertilizers.31

The separated calcium nitrate crystals are dissolved in an

ammonium nitrate solution and treated with an ammonium

carbonate solution. This solution is filtered to remove the

calcium carbonate crystals and it is used for the production of

granular calcium ammonium nitrate (CAN) fertilizer. The

resulting dilute ammonium nitrate solution is concentrated and

also used to produce CAN or NPK. The calcium nitrate solution

may also be neutralized and evaporated to obtain a solid

fertilizer.32

Three types of processes are normally used for the production

of NPK fertilizers from the NP liquor, namely prilling, drum or

pug-mill, and spherodizer granulation. In prilling, NP liquor,

mixed with the required salts and recycled product, overflows

into a rotating prill bucket from which the slurry is sprayed into

the prill tower. Fans at the top of the tower cause ambient air to

flow counter-current to the droplets formed by solidification.33

In drum or pug-mill granulation, the NP liquor, together with

required salts and recycled products, is sprayed into a rotating

drum granulator where granules formed are dried in a rotating

drying drum with hot air. The air leaving the drums contains

water vapor, dust, ammonia and combustion gases. The air

from the granulation and drying drums is treated in high

performance cyclones.34

31 Ibid. 32 Ibid 33 Ibid 34 Ibid

In spherodizer granulation, the slurry is sprayed into a special

rotating drum, called a spherodizer, where warm air, heated to

300-400°C, flows co-currently thus evaporating the water

building up on granules.35

In all processes, the dry NPK granules are screened. The on-

size fraction passes to the conditioning process, and the over-

size fractions are taken out, crushed and recycled together with

the under-size fractions. The screen, crusher, and conveyor

discharges are de-dusted using the air required for granulation.

The commercial product from the drying and screening is cooled

in a fluidized bed, a bulk flow heat exchanger, or a rotating

drum. Off-gases from these latter stages, containing minor

amounts of dust, and generally no ammonia, are de-dusted in

cyclones. Finally, the product is cooled and coated before

storage, to minimize the subsequent caking of the material. The

coating consists of a treatment with an organic agent and

inorganic powder, added in a drum. The calcium nitrate crystals

from the nitrophosphate process can be processed to a solid

calcium nitrate (CN) fertilizer, using prilling or pan-granulation

technology, as an alternative to the combination of CNTH

conversion and subsequent processing to CAN.36

Mixed Acid Route Processes applied in the mixed acid route of production are

numerous, the most common including granulation with a pipe

reactor system; drum granulation with ammoniation; and a

mixed acid process with phosphate rock digestion.37 A simplified

flow chart showing the three processes together is presented on

Figure A.3.

Granulation with a pipe reactor system works with a classical

granulation loop with one or two pipe reactors. One pipe reactor

35 Ibid 36 EFMA (2000b) 37 EFMA (2000c)


APRIL 30, 2007 17

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is fitted in the granulator and another may be used in the dryer.

Phosphoric acid or a mixture of phosphoric and sulfuric acids is

neutralized in the pipe reactors with gaseous or liquid ammonia.

A wide range of grades, including ammonium phosphates

(monoammonium phosphate – MAP, and diammonium

phosphate – DAP), can be produced.38 The required solid raw

materials such as potassium chloride, potassium sulfate,

superphosphate, secondary nutrients, micronutrients and filler

are fed into the granulator together with the recycled material.

The pipe reactor fitted in the granulator is designed to receive

phosphoric acid, part of the ammonia, and all the other liquid

feeds such as sulfuric acid and recycled scrubber liquor.

Concentrated ammonium nitrate solution may be added directly

into the granulator and ammoniation rates in the pipe reactor

vary according to the product. Further ammoniation may be

carried out in the granulator. A pipe reactor fitted in the dryer is

fed with phosphoric acid and ammonia.

Drum granulation with ammoniation consists of a classical

granulation loop using mainly solid raw materials. Ammonium

nitrate solution and / or steam is / are fed into the granulator.

The process is very flexible, and is able to produce a broad

spectrum of grades including products with low nitrogen content.

Ammonium nitrate solution is sprayed directly into the granulator

and sulfuric acid may be fed into the granulator followed by

ammoniation39. The granules obtained in both granulation

processes are dried in a drying section using a heated air

stream.40 The dry granules are managed as discussed for the

NP route.

Gases from the granulator and the dryer are scrubbed in venturi

scrubbers with recirculating ammonium phosphate or

ammonium sulfo-phosphate solution. The scrubber liquor which 38 Ibid. 39 EFMA (2000c) 40 Ibid.

is being recycled is fed to the pipe reactor in the granulator.

Finally, the gases are vented through cyclonic columns irrigated

with an acidic solution. The gases coming from the dryer are de-

dusted in high efficiency cyclones to remove the majority of the

dust before scrubbing. The air coming from the cooling

equipment is generally recycled as secondary air to the dryer

after de-dusting.41

The mixed acid process with phosphate rock digestion is very

flexible and produces grades with varying degrees of phosphate

water solubility. The first step of the process is the exothermic

digestion of phosphate rock with nitric acid resulting in a solution

of phosphoric acid and calcium nitrate. Acid gases such as

oxides of nitrogen and fluorine compounds are formed during

the digestion, depending on the type of phosphate rock. Other

raw materials such as phosphoric, sulfuric, and nitric acids or

AN solution are added after the digestion. The acid slurry is

ammoniated with gaseous ammonia and after neutralization,

and other components such as ammonium phosphates,

superphosphates, ammonium sulfate, and compounds

containing potassium and magnesium are added. Most of these

materials may also be added before or during neutralization, but

if the raw material contains chloride, the pH of the slurry should

be 5 – 6 to avoid the production of hydrogen chloride. The

reactor battery ends with a buffer tank. The slurry granulation

can then be performed by different equipment such as drum,

blunger and spherodizer.42

The gases from the digestion reactors, where phosphate rock is

digested in nitric acid, are treated separately in a spray tower

scrubber to recover NOX and fluorine compounds. The pH is

adjusted by the addition of ammonia. The ammoniation reactor

gases are scrubbed in several stages of counter-current

41 Ibid. 42 Ibid.


APRIL 30, 2007 18

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scrubbing. The pH is adjusted to the most efficient scrubbing

condition, pH 3-4, with a mixture of HNO3 and/or H2SO4. The

first scrubbing stage ensures a saturation of the gases; the

second high pressure venturi stage is designed to remove

aerosols. The subsequent stages make the recovery efficiency

high and the final stage operates with the cleanest scrubbing

liquid. A droplet separator is installed in the stack or immediately

before it. The gases from the dryer (granulator / dryer) are led

through cyclones before entering the scrubber. The scrubber

consists of a variable throat venturi with subsequent two-stage

scrubbing. The last stage should be operated with the cleanest

liquid. A part of the liquor, after the circulation, goes to a settler

for the separation of solids. The thickened part is fed to the

reactors.43

43 EFMA (2000c)

H2SO4

K, Mg, S

Figure A.1: Integrated Phosphate Fertilizer Plants

Phosphoric acid

Nitric acid Sulfuric acid

Water Water Sulfur Water Air

TSP SSP NPK

Mixed acid route

NPK Nitrophosphate

route

Phosphate rock

NH8

CO2

NH8

HNO8

Phosphate rock

NH8 HNO8

H8PO4 H2SO4

H2SO4 H8PO4

Phosphate rock

TSP SSP NPK NPK,

AN/CAN

Phosphate rock


APRIL 30, 2007 19

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Ca(NO8)2

CaCO3

NH4NO3

H8PO4

HNO3

Figure A.2: Compound Fertilizers: Nitrophosphate Route

Nitrophosphoric acid

HNO3

Phosphate

rock

NPK

Calcium nitrate conversion

NH8

H2SO4

K, Mg, S

Complex fertilizers

NH8

NH8

CO2

Calcium ammonium

nitrate fertilizers

AN / CAN

Calcium nitrate fertilizers

Ca(NO3)2


APRIL 30, 2007 20

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Dust

Scrubbing liquid

Gas / dusty air

Dusty air

Gas

Gas

Off-spec

Digestion reactors

HNO8

Phosphate rock

NPK

Scrubbing system

AN solution

NH3 H2SO4 / H3PO4

K, Mg, S

Ammoniation / Granulation & Pipe reactor /

Granulator

Off-gas

Dryer / Screener / Cooler & Coating

Hot air, Coating agents

Cyclones / Bag filters

General dedusting system Off-gas

Figure A.3: Mixed Acid Route

Fluoride - Should We Be Drinking This? An EPA study

links fluoride to Attention Deficit Disorder and lead poisoning

http://www.nofluoride.com/kalamazoo.html

By Jane Louise Boursaw

You come in from working outside and pour yourself a glass

of refreshing, ice-cold water. But what if it was

contaminated with a hazardous waste product of the aluminum, uranium, and

phosphate fertilizer industry? Guess what? It is. It's called silicofluoride, a highly-

toxic chemical added to over 90 percent of America's drinking water, according to a

recent study, funded in part by the Environmental Protection Agency.

UNTESTED TOXIC

For years, dentists have touted the benefits of fluoride, claiming it helps prevent

tooth decay. And that may be true with regard to "sodium" fluoride. But

silicofluoride, the kind now used to treat water supplies, has been linked to cancer,

infertility, bone fractures, and premature joint and ligament aging.

What's more, the EPA study, just released in September of 1999, shows a new

correlation between silicofluorides and high levels of lead in children's blood, which

has been linked to learning disabilities, hyperactivity, substance abuse, and the root

causes of crime.

"Silicofluorides are largely untested," said Roger Masters, Emeritus professor of

government at Dartmouth College, who led the study. "Virtually all research on

fluoridation safety has focused on sodium fluoride, even though studies in the 1930's

showed important biological differences between these chemicals."

A.D.D. CONNECTION

In particular, a large number of children diagnosed with Attention Deficit Disorder

(ADD) have been shown to have dangerously high levels of lead, manganese, or

cadmium in bodily tissues, noted the study.

This information was of special interest to Bill Siegmund, a microbiologist, certified

water specialist, and managing director of Pure Water Works in Traverse City.

Siegmund's son -- who was raised in Grand Rapids, the first U.S. city to be

fluoridated in the 1950's -- has been diagnosed with ADD. In fact, Grand Rapids has

an extremely high incidence of ADD, noted Siegmund.

"I have heard numbers like the highest percentage in the United States," he said.

"What they discovered is that heavy metals in the blood stream during the formative

years of prenatal to puberty will prevent you from making the neurological function

to transfer messages from short-term to long-term memory. That, in essence, is

what ADD is.

"It's not the silicofluorides that are causing ADD, but the fact that they cause you to

absorb more lead," Siegmund adds. "So even though lead exists in a very small amount in a municipal system, you absorb more of it in the presence of fluoride."

HEAVY METAL OVERLOAD

He added that this neurological glitch occurs at any age, not just childhood. He also

noted that heavy metals accumulate in a person's body over a lifetime. "It is difficult

or impossible to get rid of them," said Siegmund. "So a small exposure over a period of time is what the danger is."

A source at the Grand Rapids-Lake Michigan Filtration facility, who did not wish to be

identified, noted that they recently switched from powdered silicofluorides to a liquid form called hydrofluosilicic acid (HFS).

"They're both poisonous," said the source, "but I think they wanted to get away from

the powder, because even with the dust collection system, you did have some of it in

the atmosphere throughout the plant...it wasn't hazardous to the people, but I think they wanted to get away from that."

But hydrofluosilicic acid, although greatly diluted, has it's own problems, he noted.

"The quality of the piping and the molds and everything have to meet the standards

for an acid like that. You've got the hazards there, too, but you don't have anything in the atmosphere, unless you have a leak or something." (See sidebar)

IN DEFENSE OF FLUORIDE

John Wierenga, plant supervisor for the Grand Rapids-Lake Michigan Filtration

facility, agreed that hydrofluosilicic acid is preferable to the powder they used to use,

"simply because the powder presented a dust hazard to the employees," he said.

"But basically, whatever compound you use, you feed it into the water to derive the

same amount of fluoride."

Wierenga believes there is no difference between food-grade sodium fluoride and

industrial-grade hydrofluosilicic acid. "The purity of both would be very high," he

said. "We're only feeding one part per million, so if there is an impurity there, it would have to be exceedingly high to be measurable."

The Grand Rapids plant receives their hydrofluosilicic acid in 4000-gallon tanker

shipments from Florida. "The air pressure just puts it in our tank, and that's all there

is to it," said Wierenga. "It's a sealed system."

He added that, among other things, fluoride is used in many insecticides. "Like so

many things, it's all a question of dose. In the small amounts that we take it in for

public health, it's healthful and without side effects. But if that amount is exceeded,

then there can be side effects... an enormous number of accusations have been

made about fluoride. I think, almost without exception, they've been proven false.

The anti-fluoridationists today are still very active, perhaps because of their

opposition to what some would term 'enforced medication.' But, of course, put in the

water, [fluoride] is widely available and widely beneficial."

MANY STUDIES

Still, even Wierenga has his doubts about fluoride, even though he works around it

every day and has a chemistry background. He cited an article written several years

ago for "Chemical and Engineering News," a widely disseminated publication for

professional chemists, in which the author raised a number of legitimate concerns

about fluoride.

"I thought the article was well researched, and I guess I've always held the belief

that if you tried to get fluoride in the water today, you would have great difficulty

doing so," said Wierenga.

For one thing, things weren't studied in 1945 like they are today, he noted. "The

dentists knew it was good for the teeth and in the water it went. But how much

study was done at that time on other health effects? If there were any, they were

very few. Since then, there have been enormous numbers of studies.

Wierenga was not aware of the recent study linking fluoride with Attention Deficit Disorder.

50-YEAR BLUNDER?

If all this isn't enough, here are a few more facts about fluoride from an article

entitled "Fluoridation: a 50-Year-Old Blunder and Cover-Up," by David C. Kennedy,

D.D.S., published by the Preventive Dental Health Association (PDHA), a non-profit educational corporation:

1) Fluoride has been linked to cancer. In 1956, Dr. John Chaffey, a professor of

clinical pediatrics at the College of Physicians and Surgeons, Columbia University,

noted cortical defects in the bone X-rays of 13.5 percent of the children living in

fluoridated Newburgh, compared to only 7.5 percent in the neighboring non-

fluoridated Kingston. Studies have now confirmed a dramatic increase in bone cancer

in young males exposed to fluoride during growth of the bones, and a 5 percent increase in all types of cancers in fluoridated communities.

2) Studies have shown that fluoride in the drinking water adversely affects fertility

rates in women. A review of animal studies shows that fluoride affects fertility in

most other animal species, as well.

3) According to the National Research Council, fluorosis, a disease characterized by

brown and white spots on the

Drink up...

not Hydrofluosilicic acid, the chemical agent most used for water fluoridation in the

U.S., is the most corrosive chemical agent known to man. It is derived from toxic

gases produced in the manufacture of phosphoric acid and phosphate fertilizers. It

contains lead, mercury, arsenic, and high concentrations of radionucleides.

Even bystanders who witnessed a 1994 tanker truck accident which spilled 4,500

gallons of industrial grade hydrofluosilicic acid near Deltona, Florida, were close to

death, according to Orlando Sentinel reporter Bo Poertner, an eyewitness to the

accident.

"We began to worry when an emergency service officer introduced himself and

declined to shake Mike's hand," said Poertner. "We knew we had been exposed to a

dangerous chemical; after that we began to feel contaminated. A towing service worker reminded me the next day, 'You don't know how close to death you came.'"

TOXIC BYPRODUCTS

Because the industrial grade fluosilicic acid is a toxic waste byproduct recovered

from chimney pollution scrubbers ("scrubber liquor"), the volume of contaminants

is profoundly influenced by the method of manufacture and the quality of raw

materials used.

A co-product from phosphate fertilizer manufacture is yellow-cake uranium, a

radioactive substance used in the manufacture of nuclear weapons and the nuclear

power industry. The wastes (fluosilicic acid) from the manufacture of phosphate

fertilizers are also contaminated with radium and are among the most concentrated

radioactive wastes produced from natural materials. These radioactive wastes are

referred to as naturally occurring radioactive materials (NORM), and the EPA has no regulations for NORM waste disposal.

The manufacturers of fluosilicic acid do not routinely monitor for levels of uranium

contaminating the acid. No testing is done for NORM levels in Florida where much

of the fluosilicic acid used to fluoridate municipal water supplies is produced.

The EPA's position on the use of industrial grade fluosilicic acid for the fluoridation

of municipal water supplies is that it is the ideal solution to the long-standing

dilemma of disposing of the hazardous waste by-product produced from the

manufacture of phosphate fertilizers. They contend that by recovering fluosilicic

acid, water and air pollution are minimized and water utilities are afforded a low-

cost source of fluoride.

COSTLY MISTAKE

Are you wondering why food grade fluoride isn't used in the water fluoridation

process? The bottom line, of course. Although it would ensure purity and

consistency, the cost factors would be prohibitive.

Another issue is that fluoride, heavy metals and insoluble contaminants contained

in chemically treated water are concentrated with cooking (heating). There are no

required or recommended tests to determine the cumulative contaminant levels

ingested daily from chemically treated water. The EPA bases the "maximum

contaminant levels" for the average amount of water ingested (drunk by an

individual) in liters per kilogram of body weight (not to exceed a concentration of

4.0 milligrams per liter). It does not account for incidental sources like foods,

processed or cooked, or soft drinks made with chemically treated water.

And, although the EPA/National Research Council cites many "safety and

effectiveness" studies in their 1993 publication, "The Health Effects of Ingested

Fluoride," they never state what grades of fluoride products were used for the

clinical studies. There are industrial, food, and pharmaceutical grades of fluoride,

and the results of those studies would depend greatly upon the grade of chemicals

used.

Source: "Water A Toxic Dump?" by George Glasser, printed in the December, 1994,

Sarasota ECO Report.

teeth, affects 8 to 51 percent of children and as many as 80 percent of children

growing up in areas where drinking water contains one part per million (1 ppm) fluoride.

4) Fluoride can also have a detrimental effect on bone growth and can cause

premature joint and ligament aging, according to a 1993 report by the U.S. Dept. of

Health and Human Services. "Postmenopausal women and elderly men in fluoridated communities may be at increased risk of bone fractures."

NEVER APPROVED BY FDA

Fluoride in any form -- be it drops, tablets or vitamins -- has never been approved

by the Food and Drug Administration (as required by law since 1938). And no

application is pending either. This means that the FDA has no proof of the safety or

effectiveness of fluoride. Also, the International Academy of Oral Medicine and

Toxicology has classified fluoride as an unapproved dental medication, due to its high toxicity.

All this came to light in 1993, when New Jersey State Assemblyman John V. Kelly

sought an FDA ban on fluoride supplements and led an investigation which revealed

that neither the FDA, National Institute of Dental Research, or American Academy of

Pediatric Dentistry had proof of fluoride's safety or effectiveness. Although virtually

every American is exposed daily to fluoride, the official FDA classification for fluoride

is "Unapproved New Drug."

OVERDOSED ON FLUORIDE

In 1997, the Sierra Club issued a paper proclaiming that the FDA should be required

to put fluoride through the "rigorous controlled studies necessary for FDA Approval."

They also contend that if fluoride gains FDA approval, it should be treated as a

prescribed medication in order to prevent over-exposure.

Exposing the population to fluoride via drinking water invariably leads to uncontrolled

random dosages, noted the Sierra Club. Infants and adults who drink more

beverages than others will be significantly overdosed on fluoride.

There is also a wide variation in fluoride levels in food and water. The fluoride at the

faucet may vary from .1 ppm to as high as 4 ppm, according to the EPA mean

contaminant levels. Excessive fluoride in the water from accidental overfeed has

poisoned literally thousands of people and recently killed a Native American in Alaska, noted the Sierra Club paper.

THE TOOTH DECAY MYTH?

What's more, adding silicofluorides to drinking water has not been proven to reduce

tooth decay. Studies done in the 1940s indicated that as the level of "natural"

fluoride in the drinking water increased, the prevalence of tooth decay declined; so

says a 1991 report published by the United States Public Health Service's Committee

to Coordinate Environmental Health and Related Programs.

These early studies led to the practice of adding food-grade sodium fluoride to

municipal drinking water to bring the total level of fluoride to approximately 1 part

per million (ppm). The optimal range of community water fluoridation (optimal with

respect to reducing tooth decay and minimizing the risk of dental fluorosis) has been

determined by the United States Public Health Service to be 0.7- 1.2 parts per

million.

However, in a more recent study on the newer silicofluorides and tooth decay (the

largest ever) done by the U.S. Public Health Service, dental records of over 39,000

children showed that the decay rate of permanent teeth was virtually the same in

areas treated with silicofluorides as non-fluoridated areas. In fact, tooth decay has

decreased more in some non-fluoridated communities than in fluoridated ones.

The scary thing is we're consuming more fluoride than ever. In the 1940s, the U.S.

Public Health Service reported a total daily fluoride intake from typical diets in the

range of 0.2 to 0.3 milligrams. By the 1970s, the total from dietary sources had

increased to as much as 3.44 mg/day, even in non-fluoridated areas. By 1991, the

range in total daily dosage had exceeded 7 mg/day in some areas.

Care for some toxic waste for dinner tonight?

Fluoride: An Invisible Killer by Floyd Maxwell, BASc

Author of the International Anti-Fluoridation Database

http://www.just-think-it.com/no-f.htm

* * * * * * * * *

"We would not purposely add arsenic to the water supply. And we would not purposely add lead. But we add fluoride. The fact is that fluoride is more toxic than lead and just

slightly less toxic than arsenic." (source) * * * * * * * * *

"The federal maximum contaminant level (MEL) for lead is 15 parts per billion (ppb), 5 ppb for arsenic and 4000 ppb for fluoride." (source)

* * * * * * * * *

1952: The Delaney Committee 82nd Congress Hearings on Fluoride revealed that there was no actual scientific basis for the fluoridation of water supplies in the prevention of tooth decay. The recommendation of the Committee was that more research be done,

before proceeding with this national mass medication. Their recommendation was totally ignored.

* * * * * * * * *

A common obstacle one runs into when trying to inform others of the dangers of a product is being told you are not an "expert". This can, however, be used to one's advantage if one happens to find an "expert" who verifies your own views on the benefits of natural versus chemical approaches to health.

My background is that of a Chemical Engineer, having earned my B.A.Sc. from the University of British Columbia in 1984. When it comes to chemistry I can say that I am an "expert" in this area due to studying it full time for over 10 years.

Luckily I also retained the ability to think for myself...

* * * * * * * * *

Built on Basics

Chemistry is built on basic principles. For example, "like dissolves like" means that salt (a polar molecule) dissolves in water (highly polar) but does not dissolve in oil (non polar).

In studying the elements (see the Periodic Table of the Elements graphic above), application of just a few basic principles can lead to a grouping of families of elements based on their similar chemical properties.

As one goes down the Table, the size of elements increases while the reactivity decreases.

The second-to-last column of the Periodic Table are the halides, and start with F (Fluoride), then Cl (Chlorine), Br (Bromine), I (Iodine) and As (Astatine).

Applying the reactivity rule one can accurately say that Fluorine is more reactive than Chlorine, that is more reactive than Bromine, that is more reactive than Iodine.

This reactivity rule also holds true for molecules/compounds (composed of two or more atoms that may be the same element or different ones) provided that one atom remains the same and only the halide changes.

Thus, we can infer that HF is more reactive than HCl. HCl (Hydro Chloric acid) was the strongest acid we used in school. But HF is so reactive, and so deadly that it was never seen or used in any of the 10 years of chemistry demonstrations and labs I took part in. Allen Hoffmann ([email protected]), a former Scientific Glassblower, was forced to be in contact with HF as part of his work (and is now seeking Worker's Compensation for the damage it did to his body) notes that:

HF can't be smelled until 24ppm but has an IDLH (Immediately Dangerous to Life or Health) concentration level of 30ppm. In other words, by the time you smell it, your life is danger! -- hence the title of this article: "Fluoride: An Invisible Killer".

* * * * * * * * *

How strong, and prevalent, are fluorine-containing compounds?

HF is one of the strongest acids in the world. So strong it can etch glass (in fact, this is a common test for the presence of fluoride), making storage of this compound rather difficult!

Not to mention the danger in handling it!

Searching for "hydrofluoric acid" on Google produced about 12,000 web pages, evenly divided between typical chemical data sheets [with stringent handling procedures!] and health warning pages!

In fact, Fluorine is the most reactive of all the elements (elemental Fluoride is never found by itself in nature) and it was only the relatively recent laboratory-induced joining of Fluoride to Xenon, one of the previously "inert" elements (those in the right-most column in the picture above) that caused this group of elements to be renamed "noble" instead.

This photograph shows what the fluorine added to Calgary, Alberta's drinking water has done to a thick and "corrosion resistant" steel water supply valve.

Fluoride is used extensively in computer chip and Aluminum and steel manufacture, causing a staggering amount of environmental damage.

In fact, in May, 2000, 3M Corporation announced it was discontinuing a whole family of fluorinated compounds, including Scotchgard, due to their incredible destructiveness to the environment.

Fluoridated compounds are also extremely effective in killing bugs. The wholely predictable side effect of spraying crops with fluoridated pesticides is that fluoride remains on the produce, making fluoride-caused food contamination a very real concern and a good reason, by itself, to consider eating only organic food. Beverage drinkers are not safe either.

Fluorine is also found in mind-affecting drugs like Prozac and the "date rape" drug Rohypnol. Click here for a more complete list of drugs containing fluorine.

* * * * * * * * *

What are "Free Radicals"?

Perhaps some of you have heard of "free radicals" in recent years. The natural health industry has worked on finding compounds that can absorb, prevent the formation of or ameliorate the consequences of "free radicals".

But what are they?

Free radicals are what you get when you break a molecule into unstable pieces. This is achieved by subjecting an otherwise stable molecule to a jolt of energy of some sort (sunlight, heat, flame, etc.). Thus, too much sunlight can cause the formation of free radicals, as can heat or partial combustion (ie. smoke).

We are all already aware of the damaging effects of the sun. And we are increasingly aware of the harmful effects of smoke. But did we know that "free radicals" are one of the biggest and most dangerous by-products of smoking? Has anyone told us this?

Free radicals are so destructive because they are unstable and extremely reactive. So reactive, in fact, that they will react with almost anything, and in doing so will alter what they reactive -- in plain terms, healthy tissue becomes unhealthy tissue due to the action of free radicals. It's that simple.

Many of us are already aware of something similar to this regarding the Chlorine that is sometimes added to municipal water supplies -- that it forms families of compounds in the water. Well, Fluorine is much more reactive than Chlorine, so one can only imagine the range of deadly compounds it is capable of creating when it is added to drinking water.

I just want to emphasize that, chemically, free radicals are much worse than most cancer causing compounds because free radicals can do "whatever they want" when they contact your body. They can alter virtually anything they contact -- cells, blood vessels, organs, etc.

* * * * * * * * *

Recapping:

• Chlorine is known to form numerous compounds after it is added to municipal water supplies.

• Fluorine is much more reactive than Chlorine.

* * * * * * * * *

So, what happens when you add F to municipal water?

It turns out that there are vast ramifications from adding F, and va$t rea$on$ for doing it.

In essence, the fertilizer, aluminum and steel industries produce, in the process, massive quantities of fluoride that used to be industrial waste. To save large amounts of money, they came up with the idea of dumping this industrial waste into drinking water. Now, instead of having to pay to have the fluoride waste hauled away, they are paid to poison us.

Here are just a few of the numerous web links that I encourage you to explore:

Ask the government for your 1992 Fluoridation Census report http://www.cdc.gov/ The Fluoridation Fiasco: Poison In Your Water: http://rense.com/health/fluoride1.htm The Fluoride Stop: http://bruha.com/pfpc/ NoFluoride.com http://www.nofluoride.com/ Why EPA's Headquarters Union Of Scientists Opposes Fluoridation http://www.fluoridation.com/epa2.htm Fluoride Pollution: An Overview http://www.fluoridealert.org/f-pollution.htm

* * * * * * * * *

Just Think It's International Anti-Fluoridation Dat abase: http://www.just-think-it.com/the-f-db.htm

150+ facts, horror stories and cover-ups about Fluoride http://www.just-think-it.com/f-facts.htm

* * * * * * * * *

Call to ACTION

Assuming that Fluoride is "bad", how should we minimize or eliminate the problem?

(1) Lobby

Quite simply, most of you are being poisoned and you should be very concerned about this and should tell your official representatives of your concern.

And you should not stop until they stop adding it.

Find articles about Fluoride. Print them. Fax them. Send letters to local newspapers. Find out if your community is being poisoned and if it is and we don't already know about it, tell us so we can tell other people in your community.

Do something.

Or suffer...

(2) Avoid it

Note that I did not say "Remove it" because this is not possible, contrary to what countless manufacturers are claiming. The key reasons why not: (1) Fluorine's extreme reactiveness, causing it to "cling" more tightly to water than anything I am aware of, and (2) the size of the F atom.

We have already dealt with one aspect of the Fluorine atom's size -- that it makes the atom extremely reactive.

The second aspect of Fluorine can be revealed by comparing the weight of a "mole" (602,000,000,000,000,000,000,000 atoms) of F to that of a mole of H2O (water). [To confirm the calculation, refer to the Periodic Table of the Elements graphic above.] F weighs 19 grams per mole (g/M), H2O weighs 18 g/M.

Summoning another well known rule of chemistry, that the size of a molecule/atom is directly related to its molecular weight and we can infer that these two molecules are almost identical in size.

Ineffectiveness of Reverse Osmosis units

Reverse Osmosis [RO] manufacturers' claim they can remove fluoride. Don't believe their claim$.

RO units work on the same principle as our kidneys. Think of a mesh, like the mosquito netting on your screen door. The mesh lets in air, but not mosquitos, because air molecules are smaller than mosquitos.

An RO unit is thus great for removing "heavy metals" like Pb (Lead), Hg (Mercury) and Cd (Cadmium), as well as Cl- family compounds like PCBs and PCP's (Poly Chlorinated Phenyls and BiPhenyls) because these are all large molecules relative to the size of H2O. In fact, even Cl (the smallest of these) is relative large (molecular weight of 35 g/M) and so if the RO unit is new and it is well made (ie. with precision tolerances on the RO membrane) it might even filter out some of the Cl. Note the "ifs" and conditions in the last sentence.

So, an RO unit will not filter out F atoms, as F atoms are too similar in size to H2O molecules.

Equally Ineffective Distillation units

Distillation units will also not work because similar sized polar molecules have similar boiling and freezing points.

Water boils at 212 degrees Fahrenheit and FH boils at 203 to 239 degress Fahrenheit. So, when your distillation unit has warmed up the water to 212 degrees Fahrenheit, and the water starts to boil off (evaporate), *so* does the Fluoride! It stays right with the water vapor, and gets condensed back into liquid at the end of the process.

So, don't let anyone tell you otherwise and don't trust those that do.

(3) Don't trust your water

Unlike Chlorine, Fluoride is colorless, odorless and tasteless so you have almost no way of knowing if it is present in the water you are drinking or using.

Even bathing or showering in fluoridated water will cause you to absorb an unhealthy amount of it through your skin.

Fruit juices often have very high concentrations of Fluorine, due to the use of Fluorine in pesticides.

Pop and other packaged beverages are also common and substantial sources of Fluorine, not only because of the fluoridated water but because of fluoride-laced ingredients, and the concentration of same during the manufacturing process.

Bottled water can be an option, but choose carefully. Mineral Waters of the World provides a free and very detailed analysis of the composition of over 600 types of bottled water available throughout the world.

(4) Don't trust the experts

Before you even listen to someone's opinion about Fluoride, figure out what they have to gain by their opinion.

RO manufacturers would see sales "dry up" if they admitted that their units can not remove it. They will thus never admit it, and will try to "poison" our efforts to give people unbiased information.

Fluoride producers (the multi-billion dollar aluminum, fertilizer and steel industries) have everything to lose and nothing to gain by admitting that Fluoride is even remotely bad for anyone.

Ditto toothpaste manufacturers and thus dentists. Yes, dentists have a lot to gain by fluoridation -- dental fluorosis, caused by fluoridation, produces mottled teeth (in advanced stages, fluorosis can turn teeth into black stumps -- see for yourself, or view this 46 page slide show) and this leads people to get very expensive cosmetic dental work performed...by dentists.

As to the supposed benefits of drinking fluoridated water, read the results of this study, or this one, or this one, or this:

Any tooth decay reducing effect attributable to fluoride occurs by topical mechanisms involving action on tooth surfaces and on oral bacteria that promote dental caries. There is negligible anti-caries benefit from ingested fluoride that does not have actual contact with the surfaces of the teeth. - "Fluoride in Dentistry", 2nd Edition (source)

Of course, topical application has its own problems:

Children under age 4 swallow 40% or more of the toothpaste they use. - Oregon Citizens for Safe Drinking Water

And "public" health officials will definitely *not* want to admit that they have been officially encouraging the largest act of public poisoning the world has ever known.

"Anti-Expert" shields up!

(5) Hound the water bottling companies

For some reason (worth an investigation itself) water bottling companies in the U.S. are not required to report the content of water on the label (and thus most don't).

Oh sure, they report how many calories the water has (zero), how much of the recommended daily allowance of protein, carbohydrates, and vitamins xyz (all zero) but there is no mandatory listing of the amounts of such common elements as Ca (Calcium), Na (Sodium), Cl (Chlorine) and (F) Fluoride!

Then visit their web sites. I did this for the largest bottlers in the Phoenix area and learned exactly nothing about the content of the water they are selling. I also learned that many are owned by larger companies, such as Perrier. And that they have "zero point zero" (ie. no) interest in communicating with the people who buy their product. On the Perrier site there was no way to contact them. No forms to fill out, no email addresses to use and, when I used my Internet knowledge to send to standard email addresses that every domain usually has I still got exactly zero response. Why?! Think about it...

I finally went with Sedona Springs because they told me the (low and naturally occuring) Fluoride content of their spring water. [Free plug: Sedona Springs, 602-254-0000, home or office delivery, sport bottles, half or full size jugs for your/rented water cooler...and "6 gallons for the price of 5"]

We encourage everyone to adopt this approach as well. Check the chemical analysis of your local water bottlers online at Mineral Waters of the World. If some or all of your local brands are not on the list, try to contact your local bottlers/sellers. Ask them for a chemical analysis of their water, and especially the fluoride content. If you should manage to obtain this information, give it to Mineral Waters of the World and they will update their database.

Our children thank you. For your action.

Sincerely,

Floyd Maxwell

Contact: [email protected]

* * * * * * * * *

NOTES:

[1] Dr. John Yiamouyiannis, "Clinical Toxicology of Commercial Products", Fifth Ed., Williams and Wilkins. Quote at: http://rense.com/health/fluoride1.htm

zzz z

F-

F-

F-

FLUORIDE

FATIGUE

Paua

Bruce Spittle Forewords by Albert W Burgstahler and AK Susheela

FLUORIDE POISONING: is fluoride in your drinking water—and from other sources—making you sick?

FLUORIDE FATIGUERevised 3rd printing

FLUORIDE FATIGUE FLUORIDE POISONING: is fluoride in your drinking water—and from other sources—making you sick?

Bruce Spittle

FLUORIDE FATIGUE FLUORIDE FATIGUE

Paua PressDunedin, New Zealand

INFORMATION ON PAUA PRESS LIMITED AND COPYRIGHT STATEMENT

I formed Paua Press Limited in 2007 with the goal of publishing books ontopics of interest. The paua is an abalone, a large edible New Zealand shellfish ofthe genus Haliotis with attractive blue and purple colours on the inner surface ofthe shell but with a rough unattractive outer shell. The vivid colouration within canbe revealed by grinding and polishing the outer surface and the shell is thensometimes used in jewellery. Just as a paua appears dull and nondescript on theoutside but is of compelling interest when the surface dross is taken away, I am hopeful that thebooks my press publishes will have, at their centre, something of substance for the reader.

Bruce Spittle. Paua Press Limited, 727 Brighton Road, Ocean View, Dunedin 9035, New Zealand;Phone/Fax: 64 3 4811418; E-mail: [email protected]; www.pauapress.com.

Fluoride fatigue. Fluoride poisoning: is fluoride in your drinking water—and from other sources—making you sick? Copyright © Bruce Spittle, 2008. The right of Bruce Spittle to be identified as theauthor of this work in terms of the Copyright Act 1994 is hereby asserted. Designed, including cover,by Bruce Spittle. First published by Paua Press Limited, 1 January 2008. First printing ofprepublication copies December 2007. Revised 2nd printing January 2008. Revised 3rd printing,printed and bound in Australia, March 2008.

Available from: All Seasons CLS, PO Box 3459, Mount Gambier SA 5290, Australia. Contact details: Phone +61 8 8724 8611, E-mail: [email protected]. ISBN 978–0–473–12991–0

QUOTATIONS EMBODYING THE SPIRIT OF PAUA PRESS LIMITED

Sapere aude. Motto of the University of Otago. It can be translated to mean: dare to be wise, have thecourage to think for yourself rather than blindly accepting the opinions of authorities.

All great truths begin as blasphemies. George Bernard Shaw

All truth passes through three stages: first it is ridiculed, second it is violently opposed, thirdit is accepted as being self-evident. Arthur Schopenhauer

Great thinkers have always encountered violent opposition from mediocre minds. Albert Einstein

Don’t worry about people stealing your ideas. If your ideas are that good, you’ll have to ramthem down people’s throats. Howard Aitken

Time’s glory is to calm contending kings, To unmask falsehood, and bring truth to light. Shake-speare

In an age of conformism and “team work,” where compromise and harmony are offered asthe watchwords of human activity, being critical may be considered antisocial. But sciencewithout criticality is unthinkable, for the only route to scientific objectivity is to question, notto “accept.” Anon. Statistics, science and sense [editorial]. JAMA 1963;186:508. Cited before the prefacein: Waldbott GL. A struggle with titans. New York: Carlton Press; 1965.

As every past generation has had to disenthrall itself from an inheritance of truisms andstereotypes, so in our time we must move on from reassuring repetition of stale phrases to anew, difficult, but essential confrontation with reality.

For the great enemy of truth is very often not the lie—deliberate, contrived, and dishonest—but the myth, persistent, persuasive, and unrealistic. Too often we hold fast to the cliches of ourforebears. We subject all facts to a prefabricated set of interpretations. We enjoy the comfort ofopinion without the discomfort of thought. President John F Kennedy, Commencement address,Yale University, 11 June 1962. Cited after the dedications in: Waldbott GL, Burgstahler AW, McKinney HL.Fluoridation: the great dilemma. Lawrence, Kansas: Coronado Press; 1978.

Paua

CONTENTS

v. ............. DEDICATION

v...............FOREWORD BY ALBERT W BURGSTAHLER

vi ............. FOREWORD BY AK SUSHEELA

vi..............ACKNOWLEDGEMENTS

1–2.......... INTRODUCTION

2–4...........THE SYMPTOMS AND SIGNS OF THE CHRONIC FLUORIDE TOXICITY SYNDROME

4–6...........THE PATHOPHYSIOLOGY OR MECHANISMS UNDERLYING THE SYMPTOMS

6–9.......... MAKING THE DIAGNOSIS OF THE CHRONIC FLUORIDE TOXICITY SYNDROME

9–10 ........ WHAT TO DO IF THE DIAGNOSIS OF CHRONIC FLUORIDE TOXICITY IS MADE

10............ CASE REPORTS OF FLUORIDE TOXICITY

11–12...... ILLNESS IN PEOPLE IN CANADA

12–18...... ILLNESS IN PEOPLE IN THE USA

18–20...... ILLNESS IN PEOPLE IN NEW ZEALAND

20–22...... ILLNESS IN PEOPLE IN THE NETHERLANDS

22–23...... ILLNESS IN PEOPLE IN INDIA

23–26...... OTHER ILLNESSES DUE TO FLUORIDE

26–27...... WHAT TO DO IN THE FACE OF SKEPTICISM ABOUT THE VALIDITY OF THE EXISTENCE OF A CHRONIC FLUORIDE TOXICITY SYNDROME FROM FLUORIDATED DRINKING WATER

27–32...... ILLUSTRATIONS OF SOME OF THE ABNORMALITIES UNDERLYING THE SYMPTOMS OF CHRONIC FLUORIDE TOXICITY

32–48...... AN EXAMPLE OF THE OPPOSITION TO THE CONCEPT OF A CHRONIC FLUORIDE TOXICITY SYNDROME FROM FLUORIDATED WATER

49............ FURTHER COMMENTS ON THE SUGGESTION THAT THE CHRONIC FLUORIDE TOXICITY SYNDROME IS PSYCHOSOMATIC

50–58...... ILLNESS IN ANIMALS

58–59...... FURTHER COMMENTS ON CANARIES IN THE COAL MINE

59–75...... CLOSING COMMENTS

76............ ABOUT THE AUTHOR

77–78...... INDEX

ILLUSTRATIONS

2........... FIGURE 1. GEORGE L WALDBOTT

2........... FIGURE 2. ALBERT W BURGSTAHLER

2........... FIGURE 3. H LEWIS MCKINNEY

3........... FIGURE 4. AK SUSHEELA

4........... FIGURE 5. ANNA STRUNECKÁ

4........... FIGURE 6. JIRI PATOCKA

4........... FIGURE 7. RUSSELL L BLAYLOCK

7.......... FIGURE 8. POWDERED COAL AND CLAY

8.......... FIGURE 9. CHILLIES DRYING

8.......... FIGURE 10. CORN DRYING

8.......... FIGURE 11. CORN DRYING

16 ....... FIGURE 12. HARVEY PETRABORG

21 ....... FIGURE 13. HANS MOOLENBURGH

27 ........ FIGURE 14. SKELETAL MUSCLE

27 ........ FIGURE 15. SKELETAL MUSCLE

27 ....... FIGURE 16. SKELETAL MUSCLE

28 ........ FIGURE 17. STOMACH



29 ........ FIGURE 20. SPERM

29 ........ FIGURE 21. SPERM

29 ........ FIGURE 22. SPERM

29 ........ FIGURE 23. SPERM

30 ........ FIGURE 24. MEMBRANE CALCIFICATION

30 ........ FIGURE 25. PERIOSTITIS DEFORMANS



31 ...... FIGURE 28. PERIOSTITIS DEFORMANS

31 ...... FIGURE 29. PERIOSTITIS DEFORMANS


32 .... .... FIGURE 31. PERIOSTITIS DEFORMANS

32 .... .... FIGURE 32. PERIOSTITIS DEFORMANS

49 ........ FIGURE 33. KAJ ROHOLM

50 . ...... FIGURE 34. CHINCHILLA

52 ........ FIGURE 35. ALLIGATOR




53 ........ FIGURE 39. CAIMAN

53 ........ FIGURE 40. CAIMAN

54 ........ FIGURE 41. HORSE’S TEETH



55 . ...... FIGURE 44. HORSE’S HOOF

56 ........ FIGURE 45. HORSE RADIOGRAPHS

56 ........ FIGURE 46. HORSE’S METACARPUS

57 ........ FIGURE 47. ALLERGY TO FLUORIDE IN A HORSE

57 . ...... FIGURE 48. ALLERGY TO FLUORIDE IN A HORSE

58 ........ FIGURE 49. ALLERGY TO FLUORIDE IN A HORSE

63 ........ FIGURE 50. WESTON A PRICE

64 ........ FIGURE 51. NILOUFER J CHINOY

65......... FIGURE 52. JOHN COLQUHOUN

66 ........ FIGURE 53. TOOTH DECAY



69......... FIGURE 56. TOOTH DECAY


70......... FIGURE 58. TOOTH DECAY

71 . ...... FIGURE 59. TOOTH DECAY

71 . ...... FIGURE 60. RICHARD G FOULKES

72 . ...... FIGURE 61. HARDY LIMEBACK

73 ........ FIGURE 62. PAUL H CONNETT

76 ........ FIGURE 63. ALBERT BURGSTAHLER AND BRUCE SPITTLE

v

DEDICATION

Dedicated to all those who have struggled, in the face of criticism, to see an endto the irrational policy of fluoridating public water supplies.

FOREWORD BY PROFESSOR EMERITUS ALBERT W BURGSTAHLER

This is a vitally important book that has been long needed and begging to bewritten. Although dental public health officials in countries promoting waterfluoridation adamantly deny the existence of illness caused by fluoride indrinking water, undeniable medical ill effects from fluoride added to drinkingwater have been known and reported since the start of water fluoridation over50 years ago. Even today, those who experience these adverse effects, whetherfrom fluoride in their drinking water or from other sources, know only too wellhow insidious these ailments can be, what a relief it is to find out what iscausing them, and how easily they can often be overcome simply by reducingexcessive intake of fluoride.

Those who deny reality and persist in discounting sensitivity to fluoride indrinking water are like ostriches with their heads in the sand. They would dowell to heed what Dr. Spittle has reported here and stop continuing to promoteand be misled by scientifically indefensible claims that do not hold up underscrutiny.

Albert W Burgstahler, PhD (Harvard, 1953)Professor Emeritus of Chemistry

The University of Kansas, USAEditor, Fluoride

Website for Fluoride: http://www.fluorideresearch.org

vi

FOREWORD BY PROFESSOR AK SUSHEELA

I am delighted with this book which very capably addresses a burning healthproblem in many developed and developing countries that is afflicting millionsof men, women, and children. In particular, the damage caused by fluoride toexpectant mothers and the growing embryo and foetus in utero is extremelydevastating in terms of growth retardation and impaired brain development—somuch so that it is hard to compensate for such harmful effects.

I sincerely hope that, besides the general public, policy makers and healthofficials, in the interest of the nation and the people they are sworn to serve, willlearn from reading this book to recognize and desist from the “madness” beingexercised by “fluoridation of drinking water.” I wish the very best for bringingthis vitally important message to the people who need help and guidance inunderstanding the harmful effects of fluoride on health and, in the event thatthey are victims, in learning how they can deal with the health problems bysignificantly minimizing fluoride entry into the body.

Professor AK Susheela, PhD, FAMS (India), FASc, Ashoka FellowExecutive Director

Fluorosis Research and Rural Development FoundationDelhi, India

Website for the Foundation: http://www.fluorideandfluorosis.com

ACKNOWLEDGEMENTS

The author acknowledges the advice of Albert W Burgstahler, BSc (Magnacum Laude, Notre Dame, 1949), MA, PhD (Harvard, 1950, 1953), ProfessorEmeritus of Chemistry, The University of Kansas, Lawrence, Kansas, USA, andEditor, 1999–2007, of Fluoride, Quarterly Journal of the International Societyof Fluoride Research. Previously he was Co-editor, 1968–1981, Acting Editor1982–1991, Co-Editor 1992–1997, and Scientific Editor, 1998. He co-authoredFluoridation: the great dilemma with Dr George L Waldbott, MD, andProfessor H Lewis McKinney (Lawrence, Kansas: Coronado Press; 1978).

The author is likewise grateful for the kindness of Professor AK Susheela,PhD, FAMS (India), FASc, Ashoka Fellow, Executive Director, FluorosisResearch and Rural Development Foundation, Delhi, India, for givingpermission for her photographs of structural changes due to fluoride to be usedand for her work to be referred to, of Dr Bao-shan Zheng, for the use of hisphotographs related to food contamination by fluoride, and of Sarah Hamilton,New Zealand Chinchilla Rescue, for allowing the use of a photograph of achinchilla.

FLUORIDE FATIGUE FLUORIDE POISONING: IS FLUORIDE IN YOUR DRINKING WATER—AND FROM OTHER

SOURCES—MAKING YOU SICK?

INTRODUCTION

The focus of this book is the fatigue, not relieved by sleep, and various othersymptoms experienced by many when they drink fluoridated water. As such it isnot a comprehensive account of fluoride toxicity but looks at only a part of theoverall picture. Fluoride is ingested from other sources apart from fluoridatedwater such as pesticides, post-harvest fumigants, air, food, salt, medications,toothpaste, dental restorations, and health supplements. Fluoride also causes otherillness such as osteosarcoma and hip fractures.

Fluoridated water may be having its most devastating effects on the mostvulnerable, those in utero and infants less that one year old, whose brains are mostsensitive to developmental neurotoxins such as fluoride.a When body weight istaken into account, non-nursing infants receiving formula made with waterfluoridated at or near the level of 1 mg fluoride (F)/litre (L) or 1 part per million(ppm), less than one year old, have been estimated to have a fluoride intake onaverage of about three times that of adults (0.086 mg/kg/day of F for infantscompared to 0.03 mg/kg/day of F for adultsb). About 30% of children influoridated areas have chalky white areas on the teeth due to dental fluorosis.However the mottled appearance is due only in part to the presence of fluoride perse in the erupted teeth and is a sign that fluoride resulted in a thyroid hormonedeficiency during a critical time of tooth development, from in utero toapproximately 30 months for deciduous teeth (milk teeth, the first teeth to erupt)and permanent incisors (the upper and lower two teeth on each side, closest themidline, and medial to the canine teeth).c

Thyroid hormone is the crucial regulator of all the tissue-specific differentiationprogrammes during development and appropriate levels are critically important forthe coordination of developmental processes. When fluoride reduces the level ofthyroid hormone during tooth development, by activating a calcium-transducingG-protein receptor G q/11, there is delayed tooth eruption, delayed removal ofenamel matrix proteins, and delayed enamel maturation. The evidence of thedeficiency is seen later with mottled teeth. While the teeth are developing so alsois the brain. There is a growing concern about the effect of fluoride on thedeveloping brainb and a possible connection between fluoride and autism has beenqueried.d

Another emerging area of interest is the interaction between fluoride and iodineresulting in a functional iodine deficiency. Iodine is required for the proper

aGrandjean P, Landrigan PJ. Developmental neurotoxicity of industrial chemicals. Lancet 2006;368:2167-78.bDoull J, Boekelheide K, Farishian BG, Isaacson RL, Klotz JB, Kumar JV, Limeback H, Poole C, Puzas JE, Reed N-MR,Thiessen KM, Webster TF, Committee on Fluoride in Drinking Water, Board on Environmental Studies and Toxicology,Division on Earth and Life Studies, National Research Council of the National Academies. Fluoride in drinking water: ascientific review of EPA’s standards. Washington, DC: The National Academies Press; 2006. Available for purchase onlineat: http://www.nap.edu. p. 85.

cSchuld A. Is dental fluorosis caused by thyroid hormone disturbances? [editorial]. Fluoride 2005;38:91-4. dRookard CJ. Fluoride and autism: is there a connection? [letter]. Fluoride 2000;33:99-100.

FLUORIDE FATIGUE. FLUORIDE POISONING: is fluoride in your drinking water—and from other sources—making you sick?

2

functioning of many organs of the body and reduced tissue iodine levels, possiblythrough the inhibition of mammary gland deiodinases by fluoride, may be a factorin the development of breast cancer.ab

However, this book will concentrate on the fatigue, not relieved by sleep, andother symptoms due to fluoride from drinking water and other sources. The veryexistence of this problem is being denied on the basis of seemingly authoritativereports which can have such restrictive inclusion criteria that they can excludefrom consideration reports of fluoride causing fatigue and other symptomsc andthen be quoted as evidence that fluoride does not cause such illnesses.d Thus thereis a need to spell out the clinical features of this illness—the chronic fluoridetoxicity syndrome or preskeletal fluorosis.

THE SYMPTOMS AND SIGNS OF THE CHRONIC FLUORIDE TOXICITY SYNDROME

George L Waldbott, MD, studied about 500 people affected by chronic fluoridetoxicity and, together with Professor Albert W Burgstahler, PhD, and ProfessorLewis McKinney, PhD, in Fluoridation: the great dilemma, made a list of theclinical features (Figures 1–3).e

aEskin BA, Anjum W, Abraham GE, Stoddard F, Prestrud A, Brooks AD. Identification of breast cancer by differences inurinary iodide. Proc Am Assoc Cancer Research 2005;46:504.

bEskin BA. Iodine and mammary cancer. Adv Exp Med Biol 1977;91:293-304.cMcDonagh M, Whiting P, Bradley M, Cooper J, Sutton A, Chestnutt I, Misso K, Wilson P, Treasure E, Kleijen J. Asystematic review of public water fluoridation. Report 18. York: NHS Centre for Reviews and Dissemination, University ofYork; 2000.

dCutress TW. Response to a list of “50 reasons to oppose fluoridation,” compiled by Dr Connett. 2005. A copy is availablein the McNab Room, 3rd floor, Dunedin Public Library, Dunedin. It is included as part of a report on Fluoridation of PublicWater Supplies to the Infrastructure Services Committee, Dunedin City Council, from the Water and Waste ServicesManager, for the meeting on 12 March 2007, as appendix 4 to a letter, dated 6 March 2007, to Mr Gerard McCombie,Water Operations Team Leader, Dunedin City Council, by Dr John Holmes, Medical Officer of Health and Dr DorothyBoyd, Senior Public Health Dentist, written in response to a submission made by Dr Bruce Spittle to the 2006/07Community Plan opposing the use of fluoride in Dunedin’s water supply.

eWaldbott GL, Burgstahler AW, McKinney HL. Fluoridation: the great dilemma. Lawrence, Kansas: Coronado Press; 1978.p.392-3.

Figure 1. George L Waldbott,MD. 14 January 1898 –17 July 1982.

Figure 2. Professor Albert W Burgstahler, PhD.

Figure 3. Professor H Lewis McKinney, PhD. 20 December 1935 – 5 February 2004.

The symptoms and signs of the chronic fluoride toxicity syndrome 3

He noted, however, that the symptoms could have other origins even in someonesuffering from chronic fluoride poisoning.1 chronic fatigue, not relieved by extra sleep or rest2 headaches3 dryness of the throat and excessive water consumption4 frequent need to urinate5 urinary tract irritation6 aches and stiffness in the muscles and bones; arthritic-like pains in the lower back, neck,

jaw, arms, shoulders and legs7 muscular weakness8 muscle spasms, involuntary twitching9 tingling sensations in the feet and, especially, in the fingers

10 gastrointestinal disturbances: abdominal pains, diarrhoea, constipation, blood in stools,bloated feeling or gas, and tenderness in the stomach area

11 feeling of nausea, flu-like symptoms12 pinkish-red or bluish-red spots, like bruises but round or oval, on the skin, that fade and

clear up in 7–10 days (Chizzola maculae.a They were first recognized by an Italian generalpractitioner, Dr M Cristofoloni, in the neighbourhood of an aluminium factory near the villageof Chizzola in northern Italy).

13 skin rash or itching, especially after showers or bathing14 mouth sores, also with using fluoridated toothpaste15 loss of mental acuity and the ability to concentrate16 depression17 excessive nervousness18 dizziness19 tendency to lose balance20 visual disturbances, temporary blind spots in the field of vision, a diminished ability to focus 21 brittle nails

Professor AK Susheela, ExecutiveDirector of the Fluorosis Research and RuralDevelopment Foundation, Delhi, India,(Figure 4), made a similar list and addedthat, when patients came from an area withhigh fluoride levels in the water, fluoridetoxicity should be suspected when therewere complaints of:b 22 repeated miscarriages or still births23 male infertility24 dental fluorosis with discolouration of the

enamel of the front teeth, the central or lateralincisors of the upper and lower jaws

She noted that the presence of dentalfluorosis may be a clue that there has beenexposure to drinking water contaminatedwith fluoride. Dental fluorosis can onlyoccur if the fluoride exposure is during thefirst years of life while the teeth are forming.

aCristofoloni M, Largaiolli D. Su di una probabile tossidermia da fluoro. Rivista Med Trentina 1966;4:1-5. [in Italian].bSusheela AK. A treatise on fluorosis. Delhi, India: Fluorosis Research and Rural Development Foundation; 2001. p. 53-60,78-9.

Figure 4. Professor AK Susheela, PhD,FAMS (India), FASc, Ashoka Fellow.


4

The discolouration starts with the teeth losing their shine and developing whiteand yellow spots, or chalky white patches. The discolouration may turn brown andform horizontal streaks or spots on the enamel surface. She considered brownstreaks near the tip of the permanent teeth occurred with exposure to fluoride up tothe 2nd year, in the middle of the teeth from 2–4 years, and in the part of the teethclosest to the gums from 4–6 years.

THE PATHOPHYSIOLOGY OR MECHANISMS UNDERLYING THE SYMPTOMS

How fluoride is toxic is complicated,a and a recent review by Professor AnnaStrunecká, DSc, Professor J Patočka, DrSc, Dr Russell L Blaylock, and the lateProfessor Emerita Niloufer J Chinoy, PhD, with 331 references is especiallynoteworthy (Figures 5–7 and 51).b

In the acidic environment of the stomach, with a pH of 1–4, fluoride formshydrofluoric acid which penetrates the tissues and causes corrosion, irritation, andinflammation.c The mechanism for the occurrence of urinary urgency is less clear.Tissue irritation from hydrofluoric acid is again a possibility but the pH of urine isusually close to neutral, i.e. 7, although it can vary between 4.5 and 8. At pH 7,only about 0.015% of the F is present as undissociated HF. Whether this is enoughto produce this clinical symptom is uncertain and it may be due to indirect effects.

Fluoride, maybe in the form of HF, has been reported to form strong hydrogenbonds with amide groups and thereby alter the shape of proteins and thusenzymes.de

aSpittle B. Psychopharmacology of fluoride: a review. Int Clin Psychopharmacol 1994;9:79-82. bStrunecká A, Patočka J, Blaylock RL, Chinoy NJ. Fluoride interactions: from molecules to disease. Current SignalTransduction Therapy 2007;2:190-213.

cWaldbott GL, Burgstahler AW, McKinney HL. Fluoridation: the great dilemma. Lawrence, Kansas: Coronado Press; 1978.p. 246-7, 359.

dEmsley J, Jones DJ, Miller JM, Overill RE, Waddilove RA. An unexpectedly strong hydrogen bond: ab initio calculationsand spectroscopic studies of amide–fluoride systems. J Am Chem Soc 1981;103:24-8.

eDeLauder SF, Mauro JM, Poulos TL, Williams JC, Schwarz FP. Thermodynamics of hydrogen cyanide and hydrogenfluoride binding to cytochrome c peroxidase and its Asn-82→Asp mutant. Biochem J 1994;302:437-42.

Figure 7. Russell L Blaylock, MD.

Figure 6. Professor Jiří Patočka, DrSc.

Figure 5. Professor Anna Strunecká, DSc.

The pathophysiology or mechanisms underlying the symptoms 5

After the discovery of the ability of fluoride to release, in conjunction withcalcium, inflammatory mediators such as histamine from white blood cells,including mast cells,ab the focus moved to G-proteins. Aluminium fluoride hasbeen shown to act as a phosphate analogc and stimulate G-protein receptors andsignalling pathways, such as the phosphatidylinositol pathway, which controlprotein phosphorylation, the uptake of calcium into cells, and the release ofcalcium from intracellular stores.d These processes are involved in hormonal andimmunologic responses, transmission of nerve impulses, cell division, and evenneoplastic transformations.e

Many of the symptoms of chronic fluoride toxicity are identical to thoseobserved in thyroid or iodine deficiency disorders (IDD).f Aluminium fluoride canmimic the action of TSH (thyroid stimulating hormone) by activating a calcium-transducing G-protein receptor, G q/11, in the thyroid leading, via a feedbackmechanism with increased intracellular cAMP, to desensitization of the TSHreceptorg and ultimately hypothyroidism. Fluoride, like TSH, has the ability toinfluence all aspects of thyroid hormone homeostasis in all tissues where the TSHreceptor is expressed, which includes the brain and bone as well as the thyroid,including iodine uptake and utilization, thyroid hormone homeostasis,deiodination, and thyroid peroxidase (TPO) activity. Deiodination involves theconversion of the hormone produced in the thyroid gland, thyroxine or T4, to theactive thyroid hormone triiodothyronine, T3.hij Moreover, Dr Russell Blaylock hassuggested that fluoride may lead to excitotoxicity with cell death in the brain fromoverstimulation. It may also induce, via brain NMDA receptor stimulation, achronic activation of the microglial cells in the brain, with the release of highlevels of the excitotoxic aminoacids glutamate and aspartate, and the secretion ofhigh levels of immune cytokines, and other immune factors, which can enhanceexcitotoxicity.klmn

Some persons are evidently more sensitive than others for developing thesymptoms of chronic fluoride toxicity, particularly those with renal (kidney)

aPatkar SA, Kazimierczak W, Diamant B. Histamine release by calcium from sodium fluoride-activated rat mast cells:further evidence for a secretory process. Int Arch Allergy Appl Immunol 1978;57:146-54.

bKuza M, Kazimierczak W. On the mechanism of histamine release from sodium fluoride-activated mouse mast cells.Agents Actions 1982;12:289-94.

cStrunecká A, Patocka J. Pharmacological and toxicological effects of aluminofluoride complexes. Fluoride 1999;32:230-42.dHunter T. Protein kinases and phosphatases: the yin and yang of protein phosphorylation and signaling [review]. Cell1995;80:225-36.

eBirnbaumer L. Expansion of signal transduction by G proteins The second 15 years or so: from 3 to 16 alpha subunits plusbetagamma dimers. Biochim Biophys Acta 2007;1768(4):772-93.

fSchuld A. Fluoride effects on thyroid function. Fluoride 2003;36:72.gTezelman S, Shaver JK, Grossman RF, Liang W, Siperstein AE, Duh QY, et al. Desensitization of adenylate cyclase inChinese hamster ovary cells transfected with human thyroid-stimulating hormone receptor.Endocrinology.1994;134(3):1561-9.

hLubkowska A, Zyluk B, Chlubek D. Interactions between fluorine and aluminium [editorial]. Fluoride 2002; 35:73-7. iStrunecká A, Patocka J. Pharmacological and toxicological effects of aluminofluoride complexes. Fluoride 1999;32:230-42. jSchuld A. Is dental fluorosis caused by thyroid hormone disturbances? [editorial]. Fluoride 2005;38:91-4.kBlaylock RL. Fluoride neurotoxicity and excitotoxicity/microglial activation: critical need for more research. Fluoride2007;40:89-92.

lBlaylock RL. Excitotoxicity: a possible central mechanism in fluoride neurotoxicity. Fluoride 2004;37:301-14.mBlaylock RL. Health and nutrition secrets that can save your life. Revised ed. Albuquerque, New Mexico: Health Press;2006. p. 93-131.

nBlaylock RL. Excitotoxins: the taste that kills. How monosodium glutamate, aspartame (Nutrasweet®) and similarsubstances can cause harm to the brain and nervous system and their relationship to neurodegenerative diseases such asAlzheimer’s, Lou Gehrig’s disease (ALS) and others. Santa Fe, New Mexico: Health Press; 1997.


6

disease, diabetes mellitus, and allergies. Patients with renal impairment are lessable to eliminate fluoride promptly, diabetics tend to drink more water thanaverage, and allergic individuals are less tolerant to noxious agents than arenormal individuals. Dr Waldbott estimated that about 1% of persons exposed tofluoridated water develop the chronic fluoride toxicity syndrome, while Dr HansMoolenburgh, a general practitioner in the Netherlands, considered the proportionto be about 5–6%.ab Subtle toxicity may affect many more.

MAKING THE DIAGNOSIS OF THE CHRONIC FLUORIDE TOXICITY SYNDROME

Not all the symptoms are necessarily present at the same time. Their severity andduration, which is often episodic, depend on a person’s age, nutritional status,environment, kidney function, amount of fluoride ingested, genetic background,tendency to allergies, and other factors such as the degree of “hardness” of thefluoridated water due to the amount of calcium and magnesium present.

Dr Waldbott, together with Professors Albert Burgstahler and Lewis McKinney,noted that to test whether or not fluoride is causing symptoms of ill health thefollowing must, as far as possible, be rigorously avoided:

1 all fluoridated water (Substitute distilled or other nonfluoridated water such as that obtained witha reverse osmosis filter. Ordinary charcoal or carbon water filters do not remove fluoride. DrMichael Easley, a profluoridationist and dental coordinator for the state Department of Health,Florida, notes “Nobody drags anyone to a water faucet and makes them drink. Dig a well. Moveout of the country.” but his comments are both unsympathetic and impractical.c)

2 fluoridated beverages3 fluoride-rich foods such as tea, ocean fish, gelatin, skin of chicken, fluoridated salt, food

contaminated with fluoride-containing insect or post-harvest fumigants (e.g. sulfuryl fluoride) andpesticides (e.g. cryolite, sodium aluminium fluoride, Na3AlF6, which may be used on grapes),etc.

4 fluoridated toothpastes5 fluoride from any other environmental source, including cigarette smoke and industrial pollution,

e.g. fluoride in dust and fumes from industries such as those manufacturing steel, aluminium,denamel,e pottery, glass, bricks, phosphate fertilizer, and others involved with power, welding,water fluoridation plants,f refrigeration, rust removal, oil refining,g plastics, pharmaceuticals,tooth-paste, chemicals, and automobiles.h

Dr Susheela notes that other sources of fluoride may include:i6 medications containing fluoride and fluoride mouth rinses7 black rock salt (fluorite, CaF2) and foods containing black rock salt (Kala Namak) for flavour, e.g.

Dhalmoth, other salty snacks, chat masala, etc.8 red rock salt and foods made using red rock salt9 tobacco or supari (Aracanut) when they are chewed by themselves

In China, fluoride toxicity occurs with:10 brick tea made, in Tibet, by compressing the older tea leaves, which have a higher fluoride

content, into “bricks.” Part of the brick is broken off to prepare the tea.j

aWaldbott GL. Affidavit in: Dr Waldbott presents affidavit to assist Massachusetts Superior Court Case. NationalFluoridation News 1980;XXVI(3):1-2.

bMoolenburgh HC. Dutch doctor describes hazards of fluoridated water. National Fluoridation News 1979;XXV(4):3.cAnton M. For some fluoridated water still hard to swallow. Los Angeles Times. 2007 Dec 27.dWaldbott GL. Fluoridation: a clinician’s experience. South Med J 1980;73:301-6.eWaldbott GL. Preskeletal fluorosis near an Ohio enamel factory: a preliminary report. Vet Hum Toxicol 1979;21:4-8.fWaldbott GL. Subacute fluorosis due to airborne fluoride. Fluoride 1983;16:72-82.gWaldbott GL, Lee JR. Toxicity from repeated low-grade exposure to hydrogen fluoride: case report. Clin Toxicol1978;13(3):391-402.

hSusheela AK. A treatise on fluorosis. 3rd ed. Delhi, India: Fluorosis Research and Rural Development Foundation; 2007.p. 17-8.

iSusheela AK. A treatise on fluorosis. Delhi, India: Fluorosis Research and Rural Development Foundation; 2001. p. 100.jCao J, Liu JW, Tang LL, Sangbu DZ, Yu S, Zhou S, et al. Dental and early-stage skeletal fluorosis in children induced byfluoride in brick-tea. Fluoride 2005;38:44-7.

Making the diagnosis of the chronic fluoride toxicity syndrome 7

11 food contaminated with fluoride. In some parts of China, food, such as chillies and corn,becomes contaminated with fluoride over a period of months as it is dried in dwellings in whichthe heating and cooking is done with coal briquettes made by mixing cheaper powder coal withclay which is high in fluoride. The presence of clay results in smoke with a high fluoride level and,in the absence of a chimney flue, the food stored in the dwelling gradually becomescontaminated with fluoride (Figures 8-11).ab

If the symptoms are in fact caused by fluoride, they should diminish markedlywithin a week and largely disappear within several weeks. If symptoms persist,consult a physician for possible alternative explanations. True fluoride toxicosiscan be reproduced by re-exposure to fluorides from whatever source. Dr Susheelafound the gastrointestinal symptoms settled within 15 days.c She noted that fordiagnosing skeletal fluorosis, measuring the levels of fluoride, in the blood andurine, was helpful along with taking radiographs of the forearm to look for thepresence of calcification of the interosseous membrane or a wavy outline of thebones of the forearm, and of any region or joint where there was pain, rigidity orstiffness, looking for increased bone density, or, in patients with calciumdeficiency, a weakening of the bone (osteomalacia).

aZheng BS, Wu DS, Wang BB, Liu XJ, Wang AM, Chen XZ, et al. Fluorosis caused by indoor coal combustion in China:discovery and progress. Proceedings of the XXVIIth conference of the International Society for Fluoride Research; 2007Oct 9-12; Beijing, PR China.

bWu DS, Zheng BS, Wang AM, Yu GQ. Fluoride exposure from burning coal-clay in Guizhou Province, China. Fluoride2004;37:20-7.

cSusheela AK. A treatise on fluorosis. 3rd ed. Delhi, India: Fluorosis Research and Rural Development Foundation; 2007.p. 95.

powdered coal

clay

Photograph by BS ZhengFigure 8. Powered coal, which is one third of the price of lumps of coal, is mixed with clayto form briquettes so that air spaces are present in the fire to allow the coal to burn. The clayacts as an adhesive to form lumps of a mixture of coal powder and clay. The air can enterbetween the lumps in the fire thus allowing the coal to burn.


8

Photograph by BS ZhengFigure 9. Chillies drying above a stove without a flue burning powdered coal briquettes made with high fluoride clay and becoming contaminated with fluoride from the smoke.

Photograph by BS ZhengFigure 10. Corn drying above a stove without a flue burning powdered coal briquettes made with high fluoride clay.

Photograph by BS ZhengFigure 11. Corn drying above a stove without a flue burning powdered coal briquettesmade with high fluoride clay.

Making the diagnosis of the chronic fluoride toxicity syndrome 9

She considered that if the patient has joint pain, such as in the neck, back, knee,or shoulder, then, when taking a radiograph of the affected region, it was importantto take a radiograph of the forearm.ab The forearm has two long bones in it, theradius on the thumb side and the ulna on the side of the little finger, with a fibrousmembrane between the bones (interosseous membrane). Normally there is no bonein the membrane and it does not show up as an opacity in radiographs or “X-rays.”When fluoride toxicity is present, bone containing calcium is laid down inmembranes, ligaments, and joints where it does not normally appear. When it islaid down in the membrane between the two bones in the forearm, it is calledforearm interosseous membrane calcification.

In the chronic fluoride toxicity syndrome or preskeletal fluorosis, Dr Waldbottfound that although fluoride levels in the urine are occasionally elevated or lowerthan normal, the lack of consistency does not permit the use of these tests asabsolute diagnostic criteria for fluoride poisoning.c He found the degree ofpoisoning does not necessarily parallel the amount of the toxic agent stored inorgans or present in the blood stream and that merely the flow of a toxic agentthrough a person could damage their health. He noted that an elevation of theurinary fluoride is not a prerequisite for the diagnosis of nonskeletal fluorosis.

Although fluoride may be present in a medication or an anaesthetic agent, it maybe less toxic by being in a bound rather than a free form. Unless fluorinatedorganic chemicals are metabolised in the body to release the fluoride they contain,the covalently bound fluoride may be eliminated from the body without havingbeen released as free fluoride ions. A small increase in the serumd fluoride leveloccurs with the partially metabolized ciprofloxacin, a fluoroquinolone antibiotic,while a larger increase occurs with fluorinated anaesthetics such as halothane,which are metabolised to a greater extent.e It is possible that small amounts offluoride released from fluoride-containing medications may be a cause of illness,particularly if the release is in an area, such as the brain, where even minuteconcentrations may have a very potent effect.

WHAT TO DO IF THE DIAGNOSIS OF CHRONIC FLUORIDE TOXICITY IS MADE

If symptoms remit after avoiding fluoride, little encouragement should beneeded to continue to avoid it. Neither laboratory studies on animals nor data onhuman teeth and bones have provided conclusive evidence that fluoride isessential for life.f

aSusheela AK. A treatise on fluorosis. 3rd ed. Delhi, India: Fluorosis Research and Rural Development Foundation; 2007.p. 63-7.

bSusheela AK. Fluorosis: an easily preventable disease through practice of interventions for doctors functioning in all healthdelivery outlets in endemic districts in India. India: Fluorosis Research and Rural Development Foundation; 2005. p. 10-1.

cWaldbott GL, Burgstahler AW, McKinney HL. Fluoridation: the great dilemma. Lawrence, Kansas: Coronado Press; 1978.p. 243, 255.

dSerum is the clear straw coloured fluid that is left after blood coagulates or clots, or the clear supernatant left after the redand white blood cells (erythrocytes and leukocytes) in the blood are separated, usually by centrifugation.

eDoull J, Boekelheide K, Farishian BG, Isaacson RL, Klotz JB, Kumar JV, Limeback H, Poole C, Puzas JE, Reed N-MR,Thiessen KM, Webster TF, Committee on Fluoride in Drinking Water, Board on Environmental Studies and Toxicology,Division on Earth and Life Studies, National Research Council of the National Academies. Fluoride in drinking water: ascientific review of EPA’s standards. Washington, DC: The National Academies Press; 2006. Available for purchase onlineat: http://www.nap.edu. p. 49-51.

fWaldbott GL, Burgstahler AW, McKinney HL. Fluoridation: the great dilemma. Lawrence, Kansas: Coronado Press; 1978.p. 243, 76-85.


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Rather than medication for remediation, Dr Susheela recommends propernutrition to give a diet containing at least 1.0 g of calcium a day together withvitamin C, vitamin E, and other antioxidants such as β-carotene, glutathione,quercetin, allicin, capasaican, ellagic acid, gallic acid, epicatechin, lycopene,glucosinolates, lutein and zeaxanthin.ab Antioxidants are particularly important inprotecting the body from fluoride toxicity. They act as “scavengers” to remove“free radicals” and occur naturally in fresh fruit and vegetables. Vitamin E (α-tocopherol), a potent antioxidant, exerts its protective effect primarily throughdestruction of cell damaging free oxygen species.c Vitamin C (ascorbic acid) is anantioxidant with detoxification properties. Calcium may help overcome thehypocalcaemia induced by fluoride and act synergistically with vitamin C.

CASE REPORTS OF FLUORIDE TOXICITY

The 507-page, 2006 National Research Council report, Fluoride in drinkingwater: a scientific review of EPA’s standards (2006 NRC report),d notes that theprimary symptoms of gastrointestinal injury are nausea, vomiting, and abdominalpain, and that these had been reported in case studies by Waldbotte and Petraborgf

as well as in a double-blind clinical study by Grimbergeng involving the researchgroup of doctors in the Netherlands with Dr Hans Moolenburgh. The report notedthat the case reports were well documented and that the authors could have beenexamining a group of patients whose gastrointestinal (GI) tracts were particularlyhypersensitive. It noted:

“The possibility that a small percentage of the population reacts systematically to fluoride,perhaps through changes in the immune system, cannot be ruled out. …

“Perhaps it is safe to say that less than 1% of the population complains of GI symptoms afterfluoridation is initiated (Feltman and Kosel 1961h). The numerous fluoridation studies in thepast failed to rigorously test for changes in GI symptoms and there are no studies ondrinking water containing fluoride at 4 mg/L in which GI symptoms were carefullydocumented. …

“In a recent study, Machalinski et al. 2003i) reported that the four different human leukemiccell lines were more susceptible to the effects of sodium hexafluorosilicate, the compoundmost often used in fluoridation, than to NaF [sodium fluoride].”

Feltman and Kosel, whose large controlled clinical study was conducted bydental supporters of fluoride.wrote:aSusheela AK. A treatise on fluorosis. 3rd ed. Delhi, India: Fluorosis Research and Rural Development Foundation; 2007.p. 89-94.

bSusheela AK. A treatise on fluorosis. 3rd ed. Delhi, India: Fluorosis Research and Rural Development Foundation; 2007.p. 89-94.

cChinoy NJ, Nair SB, Jhala DD. Arsenic and fluoride induced toxicity in gastrocnemius muscle of mice and its reversal bytherapeutic agent. Fluoride 2004;37:243-8.

dDoull J, Boekelheide K, Farishian BG, Isaacson RL, Klotz JB, Kumar JV, Limeback H, Poole C, Puzas JE, Reed N-MR,Thiessen KM, Webster TF, Committee on Fluoride in Drinking Water, Board on Environmental Studies and Toxicology,Division on Earth and Life Studies, National Research Council of the National Academies. Fluoride in drinking water: ascientific review of EPA’s standards. Washington, DC: The National Academies Press; 2006. Available for purchase onlineat: http://www.nap.edu. p. 269, 293, 303.

eWaldbott GL. Incipient chronic fluoride intoxication from drinking water. II. Distinction between allergic reactions and drugintolerance. Int Arch Allergy Appl Immunol 1956;9(5):241-9.

fPetraborg HT. Chronic fluoride intoxication from drinking water (preliminary report). Fluoride 1974;7:47-52.gGrimbergen GW. A double blind test for determination of intolerance to fluoridated water (preliminary report). Fluoride1974;7:146-52.

hFeltman R, Kosel G. Prenatal and postnatal ingestion of fluoride: fourteen years of investigation; final report. J Dent Med1961;16:190-8.

iMachaliński B, Baskiewicz-Masiuk M, Sadowska B, Machalinska M, Marchlewicz M, Wiszniewska B, et al. The influence ofsodium fluoride and sodium hexafluorosilicate on human leukemic cell lines: preliminary report. Fluoride 2003;36;231-40.

Case reports of fluoride toxicity 11

“One percent of our cases reacted adversely to the fluoride (1 mg/day tablets). By theuse of placebos, it was definitely established that the fluoride and not the binder wasthe causative agent. These reactions, occurring in gravid women and in children of allages in the study group, affected the dermatologic, gastro-intestinal, and neurologicalsystems. Eczema, atopic dermatitis, urticaria, epigastric distress, emesis, andheadache have all occurred with the use of fluoride and disappeared upon the use ofplacebo tablets, only to recur when the fluoride tablet was, unknowingly to thepatient, given again. When adverse reactions occur, the therapy can be readilydiscontinued and the patient or parent advised of the fact that sensitivity exists andthe element is to be avoided as much as possible.”

Some case reports from Canada, the USA, New Zealand, the Netherlands, andIndia will now be presented to illustrate the chronic fluoride toxicity syndrome.

ILLNESS IN PEOPLE IN CANADA

Sickness occurred with people after fluoride has been added to their drinkingwater. Fluoride was added to the drinking water in Windsor, Ontario, Canada, on11 September 1962.a However, the local health department did not announceimmediately that the change had been made because they feared an adversereaction by the citizens. This situation provided an excellent opportunity to testwhether fluoridated water produced sickness. When the press announced thecommencement of fluoridation to the public two weeks later, eight individualswere able to diagnose their own disease.

Mrs MH and Mrs EK:b Two of the eight, Mrs MH, a nurse, age 57, and Mrs EK,age 38, had been in the habit of drinking one or two glasses of water beforebreakfast. For some unknown reason, they suddenly experienced abdominalcramps and vomited immediately after their customary morning drink. During thecourse of the day they developed headaches, pains in the lower spine, andnumbness and pains in the arms and legs. They had never before had any suchdiscomfort and were not aware that Windsor’s water had been fluoridated. Thedoctor for Mrs MH, Dr FS, considered at first that she had a stomach ailment butmedication did not help. After several days of careful observation he suspectedthat the water might somehow be involved in her illness and advised her todiscontinue drinking it. She then promptly recovered. Mrs EK resorted to the useof distilled water on her own and also promptly recovered.

Miss CD:c Another of the eight was a 13-year-old schoolgirl, Miss CD, who inmid-September 1962 developed increasingly severe migraine-like headaches,pains and numbness in her arms and legs, and a distinct deterioration in her mentalalertness which interfered with her attendance at school. A consulting neurologistruled out the possibility of a brain tumour. Tests to determine whether theheadaches were caused by allergy were negative. On the advice of another patientwho had been similarly affected, she stopped drinking the Windsor drinking water.Her illness began to subside immediately and she had recovered completely after10 days. On Mondays and Thursdays however the headaches recurred when, after

aWaldbott GL, Burgstahler AW, McKinney HL. Fluoridation: the great dilemma. Lawrence, Kansas: Coronado Press; 1978.p.121.

bWaldbott GL, Burgstahler AW, McKinney HL. Fluoridation: the great dilemma. Lawrence, Kansas: Coronado Press; 1978.p.121-2.

cWaldbott GL, Burgstahler AW, McKinney HL. Fluoridation: the great dilemma. Lawrence, Kansas: Coronado Press; 1978.p.122-3.


12

gym classes, she quenched her thirst with Windsor drinking water. Theserecurrences stopped after she began carrying her own distilled drinking water toschool. Proof that the fluoride caused the illness was obtained when the diseasewas reproduced by a Windsor doctor giving fluoride in water in a double-blindmanner. After the symptoms had subsided with being on a fluoride-free watersupply, the condition recurred when water was used containing 1 part per millionof fluoride (2.2 ppm of sodium fluoride) with neither the patient nor the testingdoctor being aware of when the fluoride was reintroduced.

ILLNESS IN PEOPLE IN THE USA

Mrs SS:a In 1954, Mrs SS, age 40, a resident of Bay City, Michigan, USA, wasreferred to an allergy specialist in Warren, Michigan, George L Waldbott, MD,because of painful spastic bowels, frequent nausea and vomiting, bloating of thestomach, and persistent migraine-like headaches. She mentioned that everymorning on awakening she was so thirsty that she had to drink several glasses ofwater. She wondered if the Bay City’s water could account for her stomach andbowel upsets because they usually occurred in the morning after she hadconsumed water. She gave the clue to her diagnosis by noting that whenever shewas away from the city, her mouth and throat no longer felt dry, she was no longerthirsty, the cramps in her abdomen stopped, and her headaches did not occur.Neither she nor Dr Waldbott realized that Bay City’s water was fluoridated in1951. This was the first case of fluoride toxicity Dr Waldbott encountered.

Mrs MJ:bcd Dr Waldbott met another patient a few months later in 1954. MrsMJ, age 35, of Highland Park, Michigan, USA, had a mysterious illness with avariety of symptoms. Highland Park’s water had been fluoridated since 1952. Hercondition was more severe than the Bay City patient. She was constantlynauseated, vomited frequently, had periodic pains in the stomach, suffereddiarrhoea, and had pains in the lower back. Her general health deteriorated so thatshe became bedridden and reported a progressive weight loss, passed bloodrepeatedly from her kidneys and uterus, had a constant and frequently unbearablepain in her head, and had a problem with her eyesight, noticing blind spots ormoving spots in both eyes. She had lesions on her skin that she thought were theresult of bleeding or bruises, and the muscles of her hands and arms weakened sothat she often dropped potatoes when she was peeling them. She often lost controlof her legs, could no longer coordinate her thoughts, and became incoherent,drowsy, and forgetful. She had lived near Hanchow, China, an area with a highfluoride level, until the age of 5, and had had mottled teeth since early childhood.This gave a clue to her diagnosis.

She was admitted to hospital in Detroit and examined by eight specialists whoconsidered her illness to be serious but could not make an overall diagnosis. Untilthe preliminary tests were completed she had been instructed to continue to use thefluoridated Highland Park water. She was then changed to the nonfluoridated

aWaldbott GL, Burgstahler AW, McKinney HL. Fluoridation: the great dilemma. Lawrence, Kansas: Coronado Press; 1978.p.114-5.

bWaldbott GL, Burgstahler AW, McKinney HL. Fluoridation: the great dilemma. Lawrence, Kansas: Coronado Press; 1978.p.115-8.

cWaldbott GL. Chronic fluorine intoxication from drinking water. Int Arch Allergy 1955;7:70-4.dWaldbott GL. Incipient fluorine intoxication from drinking water. Acta Medica Scandinavica 1956;CLVI:157-68.

Illness in people in the USA 13

Detroit water with 0.1 ppm of fluoride. Within two days the stomach symptomsand headaches subsided and she was soon well enough to be discharged. Neither inthe hospital nor after her discharge was she given any medication. Instead she wasinstructed to strictly avoid fluoridated water, not only for drinking but also forcooking her food. She was also told to avoid both tea and seafood because of theirhigh fluoride content. The headaches, eye disturbances, and muscular weaknessdisappeared in a most dramatic manner. After about two weeks her mind began toclear and she underwent a complete change in her personality. For the first time intwo years she was able to undertake her household duties without having to stopand rest. Within a four-week period she had gained five pounds.

Subsequently the patient was subjected to a series of tests which definitelyproved that her disease was related to fluoridated water. Without being aware ofwhat she was receiving, she developed symptoms with fluoridated water but notdistilled water. A classical attack of migraine headache was produced by onemilligram of fluoride in two glasses of water.

She recovered completely without any treatment other than the elimination ofHighland Park fluoridated water for drinking and cooking. A feature of her diseasewas that the more water, she drank the thirstier she became. The numbness in herarms, hands, and legs, and the arthritic pains in the spine were worse uponawakening in the morning, whereas one would usually have expected the reverseafter a night’s rest.

Mrs HM:abA few weeks later, in November 1954, Dr Waldbott saw 30 people inSaginaw, Michigan, USA, who had been ill there, and who had become suspiciousof fluoridated water because their health improved immediately, and their illnessesgradually cleared up completely, following the termination of fluoridation inSaginaw. Nine of the 30 had a disease that matched that of the Highland Park caseof Mrs MJ. Some of them had experienced relief when they were away fromSaginaw, even for short periods. Most of them had been unaware that fluoride wasbeing added to their drinking water until they were confronted with voting in areferendum on fluoridation. Some of the individuals suffered exclusively frombladder and bowel symptoms. Mrs HM, age 49, had mottled teeth like Mrs MJ andhad spent her childhood near Toronto, Canada, where the well water was said tocontain fluoride. During July 1953, two years and three months after Saginawfluoridated its water supply, she noted a peculiar gnawing sensation in her stomachafter eating “as though there was something burning inside.” At the same time sheexperienced increasing stiffness of her back which was partly relieved by using aboard on her bed. Her hands began to tingle in the areas around her ring and littlefingers. She could not finish peeling her potatoes. She lost control of her legswhich “seemed to collapse” under her. Gradually she developed severe muscularpains in her arms and legs. Her throat, eyes, and nose became extremely dry. Themore drinking water she drank the thirstier she became. Her head became “foggy,”her thinking “not clear,” her hair began to fall out, and her finger nails becamebrittle and ridged. On hot days, when she drank more water, the general weakness,


bWaldbott GL. Incipient fluorine intoxication from drinking water. Acta Medica Scandinavica 1956;CLVI:157-68.


14

mental sluggishness, and dryness of the throat became worse. On 19 October 1953she started to use bottled water for drinking and distilled water for cooking afterlearning, for the first time, that the Saginaw water was fluoridated. Within a fewdays her illness began to clear up. The pain in the stomach and dryness of themouth improved first. The backache and muscular pains lasted for about threemore weeks. The nails became normal after several months and she then remainedin excellent health.

Mr RM:a Mr RM, age 42, was also in the Saginaw group of 30. He was about togive up his job because of progressive pains and weakness in his hands thatprevented him from grasping the steering wheel of his car. The condition becameso severe that he often had to stop on the highway. He finally became suspicious ofSaginaw’s water because the disease invariably lessened when he was on extendedsales trips away from Saginaw. When fluoridation was abandoned there in 1954 hequickly recovered.

Dr Waldbott also cared for the next two patients, Mrs CMK and Miss GL.Mrs CMK:b “Mrs CMK, a 30-year-old ragweed, hayfever patient, under my care

since March 1963, had allergic reactions to many drugs including codeine, iodine,penicillin and xylocaine. On 15 June 1965, two years and nine months after theWindsor, Ontario water supply had, unbeknown to her, become fluoridated, shehad extensive laboratory studies in a Windsor hospital because of periorbitaledema, a tendency to generalized fluid retention associated with headaches,scintillating scotomata, and spastic bowels. The EEG had suggested a tendency to“convulsive disorders,’ but otherwise no diagnosis had been made.

“On 20 May 1966 she was hospitalized at Harper Hospital, Detroit, by Dr JPG.In addition to the above complaints, she stated that she had frequent episodes ofabdominal pains, dysuria and urinary tenesmus, and muscular weakness with atendency to fall down without warning and without losing consciousness. She hadnoted slurred speech, pains, paraesthesias in the arms and legs, general malaise,marked mental sluggishness, and a gradual deterioration of the eyesight which wasnot corrected by glasses.

“On examination she showed fibrillation of the facial muscles and grayish-bluesuffusions [coloured areas] on the arms and legs, 2 to 3 cm in diameter, which shestated came on frequently without trauma. The neurological examination (Dr JEG)showed slightly increased tendon reflexes. Electromyographic tests (Dr FSS) wereindicative of hypocalcaemic tetany. Retinoscopy [viewing the retinae of the eyes](Dr OAB) showed slight edema of the optic discs in both eyes. Cystoscopicexamination (Dr HVM) of the bladder revealed evidence of mild urethritis[inflammation of the ureters] and cystitis [inflammation of the bladder].

“A test dose of 6.8 mg of fluoride (15 mg sodium fluoride, NaF), [given on 19May 1966], 24 hours prior to admission, resulted in a marked aggravation of hercondition and precipitated an episode of urticaria [an allergic skin reaction withswelling and itching similar to that produced by the sting of a nettle] which


bWaldbott GL. Hydrofluorosis in the U.S.A. Fluoride 1968;1:94-102.

Illness in people in the USA 15

persisted for two days. Throughout the hospital stay, while on low fluoride water(0.1 mg/L or ppm) she improved progressively. Upon discharge, on 6 June 1966,she was free of symptoms. Serum calcium levels ranged from 8.2 to 9.2 mg/dL ormg% (normal 8.8–10.0 mg/dL), shortly after admission, and urinary calcium from86 to 150 mg/24 hours (normal <250 mg/24 hr). Otherwise the laboratory testswere unremarkable.

“On 9 June 1966 she was given a double-blind test under supervision of Dr JPG.She was able to identify the bottle which contained the fluoride in water becauseof the gradual return of her previous illness, particularly the general edema and theabdominal symptoms.

“Three identical bottles labelled #1, 2, and 3, are prepared by the pharmacist: Two containplain distilled water, the third, 1 mg of fluoride (2.2 mg sodium fluoride, NaF) per tablespoon ofwater, the daily dose recommended for the prevention of tooth decay. Neither the patient nor thephysician knows which bottle contains fluoride. The patient is instructed to take half atablespoon twice a day in one pint of water (before breakfast and before dinner) from bottle #1for one week, from bottle #2 the second week, and from bottle #3 the third week. Usually thefluoride water causes the symptoms to recur within 1 to 3 days. During the test, urinary fluoridedeterminations are made.

“Since avoiding tea, seafood, and fluoridated water, she had remained wellexcept for minor recurrences which have been due to inadvertently imbibingWindsor fluoridated water. On 20 May 1966, after she was given the above test,the 24 hour urinary fluoride excretion was 2.8 mg; on 6 June 1968, the day aftershe was discharged from the hospital, 0.27 mg.”

Miss GL:a “Miss GL, 27 years old, had been under my care since July 1966because of allergic nasal and sinus disease of about six years’ duration. Shecomplained also of frontal and occipital headaches, of paresthesias and pains in thearms and hands, of backache, of arthritis in the interphalangeal joints [the joints inthe fingers and toes], of persistent gastralgia [stomach pain] and spasticconstipation, of frequent episodes of ulcers in the mouth, and of pyelocystitis forwhich she was being treated by other specialists. Desensitization for ragweed,grass pollen, and fungi to which she was sensitive cleared up the nasal allergy butfailed to affect any of the other symptoms.

“The urinary tract disturbances and the marked generalized weakness progressedto such an extent that they interfered with her employment as a teacher andnecessitated hospitalization at Hutzel Hospital on 1 February 1967.

“Laboratory tests, including kidney function studies were unremarkable. Acystoscopy and pyelography [radiograph or “X-ray” showing kidney function byusing a dye, IVP, intravenous pyelogram] revealed an ectopic left kidney whichfailed to excrete the indigo carmine dye. The urologist (Dr FSB) considered thiskidney without function and advised its removal. There was also a congenitalfusion of the lumbar vertebrae, congenital absence of two lumbar segments anddisc spaces; the right leg had been amputated at age 8 because of a congenitalabnormality.

“Because the patient’s condition failed to respond to therapy and because of thesimilarity of the clinical picture with that encountered in other individuals

aWaldbott GL. Hydrofluorosis in the U.S.A. Fluoride 1968;1:94-102.


16

intolerant to fluoride—without being aware of it she been drinking fluoridatedwater for 17 years in Highland Park, Michigan—she was placed on distilled waterfor cooking and drinking, and instructed to avoid “high fluoride” food (tea andseafood). The gastrointestinal symptoms and headaches disappeared completelywithin 10 days. On 12 June 1967, pyelography and cystoscopy revealed that thefunction of the ectopic left kidney had returned to normal. No blind or double-blind tests were carried out in this case because of the risk involved, particularlywith respect to the kidneys.

“The patient has had no further urinary disturbances and has remained symptom-free. The 24-hour urinary fluoride, on 9 December 1966, prior to thehospitalization on 1 February 1967, was 1.3 mg. On 14 June 1967 no fluoride wasdetected in the urine.”

In 1972, Mr J Quirk brought to theattention of Dr Harvey T Petraborg, MD, ofAitkin, Minnesota, USA, the plight of sixpeople in Cudahy, Wisconsin, USA, whohad developed a variety of systemicsymptoms after their water supply wasfluoridated on 8 November 1966 and whosesymptoms cleared up promptly after theystopped using fluoridated water (Figure 12).Dr Petraborg interviewed these six peopletogether with a seventh person, alsoidentified by Mr Quirk, in fluoridated SaintFrancis, Wisconsin, on 3–5 August 1972.a

Mr EH: Mr EH, age 52, became ill in thesecond week of November 1966, within aweek of fluoridation starting. After havingbeen in excellent health, he developedbloating in the lower portion of the abdomen, oedema in the extremities and painin the feet and fingers. As the illness progressed he developed diarrhoea with 7–8watery stools daily which were often tinged with blood. He was admitted tohospital for 4 days and had a variety of tests which did not show the cause of hisillness. The diarrhoea persisted after his discharge from hospital. He developedmarked itching on his legs when he showered but no itching occurred withshowers at his workshop where the water was not fluoridated. He developedgeneral dermatitis when he took a bath. This drew his attention to the possibilitythat his illness might be related to drinking water. He switched to nonfluoridatedwater and the bleeding and diarrhoea stopped. On several subsequent occasionswhenever, unbeknown to himself, he drank fluoridated water the diarrhoeapromptly recurred.

Mrs RAJ: Mrs RAJ, age 31, became unwell in November 1966 with persistentheadaches, intermittent abdominal cramps with diarrhoea, and increasing fatiguewhich gradually became more severe and made it difficult for her to do her

aPetraborg HT. Chronic fluoride intoxication from drinking water (preliminary report). Fluoride 1974;7:47-52.

Figure 12. Harvey T Petraborg, MD. 3 February 1895–24 August 1981.

Illness in people in New Zealand 17

housework. The condition promptly subsided in 1971 when she moved with herfamily to Stratford, Wisconsin, which was not fluoridated. In April 1972, thefamily moved to fluoridated Milwaukee, Wisconsin, and within 24 hours theheadaches returned, followed shortly afterwards by diarrhoea and abdominalcramps. At first the intestinal disorders occurred once or twice a week and lasted1–2 days but gradually they became persistent. Her abdomen was constantlybloated and severe general disability followed. On being advised aboutfluoridation by Mr Quirk she began to use spring water for cooking and drinking.Within a few days her health improved remarkably and by continuing to avoidfluoridated water she remained in good health.

Mrs RM: Mrs RM, age 31, also became ill in November 1966 after fluoridationstarted. She experienced a gradual deterioration in her strength with a loss ofappetite and weight. She became so weak that it was a great effort for her to do herhousework. On the advice of Mr Quirk she switched to nonfluoridated springwater and within a short time her appetite returned, she gained weight, she sleptwell, and her energy and strength recovered. By continuing to use nonfluoridatedwater she remained in good health.

Mr FT: Mr FT, a machinist, age 36, had been in perfect health until soon afterfluoridation began when he began to be tired and lethargic. He became tense,mentally depressed, and experienced frequent headaches. After a day’s work hefound it necessary to lie down and sleep for several hours. He developedgeneralized itching after bathing. The symptoms all went when, on the advice ofMr Quirk, he stopped using the fluoridated Cudahy water. After several weeks onthe low fluoride regime he returned to Cudahy water because he found itinconvenient and expensive to keep himself supplied with nonfluoridated water.The itching, headaches, general malaise, and mental depression then promptlyreturned. His symptoms again disappeared when he resumed using nonfluoridatedwater.

Mrs JM: Mrs JM, age 31, had excellent health while living in nonfluoridatedBoyceville, Wisconsin, but within 24 hours of moving to fluoridated Cudahy, on 4July 1971, she experienced constant abdominal pains, bloating, and diarrhoea.This was soon followed by persistent vertigo and general malaise whichprogressed to the point where she was unable to walk without assistance. Hervision became blurred and her comprehension began to fail. Her legs collapsedfrequently and she was unable to rise from the floor. She found that she wasalways thirsty and drank excessive amounts of the Cudahy water. In the latter partof July 1971, she developed severe pain in the right side of her head andparesthesias in the right part of her face. She underwent extensive tests at ahospital including having a lumbar puncture but no diagnosis was made. Aboutone week after leaving hospital she was given nonfluoridated spring water as atrial and instructed to avoid the Cudahy water for drinking and cooking. Within aweek the dizziness, lethargy, pain, and gastrointestinal symptoms cleared up andshe has enjoyed perfect health since.

Mrs AM: Mrs AM, age 74, was in good health until 1965 when the family movedto Saint Francis, Wisconsin, which uses Milwaukee fluoridated water. Within afew days she developed headaches, vertigo, nausea, abdominal pains with


18

diarrhoea, and a gradual loss of weight. The headaches became severe and thevertigo so pronounced that she could no longer walk from one room to anotherwithout colliding with the furniture. The general exhaustion rendered herbedridden during part of the day. Gradually she developed back pain as well asarthritis in both knees and right shoulder joint. On the recommendation of MrQuirk, she started using nonfluoridated spring water in 1969. Within one to twoweeks, a remarkable change in her physical condition took place. All hersymptoms cleared except for her arthritic pains in her back and knees whichgradually lessened. Subsequently she has enjoyed good health.

Mr AA: Mr AA, 47 years, stated that about 4 years ago in 1968 he had an acuteepisode involving kidney stones [nephrolithiasis]. He was hospitalized for 4 daysand passed 5 kidney stones. On his discharge from hospital he was advised todrink large quantities of water. Shortly after carrying out this advice, he began tocomplain of fatigue, vertigo, irritability, and had to restrict his activity at work. Hedeveloped continuous headaches involving the whole skull bilaterally [on bothsides]. Although he had been flying his own aeroplane for 25 years, he could nolonger perform any precision maneuvering. At night, he could not see as well asformerly. Because of the dizziness, he no longer felt safe flying his plane. In 1970,on the advice of Mr Quirk, he switched from the fluoridated Cudahy water tononfluoridated spring water. Within a few days, the headaches, vertigo, and lack ofenergy disappeared and he was able to pilot his airplane as well as ever.

ILLNESS IN PEOPLE IN NEW ZEALAND

Mrs PA (pseudonym A): In 1997, Mrs PA, a 77-year-old woman in Dunedin,New Zealand, where fluoride was added to the water in 1967, had a ten yearhistory of weight loss and abdominal pain from a gastric ulcer, which was shownby biopsy to be severe chronic active gastritis with campylobacter pylori present.aShe obtained only temporary relief from the medication given to her. She said thatfor many years her activities were restricted by abdominal pain and that sheexisted on plain yoghurt. She said she could eat only about four tablespoonfuls ofa meal and was unable to tolerate foods like vegetables. Her symptoms remittedwithin about two weeks of her commencing to use, in 1997, water from which thefluoride had been removed with a reverse osmosis filter. She also noted a markedimprovement in the arthritis that she had in her back, shoulders, and jaw. Ten yearslater, in 2007, at the age of 87, she remained well and had gained 6.4 kg in weight.She continued to use filtered water which she said had been “like magic.” She saidthat the improvement in her health had been “just a miracle.”

Mrs PB: On 30 July 2007, Mrs PB, a 67-year-old Dunedin woman, reportedhaving multiple symptoms and having noted that she became worse after beingback in Dunedin for about a month after being away for several weeks in otherparts of New Zealand that did not have fluoridated water. After a month back inDunedin, she noticed that her balance was poorer, she had tingling in her toes atnight that she tried to relieve by getting up and walking about, she felt that hermouth was dry and that she should drink more during the day, she became aware

aSpittle B. Dyspepsia associated with fluoridated water. Proceedings of the XXVIIth conference of the International Societyfor Fluoride Research; 2007 Oct 9-12; Beijing, PR China.

Illness in people in New Zealand 19

of “blind spots” in her vision for the first time, she felt tired, and she had rightupper abdominal tenderness. She said that she had had the abdominal pain severalyears previously and that it was attributed to “a twisted bowel.” She said that shehad a pain in her jaw and that she had a bluish spot on the inner aspect of her leftarm that came and went. It was about 10 mm in diameter and was not a bruise dueto an injury. It did not turn yellow or brown. She said she had headaches, feltnervous, and was aware of palpitations. She also reported nausea, constipation,and pain in her lower-mid thoracic spine. She was aware of a weakness in her armsand was playing poorly at sport involving her arms. She said she tended to bedizzy and that her nails broke easily. She commenced a trial of avoidingfluoridated water by using nonfluoridated water, and not using fluoridatedtoothpaste or tea. On 13 August 2007 she reported that her balance was “so muchbetter” and that she was less tired than before. She said that the tingling in her legsat night, which she had had for a long time and which had been getting worse, hadlessened. She said that her right upper abdominal pain had improved. She reportedthat her constipation had improved without any change in medication, that hernausea was better, and that the headaches had gone. She said that the pain in hermid-lower thoracic spine was better, her vision was better, and that thetroublesome spots had gone. She said that the dryness of her throat had gone andshe was not experiencing a lack of energy. Her ability to play sport had improvedand she was better able to anticipate her opponents’ moves. She said that hernervousness had gone and that she had not had any more palpitations. She said thatshe had lost the pain in her jaw and that the improvement had been remarkable. On4 September 2007 she remained improved with not having the dark spots in hervision, dry mouth, or constipation and with a better sense of balance. She said thatshe could put her shoes on standing on one leg. The other areas of improvementalso remained and she planned to continue to avoid fluoridated water, fluoridatedtoothpaste, and tea. The cause of her improvement could not be proven to berelated to avoiding fluoride, but the pattern of improvement is consistent with thatdescribed for chronic fluoride toxicity.

Mr PC: On 8 June 2006, Mr PC, a 38-year-old man in Dunedin described havinga long standing problem with chronic fatigue, gastro-intestinal difficulties, andproblems with his memory and concentration. He said that he drank a lot of water,up to about 4 L a day of the fluoridated Dunedin water. He said that he used toswallow fluoridated toothpaste when he was younger. He commenced a trial ofusing nonfluoridated spring water from a public source at Speight’s Brewery,Rattray Street, Dunedin, with 0.1 ppm of fluoride, and avoiding fluoridatedtoothpaste. He reported a week later that his energy had improved and that he hadbeen for a run, something he had previously been unable to do. He continued toimprove in his energy and on 22 June 2006 said that he felt his energy was at ahigher level than it had ever been before. On 29 June 2006 he reported that he wasgoing for small runs on three mornings a week and that he was managing on 6hours sleep a night, which was less than he had previously slept for. On 27November 2007, 17 months later, he remained well on nonfluoridated water,continued to experience an increased energy level, and had further increased hiscapacity for running.


20

Mrs PD: On 24 September 2007, Mrs PD, a 59-year-old Dunedin woman with along history of urinary urgency that had been investigated and considered to bedue to a small bladder capacity and for which an appropriate treatment would bean operation to dilate the bladder, reported that her bladder problem had settledafter a trial of some weeks of using nonfluoridated spring water and reducing hertea consumption from about 1.5 L a day to about 400 mL daily. On 18 October2007 she reported a further improvement in the urgency and that she had hadseveral good days without any symptoms. She said that she was pleased with thisand felt that it meant that she did not have to have “a bladder stretching operation.”She said that she had also had less stomach pain than she usually had and that shedid not have the bloating that she usually experienced. She reported that she hadskin itching after showering. Although a causative relationship cannot be proven,the improvement in her symptoms is consistent with that described by others withchronic fluoride toxicity.

Mrs IH:a Also in the South Island of New Zealand, in late 1973, Mrs IH, a 47-year-old Timaru woman, found that, soon after fluoride was introduced into thewater supply, she became constipated for the first time in her life. She said that shetried everything from bran to fresh fruit but nothing worked. She said that sheknew it must be something that she was taking but could not work out what it was.She said somebody suggested it could be fluoride but she scoffed at the idea.When she stayed with her son in nonfluoridated Christchurch her problemvanished. Back in Timaru, her illness did not return while she used nonfluoridatedwater from a reservoir on the outskirts of town but as soon as she went back to thefluoridated water she became constipated again. She was convinced by herexperience that her constipation had been due to the fluoridated water.

Mrs PE: Mrs IH also reported that another woman had had a bad skin rash fortwo years, ever since fluoridation started in Timaru, for which medical treatmenthad been unsuccessful. Tests by her doctor suggested fluoride might be the cause.The woman then switched to nonfluoridated water and within two weeks her rashwas gone.

ILLNESS IN PEOPLE IN THE NETHERLANDS

Dr Hans Moolenburgh, a family physician, in Haarlem, the Netherlands, with aninterest in allergy, reported his experiences when fluoridation was introduced on20 March 1972 to half of his practice in nearby Heemstede, which received waterfrom Amsterdam, while the other half of his practice in Haarlem remained freefrom fluoridation (Figure 13).b

Miss PF: He said that he would never forget his first patient with fluoridetoxicity.c A 14-year-old girl, Miss PF, got colicky pains in her stomach two weeksafter fluoridation started that prevented her from going to school. He suggestedthat she use nonfluoridated water. It was difficult to convince her parents to do thisbecause they had not known that fluoridation had started but with the

aAnon. Fluoridation stopped in Timaru, New Zealand. National Fluoridation News 1986; XXXI(4):2.bMoolenburgh H. Fluoride: the freedom fight. Edinburgh: Mainstream Publishing; 1987. p. 64cMoolenburgh H. Fluoride: the freedom fight. Edinburgh: Mainstream Publishing; 1987. p. 65

IIlness in people in the Netherlands 21

nonfluoridated water the girl had immediate pain relief. However, one Sundaymorning, the pain suddenly came back. The father commented that it was notfluoridated water after all. Dr Moolenburgh asked him to think carefully. Thefather then began to laugh and said “You’re right doc, I remember bringing up thetea this morning and making it with drinking water.”

Mr PG: His second patient, Mr PG, had anitchy rash all over his body.a

Dr Moolenburgh reported that one of the firstsymptoms seen in fluoridated Amsterdam wassmall, white, very painful sores in the mouth(aphthous stomatitis). Later he saw thisregularly in the users of fluoridated toothpaste.

There were people with nagging pains in theabdomen who often had another side-effect ofincreased thirst which led them into a viciouscircle in which, the more drinking water theydrank, the more their symptoms increased.

Baby PH: He also noted “A five-week-oldbaby started crying and cried on and on, day andnight. It was taken to the hospital where nothing could be found wrong with thechild. It went on crying after returning home and was in pain from something.After some weeks when the parents were frantic with despair, I suggestednonfluoridated water. (This baby was not in my practice and the parents only heardabout our research when the illness of the child had continued for several weeks.)With nonfluoridated water in the bottle the baby changed overnight to a sweetcontented child and stayed that way.”

Baby M: Dr Moolenburgh saw respiratory problems. He wrote “A boy, Michael,two weeks old, was taken to the doctor because his breathing was not right.b Themother had three older children. She said, ‘His breathing is different from the otherones. It is laboured.’ Neither the doctor nor the specialist could find anythingwrong. The breathing grew steadily worse. As I am very interested in allergy, thisboy was brought to me when he was five months old. Here was typical asthmaticbreathing, and the child was not so bright and kicking as might be expected from ahealthy baby. He looked a little bit drowsy. I suggested nonfluoridated water in thebottle to begin with, and in three days the child was healed. … The boy is now 11years old and absolutely healthy.”

Baby PI: Dr Moolenburgh observed that, when using fluoridated water, allergicchildren showed a tendency to fall back into old allergic complaints or show asevere worsening of still existing complaints. He recorded “For instance, there wasa ten-month-old boy in my practice who had been healed from getting eczema bychanging the cow’s milk in the bottle for soy milk. Three days after the

aMoolenburgh H. Fluoride: the freedom fight. Edinburgh: Mainstream Publishing; 1987. p. 65bMoolenburgh HC. Dutch doctor describes hazards of fluoridated water. National Fluoridation News 1979;XXV(4):3.

Figure 13. Dr Hans Moolenburgh.


22

introduction of fluoridation the eczema was back all over the skin (without cows’milk!) and only healed after the tap water had been thrown out.”a

Mrs PJ: Dr Moolenburgh stated that apart from skin troubles, gastrointestinalcomplaints, and respiratory illnesses, other troubles during these first months offluoridation were headache, excessive thirst, a general feeling of being unwell, anddifficulty in concentration. He referred also to the side-effect of arthritis-likecomplaints that came on much later, after several months, and went away moreslowly, over several weeks. They were mostly located in the lower part of the backand in the small finger joints. One lady, Mrs PJ, was nearly crippled by thesecomplaints and, because even small amounts of fluoridated water were enough tokeep the illness going, she eventually had to move to a nonfluoridated region.b

Dr PK: Dr Moolenburgh formed a group with other doctors to conduct researchinto the side-effects of fluoridation.c One day, Dr PK, a 60-year-old doctor in hisresearch group, looked pale and gloomy.d They asked him if he did not feel welland he confessed that he had had a slowly increasing pain in his abdomen for somemonths and was afraid that he had cancer. One of them, as a joke, suggested it wasthe fluoridated water. He replied that that was “Stuff and nonsense” and that it didnot happen to him. Dr Moolenburgh suggested he try nonfluoridated water. He didand was healed in three days. However a week later his complaints suddenlyreturned and he did not understand why until he discovered that he had drunksome coffee made with fluoridated water while attending a home delivery. Hecontinued to avoid fluoridated water and his complaints never returned.

ILLNESS IN PEOPLE IN INDIA

Professor AK Susheela described patients who became ill from fluoride inIndia. Mr PL: Mr PL, a 45-year-old man who drank water with an elevatedfluoride level, complained of aches and pains in his joints and a 12-year history ofnon-ulcer dyspepsia (nausea, loss of appetite, pain in the stomach, gas formationand a bloated feeling, constipation followed by intermittent diarrhoea, andheadache).e He took a laxative magnesium hydroxide (Milk of magnesia) for theconstipation. The presence of skeletal fluorosis was confirmed by radiographsshowing forearm interosseous membrane calcification, and increased bone massand density. The fluoride levels in his blood and urine were also increased. Afterthree weeks of hospitalization and using water with less than 0.5 ppm of fluoride,he was discharged with the abdominal pain, and the joint aches and pains, largelyrelieved.

Master PM and Mr PN: Master PM, a 10-year-old boy suffered from excessivethirst (polydipsia), drinking 4 L of water a day at school between 7 am and 2 pm,and frequent urination (polyuria).f He limped when he got out of bed and also had

aMoolenburgh HC. Dutch doctor describes hazards of fluoridated water. National Fluoridation News 1979;XXV(4):3.bMoolenburgh HC. Dutch doctor describes hazards of fluoridated water. National Fluoridation News 1979;XXV(4):3.cGrimbergen GW. A double blind test for determination of intolerance to fluoridated water (preliminary report). Fluoride1974;7:146-52.

dMoolenburgh HC. Dutch doctor describes hazards of fluoridated water. National Fluoridation News 1979;XXV(4):3.eSusheela AK. A treatise on fluorosis. Delhi, India: Fluorosis Research and Rural Development Foundation; 2001. p. 105. fSusheela AK. A treatise on fluorosis. Delhi, India: Fluorosis Research and Rural Development Foundation; 2001. p. 111-3.

Illness in people in India 23

constipation with a bowel movement every three days. His serum and urinefluoride levels were elevated at 0.08 mg/L (ppm, normal range ≤ 0.02 mg/L) and8.0 mg/L (normal ≤ 0.10 mg/L) respectively. His father, Mr PN, also hadsymptoms with abdominal pain, a bloated feeling with gas formation, nausea,constipation followed by intermittent diarrhoea, extreme weakness, and fatigue.Both were receiving excessive amounts of fluoride through water, food, andtoothpaste and responded to avoiding fluoridated toothpaste and a lowered intakeof fluoride in the food and water. After 7 months of intervention the boy’s serumfluoride had fallen to 0.02 mg/L and the urine fluoride to 0.60 mg/L. Both MasterPM and Mr PN continued to be well.

While a urine fluoride level of ≤ 0.10 mg/L would be normal on a low fluoridediet, a level of 0.2–0.3 mg/L might still be considered fairly normal in today'senvironment even without fluoridated water.

Mr PO: Mr PO, a 59-year-old man, was diagnosed with fluoride toxicity afterforearm interosseous membrane calcification was found by an orthopaedicsurgeon.a He had a 15-year-history of back ache, found it difficult to climb stairs,and was very depressed. He was found to have severe non-ulcer dyspepsiasymptoms with gas formation, a bloated stomach, nausea, and constipation withintermittent diarrhoea. His serum and urine fluoride levels were elevated at 0.08mg/L (normal range ≤ 0.02 mg/L) and 2.50 mg/L (normal ≤ 0.10 mg/L),respectively. His drinking water fluoride was not elevated but he was usingfluoridated toothpaste, and consuming 100–150 g of Dhalmoth, a salted snackwith black rock salt, and was treating himself with an Ayurvedic tablet, Hajmola,which also contained black rock salt. Black rock salt (Kala Namak, fluorite, CaF2)has a high fluoride content, about 250 ppm. With a nutritional intervention,avoiding fluoridated toothpaste and black rock salt, and taking a diet with 1.0 g ofcalcium a day, vitamins C and E, and antioxidants, he improved remarkably over10 months, at which stage his serum and urine fluoride levels were 0.03 mg/L and0.70 mg/L.

OTHER ILLNESSES DUE TO FLUORIDE

An apparent, but statistically non-significant, association has been foundbetween fluoridation and the earlier onset of female sexual maturity. Girlsexamined in fluoridated Newburgh, New York, had an average age for starting tomenstruate (menarche) of 12 years compared to 12 years 5 months in thenonfluoridated control city of Kingston.b Animal studies with Mongolian gerbilsfound a similar effect.cd A hormone, melatonin, produced in the pineal gland in thebrain, normally controls the onset of sexual maturity. Fluoride is concentrated inthe pineal gland, which has a rich blood supply, and the 2006 NRC report calls for

aSusheela AK. A treatise on fluorosis. Delhi, India: Fluorosis Research and Rural Development Foundation; 2001. p. 109-11.

bSchlesinger ER, Overton DE, Chase HC, Cantwell KT. Newburgh-Kingston caries-fluorine study, XIII. Paediatric findingsafter ten years. J Am Dent Assoc 1956;52(3):296-306.

cLuke JA. The effect of fluoride on the physiology of the pineal gland [thesis]. Guildford: University of Surrey; 1997.dLuke J. Effects of fluoride on the physiology of the pineal gland in the Mongolian gerbil Meriones unguiculatus. Fluoride1998;31(3):S24.


24

further research to determine if it reduces melatonin production and causes anearlier menarche.a

Fluoride has been linked to other illnesses such as the occurrence of a rare formof bone cancer, osteosarcoma, in young men after exposure to fluoridated water asyoung boys. Exposure of 6–8-year-old-boys to fluoridated water resulted insignificant increase, 500% at age 7, in the occurrence of osteosarcoma by age 20years.bc Ingested fluoride is partly excreted in the urine and partly stored in boneswhere it can inhibit the normal cycle of bone breaking down and being rebuilt.Fluoride first affects the bone-resorbing cells, resulting in more bone being formed(osteomegaly).d Over time, or with greater fluoride exposure, bone-forming cellsare also affected, resulting in less bone being present (osteopaenia). Thus fluorideinitially stimulates bone formation resulting in bones that are more dense but thequality of the bone is inferior. Bones with high fluoride levels are more brittle andhip fractures increase as the level of fluoride in the water supply increases.efg

Fluoride causes thyroid hormone disturbances. A close similarity exists betweenthe numerous symptoms and signs of hypothyroidism and those for fluoridetoxicity including dental fluorosis.hij There is also evidence that Down Syndromeis associated with fluoridation.klmno

Increased violent crime has been linked to fluoridation with silicofluorides suchas sodium silicofluoride or hydrofluosilicic acid.p These are the forms of fluorideusually used in fluoridation rather than sodium fluoride, are by-products ofindustrial processes such as the manufacture of phosphate fertilizers rather thanbeing of pharmaceutical grade, have not been properly tested for safety influoridating water, and differ in their effects from those of sodium fluoride bybeing more potent in inhibiting acetylcholinesterase and increasing leadabsorption into the body, resulting in an impairment of brain functioning with alessened control over violent behaviour.q Silicofluorides act as a solvent for lead,

aDoull J, Boekelheide K, Farishian BG, Isaacson RL, Klotz JB, Kumar JV, Limeback H, Poole C, Puzas JE, Reed N-MR,Thiessen KM, Webster TF, Committee on Fluoride in Drinking Water, Board on Environmental Studies and Toxicology,Division on Earth and Life Studies, National Research Council of the National Academies. Fluoride in drinking water: ascientific review of EPA’s standards. Washington, DC: The National Academies Press; 2006. Available for purchase onlineat: http://www.nap.edu. p. 264, 267.

bBassin EB, Wypij D, Davis RB, Mittleman MA. Age-specific fluoride exposure in drinking water and osteosarcoma (UnitedStates). Cancer Causes Control 2006;17:421-8.

cBryson C. The fluoride deception. New York: Seven Stories Press; 2006. [trade paperback edition]. p.xiv-xxx.dKrook LP, Justus C. Fluoride poisoning of horses from artificially fluoridated drinking water. Fluoride 2006;39:3-10. eConnett P. Waterborne fluoride and bone fractures [editorial]. Fluoride 2001;34:91-4.fDiesendorf M, Colquhoun J, Spittle BJ, Everingham DN, Clutterbuck FW. New evidence on fluoridation. Aust NZ J PublicHealth 1997;21:187-90.

gLindsay R. Fluoride and bone: quantity versus quality [editorial]. N Engl J Med 1990; 322:845-6. hSusheela AK, Bhatnagar M, Vig K, Mondal NK. Excess fluoride ingestion and thyroid hormone derangements in childrenliving in Delhi, India. Fluoride 2005;38:98-108.

iSchuld A. Fluoride effects on thyroid function. Fluoride 2003;36:72.jSchuld A. Is dental fluorosis caused by thyroid hormone disturbances? [editorial]. Fluoride 2005;38:91-4. kSusheela AK, Bhatnagar M, Vig K, Mondal NK. Excess fluoride ingestion and thyroid hormone derangements in childrenliving in Delhi, India. Fluoride 2005;38:98-108.

lBurgstahler AW. Fluoride and Down’s syndrome (Mongolism) [editorial review]. Fluoride 1975;8:1-11.mBurgstahler AW. Fluoridated water and Down’s syndrome [abstract]. Fluoride 1997;30:113.nTakahashi K. Fluoride-linked Down syndrome births and their estimated occurrence due to water fluoridation [review].Fluoride 1998;31:61-73.

oBurgstahler AW. Fluoride and Down syndrome: an update. Proceedings of the XXVIIth conference of the InternationalSociety for Fluoride Research; 2007 Oct 9-12; Beijing, PR China.

pMasters RD. A moratorium on silicofluoride usage will save $$millions [editorial]. Fluoride 2005;38:1-5. qCoplan MJ, Masters RD. Silicofluorides and fluoridation [editorial]. Fluoride 2001;34:161-4.

Other illnesses due to fluoride 25

dissolving it into a solution, so that lead ingested from the environment, such assoil contaminated by lead paint or from plumbing fittings containing lead, is morereadily absorbed.a In combination with water disinfection agents, such aschloramines and ammonia, silicofluorides cause a greater leaching of lead fromleaded-brass plumbing parts.b Another factor leading to a raised blood leadconcentration may involve increased fluoride exposure increasing the dietaryrequirement for calcium, and higher blood and tissue concentrations of leadoccurring when the diet is low in calcium.c A study by Jay Seavey suggested thatsodium fluoride was associated with violent crime independently of lead.d

Lowered intelligence has been reported in children from high fluoride areas,particularly when associated with iodine deficiency, and the toxic effects offluoride on the development of the brain are supported by animal studies.efghijkl

A rare form of skin cancer affecting the genital area in women, vulvarextramammary Paget’s disease (EMPD), has also been linked to fluoridatedwater.m Ms CH: Ms CH, age 67, first encountered fluoridated water when shemoved to a fluoridated community in Washington State, USA, in 1994. Within fiveyears she developed a small itchy area in the perineal area that was initiallydiagnosed as a fungal infection and later as a “chronic perianal and vulvardermatitis.” Treatment with antifungal and topical medication was ineffective andthe condition came and went for several years. In 2003 she had an ovarian cystremoved and a partial colectomy for the treatment of diverticulitis. One monthlater, the perineal rash doubled in size and became unbearably painful. In addition,she experienced other symptoms including dry skin, rashes on her arms and body,earaches, a build up of “a white wax-like substance in her tonsils (‘tonsil stones’),”dizzy spells, pain in her legs, and an allergy to latex (rubber). She was found tohave high blood pressure and blood tests showed high calcium and parathyroidhormone levels. A biopsy showed extramammary Paget’s disease and surgicalremoval of the affected skin was recommended. She had trained as a nurse andsuspected that she may be allergic to something. She tested various foods over a

aHirzy JW. Silicofluorides and blood-lead: a mechanistic investigation [abstract]. Fluoride 2005;38:231.bMass RP, Patch SC, Christian AM, Coplan MJ. Effects of fluoridation and disinfection agent combinations on lead leachingfrom leaded-brass parts. Neurotoxicology 2007;28:1023-31.

cDoull J, Boekelheide K, Farishian BG, Isaacson RL, Klotz JB, Kumar JV, Limeback H, Poole C, Puzas JE, Reed N-MR,Thiessen KM, Webster TF, Committee on Fluoride in Drinking Water, Board on Environmental Studies and Toxicology,Division on Earth and Life Studies, National Research Council of the National Academies. Fluoride in drinking water: ascientific review of EPA’s standards. Washington, DC: The National Academies Press; 2006. Available for purchase onlineat: http://www.nap.edu. p. 52.

dSeavey J. Water fluoridation and crime in America. Fluoride 2005;38:11-22.eLi XS, Zhi JL, Gao RO. Effect of fluoride exposure on intelligence in children. Fluoride 1995;28:189-92.fZhao LB, Liang GH, Zhang DN, Wu XR. Effect of a high fluoride water supply on children’s intelligence. Fluoride1996;29:190-2.

gGe YM, Ning HM, Feng CP, Wang HW, Yan XY, Wang SL, et al. Apotosis in brain cells of offspring rats exposed to highfluoride and low iodine. Fluoride 2006;39:173-8.

hTrivedi MH, Verma RJ, Chinoy NJ, Patel RS, Sathawara NG. Effect of high fluoride water on intelligence of school childrenin India. Fluoride 2007;40:178-83.

iXiang Q, Liang Y, Chen L, Wang C, Chen B, Chen X, et al. Effect of fluoride in drinking water on children’s intelligence.Fluoride 2003;36:84-94.

jXiang QY, Liang YX. Blood lead of children in Wamiao-Xinhuai intelligence study [letter]. Fluoride 2003;36:198-9.kBurgstahler AW. Influence of fluoride and lead on children’s IQ: U.S. tolerance standards in question [editorial]. Fluoride2003;36:79-81.

lSpittle B. Fluoride and intelligence [editorial]. Fluoride 2000;33:49-52.mConnett MP. Vulvar Paget’s disease: recovery without surgery following change to very low-fluoride spring and well water.Fluoride 2007;40:96-100.


26

six month period but found no relationship between any foods and the pain.Because she had not had any problem previously when living in nonfluoridatedWichita, Kansas, she decided to test whether fluoride in water affected hercondition. Within three days of using spring water for drinking and cooking, shenoticed an “immediate” improvement in her symptoms. She then continued with asix week trial of spring water followed by the long term use of low fluoride (<0.1ppm [mg/L] of fluoride). She noted:

“I stopped using the tap water for drinking and bathing and the Paget’s started clearing upimmediately. I now use well water from my son’s house and go there to bathe. I was free ofsymptoms within weeks—except the tonsil stones. It took about a year for those tocompletely go away.”

The blood pressure, calcium level, and parathyroid hormone level returned tonormal and her vulvar Paget’s cleared up completely. Apart from one briefrecurrence, when she used fluoridated water again, it has remained settled. Shesaid:

“In 2005 I had house guests and we were on the go a lot. I didn’t want to go to my kids’house to bathe so I showered at home. We ate out a lot at local restaurants that use thelocal tap water. I started itching and turning red in the same area. The symptoms cleared upin 2–3 days after I stopped [using the tap water].”

Since the improvement occurred when the change was made from usingfluoridated drinking water to low fluoride spring or well water it was consideredthat fluoride, or possibly some other component of drinking water such aschlorinated disinfection by-products, contributed to her skin disease.

Impaired glucose tolerance in humans has been found with fluoride intakes of0.07–0.4 mg/kg/day thus putting infants, children aged 1–2 years, athletes andheavy manual workers, and patients with diabetes mellitus and nephrogenicdiabetes insipidus at risk with fluoridated water with 1 mg F/L.a

WHAT TO DO IN THE FACE OF SKEPTICISM ABOUT THE VALIDITY OF THE EXISTENCE OF A CHRONIC FLUORIDE TOXICITY SYNDROME FROM

FLUORIDATED DRINKING WATER

The examples used to illustrate the occurrence in some people, perhaps 1–5% ofthe population, of a chronic fluoride toxicity syndrome from using fluoridatedwater will not be convincing to many, particularly numerous health professionalsincluding dentists and doctors. Health professionals tend to have the views taughtto them by their teachers, and their teachers, in turn, are influenced by what theysee as the views of the various authorities at the time. These things change veryslowly over decades. It has been said that “Science progresses, funeral by funeral.”The Russian novelist Leo Tolstoy identified the problem when he wrote

“I know that most men, including those at ease with problems of the greatest complexity, canseldom accept even the simplest and most obvious truth if it be such as would oblige themto admit the falsity of conclusions which they have delighted in explaining to colleagues,which they have proudly taught to others, and which they have woven, thread by thread, intothe fabric of their lives.”

aDoull J, Boekelheide K, Farishian BG, Isaacson RL, Klotz JB, Kumar JV, Limeback H, Poole C, Puzas JE, Reed N-MR,Thiessen KM, Webster TF, Committee on Fluoride in Drinking Water, Board on Environmental Studies and Toxicology,Division on Earth and Life Studies, National Research Council of the National Academies. Fluoride in drinking water: ascientific review of EPA’s standards. Washington, DC: The National Academies Press; 2006. Available for purchase onlineat: http://www.nap.edu. p. 65, 256-67.

Other illnesses due to fluoride 27

For this slowness to see the light, I have coined the term "tardive photopsia."a

Thus those with symptoms consistent with chronic fluoride toxicity have nothingto lose from having a trial of avoiding fluoride for a few weeks, to see if it resultsin improved health, and have the possibility of much to gain.ILLUSTRATIONS OF SOME OF THE ABNORMALITIES UNDERLYING THE SYMPTOMS IN

CHRONIC FLUORIDE TOXICITY

Skeletal muscle, in the arms andlegs, has actin and myosin filamentsarranged regularly to give a striped orstriated pattern on microscopicexamination (Figure 14). Withchronic fluoride toxicity the regulararrangement is disrupted by areas ofdegeneration (Figures 15–16). Thepatient with this degenerationexperiences muscle weakness.b

Photograph by AK SusheelaFigure 14. Transmission electron micrograph showing actin and myosin filaments forming the structural framework of a skeletal muscle fibre.

aSpittle B. Fluoridation promotion by scientists in 2006: an example of “tardive photopsia” [editorial]. Fluoride 2006;39:157-62.

bSusheela AK. A treatise on fluorosis. 2nd ed. Delhi, India: Fluorosis Research and Rural Development Foundation; 2003.p. 59-61.

Photograph by AK SusheelaFigure 15. Skeletal muscle from a fluorosed human subject showing widespread degenerative changes of actin and myosin filaments.

Photograph by AK SusheelaFigure 16. Skeletal muscle from a fluorosed human subject showing widespread degenerative changes of actin and myosin filaments.


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The intestinal lining or mucosa of the duodenal region normally has cells withsmall protrusions on them (microvilli) and a layer of slimy substance (mucus,Figure 14). The microvilli and mucus are lost with chronic fluoride toxicity givingrise to symptoms such as nausea, loss of appetite, pain in the stomach, gasformation and a bloated feeling, constipation followed by intermittent diarrhoea,and headache (Figures 15–16).a These symptoms of non-ulcer dyspepsia are earlywarning signs of fluoride toxicity.

aSusheela AK. A treatise on fluorosis. 2nd ed. Delhi, India: Fluorosis Research and Rural Development Foundation; 2003.p. 66-8.

Figure17 Figure 18

Figure 19

Photograph by AK SusheelaFigure 17. Scanning electron micrograph of the intestinal mucosa of the duodenal region showing the normal mucosal surface with columnar cells packed with microvilli and mucus droplets.

Photograph by AK Susheela

Photograph by AK SusheelaFigure 18. Scanning electron micrograph of the intestinal mucosa of the duodenal region showing the columnar cells with scanty microvilli and a loss of mucus droplets from a person consuming drinking water with 1.2 mg/L or ppm of fluoride.

Photograph by AK SusheelaFigure 19. Scanning electron micrograph of the intestinal mucosa of the duodenal region showing the columnar cells with a loss of microvilli and mucus droplets, and a “cracked clay appearance of the mucosa” from a person consuming drinking water with 3.2 mg/L or ppm of fluoride.

microvillimucus droplets

Illustrations of some of the abnormalities underlying the symptoms of chronic fluoride toxicity 29

Male infertility with abnormalities in sperm morphology (Figures 20–23), adeficiency in the number of spermatozoa in the semen (oligospermia), the absenceof spermatozoa from the semen (azoospermia), and low testosterone levels arevery common in those residing in areas of India where chronic fluoride toxicity iscommon due to fluoride-contaminated water.a Some individual variation in thesusceptibility to developing infertility is present.

The capacity of fluoride to induce new bone formation in areas of the bodywhere it does not normally occur such as in the forearm interosseous membrane isillustrated by the condition of periostitis deformans, described by Dr Soriano,bc

due to the habitual drinking of wine that was illegally contaminated by fluoride. It

aSusheela AK. A treatise on fluorosis. 2nd ed. Delhi, India: Fluorosis Research and Rural Development Foundation; 2003.p. 69-71.

bSoriano M. Periostitis deformans due to wine fluorosis. Fluoride 1968;1:56-64.cSoriano M, Manchón F. Radiological aspects of a new type of bone fluorosis, periostitis deformans. Radiology1966;87:1089-94.

Photograph by AK SusheelaFigure 20. Scanning electron micrograph of normal human sperm.

Photograph by AK SusheelaFigure 21. Scanning electron micrograph of abnormal double-headed human sperm from an infertile male consuming fluoride-contaminated water.

Photograph by AK SusheelaFigure 23. Scanning electron micrograph of abnormal human sperm with an abnormal head and midpiece from an infertile male consuming fluoride-contaminated water.

Photograph by AK SusheelaFigure 22. Scanning electron micrograph of abnormal human sperm with multiple and coiled tails from an infertile male consuming fluoride-contaminated water.


30

is a rare condition and the extra bone formation was much greater in Dr Soriano’spatients than that usually seen in fluoride toxicity (Figure 24).abc This may havebeen due to the higher levels of fluoride in the contaminated wine, 8–72 mg/L orppm, and the presence of poor nutrition with a lack of protection from adequateamounts of calcium and antioxidants in persons with alcohol dependence. Withpoor nutrition there is a lack of the dietary factors that give protection againstfluoride toxicity. Other factors such as alcohol and impaired liver function mayalso have contributed to the excessive bone formation in areas where bone doesnot usually occur such as in membranes and tendons (fibrosititis ossificans), andmuscles (myositis ossificans, Figures 25–31). The initial change in the bones of anincreased bone density (osteosclerosis) can be followed by a later stage of reducedbone density (osteoporosis) and bone atrophy. Bones affected by fluoride areweaker and fracture more readily (Figure 32).

aKhandare AL, Rao GS, Balakrishna N. Dual energy X-ray absorptiometry (DXA) study of endemic skeletal fluorosis in avillage of Nalgonda District, Andhra Pradesh, India. Fluoride 2007;40:190-7.

bSoriano M. Periostitis deformans due to wine fluorosis. Fluoride 1968;1:56-64.cWaldbott GL. New observations on fluorosis [editorial]. Fluoride 1968;1:54-5.

24A 24B

Interosseous membrane calcification

Figure 24. Forearm radiographs. 24A: 51-year-old with normal forearm. 24B: 54-year-old with calcification of the interosseous membrane due to fluoride toxicity. (Khandare, Rao, Balakrishna, 2007).

Figure 25. Forearms with swellings simulating bone tumours due to periosteal stimulation due to fluoride toxicity in a patient in Spain who had been drinking wine to which fluoride had been added to retard fluoridation resulting in fluoride levels of 8–72 mg/L (8–72 ppm). The condition is called periostitis deformans. (Soriano, 1968).

Figure 26. Periosteal growth in the forearm (pseudotumours) involving the interosseous membrane (invading osteophytosis). The osseous lamellae with irregular margins at the interosseous membrane of the forearm are typical of wine fluorosis. (Soriano, 1968).

Illustrations of some of the abnormalities underlying the symptoms of chronic fluoride toxicity 31

Proximal (elbow) end of forearm

Distal (wrist) end of forearm

Figure 27. Radiograph of a forearm showing the initial, osteoblastic stage, of periosteal growth with the formation of new bone (calcification). Usually growth occurs in this condition, found in Spanish drinkers of wine adulterated with fluoride, for 3–5 months and the growths, on the forearms and thighs, can be as large as an apple. (Soriano, 1968).

Distal (wrist) end of forearm

Proximal (elbow) end of forearm

Figure 28. Radiograph of a same forearm as in Figure 24, one year later. After 3–5 months of growth, the lesions cease growing and their size decreases (atrophic stage). The osteophytes have a lamellar appearance on the radiographs. (Soriano, 1968).

Figure 29. Advanced periostealgrowth in the forearm in theosteoclastic phase of periostitisdeformans in another patient.After the lesions have grown for3–5 months bone resorptionoccurs (osteoclastic phase) andthe size of the lesions decreases(atrophic stage). Periostitisdeformans differs from the typicalpicture in skeletal fluorosis inwhich calcification of theinterosseous membrane of theforearm may occur but not thelarge growths. (Soriano, 1968).

Figure 30. Bone formation) in muscleof the thigh (myositis ossificans, on left)with marked osteosclerosis (increasedbone density) of the femur (on right).(Soriano, 1968).


32

AN EXAMPLE OF THE OPPOSITION TO THE CONCEPT OF A CHRONIC FLUORIDE TOXICITY SYNDROME FROM FLUORIDATED WATER

The concept of chronic low-grade poisoning by fluoride was examined in NewZealand by a Commission appointed by Command of His Excellency, theGovernor-General CWM Norrie on 6 November 1956. Wilfred Stilwell, Esquire,Judge of the Arbitration Court, chairman; Norman Edson, Esquire, Professor ofBiochemistry, member; and Percy Stainton, Esquire, Merchant, member, presentedtheir report, Report of the Commission of Inquiry on the Fluoridation of PublicWater Supplies, on 10 July 1957, to the House of Representatives.a

In paragraph 307 they noted: “We have listed in paragraph 232 (10) a number of complaints which in themselvesare of a minor nature. They included mental and physical inertia, loss of feeling in thefingers, loss of the use of limbs, the dropping of small objects, cramps in theextremities, dry mouth, thirst, nausea, and various skin troubles. It was argued thatthese minor complaints were the outward expression of chronic fluoride intoxicationat a low level of intake. It was said that some persons are more sensitive or allergic tofluoride than others, and on this account some members of the community will exhibitsigns and symptoms of low-grade poisoning while others will not. In medical literaturea group of signs and symptoms, which are said collectively to represent the effect ofa single morbid cause, constitutes a “syndrome.” We use this term to cover the signs

aStilwell WF, Edson NL, Stainton PVE. Report of the commission of inquiry on the fluoridation of public water supplies.Wellington: RE Owen, Government Printer; 1957.

Figure 31. Bone formation in muscle ofnear the knee (myositis ossificans) in“Wine fluorosis. (Soriano, 1968).

Figure 32. Endosteal lesions of the femur.Fracture in an osteoporotic (reduced bonedensity) zone of the striated compact bone;atrophy (wasting) of the femoral head; andosteosclerosis of the pelvis. (Soriano, 1968).

An example of the opposition to the concept of a chronic fluoride toxicity syndromefrom fluoridated water

33

and symptoms collectively, although it should be emphasized that any one personmay not exhibit all these manifestations or all simultaneously.”

It was noted that Dr Leo Spira and Dr George Waldbott were the most prominentof the medically qualified persons who had vigorously opposed fluoridation in theUnited States, and their views were considered in detail in 10 pages of text.

In paragraph 336 the case of Mrs MJ is referred to, who as discussed earlier,spent the first five years of her life near Hanchow, China, and became ill after theHighland Park water was fluoridated.

“336. As we have stated, Dr Waldbott also believes in the existence of a syndromecomprised of minor ailments which he regards as the manifestations of incipientfluorine poisoning. He states:

“‘No information on the incipient stage of this disease which would make it possible toestablish an early diagnosis can be found it the literature.’ (Waldbott, 1956.a)

“He states also that a case [Mrs MJ] which he described presented:

“‘presumptive evidence of incipient chronic fluorine poisoning from drinking water at 1part per million. …’”

The commission recorded Dr Waldbott’s views:“337. In reviewing his observations Dr Waldbott states;

“‘One is impressed by the sparsity of objective findings, by the absence of changes injoints, bones, and teeth, and by the great variety of symptoms. Nevertheless, oncarefully examining the case reports, a clear-cut disease pattern can be discerned.“…The most characteristic manifestations are backache, numbness, and pain in thelegs and arms, especially in the ulnar area, gastro-intestinal and bladderdisturbances as well as ulcers in the mouth and visual disturbances. Most impressiveare extreme malaise and mental sluggishness. Two unusual phenomena mayperhaps be considered pathognomic as they probably occur in no other disease; themore water the patient drinks the more he complains of dryness in the mouth andthroat (this is in distinction to acute poisoning in which excessive salivation is a majorsymptom). Exhaustion is most pronounced when the patient should feel most rested,namely in the morning after resting at night. Arthritis, headaches, and seborrhoeicdermatitis may or may not be a feature of this disease.’

“Elsewhere he mentions brittle and breakable nails, gastritis, and irritation of mucousmembranes in the alimentary and lower urinary tract.”

The Commission considered that the grounds on which Dr Waldbott dismissedthe syndrome as being psychosomatic in nature as being inadequate:

“338. It will be seen that Dr Waldbott’s description of the syndrome is almost identicalwith that of Dr Spira, but he appears to be more cautious. “So far,” he has said, “theevidence that this is fluorine poisoning is presumptive,” and he states the facts onwhich the presumptive conclusion is based. He discusses the possibility of apsychosomatic basis (the influence of the mind and emotions on bodily health) for thesyndrome and dismisses the possibility but on grounds which appear to be quiteinsufficient. Finally Dr Waldbott says:

“‘The evidence presented so far is lacking final substantiation by determination offluorine in urine, blood, and in bones and other organs. Such studies are now inprogress.’”

aWaldbott GL. Incipient chronic fluoride intoxication from drinking water. II. Distinction between allergic reactions and drugintolerance. Int Arch Allergy Appl Immunol 1956;9(5):241-9.


34

Dr Waldbott addressed the question of a psychosomatic basis for the syndromein his 1956 papera which was given by the Commission as a reference inparagraph 336. In this paper Dr Waldbott wrote;

“Is there a psychosomatic basis?

“In order to rule out other diseases, adequate consultation by competent specialistswas obtained in the hospitalized cases. They were unable to establish a diagnosis,but did not attribute the illness to psychosomatic causes.

“This view is supported by the following facts: In two individuals subjected toexploratory surgery (prostatectomy and exploratory laparotomy, respectively), theoperation did not relieve the urinary symptoms or the abdominal pains.1 (1 A thirdcase in Lubbock, Texas with natural fluorides at 4.2 ppm, with advanced skeletalfluorosis, the record of which I was able to study (Methodist Hosp. Record No.177822) had a laparotomy which did not reveal the cause of an acute abdomen.) Anoperation would certainly have produced a sufficient stimulus to reveal apsychosomatic basis. Months later these patients recovered completely without anytreatment when fluoride water was eliminated without their knowledge. Other patientswere neither aware that fluorides had been added to the drinking water or thatfluoridation had been discontinued. This, I believe, is a more valid test than anycarefully devised “blindfold” or placebo studies.

“It is inconceivable that these patients could have been familiar with the descriptionof this disease. Although residing in different parts of the country, they reportedexactly the same symptoms in different words. For instance, the ulnar nerve damageis described in the following manner by a different person in each case: ‘cannot grip agolf club,’ ‘cannot peel potatoes,’ ‘cannot hold a hymn book in church,’ ‘cannot gripmy steering wheel,’ ‘things are dropping from my grasp for no apparent reason.’

“The lack of control in their legs was described as follows: ‘my legs buckle under me,’‘I suddenly collapse,’ ‘my legs are not tracking,’ ‘my legs give way,’ ‘I suddenly lurchtowards buildings.’ Thus, it is clear that this syndrome cannot be explained on apsychosomatic basis.”

The Commission did not explain why they found the grounds given by DrWaldbott for dismissing a psychosomatic cause to be inadequate. It is hard to seehow Mrs MH and Mrs EK who became ill in Windsor, Ontario, Canada, after thewater was fluoridated had a psychosomatic illness when they were not aware thatfluoridation had started when they became ill.

The Commission noted Dr Waldbott’s summary and view in paragraph 339. “339. Basing his data on fifty-two cases, Dr Waldbott (1956) summarises the signsand symptoms described in paragraph 337 and goes on to state:

“‘The evidence so far is based on: The identity of the symptoms observed with thosedescribed: (a) in my first reported case from artificially fluoridated water; (b) inindustrial poisoning in men; (c) in fluorosis encountered in natural fluoride areas; (d)in animals grazing near plants emanating fluorides. Whereas there is an appreciabledeterioration of general health, laboratory and objective findings are sparse at thisstage of the disease. The cardinal features associated with advanced fluorosis,namely, changes in bones, ligaments, joints, and teeth, were not noted in its incipientstage.

aWaldbott GL. Incipient chronic fluoride intoxication from drinking water. II. Distinction between allergic reactions and drugintolerance. Int Arch Allergy Appl Immunol 1956;9(5):241-9.


35

“Further corroborating studies now in progress, indicate that a variety of diseases ofheretofore unknown origin, may be due to, or at least aggravated by, traces offluorine in air, food, and water.’”

In paragraphs 340–3 the Commission summarized and evaluated Dr Waldbott’sclaims.

“340. The evidence for the syndrome as outlined by Dr Waldbott consists of:

“(1) Identity of the symptoms with those described in the first case (Waldbott, 1955b a[Mrs MJ]); and

“(2) Analogies with industrial poisoning, fluorosis due to excessive ingestion of high-fluoride water, and fluorosis in animals grazing near industrial plant from which thehazard emanates.

“We have been informed by Mr Penlington by letter dated 17 June 1957 that DrWaldbott is to publish a series of five articles, the first of which has already appeared(Waldbott, 1956). The first of this series is referred to in paragraph 339 and showsthat Dr Waldbott has not changed the basis for his theories. This basis we nowproceed to examine.

“341. There is no evidence that the symptoms exhibited by Dr Waldbott’s first casewere in fact due to either the 1 ppm of fluoride present in the water consumed or toany other fluoride ingested, and there is no rational basis for concluding that theexistence of analogies is proof that the syndrome is due to fluoride. Dr Waldbott hasintroduced a doubtful note at the conclusion of his summary where he states that

“‘a variety of diseases of heretofor unknown origin, may be due to, or at leastaggravated by, traces of fluoride in air, food, and water.’

“(The italics are ours.) These statements suggest that he is aware of the fact that hepossesses no scientific evidence to demonstrate that the syndrome is caused byfluoride.

“342. In the absence of evidence to demonstrate that the conditions described aredue to fluoride poisoning, both Dr Waldbott and Dr Spira have used ‘therapeutic tests’to support their arguments. In these tests fluoridated water has been withdrawn andlow-fluorine diets have been prescribed. Both physicians have claimeddisappearance of symptoms after these and other precautions were taken. In nocase was the urinary fluoride determined in relation to the test. These arguments areunconvincing and fail to persuade us that the effects described were due to thewithdrawal of fluoride, real or presumptive.”

In paragraph 345 the Commission stated its conclusions: “345. At this point we summarise our conclusions on the “Spira-Waldbott Syndrome”as follows:

“(1) We are of the opinion that the individual signs and symptoms of the allegedsyndrome may be due to any number of unrecognised causes; and

“(2) We are satisfied that there is no causal relationship between any of these signsand symptoms and the ingestion of water containing 1 ppm of fluoride and foodcooked in this water.”

The Commission states in paragraph 341 that there was no evidence to show thatthe symptoms present in the patient, Mrs MJ, were due to the 1 ppm of fluoride inthe water consumed. However Dr Waldbott showed that she recovered withinweeks from a serious illness when she stopped using the Highland Park water

aWaldbott GL. Chronic fluorine intoxication from drinking water. Int Arch Allergy 1955;7:70-4.


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containing 1 ppm of fluoride with no other treatment. The nausea, vomiting, andabdominal pain cleared up within a week. She gained five pounds in weight in fourweeks. When she was placed again on Highland Park fluoridated water, on 1November 1954, she became ill again within three days with general weakness,exhaustion, and lethargy; cramping of the hands and legs day and night; andtingling and numbness in the fourth and fifth fingers as high as the elbow, but withno objective findings on examination.

It is not clear how the Commission can describe as being “no evidence” thealleviation of illness after withdrawing water containing 1 ppm of fluoride and therelapse of illness with the reintroduction of this water. If they were implying thatsome other component of the water other than the fluoride was responsible theyhave given no evidence of what this is.

Dr Waldbott gave more detail about Mrs MJ in Fluoridation: the great dilemmawhere he noted:a

“Until completion of the preliminary tests in the hospital, the patient [Mrs MJ] wasinstructed to use fluoridated Highland Park water that she had brought with her to thehospital. After the tests were completed, she began drinking unfluoridated (0.1 ppm)Detroit water. Within only two days the stomach symptoms and headaches subsided,and she was soon well enough to be discharged.

“Neither in the hospital nor after her discharge was she given any medication.Instead, she was instructed to avoid fluoridated water strictly, not only for drinking butalso for cooking her food as well. She was also told to avoid both tea and seafoodbecause of their high fluoride content. The headaches, eye disturbances, andmuscular weakness disappeared in a most dramatic manner. After about two weeksher mind began to clear, and she underwent a complete change in personality. Forthe first time in two years she was able to undertake her household duties withouthaving to stop and rest. Within a four-week period she had gained five pounds.

“Subsequently, the patient was subjected to a series of tests which definitely provedthat her disease was related to fluoridated water. She was given test injections ofminute amounts of fluoride in drinking water and distilled water as a control. She wasnot aware which water contained fluoride. The fluoride solutions induced arecurrence of the symptoms, whereas the fluoride-free water showed no adverseeffects. In one of the subsequent tests a classical attack of migraine headache wasproduced by one milligram of fluoride taken in two glasses of water. This is about onefifth to one half the average amount ingested in one day by people living in afluoridated area.

“Further laboratory and other diagnostic studies were contemplated, especially astudy of the behavior of calcium, phosphorus, and magnesium, the activity of certainenzymes, and a tracing of her brain waves before and after administration of a testdose of fluoride. These plans came to an abrupt end when the patient sufferedanother sudden episode of excruciating pains in the head, muscles and spinefollowing an experimental dose of fluoride. The severity of her response to this so-called blind test made me stop all further testing. Fortunately, the patient recoveredcompletely without any treatment other than the elimination of Highland Parkfluoridated water for drinking and cooking.”

Dr Waldbott also addressed the question about whether something else in thewater other than fluoride might have caused her illness:

aWaldbott GL, Burgstahler AW, McKinney HL. Fluoridation: the great dilemma. Lawrence, Kansas: Coronado Press; 1978.p. 117-8.


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“Could something other than fluoride have caused the disease, perhaps anotherpoison in the water? This question was definitely answered by the ease with whichthis disease could be reproduced at will when extremely small amounts of fluoridewere administered to her. In order to ascertain the cause of her problem she wasgiven a test dose of fluoride in water without being told the nature of the test. Shehad, of course, given me permission to carry out any test I saw fit.”

Thus the Commission was incorrect to say in paragraph 341 that there was noevidence the symptoms in Dr Waldbott’s first case were due to fluoride. DrWaldbott had collected the evidence that fluoride was involved by eliciting thesymptom of headache after giving her a test dose of 1 mg of fluoride in two glassesof water. This detail, of giving 1 mg of fluoride in two glasses of water, waspublished by Dr Waldbott in Fluoridation: the great dilemma in 1978 and was notmentioned in the 1956 paper referred to by the Commission. However the 1956paper noted:

“This condition cleared up completely following elimination of fluoridated water at the1 P.P.M. concentration and recurred following its resumption.”

If the Commission wanted to “split hairs” and imply that some other componentof the water apart from fluoride was involved they could have asked Dr Waldbottif there was additional information available or given him the chance to commenton their conclusion before the Commission’s report was presented.

In paragraph 242 the Commission stated that it found the arguments based on“therapeutic test” where fluoridated water has been withdrawn and low-fluorinediets have been prescribed to be unconvincing and failing to persuade themwithout spelling out their reasons for so concluding. It noted that in no case had theactual fluoride intake been measured and that in only one case [Mrs MJ] was theurinary fluoride excretion determined in relation to the test.

They appear to be implying that the fluoridated water in places like HighlandPark and Caduhy in Wisconsin, USA, or in Windsor, Ontario, Canada, wherepeople became sick consuming the water may not have in fact contained the 1 ppmof fluoride that the water was claimed to have. Water engineers routinely monitorfluoridated water to check that the level of fluoride is at the intended level. DrWaldbott and Dr Petraborg have accepted the situation that the fluoridated water inthe places studied did in fact have the levels of fluoride of about 1 ppm. To dismissthe results of the “therapeutic tests” because documentation was not given to showthat water fluoridated by a water department to a level of 1 ppm did in fact have 1ppm of fluoride in it appears to be pedantic and likely to result in a type II error,the situation of “missing a winner,” where a significant result is overlooked.

Although the Commission saw monitoring the urine fluoride levels to beimportant they did not show why this information was critical to acceptance or notof the results of the “therapeutic tests.” Dr Waldbott noted:a

“The evidence presented so far is lacking final substantiation by determination of fluorine inurine, blood, and in bones and other organs. Such studies are now in progress.

aWaldbott GL. Incipient fluorine intoxication from drinking water. Acta Medica Scandinavica 1956;CLVI:157-68.


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“Symptoms of fluorine poisoning do not always parallel either fluorine levels in bones andblood, nor its elimination in the urine. It is general knowledge that relatively large amountsmay be stored and eliminated without ill effect. Seven years in one instance, and even tenyears after patients had stopped drinking fluoride-water, stored fluorine is still excreted inexcess amounts. On the other hand, there is evidence that relatively small doses can causesymptoms of poisoning in individuals or animals susceptible to the disease. The well-knownauthority on the subject, DeEdsa observed that the ‘streaming through the system offluorides, even in relatively small amounts, may cause considerable damage to the organsinvolved.’

“Urinary fluorine output depends mainly on the amount of stored fluoride mobilized from thebones under conditions not yet explained, and on the amount of fluoride ingested in food,especially tea and fish. The absorption of ingested fluoride into the blood stream from theintestinal tract varies with the presence of other minerals in the water, with the compound offluoride and the acidity of the stomach.”

Two of the case reports above by Dr Susheela, published in 2001, involving a10-year-old boy, Master PM, and a 59-year-old man, Mr PO, showed that theurinary and serum (blood) fluoride levels fell as the “therapeutic test” proceeded.b

However the availability of this additional information, from Dr Waldbott in1978 about Mrs MJ becoming ill when given 1 mg of fluoride in two glasses ofwaterc or of the urinary and serum fluoride falling during a ‘therapeutic test” fromDr Susheela in 2001, has not altered the stance taken by the Ministry of Health inNew Zealand on fluoridation.

The Ministry of Health has been reluctant to participate in meetings whereresearch on fluoride toxicity has been discussed. Although one person from theMinistry, Julia Purchas, attended and reported back on the 25th conference of theInternational Society for Fluoride Research held in Dunedin in 2003, norepresentatives from the Ministry were present at the 22nd conference inBellingham, Washington State, USA, in 1998; the 23rd conference in Szczecin,Poland in 2000; the 24th conference in Otsu, Shiga, Japan, in 2001; the 26thconference in Wiesbaden, Germany, in 2005; or the 27th conference in Beijing,China, in 2007. When Yvonne McDonald wrote to The Hon. Pete Hodgson,Minister of Health, to ask if a Member of Parliament would be attending the 26thconference at Wiesbaden, Germany, 26–29 September 2005, he replied, in a letterdated 18 May 2005,d that

“The International Society for Fluoride Research is not a reputable body so theGovernment will not be sending a representative …”

In a letter to Mr Hone Harawira, Member of Parliament, Te Tai Tokerau,Parliament Buildings, dated 19 July 2006, The Hon. Pete Hodgson, Minister ofHealth replied to a letter from Mr Harawira:e

“Tena koe Mr Harawira

aLargent EJ. Rates of elimination of fluoride stored in the tissues of man. A M A Arch Ind Hyg Occup Med 1952;6(1):37-42.bSusheela AK. A treatise on fluorosis. Delhi, India: Fluorosis Research and Rural Development Foundation; 2001. p. 100.cWaldbott GL, Burgstahler AW, McKinney HL. Fluoridation: the great dilemma. Lawrence, Kansas: Coronado Press; 1978.p.115-8.

dHodgson P. Letter to Yvonne McDonald. 2005 May 18. Unpublished.eHodgson P. Letter to Hone Harawira. 2006 Jul 6. Unpublished.


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“Thank you for your letter of 15 May 2006, with enclosed email from Mr Bill Wilson, aboutfluoridation. I apologise for the long delay in responding.

“Like other natural occurring trace elements, fluoride is essential for good health. There aremany essential nutrients, elements and vitamins which taken in excess, are toxic. Theimportant point is dosage of each element or nutrient, not the element itself. In areas in NewZealand where drinking water is fluoridated, the concentration of fluoride generally rangesfrom 0.7 to 1.0 mg/litre (or one part per million).

“The Ministry of Health holds routinely collected data on the oral health status of children atage five and year eight, from 1990 onwards. The data consistently shows that children innon-fluoridated areas have poorer oral health than children in fluoridated areas. This data isavailable on the Ministry’s website as part of the ‘Oral Health Toolkit’(www.newhealth.govt.nz/toolkits-old/oralhealth.htm).

“I have communicated in previous correspondence to Mr Wilson that I am aware of MrConnett’s infamous report 50 Reasons to Oppose Fluoridation. I am also familiar with theviews of the late John Colquhoun [Figure 52]. Ministry of Health officials recently viewed aninterview with the late Mr Colquhoun, made in 1998. The interview was conducted byProfessor Paul Connett [Figure 62] and was enclosed in Mr Wilson’s most recentcorrespondence to me concerning fluoridation.

“The views of both Professor Connett and Mr Colquhoun are regarded as highlyunconventional. Nevertheless, Ministry officials commissioned an independent review ofProfessor Connett’s report in order to be satisfied that the weight of literature supportingfluoridation remained valid.

“Independent scientists have also considered Professor Connett’s views against recentreviews by the Australian National Health Medical Research Council (1999), the York report(2000) and the World Health Organization. The conclusion of the Ministry’s review and ofthese independent reports is uniform. Evidence does not support suggestions of health risksassociated with water fluoridation.

“The benefits of water fluoridation are most pronounced for those most at risk of poor oralhealth, including the poorer areas of your consistency. The Ministry continues to believe thatwater fluoridation is effective as a means of reducing current inequalities in oral health. Todeny areas of need of an effective oral health measure would be unfortunate.

“The decision whether or not to fluoridate a region’s water supply is not made by the Ministrybut the responsible district council. Therefore, if you require further details of fluoridation inthe Far North, I suggest contracting Northland District Council directly. The contact detailsare:

“Far North District Council, Memorial Avenue, Private Bag 752, Kaikohe; Freephone: 0800920029.

“The council should also be able to provide you with information on how data sampling wascarried out in the decision to fluoridate the Far North’s water supply.

“The Government and the Ministry believe that there is overwhelming evidence of theeffectiveness and safety of water fluoridation in improving the dental health of NewZealanders. Additional information on the Ministry of Health position on water fluoridation isavailable on the Ministry’ website (www.moh.govt.nz/fluoride).

“I trust this information is useful in replying to Mr Wilson.

“Naku noa, na

“Hon Pete Hodgson

“Minister of Health”

The Hon Pete Hodgson, Minister of Health, subsequently visited Oamaru, NorthOtago, New Zealand, on 21 September 2007, shortly before a referendum on


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fluoridation was held. It was reported that he said that it would be “a sad outcome”if the Waitaki District voted against fluoridation and that he considered thebenefits of fluoridation far exceeded any perceived risks. He urged voters to makesure they were fully informed about the issues based on sound scientific evidencerather than being swayed by what he termed “scam science off the Internet.”a

Evidence based decision making is laudable but not easy to achieve. Many of thepoints made by The Hon. Pete Hodgson in his letter to Mr Harawira arecontestable. Dr AK Susheela, Director of the Fluorosis Research and RuralDevelopment Foundation, Delhi, India, also appealed to science stating:b

“The ‘take home’ message for the professionals of India is that they should … practise therecent scientific developments in the field of Fluoride and Fluorosis …”

However she had the opposite message:“The ‘take home’ message for the professionals of India is that they should not follow thepractices of the ‘West’ but should practise the recent scientific developments in the field ofFluoride and Fluorosis, which have led to the concept that fluoride should not enter the bodyas far as possible. Trace amounts entering through sources which are beyond any one’scontrol need to be overlooked. Promoting fluoridation of dental products in India should beconsidered as a ‘crime.’”

She included New Zealand on her world map showing areas where there iswidespread chronic fluoride toxicity. She considers that dental caries are not afluoride deficiency disorder and that topical fluoride as contained in toothpaste ormouthwashes does not have the potential to remineralise or rectify the damage tothe teeth due to caries.

The Hon. Pete Hodgson, Minister of Health, noted how the World HealthOrganization supported fluoridation. Waldbott, Burgstahler, and McKinney noted:

“On July 23, 1969, fluoridation was brought up again at the 22nd World Health OrganizationAssembly in Boston. The resolution recommending the measure appeared on the agendadaily but was strongly opposed and blocked by delegates from Italy, Senegal, the Congo,and elsewhere. G. Penso, head of the Italian delegation, expressed his concern regarding‘this mania of our century to add additives to anything.’ He pointed out that there areunknown amounts of fluoride in the air we breathe and in the food we eat. He cautionedparticularly about possible damage to future generations. Nevertheless, during the finalhours of the session, when only 55 to 60 of the 1,000 delegates from 131 countries were stillpresent, all bills that had not been accepted were collected into one and voted upon,including a statement on fluoridation. The mildly-worded resolution urged that memberstates examine the possibility of introducing fluoridation in those communities where fluorideintake from water and other sources ‘is below the optimal levels.’ It also requested theDirector General ‘to continue to encourage research into the etiology of dental caries, thefluoride content of diets, the mechanism of action of fluoride at optimal levels in drinkingwater, and into the effects of greatly excessive intake of fluoride from natural sources, and toreport thereon to the World Health Assembly …”c

A study published in 2007, by Oxman, Lavis, and Fretheim, found thatsystematic reviews and concise summaries of findings were rarely used for

aBruce D. Minister sees need for fluoridation. Otago Daily Times. 2007 Sept 22;21.bSusheela AK. A treatise on fluorosis. 3rd ed. Delhi, India: Fluorosis Research and Rural Development Foundation; 2007.p. 17-8.

cWaldbott GL, Burgstahler AW, McKinney HL. Fluoridation: the great dilemma. Lawrence, Kansas: Coronado Press; 1978.p.283-5.


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developing WHO recommendations.a Instead the processes usually relied heavilyon experts in a particular speciality, rather than representatives of those who haveto live with the recommendations, or on experts in particular methodologicalareas. WHO officials admitted that most recommendations and guidelines wereprepared by the special interest groups without external review. WHOrecommendations are thus nothing but special pleading like the promotion offluoridation by groups such as the US Centers for Disease Control, US PublicHealth Service, and the American Dental Association. The unsuitability of theWHO guideline of 1.5 mg/L of fluoride as the “desirable” upper limit in drinkingwater is being increasing felt and Senegal has reduced the permissible upper limitto 0.6 mg/L.b The 2006 World Health Organization publication, Fluoride indrinking water, makes no reference to the 2006 NRC report on the same topic, hasonly 20 references in chapter 3 on “Human health effects,” and does not includeany of the publications by Dr Waldbott.c

The Hon. Pete Hodgson, Minister of Health, noted that Ministry of Healthofficials had commissioned an independent review of Professor Connett’s reporton 50 reasons to oppose fluoridation and that this review did not support Connett’sview that there were health risks associated with fluoridation.

A 20-page paper by Dr Terry W Cutress, BDS, PhD, dental scientist, dated 25October 2005, Response to a list of ‘50 reasons to oppose fluoridation,’ compliedby Dr Connett (www.fluoridealert.org/50) was peer reviewed by Paul Fitzmaurice,Food Safety, Institute of Environmental Science and Research Ltd.d

The responses to reasons 12 and 30 concerned fluoride retention in the body. For reason 12 Connett stated:

“Reason 12. Fluoride is a cumulative poison. On average, only 50% of the fluoride we ingesteach day is excreted through the kidneys. The remainder accumulates in our bones, pinealgland, and other tissues. If the kidney is damaged, fluoride accumulation will increase, andwith it, the likelihood of harm.”

In his response to reason 12 Dr Cutress stated: “Fluoride is not continuously cumulative in the body tissues—see recent comprehensivereviews (NHMRC, 1999;e York Report, 2000;f MRC, 2002;g WHO, 2002h). Approximately99% of body fluoride is stored in the mineralized tissues (bones and teeth). However, these

aOxman AD, Lavis JN, Fretheim A. Use of evidence in WHO recommendations. Lancet 2007;369:1883-9.bSusheela AK. A treatise on fluorosis. 3rd ed. Delhi, India: Fluorosis Research and Rural Development Foundation; 2007.p. 15-6.

cFawell J, Bailey K, Chilton J, Dahi E. Fluoride in drinking-water. London: IWA Publishing and World Health Organization(WHO); 2006.

dCutress TW. Response to a list of “50 reasons to oppose fluoridation,” compiled by Dr Connett. 2005. A copy is available inthe McNab Room, 3rd floor, Dunedin Public Library, Dunedin. It is included as part of a report on Fluoridation of PublicWater Supplies to the Infrastructure Services Committee, Dunedin City Council, from the Water and Waste ServicesManager, for the meeting on 12 March 2007, as appendix 4 to a letter, dated 6 March 2007, to Mr Gerard McCombie,Water Operations Team Leader, Dunedin City Council, by Dr John Holmes, Medical Officer of Health and Dr Dorothy Boyd,Senior Public Health Dentist, written in response to a submission made by Dr Bruce Spittle to the 2006/07 Community Planopposing the use of fluoride in Dunedin’s water supply.

eNational Health and Medical Research Council, Australia. Review of water fluoridation and fluoride intake fromdiscretionary fluoride supplements. Melbourne: National Health and Medical Research Council, Australia; 1999.

fMcDonagh M, Whiting P, Bradley M, Cooper J, Sutton A, Chestnutt I, Misso K, Wilson P, Treasure E, Kleijen J. Asystematic review of public water fluoridation. Report 18. York: NHS Centre for Reviews and Dissemination, University ofYork; 2000.

gMedical Research Council, United Kingdom. Water fluoridation and health: working group report. London: MedicalResearch Council, United Kingdom; 2002.

hWorld Health Organization (WHO). Fluorides. Environmental Health Criteria No. 227. Geneva: WHO; 2002.


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mineralized tissues can accumulate up to a maximum 4% by weight. Kidney is the onlyorgan with soft tissue that has a changing fluoride content—reflecting its glomerular fluid.Fluoride does not accumulate over a lifetime, its levels in the blood and tissues reflect recentexposure to fluoride, with excess fluoride lost via sweat and faeces. Cumulativeconcentration of fluoride in the pineal gland is unproven. (note: Kidney tissues are notaffected by low levels of fluoride—urinary concentrations of fluoride are proportional tointake.”

For reason 30 Connett stated:“Reason 30. Once fluoride is put into the water it is impossible to control the dose eachindividual receives. This is because:“1. some people, (e.g. manual labourers, athletes, diabetics, and people with kidneydisease), drink more water than others “2. we receive fluoride from sources other than the water supply. Other sources of fluorideinclude food and beverages processed with fluoridated water (Kiritsy 1996a and Heilman1999b), fluoridated dental products (Bentley 1999c and Levy 1999d), mechanically debonedmeat (Fein 2001e), teas (Levy 1999f), and pesticide residues on food (Stannard 1991g andBurgstahler 1997h).”

In his response to reason 30 Dr Cutress stated: “Fluoride ingestion and excretion from the body achieves a balance dependent on theavailability of fluoride. Bones and teeth are the only tissue to accumulate fluoride but this islimited to less than 4% by weight. Excess fluoride is excreted via urine, sweat, saliva andfaeces within a few hours of ingestion. Less fluoride is excreted in younger people until theprimary (99%) storage tissue, bone reaches saturation at 3.8%. The variation in waterintakes by individuals determines respective fluoride intakes, but retention levels decreaseand plateau in early adulthood.”

In his response, dated 25 October 2005, to reason 12, Dr Cutress states that“Cumulative concentration of fluoride in the pineal gland is unproven.” HoweverDr Jennifer Luke published an article in 2001 on Fluoride deposition in the agedhuman pineal gland showing that by old age the pineal gland had readilyaccumulated fluoride with a level of 297±257 mg F/kg wet weight of pinealcompared to 0.5±0.4 mg F/kg wet weight of muscle.i Bone contained 2,037±1,095mg F/kg bone ash weight. In the 2006 National Research Council report, Fluoridein drinking water: a scientific review of EPA’s standards (2006 NRC report)fluoride and the pineal are discussed. The report notes that the pineal gland, asmall organ, weighing 150 mg in humans, located near the centre of the brain, is acalcifying tissue and that as with other calcifying tissues, it can accumulatefluoride. Fluoride is present in the pineal glands of older people, aged 72–100years, in concentrations of 14–875 mg of fluoride per kg of gland. The fluoride

aKiritsy MC, Levy SM, Warren JJ, Guha-Chowdhury N, Heilman JR, Marshall T. Assessing fluoride concentrations of juicesand juice-flavored drinks. J Am Dent Assoc 1996;127: 895-902.

bHeilman JR, Kiritsy MC, Levy SM, Wefel JS. Fluoride concentrations of infant foods. J Am Dent Assoc. 1997;128(7):857-63.

cBentley EM, Ellwood RP, Davies RM. Fluoride ingestion from toothpaste by young children. Br Dent J 1999;186: 460-2.dLevy SM, Guha-Chowdhury N. Total fluoride intake and implications for dietary fluoride supplementation. J Public HealthDent 1999;59:211-23.

eFein NJ, Cerklewski FL. Fluoride content of foods made with mechanically separated chicken. J Agric Food Chem2001;49: 4284-6.

fLevy SM, Guha-Chowdhury N. Total fluoride intake and implications for dietary fluoride supplementation. J Public HealthDent 1999;59:211-23.

gStannard JG, Shim YS, Kritsineli M, Labropoulou P, Tsamtsouris A. Fluoride levels and fluoride contamination of fruitjuices. J Clinic Pediatr Dent 1991;16:38-40.

hBurgstahler AW, Robinson MA. Fluoride in California wines and raisins. Fluoride 1997;30:142-6.iLuke J. Fluoride deposition in the aged human pineal gland. Caries Res 2001;35:125-8. [abstract in Fluoride 2001;34:152].


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concentration in the pineal gland is positively related to the calcium concentrationin the pineal gland, but not to the bone fluoride, suggesting that pineal fluoride isnot necessarily a function of cumulative fluoride exposure of the individual. It isnoted that fluoride has not been measured in the pineal glands of children or youngadults, and that investigations have not been made of the relationship betweenpineal fluoride concentrations and either recent or cumulative fluoride intakes. Inthe discussion the report states that whether fluoride exposure causes decreasednocturnal melatonin production or an altered circadian (daily) rhythm of melatoninproduction in humans has not been investigated but that fluoride is likely to causedecreased melatonin production and to have other effects on normal pinealfunction, which in turn could contribute to a variety of effects in humans.a In therecommendations it is noted that the major areas for investigation include pinealfunction, including, but not limited to, melatonin production. Thus the briefdismissal of the topic by Dr Cutress with “Cumulative concentration of fluoride inthe pineal gland is unproven” is not supported by the literature and does not dojustice to the complexity of the issue.

In his response, dated 25 October 2005, to reasons 12 and 30, Dr Cutress statesthat fluoride is stored in bones and teeth until a saturation point is reached at 3.8%by weight and then excess fluoride is excreted via the urine, sweat, saliva, andfaeces within a few hours, with the implication that this is safe. The overallchemical formula of fluoroapatite is Ca10F2(PO4)6 but is often simplified toCa5F(PO4)3. The formula weight is 1008.6 g/mole, and the percentage of F is (38/1008) × 100 = 3.77% or approximately 38,000 mg F/kg or 38,000 ppm F. Thisfigure represents the complete conversion of the normal dihydroxyapatite,Ca10(OH) 2(PO4)6 into fluoroapatite. Therefore 38,000 ppm F or 3.8% by weightis the maximum possible content of F in bone ash (all mineral) consisting of onlyfluoroapatite. In the 2006 NRC report, it is noted, on page 21, that 1% fluoride inbone ash is equivalent to 10,000 mg/kg or 10,000 ppm.b It is further noted, on page140, that bone ash is assumed to include 65% of the volume of viable bone. Thus3.8% by weight, 38,000 mg/kg or ppm of fluoride in bone ash is equivalent toabout 65% of 38,000 ppm or 24,700 mg F/kg or ppm of F or 2.47% by weight ofF in dry, fat-free bone before ashing. Thus the saturation point of 3.8% referred toby Dr Cutress applies to bone ash rather than to bone.

On pages 173–7 of the NRC report it is noted that in stage II skeletal fluorosisthe bone ash fluoride concentrations are 4,300–9,200 mg F/kg and 3,000–4,600mg F/kg in bone (dry fat-free material from the iliac crest or pelvis) while for stageIII skeletal fluorosis the bone ash fluoride concentrations are 4,200–12,700 mg F/kg and the mean bone concentration was 3,600 mg F/kg (dry fat-free material fromthe iliac crest or pelvis). Clinical stage II skeletal fluorosis is associated withaDoull J, Boekelheide K, Farishian BG, Isaacson RL, Klotz JB, Kumar JV, Limeback H, Poole C, Puzas JE, Reed N-MR,Thiessen KM, Webster TF, Committee on Fluoride in Drinking Water, Board on Environmental Studies and Toxicology,Division on Earth and Life Studies, National Research Council of the National Academies. Fluoride in drinking water: ascientific review of EPA’s standards. Washington, DC: The National Academies Press; 2006. Available for purchase onlineat: http://www.nap.edu. p. 252-6, 267.

bDoull J, Boekelheide K, Farishian BG, Isaacson RL, Klotz JB, Kumar JV, Limeback H, Poole C, Puzas JE, Reed N-MR,Thiessen KM, Webster TF, Committee on Fluoride in Drinking Water, Board on Environmental Studies and Toxicology,Division on Earth and Life Studies, National Research Council of the National Academies. Fluoride in drinking water: ascientific review of EPA’s standards. Washington, DC: The National Academies Press; 2006. Available for purchase onlineat: http://www.nap.edu. p. 21,140, 173-7.


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chronic joint pain, arthritic symptoms, calcification of ligaments, andosteosclerosis of cancellous bones (increased bone density of the non-corticalbone, or bone away from the surface of the bone). Stage III has been termed“crippling” skeletal fluorosis because mobility is significantly affected as a resultof excessive calcification in joints, ligaments, and vertebral bodies. This stage mayalso be associated with muscle wasting and neurological deficits due to spinal cordcompression.

The 2006 NRC report notes that the excessive intake of fluoride will manifestitself in a musculoskeletal disease, skeletal fluorosis, with a high morbidity. Theview expressed by Dr Cutress that fluoride is stored in bones and teeth until asaturation point is reached at 3.8% by weight, 38,000 mg F/kg of bone [ash], andthen excess fluoride is excreted via the urine, sweat, saliva, and faeces within afew hours, is at odds with the occurrence clinically of skeletal fluorosis withexcessive intake and the bone levels of fluoride in this condition beingconsiderably lower than 38,000 mg F/kg of bone ash, with the range for the boneash fluoride concentration in stage II skeletal fluorosis being 4,300–9,200 mg F/kg

Similar point by point replies could be made to the other responses by DrCutress. However only reason 22 will be commented on further as it is relevant tothe syndrome of chronic fluoride toxicity or preskeletal fluorosis described by DrWaldbott. For reason 22 Connett stated:

“Reason 22. In the first half of the 20th century, fluoride was prescribed by a number ofEuropean doctors to reduce the activity of the thyroid gland for those suffering fromhyperthyroidism (over-active thyroid; Stecher 1960,a Waldbott 1978b). With waterfluoridation, we are forcing people to drink a thyroid-depressing medication which could, inturn, serve to promote higher levels of hypothyroidism (under-active thyroid) in thepopulation, and all the subsequent problems related to this disorder. Such problems includedepression, fatigue, weight gain, muscle and joint pains, increased cholesterol levels, andheart disease. It bears noting that according to the Department of Health and HumanServices (1991c) fluoride exposure in fluoridated communities is estimated to range from 1.6to 6.6 mg/day, which is a range that actually overlaps the dose (2.3–4.5 mg/day) shown todecrease the functioning of the human thyroid (Galletti and Joyce 1958d). This is aremarkable fact, particularly considering the rampant and increasing problem ofhypothyroidism in the United States (in 1999, the second most prescribed drug of the yearwas Synthyroid [thyroxine sodium], which is a hormone replacement drug used to treat anunder-active thyroid). In Russia, Bachinskii (1985e) found a lowering of thyroid function,among otherwise healthy people, at 2.3 ppm fluoride in water.

In his response, dated 25 October 2005, to reasons 13–22, 24–28, and 34–35, DrCutress states that many diverse disease and health conditions, including fatigue,weight gain, muscle and joint pains, and heart disease have been claimed to belinked to the supplementation of water with low concentrations of fluoride but

aStecher PG, editor. The Merck index: an encyclopedia of chemicals and drugs. 7th ed. Rahway, NJ: Merck and Co., inc.;1960. p. 952.

bWaldbott GL, Burgstahler AW, McKinney HL. Fluoridation: the great dilemma. Lawrence, Kansas: Coronado Press; 1978.cDepartment of Health & Human Services. (U.S. DHHS). Review of Fluoride: Benefits and Risks. Report of the Ad HocCommittee on Fluoride, Committee to Coordinate Environmental Health and Related Programs. Washington, DC:Department of Health and Human Services, USA; 1991.

dGalletti PM, Joyet G. Effect of fluorine on thyroidal iodine metabolism in hyperthyroidism. J Clin EndocrinolMetab1958;18: 1102-10.

eBachinskii PP, Gutsalenko OA, Naryzhniuk ND, Sidora VD, Shliakhta AI. Action of fluoride on the function of the pituitary-thyroid system of healthy persons and patients with thyroid disorders. Probl Endokrinol (Mosk) 1985; 31: 25-9. [inRussian].


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that, according to recent major reviews, none of the conditions can be explained bya fluoride aetiology. As an example he quotes the University of York systematicreview, 2000, as stating:a

“Insufficient evidence is available to reach a conclusion that bone fractures, cancer, or otheradverse health conditions were associated with fluoride in water.”

I was unable to find this quotation in the University of York systematic review.In the section of the executive summary on other possible negative effects, pagesxiii–xiv, it is noted:

“A total of 33 studies of the association of water fluoridation with other possible negativeeffects were included in the review. Interpreting the results of studies of other possiblenegative effects is very difficult because of the small numbers of studies that met inclusioncriteria on each specific outcome, and poor study quality. A major weakness of these studiesgenerally was failure to control for any confounding factors.“Overall, the studies examining other possible negative effects provide insufficient evidenceon any particular outcome to permit confident conclusions. Further research in these areasneeds to be of a much higher quality and should address and use appropriate methods tocontrol for confounding factors.”

The quotation given by Dr Cutress did not appear in the discussion at the end ofchapter 10 on “Other possible negative effects,” page 63, which finished with:

“… Overall, the studies examining other possible negative effects provide insufficientevidence on any particular outcome to reach conclusions.”

Similarly, the quotation does not appear in chapter 12 on Conclusions in section12.4 addressing “Does fluoridation have negative effects?,” page 67, where it isnoted:

“… The miscellaneous other adverse effects studied did not provide enough good qualityevidence on any particular outcome to reach conclusions. The outcomes related to infantmortality, congenital defects and IQ indicate a need for further high quality research, usingappropriate analytical methods to control for confounding factors. While fluorosis can occurwithin a few years of exposure during tooth development, other potential adverse effectsmay require long-term exposure to occur. It is possible that this long-term exposure has notbeen captured by these studies.”

Again in section 12.9.2 addressing adverse effects studies, page 70, the quotationis not present:

“… The other possible adverse effect studies suffered greatly by not sufficiently controllingfor important confounding factors, many of which were discussed by authors in the studyreport, but not controlled for. Very few of the possible adverse effects studied appeared toshow a possible effect. High quality research that takes confounding factors into account isneeded.”

Thus I have been unable to find the exact quotation which Dr Cutress states ascoming from the University of York systematic review. The quotation

“Insufficient evidence is available to reach a conclusion that bone fractures, cancer, or otheradverse health conditions were associated with fluoride in water”

leaves some uncertainty with the reader to what extent the syndrome of chronicfluoride toxicity or pre-skeletal fluorosis described by Dr Waldbott has beencarefully examined and found to be wanting. The publications by Dr Waldbott onfluoride number 142.b The University of York systematic review has 294aMcDonagh M, Whiting P, Bradley M, Cooper J, Sutton A, Chestnutt I, Misso K, Wilson P, Treasure E, Kleijen J. Asystematic review of public water fluoridation. Report 18. York: NHS Centre for Reviews and Dissemination, University ofYork; 2000.


46

references in the bibliography but not one is by Dr Waldbott. A reference isincluded to a paper by me on “Allergy and hypersensitivity to fluoride” in which Ireferred to seven papers by Waldbott, but the reference to my paper in thesystematic review was only to reject it because it did not meet the inclusioncriteria.ab

“Although some authors (Spittle 1993) have reported cases of hypersensitivity to fluoridatedwater, no studies meeting the inclusion criteria were found.”

Thus, rather than the University of York systematic review having carefullyconsidered the work of Dr Waldbott, they set inclusion criteria for their review thatwere such as to exclude his work from consideration. The statement by Dr TerryCutress that University of York systematic review found insufficient evidence toreach a conclusion that other adverse health conditions were associated withfluoride in water cloaks the reality that the review did not in fact examine any ofWaldbott’s publications. In contrast to the 2000 University of York systematicreview, with 243 pages and 294 references, the 2006 NRC report with 507 pagesand 1077 references considered Waldbott’s work and was not dismissive of it. Asalready noted on page 9 of this book, the 2006 NRC reportc stated that the primarysymptoms of gastrointestinal injury are nausea, vomiting, and abdominal pain andthat these had been reported in well documented case studies by Waldbottd andPetraborge as well as in a double-blind clinical study by Grimbergenf involving theresearch group of doctors in the Netherlands with Dr Hans Moolenburgh and thatthese authors could have been examining a group of patients whosegastrointestinal (GI) tracts were particularly hypersensitive. Similarly the work bythese doctors on skin reactions was noted:

“In the studies by physicians treating patients who reported problems after fluoridation wasinitiated, there were several reports of skin irritation (Waldbott 1956;g Grimbergen 1974;hPetraborg 1977i). …”

The Australian National Health Medical Research Council (NHMRC, 1999)reportj has been updated by a 203-page 2007 report,k A systematic review of theefficacy and safety of fluoridation, with 113 references, but does not include any

bAnon. Fluoride publications of George L Waldbott, MD. Fluoride 1998;31:21-5. aSpittle B. Allergy and hypersensitivity to fluoride. Fluoride 1993;26:267-73. bMcDonagh M, Whiting P, Bradley M, Cooper J, Sutton A, Chestnutt I, Misso K, Wilson P, Treasure E, Kleijen J. Asystematic review of public water fluoridation. Report 18. York: NHS Centre for Reviews and Dissemination, University ofYork; 2000. p. 59.

cDoull J, Boekelheide K, Farishian BG, Isaacson RL, Klotz JB, Kumar JV, Limeback H, Poole C, Puzas JE, Reed N-MR,Thiessen KM, Webster TF, Committee on Fluoride in Drinking Water, Board on Environmental Studies and Toxicology,Division on Earth and Life Studies, National Research Council of the National Academies. Fluoride in drinking water: ascientific review of EPA’s standards. Washington, DC: The National Academies Press; 2006. Available for purchase onlineat: http://www.nap.edu. p. 269, 293, 303.

dWaldbott GL. Incipient chronic fluoride intoxication from drinking water. II. Distinction between allergic reactions and drugintolerance. Int Arch Allergy Appl Immunol 1956;9(5):241-9.

ePetraborg HT. Chronic fluoride intoxication from drinking water (preliminary report). Fluoride 1974;7:47-52.fGrimbergen GW. A double blind test for determination of intolerance to fluoridated water (preliminary report). Fluoride1974;7:146-52.

gWaldbott GL. Incipient chronic fluoride intoxication from drinking water. II. Distinction between allergic reactions and drugintolerance. Int Arch Allergy Appl Immunol 1956;9(5):241-9.

hGrimbergen GW. A double blind test for determination of intolerance to fluoridated water (preliminary report). Fluoride1974;7:146-52.

iPetraborg HT. Chronic fluoride intoxication from drinking water (preliminary report). Fluoride 1974;7:47-52.jNational Health and Medical Research Council, Australia. Review of water fluoridation and fluoride intake fromdiscretionary fluoride supplements. Melbourne: National Health and Medical Research Council, Australia; 1999.

kAustralian Government. National Health and Medical Research Council. A systematic review of the efficacy and safety offluoridation. Canberra: Australian Government. National Health and Medical Research Council; 2007.


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publications by Dr Waldbott. Similarly the World Health Organization report(2002) has been updated by a 144-page 2006 report, Fluoride in drinking-water,with 248 references, but none of Dr Waldbott’s publications.ab The AustralianNHMRC report dismisses the relevance to water fluoridation of the 2006 NRCreport, Fluoride in drinking water: a scientific review of EPA’s standards, whichincludes Dr Waldbott’s work on people affected by fluoridated water, in twosentences:

“The reader is also referred to recent comprehensive reports regarding water fluoridationpublished by the World Health Organisation (WHO, 2006) and the National ResearchCouncil of the National Academies (NAS, 2006). The NAS report refers to the adversehealth effects from fluoride at 2–4 mg/L, the reader is alerted to the fact that fluoridation ofAustralia’s drinking water occurs in the range of 0.6 to 1.1 mg/L.”

The NHMRC report does not alert the reader to the fact that it is the dosagerather than the concentration in the water that is important so that someonedrinking 3 L with 1 ppm of fluoride would receive the same amount, 3 mg, as iscontained in 1.5 L of water with 2 ppm of fluoride. Those with above averagewater intakes include some athletes, persons doing heavy manual labour, personswith diabetes, and those with renal failure. The 2006 NRC reportc is of clearrelevance to water fluoridation and, in addition to referring to two of Waldbott’spublications, reviewed animal studies showing adverse changes occurred in thebrains of rats with water containing 0.34 ppm and 1 ppm of fluoride. Similarly thereport included data on fluoride and fractures involving fluoridated water, and therelevant animal work studying fluoride and the pineal gland. The NHMRC reportrepeats uncorrected mistakes present in the York report,d e.g. in Table 62 on page122 of the NHMRC report the I.Q. difference reported by Zhao (1996)e is given as–7.7 when the correct figure from the original study is –7.5, and on page 123 it isstated:

“Lin (1991)f found a significant negative association of combined low iodine and high fluoridewith goitre and mental retardation.”

whereas Lin FF et al. found that the average I.Q. of children in high fluoride andlow iodine areas was 19–25% lower than the average I.Q. of children in controlareas.g A positive association was present between the water fluoride level andmental retardation. As the fluoride level increased, so too did the incidence of

aWorld Health Organization (WHO). Fluorides. Environmental Health Criteria No. 227. Geneva: WHO; 2002.bFawell J, Bailey K, Chilton J, Dahi E. Fluoride in drinking-water. London: IWA Publishing and World Health Organization(WHO); 2006.

cDoull J, Boekelheide K, Farishian BG, Isaacson RL, Klotz JB, Kumar JV, Limeback H, Poole C, Puzas JE, Reed N-MR,Thiessen KM, Webster TF, Committee on Fluoride in Drinking Water, Board on Environmental Studies and Toxicology,Division on Earth and Life Studies, National Research Council of the National Academies. Fluoride in drinking water: ascientific review of EPA’s standards. Washington, DC: The National Academies Press; 2006. Available for purchase onlineat: http://www.nap.edu. p. 131-80, 216-7, 252-6. An abstract of the paper Varner JA, Jensen KF, Horvath W, Isaacson RL.Chronic administration of aluminum-fluoride or sodium fluoride to rats in drinking water: alterations in neuronal andcerebrovascular integrity. Brain Res 1998;784:284-98 is in Fluoride 1998;21:91-5.

dMcDonagh M, Whiting P, Bradley M, Cooper J, Sutton A, Chestnutt I, Misso K, Wilson P, Treasure E, Kleijen J. Asystematic review of public water fluoridation. Report 18. York: NHS Centre for Reviews and Dissemination, University ofYork; 2000. p. 59-63.

eZhao LB, Liang GH, Zhang DN, Wu XR. Effect of a high fluoride water supply on children’s intelligence. Fluoride1996;29:190-2.

fLin FF, Zhao HX, Lin J, Jian JY. The relationship of a low-iodine and high-fluoride environment to subclinical cretinism inXinjiang. Yutian, Xinjiang, China: Xinjiang Institute for Endemic Disease Control and Research, Office of Leading Group forEndemic Disease Control of Hetian Prefectural Committee of the Communist Party of China and County Health andEndemic Prevention Station, Yutian, Xinjiang; 1991. Unpublished report submitted through NHS CRD web site. Thereference was omitted from the NHMRC report but included in the York report.

gGe YM, Ning HM, Feng CP, Wang HW, Yan XY, Wang SL, Wang JD. Apoptosis in brain cells of offspring rats exposed tohigh fluoride and low iodine. Fluoride 2006;39:173-8.


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mental retardation. The NHMRC report does not make it easier for the reader tocheck the Lin quotation by omitting the paper from the references. The York reportnoted an inverse association between the water fluoride level and I.Q. had beenreported by Zhao (1996) and Lin (1991). As the fluoride level increased, the I.Q.decreased. No mention is found in the discussion in the NHMRC report of theinverse association between the water fluoride level and intelligence.

Dr Cutress noted in his introductory general comments on Dr Connett’s list of 50reasons to oppose fluoridation that:

“Many of the references are from doubtful publications (e.g. 10% are published in thejournal Fluoride which specialises in anti-fluoride articles).

Publication in Fluoride is determined by the scientific merit of the articles whichare peer reviewed by an international editorial board. The International Society forFluoride Research does not hold an official position as a Society on issues such aswater fluoridation but encourages, through its conferences and the publication ofpapers, commentaries, and letters to the editor, a critical examination of thescientific basis of the views which are held by individuals and organizations.Rather than publishing “anti-fluoride” articles, the Society promotes the sharing ofscientific information on all aspects of inorganic and organic fluorides and hasdone this by publishing its quarterly journal Fluoride since 1968 and hosting 27international conferences in Spain, Austria, the Netherlands, England, the UnitedStates of America, Switzerland, India, Japan, Hungary, China, Poland and NewZealand. Fluoride, an open access journal, is available, free in full text includingthe most recent issues, at http://www.fluorideresearch.org.

The authors of the 2000 University of York systematic review did have not anydifficulties with using references from Fluoride and had 9 such references in thetotal of 294 (3.1%).a Similarly 57 of the 1077 references in the 2006 NRC reportwere from Fluoride (5.3%).b

Public health advocates of fluoridation tend to consider of little or no scientificvalue evidence contradicting their views when it is published in journals such asFluoride, not indexed by PubMed, but covered by other search engines such asSciFinder Scholar and Web of Science.cd Fluoridation promoters, from whoseranks the journal selection panels for PubMed are invariably selected, are thus“able” to maintain and safeguard their self-interests, and ignore and discount alarge body of solid research that contradicts their position.

aMcDonagh M, Whiting P, Bradley M, Cooper J, Sutton A, Chestnutt I, Misso K, Wilson P, Treasure E, Kleijen J. Asystematic review of public water fluoridation. Report 18. York: NHS Centre for Reviews and Dissemination, University ofYork; 2000.

bDoull J, Boekelheide K, Farishian BG, Isaacson RL, Klotz JB, Kumar JV, Limeback H, Poole C, Puzas JE, Reed N-MR,Thiessen KM, Webster TF, Committee on Fluoride in Drinking Water, Board on Environmental Studies and Toxicology,Division on Earth and Life Studies, National Research Council of the National Academies. Fluoride in drinking water: ascientific review of EPA’s standards. Washington, DC: The National Academies Press; 2006. Available for purchase onlineat: http://www.nap.edu

cArmfield JM. When public action undermines public health: a critical examination of antifluoridationist literature. Aust N ZHealth Policy 2007;4:25. doi:10.1186/1743-8462-4-25.

dMaupomé G, Gullion CM, Peters D, Little SJ. A comparison of dental treatment utilization and costs by HMO membersliving in fluoridated and nonfluoridated areas. J Public Health Dent 2007;67:224-33.

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FURTHER COMMENTS ON THE SUGGESTION THAT THE CHRONIC FLUORIDE TOXICITY SYNDROME IS PSYCHOSOMATIC

Dr Waldbott commented further in 1978 in Fluoridation: the great dilemma oncriticism that the so-called “fluoride intolerance” was a variety of unrelatedconditions or had a psychogenic (psychosomatic) basis.a He noted:

“Like most other kinds of chronic poisoning, intoxication from long-term fluoride intake is difficult todiagnose because it develops slowly and unobtrusively with a wide variety of symptoms of the kindthat are common to many other ailments. Dwelling on this point, WD Armstrong wrote in theAmerican Journal of Public Health:b “‘He [Waldbott] describes patients who complained of a variety of bizarre symptoms affecting a largenumber of organ systems. These symptoms, attributed by Dr. Waldbott to the use of fluoridatedwater, were present with few or no objective signs of specific disease and included gastric distress,pain in the spine, paresthesias, flatulence, polydipsia, mental aberrations, tinnitus, muscularweakness, etc. Rapid symptomatic cures were reported on withdrawal of fluoridated water, and Dr.Waldbott attempts to discount the suggestion that his patients’ complaints had a psychogenic basis.’ “ER Schlesinger elaborated further on this seemingly plausible criticism in a publication of the WorldHealth Organization:c '‘Of a selected group of 123 allergic patients tested, five developed a wide variety of symptoms andsigns which developed five minutes to three hours after the test dose and lasted from twelve hoursto ten days. Of the 21 symptoms and signs reported, only six occurred in more than one patient, andthese were mainly of a nondescript nature, such as headache, nausea, vomiting, and epigastricpain. Physical findings such as muscular fibrillation, “cystitis,” “spastic colitis,” and facial oedemawere each found in not more than one patient. “The absence of any suggestion of a clinicalsyndrome leads to the conclusion that a variety ofunrelated conditions were presented as cases of so-called “fluoride intolerance.”’This statement createsthe false impression that only a limited number ofpatients experienced chronic poisoning. Actually, thefive cases mentioned were only part of a larger groupof allergic patients without symptoms of fluorideintolerance. They were subjected to a special fluorideloading test for the purpose of recording any unusualreactions, following the test dose. My experience withthe disease now includes approximately 500 cases.“With respect to the wide spectrum of symptoms, Ihave already shown in Chapter 11 [In: Fluoridation:the great dilemma] that there is solid experimentalevidence to link every one of the above-namedmanifestations with fluoride intake. This nonskeletalphase of chronic fluoride poisoning was firstdiscussed by Roholm (Figure 33),d one of theforemost authorities on the subject, in conjunctionwith advanced skeletal fluorosis and has been wellconfirmed by other investigators. Furthermore, anyexperienced physician can usually recognize whetheror not he is dealing with a real disease orpsychosomatic complaints. Having had a lifetime ofexperience in the practice of allergic diseases—amedical speciality that concentrates, more than anyother, on the detection of the causes of a disease—Ihave learned to distinguish readily betweenimaginary and real complaints. Moreover, a carefulappraisal of the combination of the unusualsymptoms which I described suggests a distinctsyndrome that does not occur in any other disease:an attenuated phase of the acute stage of fluoridepoisoning.”

aWaldbott GL, Burgstahler AW, McKinney HL. Fluoridation: the great dilemma. Lawrence, Kansas: Coronado Press; 1978.p. 240-2.

bArmstrong WD. Books and reports: review of The American fluoridation experiment. Am J Public Health 1957;47:1022.cSchlesinger ER. Health studies in areas of the USA with controlled water fluoridation. In: Adler P, Armstrong WD, Bell ME,Bhussry BR, Büttner W, Cremer H-D, et al. Contributors. Fluorides and human health. WHO Monograph Series No. 59.Geneva: World Health Organization;1970. p. 309.

Figure 33. Professor Kaj Roholm, 1902–1948, a pioneer in fluoride research and author of the first comprehensive monograph on fluoride toxicity Fluorine intoxication: a clinical-hygienic study with a review of the literature and some experimental investigations. London: HK Lewis; 1937.


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ILLNESS IN ANIMALS

Another indicator that the chronic fluoride toxicity syndrome is notpsychosomatic is the response of animals to receiving fluoride in their water andfood. Presumably, animals are less likely to be affected by psychological factors.Like the response of canaries to methane gas in a coal mine, the health of animalsmay give a clue that an environment is becoming unsafe for humans. Miners usedto take canaries into coal mines to warn them about the build up of firedamp ormethane that could become explosive with air. It was ominous if the canary beganto sway noticeably on his perch before falling. Some examples will be given ofanimals being affected by fluoride in their water and diet.

Chinchillas: For six months in the early1970s Roy Freeman, of Auburn, Kansas,USA, successfully raised chinchillas, a SouthAmerican rodent about the size of a guinea-pig with a very soft fur (Figure 34).a Withinthree days of his changing from low-fluorideAuburn well water to drinking waterfluoridated with fluorosilicic acid, theanimals started to drink twice as much asbefore and gradually displayed inferior furquality, stillbirths and premature mortality.When half the 50 animal colony was placedon distilled water the water consumption inthis group soon decreased and becamenormal, the quality of the fur was restoredand no further stillbirths occurred. Thechinchillas became sick drinking fluoridatedwater. Earlier work in the 1950s by Dr HL Richardson at the University of Oregonshowed that fluoride in food pellets led to abortions, stillbirths, and infertility inthe chinchilla ranch of Mr WR Cox, of Gresham, Oregon, USA.bc

In an interim report, dated April 1951, Dr Richardson noted that he hadpersonally performed over 200 autopsies on Cox’s fluoride-poisoned chinchillasand had found lesions in the kidneys and testes. The kidneys had lesions in thetubules (tubular nephrosis) and the testes showed generalized testicular atrophy.Increased drinking may be sign of impaired kidney function.

Hamsters, guinea-pigs, and rabbits were also found by Dr Richardson to beaffected by fluoride with the hamsters being the most sensitive. When the hamsterswere fed pellets containing 14 parts per million (ppm) or mg/L of fluoride theydeveloped oedema (swelling of the body due to the accumulation of fluid) after 2–

dRoholm K. Fluorine intoxication: a clinical-hygienic study with a review of the literature and some experimentalinvestigations. London: HK Lewis; 1937. p. 137-8.

aBurgstahler AW, Freeman RF, Jacobs PN. Early and prolonged toxic effects of silicofluoridated water on chinchillas,caimans, alligators, and rats in captivity [abstract]. Fluoride 2002;35:259-60.

bWaldbott GL. A struggle with titans. New York: Carlton; 1965. p. 242. cCox WR. Hello, test animals …chinchillas? or you and your grandchildren. Milwaukee, Wisconsin: Lee Foundation forNutritional Research; 1953.

Photograph by Sarah Hamilton, http://www.freewebs.com/nzchinchilla-rescue/index.htm,

NZ Chinchilla Rescue, New Zealand’s ChinchillaRescue & Boarding Service.

Figure 34. A chinchilla

Illness in animals 51

3 months. On autopsy examination, they had lesions in the kidneys (tubularnephrosis), atrophy of the testes, and lesions in the adrenal glands. Mr Cox foundthat hamsters given commercial food pellets containing 26.5 ppm of fluoride werelistless and took no interest in their surroundings whereas another group withpellets containing 5 ppm of fluoride prepared by a chemist, Mr Raphael Maiers,were “full of life.”

Mr Cox found that as time went on guinea-pigs raised on commercial pelletswith a high fluoride content began to look ragged and a bit listless. He found thatthe health of the babies gradually deteriorated. At first the babies were weak andone or two of a litter would die. The next phase was that one or two of the babieswould be stillborn and finally the whole litters would be stillborn. After that therewould be no litters at all.

He noted that the same thing happened with rabbits except that it took threetimes as long for it to happen.

A similar progressive deterioration in the quality of the litters with successivegenerations of chinchillas, fed on high fluoride pellets, was also seen. After four orfive generations had been fed on high fluoride pellets, there were few litters. Theyseldom conceived and when they did conceive it was not uncommon for one to diewithin two weeks of the due date. If a pregnant chinchilla survived that period andactually delivered, the litter might have one or more stillborn babies. It they wereborn alive and it was a multiple birth, then invariably one of the babies wasscrawny and would not survive more than a day or two. Those that were left wouldprobably grow well and behave normally until weaning on day 60 when Mr Coxwould then find one dead in the morning and within a day or two the other wouldalso be dead. If this period was survived he was not surprised to see bare spots onthe animal where the fur had come out. Soon the fur would begin to grow back andshortly thereafter the animal would drop dead. Very few of these chinchillassurvived.

Rats, alligators and caimans: From 1961 until 1981 Pat Nichols Jacobs, ofKansas City, Missouri, USA, successfully bred and raised rats, alligators andcaimans, an alligator-like reptile from South and Central America.a On 9 April1981 the water supply for her animals changed to drinking water fluoridated withfluorosilicic acid. Within three days the eye membranes of the caimans and thealligators started to swell, gradually became reddened, and then ulcerated. Theanimals also began to avoid being in the water, preferring to remain on deck morethan normal and going from tank to tank, evidently in search of water less irritatingto their eyes (Figures 35–38). Within two years, without any change in the diet orhousing conditions or evidence of vector-borne disease, some of the animals beganto exhibit bloated bellies, gastric distress and spinal deformities (Figures 39–40).During the next 20 years, 32 caimans and 3 alligators died, many in apparentagony. Eighteen of the 35 reptiles were less than 10 years old compared to anormal lifespan of 25 years or more. Autopsies showed severe disintegration of the

aBurgstahler AW, Freeman RF, Jacobs PN. Early and prolonged toxic effects of silicofluoridated water on chinchillas,caimans, alligators, and rats in captivity [abstract]. Fluoride 2002;35:259-60.


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gastrointestinal tract, Crohn’s disease, and liver silicosis. None of the eggs laidsince 1981 hatched and all were found to be infertile even though matings hadoccurred. As the colony used about 2,500 L of water a day the cost ofdefluoridating the drinking water or obtaining nonfluoridated water wasprohibitive. However hatchling caimans raised on distilled water remained inexcellent health until they were switched to the fluoridated drinking water at aboutage 4 months. They then developed the eye swelling and ulceration, bloatedbellies, gastric distress, and spinal deformities.

Photograph by Pat Nichols JacobsFigure 35. Nicholas, a healthy, 3 metre long, 227 kg, 12-year-old alligator on 10 September 1980 before fluoridation commenced on 9 April 1981 in Kansas City, Missouri, USA. She was raised from 1 February 1968, age 2 months, by Pat Nichols Jacobs who described her as “Perfectly normal, absolutely flawless, a magnificent, splendid, lovely lady who was my beloved friend. She represented an enormous investment of time, work, money and love.”

Photograph by Pat Nichols JacobsFigure 36. The right eye of Nicholas on18 November 1981 after 7 months exposure to fluoridated water showing inflammation of the eye membranes or conjunctivae which were swollen and red. The lower eyelids were displaced downwards 19 mm.

Photograph by Pat Nichols JacobsFigure 37. The right eye of Nicholas on 10 September 1983 after 2 years 5 months’ exposure to fluoridated water showing inflammation of the eye membranes with downward displacement of the lower eyelids by 38 mm.

Photograph by Pat Nichols JacobsFigure 38. The left eye of Nicholas on 19 November 1984 after 3½ years exposure to fluoridated water showing conjunctival inflammation and ulceration. Pat Jacobs said “Nick got worse and worse … She moaned and cried. On 3 December 1987 after 5½ years of exposure to fluoridated water this marvelous, beloved pet suffered to death. She represented 20 years of my life too.”


Photograph by Pat Nichols JacobsFigure 39. Hiss-a-fer, a 6-year-old female caiman, with a severely bloated belly in late 1981. Hiss-a-fer had been cared for by Pat Nichols Jacobs, Technical Illustrator and Curator of Reptiles, at the Parrot Hill Croc Farm, Kansas City, Missouri, USA, since her arrival on 15 June 1975 at the age of 6 months.

Photograph by Pat Nichols JacobsFigure 40. Shep, a male caiman, hatched from an egg held in the hand of Pat Jacobs on 8 June 1978. He developed skeletal fluorosis with a spinal deformity and a bloated belly after prolonged exposure to fluoridated water and died, on 15 September 1998, aged 20 years.


54

During the six months after fluoridation began, the appearance and health of therats declined dramatically. Tumours started to appear with over 200 being countedwith as many as 6 per rat. Beginning on 1 October 1981 the rats were given onlydistilled water to drink. Their condition quickly improved and no further tumourswere detected. Their reproductivity and lifespans also increased significantly withsome of the rats reaching more than 7 years of age.

Pat Nichols Jacobs also noted that, during warm weather, pigeons and other wildbirds consistently used the open-air bird baths filled with distilled water beforeusing the ones filled with fluoridated water.

Horses: Cathy Justus, a quarter horse breeder at Pagosa Springs, Colorado,USA, noticed that after fluoridation started in 1985 her horses began to have colicon a regular basis and within two years the horses had chronic fluoride poisoningwith brown staining of the teeth (dental fluorosis, Figures 41–43), hoof and legdeformities (Figure 44), increased bone formation (Figures 45–46), decreasedthyroid hormone levels, and low conception rates.a After the fluoridation stoppedin 2005 the colic gradually ceased and other improvements occurred.

In addition some horses developed allergic reactions in the skin whichdisappeared promptly when the horse was removed from the fluoridated water andreturned quickly when the animal was re-exposed.b In one horse the lesions wereroughly circular, 1.2–10 cm in diameter, with a centre raised up to 1.5 cm whichreceded after a few days to leave a crater-like lesion with a well demarcated ringaKrook LP, Justus C. Fluoride poisoning of horses from artificially fluoridated drinking water. Fluoride 2006;39:3-10.bJustus C, Krook LP. Allergy in horses from artificially fluoridated water. Fluoride 2006;39:89-94.

Figure 41. Incisor teeth of 2-year-10-month-old Quarter horse foal introduced to the farmwith fluoridated water at 7 months of age.The upper (maxillary) permanent centralincisor teeth have extensive enamel defectsdistally (the part furthest from the gum orgingiva).

Figure 42. Incisor teeth of 6-year-8-month-old Quarter horse gelding on fluoridatedwater from birth. There is severe browndiscoloration of the central enamel of allteeth, and this enamel is thinner and hasreceded from surrounding enamel. There isalso recession of the maxillary gingiva(upper gum), and the exposed distal enamelshows extensive defects. The mandibulargingival (lower gum) has receded and isbulging, and the entire masticatory surface ofthe mandibular (lower) teeth exhibits severebrown discoloration.


(urticaria, Figures 47–48). In another horse numerous skin nodules developedranging in size from that of marbles to golf balls (1.0–2.5 cm in diameter) with ahard centre until a change was made to nonfluoridated water when they becamesofter and smaller (figure 49).

Figure 43. Incisor teeth of 23-year-8-month-old Quarter horse mare on fluoridated water for 21 years. There is brown discoloration of the enamel with extensive defects of the distal enamel of the maxillary teeth. Severe loss and recession of apical bone have resulted in exposure to the distal clinical crown and the upper part of the roots of the maxillary teeth, together with recession and bulging of the gingiva of the mandibular teeth.

Figure 44. Severe hoof deformity inleft thoracic limb of 22-year-7-month-old Quarter horse mare on fluoridatedwater for 21 years.


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Figure 45. Radiographs of lower two-thirds of left thoracicthird metacarpus (MCIII) cut longitudinally at the dorso-palmar midline (palmar is to the left). The left radiograph isfrom an old thoroughbred horse (routine necropsy at CornellCollege of Veterinary Medicine); the right radiograph is from a17-year-old Quarter horse gelding on fluoridated water for thelast 11 years.Left: The subchondral bone plate is well defined from thelamellar epiphyseal bone. The metaphyseal lamellae becomegradually thinner and disappear at the lower half of thepicture. The cortex is sharply demarcated from the medullarycavity.Right: The subchondral bone plate blends diffusely with theepiphyseal bone. The metaphyseal trabeculae remain thickand extend throughout the entire medullary cavity. Thecortical surface facing the medulla is less sharply defined,most eloquently so at the upper palmar cortex.

Figure 46. Photo of the left MCIII of 21-year-old Quarter horse mare on fluoridated water all her life. The bone is cut lengthwise in the dorso-palmar midline with the lower end, not including the joint cartilage, at the bottom. The dorsal contour is to the left. The dorsal cortex of the wall bulges severely into the marrow space, beginning just proximal to the epiphysis, creating endosteal hyperostosis “enostosis”. The added bone is less dense than the original cortex; the contour of the original cortex is well defined.

Further comments on canaries in the coal mine 57

Not long after being acquired in the late fall of 2002, the filly soon experienced

one of Colorado's most renowned commodities—snow. Apparently guided by

natural instincts, she began replacing AFW with snow and was somewhat

successful in reducing her skin lesions. More impressive results occurred when

she was taken to shows in places without AFW. There the urticaria disappeared

within 12 to 15 hours. Upon her return to AFW on the farm, the urticaria

Figure 1. This Quarter horse filly was photographed at age 1 year and 2 months, when she had been on artificially fluoridated water for 7 months. Under and below the horizontal part of the halter are well demarcated, annular remnants of allergic lesions. Receding allergic reactions are present on the neck as small nodules. The once annular remnant of the lesion below the eye is now only an irregular strand, which are so abundantly present in Figure 2.

Figure 47. This Quarter horse filly was photographed at age 1 year and 2 months, when she had been on artificially fluoridated water for 7 months. Under and below the horizontal part of the halter are well demarcated, annular remnants of allergic lesions. Receding allergic reactions are present on the neck as small nodules. The irregular strand below the eye was once annular lesion. The extent of the lesions over the body is shown in Figure 48.

Figure 48. This figure shows the extent of the allergic reactions over the body with irregular strands, nodules, and annular remnants, at the same time as in Figure 47.


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Thus sickness has been observed in animals as diverse as chinchillas, rats,alligators, caimans, and horses when they used drinking water to which fluoridehad been added. Fluoride from industrial air pollution may also cause sickness inanimals as has occurred with chronic lameness in free ranging eastern greykangaroos (Macropus giganteus) at the smelter site at Portland Aluminium atPortland, Victoria, Australia.a

FURTHER COMMENTS ON CANARIES IN THE COAL MINE

Dr Moolenburgh also referred to the canaries in the coal mine:b

“There is one thing I should like to add. As you know, we did research with the help of doubleblind cases. This was to prove our case, though for me, clinical proof was enough. Thesepeople became quite ill during these double blind cases, and I felt the procedure wasdubious from the standpoint of medical ethics. “Some of the cases were directed to the allergists in our group. These cases had beenthrough double blind tests. It had been scientifically proved that fluoride caused thecomplaints. And yet our allergist said, ‘I cannot find an allergy!’“It was only after correspondence with Dr. Waldbott that this error in our research wasdetected and eliminated. What we were seeing was not allergy (a strange reaction of acertain individual from some compound), but low-grade poisoning. This is extremelyimportant. When, during the hay fever season, the pollen concentration in the air increasesa million fold, only those allergic to pollen will begin to sneeze. With poisoning, you have adifferent proposition. When you slowly increase the concentration of the poison, more and

aClarke E, Beveridge I, Slocombe R, Coulson G. Fluorosis as a probable cause of chronic lameness in free ranging easterngrey kangaroos (Macropus giganteus). Journal of Zoo and Wildlife Medicine 2006;37(4):477-86.

bMoolenburgh HC. Dutch doctor describes hazards of fluoridated water. National Fluoridation News 1979;XXV(4):3.

Figure 4. This figure shows receding skin lesions that originally ranged in size from 1.0–2.5 cmFigure 49. This figure shows receding skin lesions that originally ranged in size from 1.0–2.5cm.

Further comments on canaries in the coal mine 59

more people will show side-effects until at last everybody will be ill (and the most sensitivewill be dead).“And this is the case with fluoridation. Those people showing ill effects are the most sensitiveones in the population. They can be compared to the little birds that coal miners take withthem into the mines. These birds are extremely sensitive to small amounts of mine gas.When the birds begin to suffer, the miners are warned of the danger. These people whohave adverse reactions to fluoridated water (between 5% and 6% of the population) are likethose little birds. They warn the population that there is a poison at large and that theyshould avoid it, or as can easily be done here, get the poison out.”

In addition to the adverse reactions found clinically by Dr Moolenburgh subtleeffects on psychological functioning have been found on detailed examination.a

CLOSING COMMENTS

In this book the focus has been on describing the clinical features of chronicfluoride toxicity as it affects people so that those in fluoridated areas experiencingill health can consider whether or not it is possible that fluoride is contributingadversely to their health and whether they should have a trial of avoiding fluoridefor a few weeks. A number of case histories involving similar symptoms havebeen presented so that readers can make up their own minds about whether there issuch a thing as a chronic fluoride toxicity syndrome associated with the use ofwater fluoridated with about 0.7–1 ppm of fluoride.

Widely divergent views are held on this point. The New Zealand Commission ofInquiry on the Fluoridation of Public Water Supplies reported in 1957 that theywere satisfied that the individual signs and symptoms of the alleged syndromemay be due to any number of unrecognized causes and that they were satisfied thatthere was no causal relationship with the ingestion of water containing 1 ppm offluoride and food cooked in this water.b The Minister of Health in New Zealand,The Hon. Pete Hodgson, in a letter, dated 19 July 2006, stated that the evidencefrom a Ministry of Health review does not support suggestions of health risksassociated with water fluoridation.c Similarly, Brian Rousseau, Chief Executive,Otago District Health Board, in a letter dated 6 September 2007, stated that addingfluoride to water was “a safe way of reducing tooth decay” and that for people incommunities where tooth decay was a serious problem “It would be a tragedy ifthey are denied an opportunity to improve their health in this way because of thevehement opposition of some people.” He noted “The World Health Organization,the New Zealand Dental Association, the New Zealand Medical Association, thePlunket Society and our own Ministry of Health fully support this initiative—highendorsement indeed.”d

Although it was reported, on 28 June 2007, that the Otago District Health Boardwould be responsible for providing impartial, balanced, information onfluoridation to voters in forthcoming referenda, no mention was made by MrRousseau of the advice given on 9 November 2006 by the American DentalAssociation that, in order to reduce the risk of enamel fluorosis in teeth, “If using a

aRotton J, Tikofsky RS, Feldman HT. Behavioural effects of chemicals in drinking water. J Appl Psychol 1982;67(2)230-8.bStilwell WF, Edson NL, Stainton PVE. Report of the commission of inquiry on the fluoridation of public water supplies.Wellington: RE Owen, Government Printer; 1957.

cHodgson P. Letter to Hone Harawira. 2006 Jul 6. Unpublished.dRousseau B. Opposition respected but fluoride necessary [letter]. Otago Daily Times 2007 Sept 6;17.


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product that needs to be reconstituted, parents and caregivers should considerusing water that has no or low levels of fluoride.”ab Similarly, no mention wasmade of the findings of the National Research Council’s 507-page report onFluoride in drinking water: a scientific review of EPA’s standardsc or of the reviewof this by Robert J Carton, PhD.d In like manner, Jason Armfield made noreference to the NRC report, published on 22 March 2006, in his defence offluoridation submitted on 24 June 2007.e

Dr Carton’s review concluded: “The NRC [National Research Council] committee’s reevaluation of EPA’s

MCLG [Environmental Protection Agency, Maximum Contaminant Level Goal]for fluoride in drinking water failed to identify a safe level of fluoride in drinkingwater. This failure can be attributed to misdirection by EPA of the intended goal ofthe effort. When the committee requested and received a change in its mandatefrom evaluating the MCL [Maximum Contaminant Level] to the MCLG, EPAstrangely omitted the key scientific criteria necessary for evaluating this standard.The committee should have been told to look for health effects that “can bereasonably anticipated, even though not proved to exist.” As a result of thisomission, the NRC panel focused only on end points that were totally certain andconcluded that the current standard of 4 mg/L did not protect against bonefractures and severe dental fluorosis. For the first time in history, a committee ofthe NRC removed severe dental fluorosis from the benign category of cosmeticeffects and added it to the list of adverse health effects. In addition, Stage IIskeletal fluorosis was added to the list, but the committee was unable to state withabsolute certainty that this was occurring at the current EPA standards.

“This review applied the necessary criteria to some but not all of the adversehealth effects discussed in the NRC report. The results are as follows:

“1 Moderate dental fluorosis is an adverse health effect occurring at fluoride levels of 0.7–1.2 mg/L, the levels of water fluoridation.

“2 The Lowest Observed Adverse Effect Level (LOAEL) for bone fractures is at least as low as 1.5 mg/L and may be lower than this figure.

“3 Stage II and Stage III skeletal fluorosis may be occurring at levels less than 2 mg/L.

“4 Stage I skeletal fluorosis, arthritis clinically manifested as pain and stiffness in joints, is an adverse health effect which may be occurring with a daily fluoride intake of 1.42 mg/day, which exceeds the amount the average person obtains in their diet in non-fluoridated areas. The Maximum Contaminant Level Goal (MCLG) should be zero.

“5 Decreased thyroid function is an adverse health effect, particularly to individuals with inadequate dietary iodine. These individuals could be affected with a daily

aADA.org [homepage on the Internet]. Chicago: American Dental Association; c1995-2008. Interim guidance onreconstituted infant formula [ADA E-Gram]. 2006 Nov 9. Available from: http://www.ADA.org

bcited in: Burgstahler AW. Fluoridated bottled water [editorial]. Fluoride 2006;39:252-4.cDoull J, Boekelheide K, Farishian BG, Isaacson RL, Klotz JB, Kumar JV, Limeback H, Poole C, Puzas JE, Reed N-MR,Thiessen KM, Webster TF, Committee on Fluoride in Drinking Water, Board on Environmental Studies and Toxicology,Division on Earth and Life Studies, National Research Council of the National Academies. Fluoride in drinking water: ascientific review of EPA’s standards. Washington, DC: The National Academies Press; 2006. Available for purchase onlineat: http://www.nap.edu

dCarton RJ. Review of the 2006 United States National Research Council report: Fluoride in drinking water. Fluoride2006;39:163-72.

eArmfield JM. When public action undermines public health: a critical examination of antifluoridationist literature. Aust N ZHealth Policy 2007;4:25. doi:10.1186/1743-8462-4-25.

Closing comments 61

fluoride dose of 0.7 mg/day (for a “standard man”). Since this exceeds the amount already in the diet, the MCLG should be zero.

“6 Fluoride has adverse effects on the brain, especially in combination with aluminum. Seriously detrimental effects are known to occur in animals at a fluoride level of 0.3 mg/L in conjunction with aluminum. The goal for this effect should also be zero.

“The committee should be applauded for their efforts in general and in particularfor ignoring directives not to include discussions of water fluoridation andsilicofluorides. Their recommendations for research should be taken seriously.EPA has sufficient information in this report to act immediately, using theappropriate criteria set forth in the Safe Drinking Water Act. Using the preventivepublic health intent of the law, the Maximum Contaminant Level Goal for fluoridein drinking water should be zero.”

Returning to the situation in Dunedin and the views of The World HealthOrganization, the New Zealand Dental Association, the New Zealand MedicalAssociation, the Plunket Society, and the Ministry of Health, no one doubts thatthese authorities are sincere and well meaning with the best interests of thepopulation, particularly vulnerable children, at heart. After the Commission ofInquiry reported in 1957 that fluoridation was safe and effective, it was left to localauthorities to implement it.a Eight referenda were planned for November 1959. InDunedin, after the announcement for a referendum was made, the OtagoChildren’s Dental Health Association was formed to promote fluoridation with animpressive list of patrons including people connected with the Schools ofDentistry and Medicine of the University of Otago and the Health Department. Allthe referenda results were of heavy majorities against the introduction offluoridation. In Dunedin 23,000 voted of the 47,000 eligible to vote, more thanthose voting in the mayoral election. The result was 14,247 (63.2%) voted againstit and 8,312 for it. The majority was so decisive that the special votes were notcounted. Fluoridation was subsequently started in Dunedin in 1967 without afurther referendum. When the Otago District Health Board, based in Dunedin,sponsored referenda in North, West, South and Central Otago in 2007 they did notgive Dunedin residents an opportunity to express their views again. The resultsfrom the Waitaki District in North Otago in October 2007 were 6,363 (68.7%)against fluoride being added to the water and 2,900 being for it.

Despite the continued endorsement of fluoridation by prestigious authorities, it iswell to consider that Galileo noted: “In questions of science, the authority of athousand is not worth the humble reasoning of a single individual.” There is nosound evidence that swallowing fluoride helps to prevent tooth decay. There isgrowing concern about the role of fluoride as a neurodevelopmental toxin.b Thehuman brain does not complete its development until early adult life and there isan awareness that exposure to toxins during that time may interfere with a person’spotential. Perhaps one day the folly of having an Otago Children’s Dental HealthAssociation promoting fluoridation will be recognized and an Otago Children’sMental Health Association will be formed in Dunedin in recognition of theaMitchell A. Fluoridation in Dunedin: a study of pressure groups and public opinion. Political Science 1960;12(1):71-93. bGrandjean P, Landrigan PJ. Developmental neurotoxicity of industrial chemicals. Lancet 2006;368:2167-78.


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fundamental importance, for having a healthy and satisfying life, of avoidingexposure to neurotoxins, such as fluoride, during the developmental period of thebrain.

There is now general agreement that it is not sensible to take fluoridesystematically by swallowing when it acts topically on the surface of the teeth.aOver 600 professionals signed a statement, released on 9 August 2007, calling foran end to the practice of water fluoridation worldwide.b In February 2008 thenumber of professional signatories was over 1400. When an editorial commentingon the statement was published in Fluoride an editor’s note commented:c

“When founded 40 years ago, the International Society for Fluoride Research(ISFR) and its journal Fluoride were responding to an acute need for a more openclimate for conducting and publishing bio-medical and environmental fluoride-related research—a climate that would be free from restrictions imposed byeditorial policies of mainstream journals bent on upholding a particular point ofview about controversial issues such as the subject of the guest editorial below.Unfortunately, this veil of forced conformity, although beginning to be pierced,has not yet been entirely lifted, and, in a number of countries, it not only continuesto stifle and prevent funding of nonconforming research, but it also impedesproper care and concern for public health and welfare that are the hallmarks ofgenuine and honest science. Although the ISFR and Fluoride do not take anofficial position on the issue of water fluoridation, it is in a spirit of openness todiffering views that we are happy to publish this guest editorial.”

Some debate exists, however, as to whether topical fluoride, as in toothpaste, isof any value. Although topical fluoride gives consumers a choice and many see itas useful, there is evidence that fluoride can be harmful to the teeth. Large-scalestudies in Japan and India indicated that dental caries rates can actually be lowerwith less rather than more natural fluoride in the drinking water.def An adequateintake of calcium, along with other important tooth nutrients, which today areoften still deficient among children, even in developed countries, is far moreimportant for caries resistance than exposure to fluoride.ghi

Weston Price, DDS (Doctor of Dental Surgery), examined many primitive orFirst Nation people in widespread parts of the world in the early decades of thetwentieth century and found they had excellent teeth when they ate their traditionaldiets (Figure 50).j These diets were diverse and based on sea foods, domesticatedaBurgstahler AW, Limeback H. Retreat of the fluoride-fluoridation paradigm [editorial]. Fluoride 2004;37:239-42. bConnett P. Professionals mobilize to end water fluoridation worldwide [editorial]. Fluoride 2007;40:155-8.cBurgstahler AW. Editor’s note. Fluoride 2007;40:155.dBurgstahler AW. Fluoridated bottled water [editorial]. Fluoride 2006;39:252-4.eImai Y. Relation between fluoride concentration in drinking water and dental caries in Japan. Koku Eisei Gakkai Zasshi1972;22(2):144-96. [Abstracted in Fluoride 1973;6(4):248-51].

fRay SK, Ghosh S, Tiwari IC, Nagchaudhuri J, Kaur P, Reddy DCS. An epidemiological study of caries and its relationshipwith the fluoride content of drinking water in rural communities near Varanasi. Indian J Prev Soc Med 1981;12(3):154-8.[Abstracted in Fluoride 1983;16(1):69].

gTeotia SPS, Teotia M. Dental caries: a disorder of high fluoride and low dietary calcium interactions (30 years of personalresearch). Fluoride 1994;27:59-66.

hBurgstahler AW. Fluoridated bottled water [editorial]. Fluoride 2006;39:252-4.iWaldbott GL, Burgstahler AW, McKinney HL. Fluoridation: the great dilemma. Lawrence, Kansas: Coronado Press; 1978.p. 243, 377-80.

jPrice WA. Nutrition and physical degeneration. 7th ed. La Mesa, CA, USA: Price-Pottenger Nutrition Foundation; 2006. p.201-15.

Closing comments 63

animals, game, or dairy products. Some contained almost no plant foods whileothers had a variety of fruits, vegetables, grains, and legumes. In some, the foodwas mainly cooked while, in others, many foods, including animal foods, wereeaten raw. However, they shared several characteristics such as not containing anyrefined foods such as white sugar or flour. He found that more vitamins, both fatand water soluble, and minerals were present compared to modern diets. He foundthat parents who had excellent teeth and facial features on a traditional diet couldhave children with poorly developed narrow dental arches with crowded teeth,poor development of the nasal passages and the middle third of the face, andmarked dental decay when they used a modern diet including white flour andsugar. He noted that the Maoris of New Zealand were:

“… reported by early scientists to be themost physically perfect race living on theface of the earth. They accomplished thislargely through diet and a system of socialorganization designed to provide a highdegree of perfection in their offspring. To dothis they utilized foods from the sea veryliberally. The fact that they were able tomaintain an immunity to dental caries sohigh that only one tooth in two thousand hadbeen attacked by tooth decay (which isprobably as high a degree of immunity asthat of any contemporary race) is a strongargument in favor of their plan of life.”

Dr Price found the Maori in NewZealand had excellent teeth with adecay rate of less than 1 tooth in 2000teeth. As a person has about 28 teeth bythe age of 12, with the last four, thefour third molars not erupting untilafter the age of 18, when the total isthen 32, this correspondsapproximately to less than one personin 62 having dental decay or less than2% of Maoris without the use of addedfluoride. In 2006, in New Zealand,over 60% of Maori children in Year 8at school, about age 12, in bothfluoridated and nonfluoridated areas,had some dental decay.a

Clearly adding fluoride to water has not restored the teeth of Maori children backto the level of excellence they had in the past. In short, fluoridation has beenineffective. The ineffectiveness is the result of the practice not being built onsound science. The attempt to improve dental health with fluoridated water has notbeen effective and never had a sound scientific basis. In my view, the use of topical

aMinistry of Health Manatü Hauora, New Zealand Health Strategy DHB Toolkits [homepage on the Internet]. Wellington;Ministry of Health; c2007 [cited 2007 Nov 11]. Available from http://www.newhealth.govt.nz/tookits/; click on “Oral Health,”then on “Age 5 and year 8 health data from the School Dental Services 2006, then click on “Y8 2006” in the menu on thebottom of the screen.

Photograph courtesy of Joan Grinzi, RN,Executive Director,

Price-Pottenger Nutrition Foundation,7890 Broadway, Lemon Grove, CA 91945, USA.

Figure 50. Weston A Price, DDS, author ofNutrition and physical degeneration,published by the Price-Pottenger NutritionFoundation, http://www.ppnf.org.


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fluoride in dental products is also unsound and fluoride does not result in teethbeing decay free. The apparent reduction in decay in the first teeth to appear, thedeciduous teeth, is related to fluoride delaying the eruption of these teeth so thatthey have less time exposed to the decay-producing environment in the mouth.The timing of the eruption of the teeth is determined by thyroid hormones, andfluoride interferes with these.a

No clinically significant differences in the ratesof dental decay are found in the permanent teethwhen factors such as socioeconomic status andethnicity are controlled for.bcde Professor JohnSpencer and Jason Armfield compared the dentalcaries prevalence in children ingesting public(fluoridated) and nonpublic (nonfluoridated)water in South Australia. For deciduous teeth, asmall apparent benefit of fluoridation wasobserved but for permanent teeth “The effect ofconsumption of nonpublic water on permanentcaries experience was not significant.” MarkDiesendorf noted that this was consistent withother studies which found that fluoridation isineffective in permanent teeth.f

I consider that the relationship of diet to dentalhealth described by Weston Price will be a morerewarding path to follow than the blind alley offluoridation and topical fluoride.

That Western countries deliberately addedfluoride to their water supplies puzzled the lateProfessor Emerita Niloufer Chinoy, who wasonly too aware of the health problems caused bynaturally occurring fluoride in Gujarat State,India, and published 66 articles on fluoride,including its effects on the liver, kidneys,muscles, brain, testes, and ovaries (Figure 51).g

The impetus for fluoridation appears to have come from the need to solve anindustrial pollution problem rather than being the result of careful studies on howto reduce tooth decay. The green light for the procedure was given by OscarEwing, Director of Social Security in charge of the United States Public Health

aSchuld A. Is dental fluorosis caused by thyroid hormone disturbances? [editorial]. Fluoride 2005;38:91-4.bArmfield JM, Spencer AJ. Consumption of nonpublic water: implications for children’s caries experience. Community DentOral Epidemiol 2004;32:283-96. [abstract in Fluoride 2004(3):316].

cSpencer J. Dental research on fluoridation misused. Fluoride 2006;39:326-7.dDiesendorf M. Response to John Spencer’s obfuscation of the results of his own paper. Fluoride 2006;39:327-30. eSpittle B. Fluoridation promotion by scientists in 2006: an example of “tardive photopsia” [editorial]. Fluoride 2006;39:157-62.

fDiesendorf M. Comments by Dr Mark Diesendorf [on Armfield JM, Spencer AJ. Consumption of nonpublic water:implications for children’s caries experience. Community Dent Oral Epidemiol 2004;32:283-96]. Fluoride 2004(3):316-7.

gRao MV, Verma RJ, Jain NK, Jhala DD. Niloufer Jamshed Chinoy—Our cherished president, 1939–2006. Fluoride2006;39:81-5.

Figure 51. Niloufer Jamshed Chinoy, PhD, Professor Emerita, Gujarat University, Ahmedabad, India. 17 October 1939–8 May 2006. She was the first to report the genotoxic effect of fluoride on humans exposed to high levels of fluoride in drinking water. She published over 300 research and review articles in the scientific literature. She was puzzled that Western countries would voluntarily add fluoride to their water supplies when she was so aware of the damage it caused in Gujarat State, India.

Closing comments 65

Service, when the trials in Newburgh, New York, USA; Grand Rapids, Michigan,USA, and Brantford, Ontario, Canada, had been under way for only five years andbefore any permanent teeth of the children, born in these cities since the trialsstarted, had erupted.a The experiments were supposed to have run for 10–15 yearsbefore a decision on implementing fluoridation was made. No reliable scientificconclusions about the benefits of fluoridation on permanent teeth could possiblyhave been made when fluoridation was approved by Mr Ewing, as none of theseteeth had erupted in the children born under fluoridation.

In 1944 Ewing was employed by theAluminium Company of America (ALCOA),which had a serious problem disposing of thefluoride produced in aluminium smeltersbecause it contaminated the atmosphere,poisoned livestock and damaged plant life, at anannual salary of $750,000, although apparentlyno major ligation was pending at the time. A fewmonths later he was made Federal SecurityAdministrator with an announcement that hewas taking a big salary cut in order to serve hiscountry,b and as a member of PresidentTruman’s cabinet, he committed the PublicHealth Service to the promotion of fluoridation.In addition to the aluminium manufacturershaving a problem with fluoride pollution, themakers of the atomic bomb faced threats ofdamages due to the release of fluoride. Uraniumhexafluoride is used in the production ofenriched uranium. Christopher Bryson hasnoted, in his book The fluoride deception, thereis evidence that the Atomic Energy Commissionsupported fluoridation in an attempt to improvethe image of fluoride.c

Slowly a new light is dawning. The late DrJohn Colquhoun (Figure 52), was once an ardentfluoride promoter and in 1977 published a paper reporting how children’s toothdecay had declined in Auckland, particularly in the low-income areas followingfluoridation of its water.d He noted “I was so articulate and successful in mysupport of water fluoridation that my public service superiors in our capital city,Wellington, approached me and asked my to make fluoridation the subject of aworld study tour in 1980—after which I would become their expert on fluoridationand lead a campaign to promote fluoridation in those parts of New Zealand which

aWaldbott GL. A struggle with titans. New York: Carlton; 1965. p. 17, 41, 135.bWaldbott GL, Burgstahler AW, McKinney HL. Fluoridation: the great dilemma. Lawrence, Kansas: Coronado Press; 1978.p. 310-4.

cBryson C. The fluoride deception. New York: Seven Stories Press; 2004.dColquhoun J. The influence of social rank and fluoridation on dental treatment requirements. NZ Dent J 1977;73:146-8.

Figure 52. John Colquhoun, BDS, PhD. 4 January 1924–23 March 1999. Editor of Fluoride 1991–1998. While serving as an Auckland City Councillor for Glen Eden from 1955 to 1958 he persuaded the Mayor and fellow councillors to agree to fluoridate the Auckland water supply, apart from Onehunga. He was later the Principal Dental Officer for Auckland. His account of why, in 1983, he changed his mind about fluoridation is available in Fluoride 1997;31(2):179-85 at www.fluorideresearch.org


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had resisted having fluoride put into their drinking water.” However, by 1983,after looking at the world situation and studying the treatment statistics for all the12- and 13-year-old children in New Zealand, he became thoroughly convincedthat fluoridation caused more harm than good and had the courage to change hismind.a He found that when similar fluoridated and non-fluoridated areas werecompared, child dental health was slightly better in the non-fluoridated areas. Inaddition, he noted that tooth decay had started to decline in New Zealand wellbefore the use of water fluoridation and fluoridated toothpaste commenced andthat the decline continued after children had received fluoride all their lives so thatthe continuing decline could not be because of fluoride.b He noted that the causeof the decline could justifiably be described as a “mystery” but that it correlatedwell with changes in the diet that had occurred. While sugar consumption hadremained high, there had been an increased dietary intake of fresh fruit andvegetable, which contained important micronutrients, and of cheese which haddecay-inhibiting properties.

aColquhoun J. Why I changed my mind about water fluoridation. Perspect Biol Med 1997;41;29-44. Reprinted in Fluoride1998;21:103-118. Further articles discussing the paper are: Pollick H. Critical review of Why I changed my mind aboutwater fluoridation by John Colquhoun. Fluoride 1998;21:119-26. Colquhoun J. Response to critique of Howard Pollick.Fluoride 1998;31:127-8; Spittle B. Changing one’s mind: and examination of evidence from both sides of the fluoridationdebate. Fluoride 1998;31:235-44.

bColquhoun J. Fluorides and the decline in tooth decay in New Zealand. Fluoride 1993;26:125-34.

Solid line: mean number of decayed missing or filled teeth (dmft) Broken line: tooth decay prevalence (100 minus the % that are decay-free)Fluoridation (solid line) percent of population with fluoridated waterFluoride tooth paste (broken line): percent of total toothpaste sales.

Figure 53. 50-year decline in tooth decay of 5-year-olds in New Zealand.

Closing comments 67

He noted that the overall decline in permanent tooth decay was similar to that forprimary teeth but the pattern of decline was complicated by the sudden reductionof fillings in permanent teeth, reflected in an immediate very steep decline inDMFT and decay prevalence, following a change in 1977 in the diagnosticprocedure (Figure 54).

Until 1977 New Zealand school dental operators diagnosed as “decay” evenslight surface defects in permanent teeth. They inserted fillings at that earlieststage of possible decay. Such “thorough” criteria were applied to permanent teethrather than to primary teeth, and especially to older children receiving their finaltreatment before passing into the care of private dentists. In 1977 a new fillingpolicy was adopted. Instead of “in doubt, fill” the approach became “if in doubt,wait and see and spend more time on educational and preventive procedures.”

Solid line: mean number of decayed missing or filled teeth (dmft) Broken line: tooth decay prevalence (100 minus the % that are decay-free)Fluoridation (solid line) percent of population with fluoridated waterFluoride tooth paste (broken line): percent of total toothpaste sales.

Figure 54. 50-year declines in tooth decay (mean dmft or DMFT) forchildren aged 12–13, 8–9 and 5 years in New Zealand.


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It has been acknowledged that the decline in the DMFT and decay prevalenceafter the 1977 change was too steep to be wholly due to a reduction in tooth decayprevalence and surveys revealed no increase in the “D” (decayed) component ofthe DMFT scores compared to earlier surveys. The use of X-rays by earlyexaminers complicated the interpretation of the results. X-rays revealed smoothsurface decay between teeth which was often undetectable without X-rays and theuse of X-rays declined in 1948–1950 and in 1954–1955. Thus an apparentreduction in decay might have just reflected a decreased use of X-rays indiagnosis. However, even when the “with X-rays” results are disregarded, theoverall declines from 1950 to 1993 were found to be similar for permanent andprimary teeth.a

In the USA, Bill Osmunson, DDS, MPH, has also shown graphically the lack ofa relationship between the presence of fluoridation in the water at a state or countylevel and the presence of dental decay.b He found that having very good orexcellent teeth was related to having a high income rather than fluoridated water(Figures 55 and 56).

aColquhoun J. Fluorides and the decline in tooth decay in New Zealand. Fluoride 1993;26:125-34.bOsmunson B. Water fluoridation intervention: dentistry’s crown jewel or dark hour? [guest editorial]. Fluoride2007;40(4):214-21.

p

0.0

20.0

40.0

60.0

80.0

100.0

1 4 7 1013 16 19 22 25 28 31 34 37 40 43 46 49

%

The percentage of the whole population of fifty USA States and the District of Columbia on fluoridated water and the percentage in each state of high and low income reporting very good/excellent teeth

%

Fifty USA States and the District of Columbia ranked in order of the percentage of their whole population on fluoridated water

% high income reporting very good/excellent teeth

% low income reporting very good/excellent teeth

% receiving fluoridated water

Figure 55. Fifty USA States and the District of Columbia ranked in order of the percentage of their whole population on fluoridated water and the percentage in each state of high and low income reporting very good/excellent teeth. To arrive at the percentage of whole population fluoridated, the USGS percent of those served by public water was multiplied by the percent on fluoridated public water.

Closing comments 69

At an international level, Chris Neurath found that graphs of tooth decay trendsfor 12-year-olds in 24 countries, prepared using the most recent World HealthOrganization data, show that the decline in dental decay in recent decades has beencomparable in 16 nonfluoridated countries and 8 fluoridated countries which metthe inclusion criteria of having (i) a mean annual per capita income in the year2000 of US$10,000 or more, (ii) a population in the year 2000 of greater than 3million, and (iii) suitable WHO caries data available.a The WHO data do notsupport fluoridation as being a reason for the decline in dental decay in 12 yearolds that has been occurring in recent decades (Figures 57–59). Similarly,Professor Cheng, professor of epidemiology at Birmingham University, Sir IainChalmers, UK Cochrane Centre, and Professor Sheldon, Department of HealthStudies, University of York, who chaired the Advisory Board for the 2000 Yorkreport,b found that cavity rates had declined equally in fluoridated andnonfluoridated European countries over three decades.c They noted, “This trendaNeurath C. Tooth decay trends for 12 year olds in nonfluoridated and fluoridated countries. Fluoride 2005;38(4):324-5.bMcDonagh M, Whiting P, Bradley M, Cooper J, Sutton A, Chestnutt I, Misso K, Wilson P, Treasure E, Kleijen J. Asystematic review of public water fluoridation. Report 18. York: NHS Centre for Reviews and Dissemination, University ofYork; 2000.

cCheng KK, Chalmers I, Sheldon TA. Adding fluoride to water supplies. BMJ 2007;335:699-702.

0

10

20

30

40

50

60

70

80

90

100

1 5 9 13 17 21 25 29 33 37

%%

Thirty-nine Washington State counties plotted in order of the percentage of residents receiving fluoridated public water

The percentage of thirty-nine Washington State counties plotted in order of the percentage of residents receiving fluoridated public water and 3rd grade students evaluated for treated and untreated decayed or filled tooth surfaces

Figure 56. Thirty-nine Washington State counties plotted in order of the percentage of residents receiving fluoridated public water and 3rd grade students evaluated for treated and untreated decayed or filled tooth surfaces.


70

has occurred regardless of the concentration of fluoride in water or the use offluoridated salt.” They indicated that fluoridation, touted as a safer cavitypreventive, never was proven safe or effective and may be unethical. Theyconsidered that, “In the case of fluoridation, people should be aware of thelimitations of the evidence about its potential harms and that it would be almostimpossible to detect small but important risks (especially for chronic conditions)after introducing fluoridation.”

Figure 57. Tooth decay trends, as indicated by the DMFT Index (Decayed, Missing, or Filled Permanent Teeth), for 12 year olds in eight nonfluoridated countries (Austria, Belgium, Denmark, Finland, France, Germany, Greece, Italy) using World Health Organization data.

Figure 58. Tooth decay trends, as indicated by the DMFT Index (Decayed, Missing, or Filled Permanent Teeth), for 12 year olds in eight nonfluoridated countries (Japan, The Netherlands, Norway, Portugal, Spain, Sweden, Switzerland, The United Kingdom) using World Health Organization data.

Closing comments 71

In a like manner, to Dr Colquhoun changing his mind, Dr Richard Foulkes, inDecember 1973, in a two volume report entitled Health Security for BritishColumbians (colloquially termed “The Foulkes Report”) made 264recommendations, including one advocating that “mandatory” fluoridation ofdrinking water be introduced into the Province of British Columbia, Canada,Subsequently he realised the practice was no longer tenable and worked towardsending it (Figure 60).a

aBurgstahler AW. Richard Gordon Foulkes, MD. 1923–2007[in memoriam]. Fluoride 2007;40(4):225-7.

Figure 59. Tooth decay trends, as indicated by the DMFT Index (Decayed, Missing, or Filled Permanent Teeth), for 12 year olds in eight fluoridated countries (Australia, Canada, Hong Kong, Iceland, Israel, New Zealand, Singapore, The United States of America) using World Health Organization data.

Figure 60. Richard G Foulkes, MD. 15 January 1923–3 September 2007. Associate Editor of Fluoride 2000–2007. After recommending, in December 1973, in a two volume report Health security for British Columbians the “mandatory” fluoridation of drinking water, he changed his mind, in 1990, and spent much of his time speaking and writing on fluoride and fluoridation. He noted the impact of fluoridation on salmon species in an article published in Fluoride 1994;27:220-6.


72

Similarly, in April 1999, AssociateProfessor Hardy Limeback, Head ofPreventive Dentistry, Faculty ofDentistry, University of Toronto tooka public stand against waterfluoridation (Figure 61).a Togetherwith Professor Emeritus AlbertBurgstahler he noted that correctingcalcium deficiency is a much morecritical need than fluoride to preventtooth decay.bcdThey observed thatnutritionally deficient, refined sugar-rich diets—not lack of fluoride—areincreasingly recognized as theprincipal cause of continued andeven increasing high rates of toothdecay, especially in early childhood,occurring in fluoridated as well asnonfluoridated communities. Inaddition, they pointed out that therewas unrefuted evidence for caries-resistant teeth being formed byoptimal, complete dental nutritionand that the teeth of monkeys,hamsters, and rats, raised on anatural diet “do not developappreciable caries later on very highsugar diets but do develop carieswith an early high sugar diet duringtooth development.”e Domestic animals including young and adult cats and dogskept as pets, when fed nutritionally balanced diets rich in calcium and phosphorus,do not develop dental caries.

Emeritus Professor Paul Connett has spent over a decade working tirelessly inan attempt to bring science into the fluoridation debate (Figure 62). He considersthat the evidence is now clear that fluoridation is ineffective and unsafe that it isnow a matter of ensuring that this is reflected in legislation. He has helpedmobilize professionals representing a variety of disciplines but all having anabiding interest in ensuring that government public health and environmental

aLimeback H. Recent studies confirm old problems with water fluoridation: a fresh perspective [editorial]. Fluoride2001;34:1-6.

bPrice WA. Nutrition and physical degeneration: a comparison of primitive and modern diets and their effects. Los Angeles:Am Acad Appl Nutr; 1948, especially Ch.16.

cÅslander A. The technique of complete tooth nutrition. Pakistan Dent Rev 1968;18(4):2-9. Cf. Laplaud P. Preventionsociale de la carie dentaire. Thése pour le doctorat en chiurgie dentaire. Dactylo-Sorbonne, Paris, 1969. p. 125-6.

dTeotia SPS, Teotia M. Dental caries: a disorder of high fluoride and low dietary calcium interactions (30 years of personalresearch). Fluoride 1994;27:59-66.

eSognnaes RF. Is the susceptibility to dental caries influenced by factors operating during the period of tooth development?J Calif State Dent Assoc 1950;26(3) Suppl:37-52.

Figure 61. Hardy Limeback, BSc, PhD(Biochemistry), DDS. Associate Professor andHead, Preventive Dentistry, Faculty of Dentistry,University of Toronto, Ontario, Canada. In April2000 he wrote an open letter indicating that hewas now officially opposed to adding fluoride,especially hydrofluosilicic acid, to drinking waterbecause of new evidence for the lack ofeffectiveness of fluoridation in modern times andnew evidence for potential serious harm fromlong-term fluoride ingestion.

Closing comments 73

policies be determined honestly, with full attention paid to the latest scientificresearch and to ethical principles, to call for an end of the practice of waterfluoridation worldwide. He notes:a

“In the wake of a number of importantresearch reports, reviews, andgovernment advisories that have beenpublished or issued over the last fewyears, opponents of water fluoridationhave been reaching out to professionalsin medical, dental, scientific, academic,legal, and environmental fields, fromaround the world, to sign a statementcalling for an end to this practice.

“The Professionals’ Statement refers toeight “events” as the basis for an urgentcall to end fluoridation worldwide. Themost important event cited is thepublication in March 2006, of the 507-page National Research Council (NRC)report Fluoride in Drinking Water: AScientific Review of EPA'sStandards.bThis report, which took overthree and half years to complete, wasconducted by one of the most balancedpanels ever assembled in the US to lookat fluoride. Not directed to look at waterfluoridation per se, the panel reviewed alarge body of literature in which fluoridewas shown to have a statisticallysignificant association with a wide rangeof adverse effects. These include anincreased risk of bone fractures,decreased thyroid function, lowered IQ,arthritic-like conditions, and dentalfluorosis. Based on their analysis ofthese findings, the Statement emphasizes that, ‘Considering the substantial variation inindividual water intake, exposure to fluoride from many other sources, its accumulation inthe bone and other calcifying tissues, and the wide range of human sensitivity to any toxicsubstance, fluoridation provides NO margin of safety for many adverse effects, especiallylowered thyroid function.’

“Even though fluoridation promoters in the US and other fluoridating countries haveessentially ignored the NRC fluoride report, it did trigger at least one change in policy. TheAmerican Dental Association (ADA) is now advising parents not to use fluoridated tap waterto make up baby formula.cAlthough the ADA issued this advisory to reduce the risk of dentalfluorosis, which now impacts 32% of all American children and up to 40% in fluoridatedcommunities, the Professionals’ Statement points to the fact that fluoridated water contains

aConnett P. Professionals mobilize to end water fluoridation worldwide [editorial]. Fluoride 2007;40:155-8.bDoull J, Boekelheide K, Farishian BG, Isaacson RL, Klotz JB, Kumar JV, Limeback H, Poole C, Puzas JE, Reed N-MR,Thiessen KM, Webster TF, Committee on Fluoride in Drinking Water, Board on Environmental Studies and Toxicology,Division on Earth and Life Studies, National Research Council of the National Academies. Fluoride in drinking water: ascientific review of EPA’s standards. Washington, DC: The National Academies Press; 2006. [Contract No.: 68-C-03-013.Sponsored by the U.S. Environmental Protection Agency].

cAda.org [homepage on the Internet]. Chicago: American Dental Association; c1995–2007 [cited 2007 Aug 7]. Availablefrom: http://www.ada.org/public/topics/fluoride/infantsformula_faq.asp

Figure 62. Paul H Connett, BS (Honors), PhD., Emeritus Professor of Chemistry, St Lawrence University, Canton, New York, USA; Executive Director, Fluoride Action Network (FAN) www.FluorideAction.netHis 50 reasons to oppose fluoridation are posted on the FAN website together with the response from the Irish Government, and his detailed 87-page reply, dated January 20, 2006, to Mr John Molonoy.


74

250 times more fluoride than naturally present in mothers’ milk in nonfluoridatedcommunities (i.e., 1 ppm versus 0.004 ppm F ion).ab

“Buttressing health concerns, the Statement cites an extensive list of publications since1982 indicating there is little evidence of any significant difference in tooth decay betweenfluoridated communities and non-fluoridated communities. It also refers to the UKgovernment sponsored “York Review,” the first systematic review of water fluoridation, whichcould find no grade A studies (“high quality, bias unlikely”) demonstrating anti-caries benefitsof fluoridation.c Such dismal evidence for the benefits of fluoridation, despite theenthusiastic support given to this practice by the US Public Health Service for over 50 years,is consistent with another event discussed in the Statement: the concession by the Centersfor Disease Control and Prevention (CDC) in 1999 and again in 2001 that the predominantaction of fluoride on the teeth is topical, not systemic.de

“With such findings in hand, the Statement concludes that whatever the meager dentalbenefits may be, they do not justify the serious risks involved. The seriousness of those risksreceived further reinforcement by another event: the publication in May 2006 of a peer-reviewed, case-control study from Harvard University that found a 5- to 7- fold increase inosteosarcoma in young males associated with exposure to fluoridated water during their 6th,7th, and 8th years of life.f While the Statement cautiously admits that “this study does notprove a relationship between fluoridation and osteosarcoma beyond any doubt, the weightof evidence and the importance of the risk call for serious consideration.” As the late Dr JohnColquhoun, former editor of this journal, asked me in a videotaped interview in 1998, “Is onedeath of a teenage boy from osteosarcoma an adequate exchange for saving a part of acavity in a child’s tooth? I think when you put that issue to the lay public, they are mostlycommon sense people, they say no. If there is the slightest possibility of harm we shouldn’tbe adding it to the water, even if it does prevent cavities, for which there is now considerabledoubt.” The fact that this type of bone cancer is frequently fatal tilts the balanceoverwhelmingly in favor of ending water fluoridation.

“The Statement further calls upon “medical and dental professionals, members of waterdepartments, local officials, public health organizations, environmental groups and themedia to examine for themselves the new documentation that fluoridated water is ineffectiveand poses serious health risks.” In addition, the Statement points out: “It is no longeracceptable to simply rely on endorsements from agencies that continue to ignore the largebody of scientific evidence on this matter—especially the extensive citations in the NRC(2006) report.” …

“In summary, the Statement concludes: “It is time for the US, and the few remainingfluoridating countries, to recognize that fluoridation is outdated, has serious risks that faroutweigh any minor benefits, violates sound medical ethics, and denies freedom of choice.Fluoridation must be ended now.”

aBeltrán-Anguilar ED, Barker LK, Canto MT, Dye BA, Gooch BR, Griffen SO, Hyman J, Jaramillo F, Kingman A, Nowjack-Raymer R, Selwitz RH, Wu T. Surveillance for dental caries, dental sealants, tooth retention, edentulism, and enamelfluorosis—United States, 1988–1994 and 1999–2002 [surveillance summary]. MMWR Morb Mortal Wkly Rep 2005 Aug26;54(SS-3):1-43.

bDoull J, Boekelheide K, Farishian BG, Isaacson RL, Klotz JB, Kumar JV, Limeback H, Poole C, Puzas JE, Reed N-MR,Thiessen KM, Webster TF, Committee on Fluoride in Drinking Water, Board on Environmental Studies and Toxicology,Division on Earth and Life Studies, National Research Council of the National Academies. Fluoride in drinking water: ascientific review of EPA’s standards. Washington, DC: The National Academies Press; 2006. [Contract No.: 68-C-03-013.Sponsored by the U.S. Environmental Protection Agency]. p. 40.

cMcDonagh MS, Whiting PF, Wilson PM, Sutton AJ, Chestnutt I, Cooper J, Misso K, Bradley M, Treasure E, Kleijen J.Systematic review of water fluoridation. BMJ 2000;321:855-9. Full report available from: http://www.york.ac.uk/inst/crd/fluorid.htm. Analysis and comment available from: http://www.fluoridealert.org/york.htm.

dDivision of Oral Health, National Center for Chronic Disease Prevention and Health Promotion, Centers for DiseaseControl and Prevention. Achievements in Public Health, 1900–1999: Fluoridation of Drinking Water to Prevent DentalCaries. MMWR Morb Mortal Wkly Rep 1999 Oct 22;48(41):933-40. Available at: http://www.cdc.gov/epo/mmwr/preview/mmwrhtml/mm4841a1.htm

eAdair SM, Bowen WH, Burt BA, Kumar JV, Levy SM, Pendrys DG, Rozier RG, Selwitz RH, Stamm JW, Stookey GK,Whitford GM. Centers for Disease Control and Prevention. Recommendations for using fluoride to prevent and controldental caries in the United States [recommendations]. MMWR Morb Mortal Wkly Rep 2001 Aug 17;50(RR14):1-42.Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5014a1.htm.

fBassin EB, Wypij D, Davis RB, Mittleman MA. Age-specific fluoride exposure in drinking water and osteosarcoma (UnitedStates). Cancer Causes Control 2006;17:421-8. [abstracted in Fluoride 2006:39(2):152]

Closing comments 75

Dan Fagin, writing in Scientific American, January 2008, noted that theoverconsumption of fluoride can raise risks of disorders affecting the teeth, bones,the brain, and the thyroid gland.a He noted that the committee of the NationalResearch Council (NRC) that released the 2006 report Fluoride in drinking water:a scientific report on EPA’s standards concluded that fluoride could subtly alterendocrine function, especially in the thyroid and that the effects appeared to bestrongly influenced by diet and genetics.b Fagin reported that John Doull,Professor Emeritus of Pharmacology and Toxicology at the University of KansasMedical Center, who chaired the report said, “The thyroid changes do worry me.There are some things there that need to be explored. … What the committeefound is that we’ve gone with the status quo regarding fluoride for many years—for too long, really—and now we need to take a fresh look. In the scientificcommunity, people tend to think this is settled. I mean, when the U.S. surgeongeneral comes out and says this is one of the 10 greatest achievements of the 20thcentury, that’s a hard hurdle to get over. But when we looked at the studies thathave been done, we found that many of these questions are unsettled and we havemuch less information than we should, considering how long this [fluoridation]has been going on. I think that’s why fluoridation is still being challenged so manyyears after it began. In the face of ignorance, controversy is rampant.”

Dr Waldbott foresaw an end to the controversy but only when medicalpractitioners recognized the existence of the chronic fluoride toxicity syndromeand water fluoridation was made illegal. In 1978, four years before his death in1982, he wrote:

“As I enter the twilight of my long and active medical career, I know that the path I chose longago, though strewn with many obstacles, is the only one I could have taken. No moresatisfying nor humane goal can be attained than the truth which alleviates the suffering ofmankind. When medical practitioners everywhere also recognize the severity of theproblems of chronic fluoride toxicosis, and laws mandating truly safe drinking water aresincerely enforced, the health of millions will dramatically improve. Only then will fluoridationcease to be The Great Dilemma.”c

Twenty-five years later Dr Susheela has echoed these sentiments in her forewordto this book:

“I sincerely hope that, besides the general public, policy makers and health officials, in theinterest of the nation and the people they are sworn to serve, will learn from reading thisbook to recognize and desist from the ‘madness’ being exercised by ‘fluoridation of drinkingwater.’ “

In the meantime, many people using fluoridated drinking water will have illnesswith fatigue that is not relieved by sleep. Hopefully, this book will help those soaffected to realise that their health is in their own hands and that a cure is possible.

Feedback from readers will be welcomed by the author (contact details on p. ii.).

aFagin D. Second thoughts about fluoride: new research indicates that a cavity-fighting treatment could be risky if overused.Sci Am 2008:298:74-81.

bDoull J, Boekelheide K, Farishian BG, Isaacson RL, Klotz JB, Kumar JV, Limeback H, Poole C, Puzas JE, Reed N-MR,Thiessen KM, Webster TF, Committee on Fluoride in Drinking Water, Board on Environmental Studies and Toxicology,Division on Earth and Life Studies, National Research Council of the National Academies. Fluoride in drinking water: ascientific review of EPA’s standards. Washington, DC: The National Academies Press; 2006. Available for purchase onlineat: http://www.nap.edu.

cWaldbott GL, Burgstahler AW, McKinney HL. Fluoridation: the great dilemma. Lawrence, Kansas: Coronado Press; 1978.p. 384.


76

ABOUT THE AUTHOR

Bruce J Spittle, MB ChB withdistinction, DPM (Otago),Fellow of the Royal Australianand New Zealand College ofPsychiatrists (Figure 46).

Recipient of John MalcolmMemorial Prize in Physiologyand Biochemistry, WilliamLedingham Christie Prize inApplied Anatomy, GeigyPsychiatric Essay Prize, DunedinHospital Staff Fund Prize inPsychological Medicine,Ophthalmological Society ofNew Zealand Prize, Sir GordonBell Prize in Clinical Surgery,Batchelor Memorial Medal andPrize in Gynaecology andObstetrics (shared), Rita GilliesGardener Memorial Prize,Undergraduate distinctions inAnatomy, Physiology andBiochemistry, MedicalMicrobiology, and Preventiveand Social Medicine, SeniorScholarship in Medicine 1966, Fowler Scholarships in Medicine 1967 and 1968, andthe Travelling Scholarship in Medicine 1969.

Part-time Student Lecturer in Anatomy and Physiology to the Physiotherapy Class,Department of Anatomy, University of Otago Medical School, 1967–1969. StudentProsector for the Royal Australasian College of Surgeons, Department of Anatomy,University of Otago Medical School, 1967–1968. House Surgeon, Otago HospitalBoard, 1970–1971. Assistant Lecturer and Registrar, Department of Medicine,University of Otago Medical School and Otago Hospital Board, 1972. AssistantLecturer and Registrar, Department of Psychological Medicine, University of OtagoMedical School and Otago Hospital Board, 1973–1975. Otago Postgraduate MedicalFellow, 1976. Fulbright-Hays Research Scholar and Post-doctoral Fellow inPsychiatry, University of Missouri, Columbia, USA, 1977. Senior Lecturer,Department of Psychological Medicine, Dunedin School of Medicine, University ofOtago, New Zealand, and Consultant Psychiatrist for the Otago District Health Board,1978–2004.

Co-editor 1994–1998, Managing Editor 1999–2007 of Fluoride Quarterly Journal ofthe International Society for Fluoride Research. Dr Spittle has published severalarticles on the effects of fluoride on health and was a peer reviewer for the 2000University of York systematic review, A systematic review of water fluoridation. Hiswork is referred to in both the York review and the 2006 NRC report, Fluoride inDrinking Water: a scientific review of EPA’s standards. He received a distinctionaward in 2000 at the XXIIIrd conference of the International Society for FluorideResearch in Szczecin, Poland, for service to the Society

Figure 63. Professor Emeritus Albert W Burgstahler (left) and the author (right) at the Badaling section of the Great Wall of China prior to their attending the XXVIIth conference of the International Society for Fluoride Research, Beijing, China, 9–12 October 2007.

77

ALCOA 65allergies 4alligators 51, 58aluminum 61American Academy of

Allergy 47American Dental

Association 41anaesthetics 9antioxidants 10Armfield J 48, 60, 64Armstrong WD 48aspartate 5atomic bomb 65Atomic Energy Commission

65Austen KE 47Bachinskii PP 44Bassin EB 74Bentley EM 42Blaylock RL 4blood fluoride levels 7bone fluoride 43bone fractures 24Books: A struggle with

titans ii, 50A treatise on fluorosis 3-9, 22, 40-41

Fluoridation the great dilemma 2-6, 11-4, 36-8, 40, 44, 48-9, 62, 65, 75

The fluoride deception 24, 65

brain 1,60, 75breast cancer 2brick tea 6Bryson C 65Burgstahler AW v-vi, 2, 6,

42caimans 51, 53, 58calcification of membranes

9Carton RJ 60-1Centers for Disease Control

41

Case histories:Baby M 21Baby PH 21Baby PI 21-2Dr PK 22Master PM 22-3, 38Miss CD 11-2Miss GL 15-6Miss PF 20-1Mr AA 18Mr EH 16Mr FT 17Mr PC 19Mr PG 21Mr PL 22Mr PN 22-3Mr PO 23, 38Mr RM 14Mrs AM 17-8Mrs CMK 14-5Mrs EK 11, 34Mrs HM 13-4Mrs IH 20Mrs JM 17Mrs MH 11, 34Mrs MJ 12-3, 33, 35-8Mrs PA 18Mrs PB 18-9Mrs PD 20Mrs PE 20Mrs PJ 22Mrs RAJ 16-7Mrs RM 17Mrs SS 12Ms CH 25-6

Chalmers I 69Cheng KK 69chinchillas 50-1, 58Chinoy NJ 4, 64Chizzola maculae 3chloramines 25chronic fluoride toxicity 2-3,

9ciprofloxacin 9Colquhoun J 39, 65-7, 71-4Connett PH 39, 42, 44, 72-3

Cox WR 50-1Cristofoloni M 3Cutress TW 41-6, 48deiodinase enzymes 4dental fluorosis 3-4, 24, 59-

60Department of Health & HS

44developmental neurotoxins

1diabetes mellitus 4diagnosis of chronic F

toxicity 6Diesendorf M 64diet 62-3, 65, 67, 72Doull J 75Down Syndrome 24Dunedin 61duodenal mucosa 28Easley M 6Edson N 32EPA 60essentiality of fluoride 9Ewing O 64excitotoxicity 5extramammary Paget’s

disease 25Fagin D 75Fein NJ 42Feltman R 10-1Fitzmaurice P 41fluoridation 68-9fluoride in medication 9fluoride in milk 74Fluoride journal 48fluoroquinolone 9food contaminated with

fluoride 7-8Foulkes RG 71Galileo G 61Galletti PM 44glucose tolerance 26glutamate 5G-proteins 1, 4Grimbergen GW 10, 46-7guinea pigs 50

INDEX


78

halothane 9hamsters 50Harawira H 38-9Health Department 61Hileman B 42Hodgson Hon P 38-40, 59horses 54-8hydrofluosilicic acid 24hydrogen bonds 4hypothyroidism 4, 24, 44income 68-9infertility 29Institute of Environmental

Science and Research 41

intelligence 25iodine 1-2, 60ISFR 38, 48, 76Jacobs PN 51Justus C 54Kangaroos 58Kiritsy MC 42Kosel G 10-1lead 24-5Levy SM 42Limeback H 72Lin FF 47-8LOAEL 60Luke J 42Machaliński B 10,Maiers R 50Maoris 63Maupomé G 48McKinney L 2, 6MCL and MCLG 60mechanisms 4-5melatonin 23, 43microglial cells 5Ministry of Health 59Moolenburgh H 6, 10, 20-1,

46, 58-9

muscle weakness 27Neurath C 69-71New Zealand Commission

32, 59New Zealand Dental

Association 59NZ Medical Association 59non-ulcer dyspepsia 28Norrie CWM 32nutrition 10Osmunson B 68osteosarcoma 24, 74Otago Children’s Dental

Health Association 61Otago District Health

Board 59Oxman AD 40Patocka J 4Penso G 40Petraborg HT10,16, 37,

46-7phosphate fertilizers 24pineal gland 23-4, 42Plunket Society 59preskeletal fluorosis 9Price WD 62-4professionals statement

61, 73-4psychosomatic basis 34Public Health Service 41,

64-5Purchas J 38Quirk J 16-7rabbits 50radiograph of the forearm 9rats 51, 54, 58Reasons: fifty reasons 39,

41reason 12: 41, 43reason 22: 44reason 30: 42-3

referenda 61renal impairment 4Reviews: NHMRC 38, 46-

7NRC 10, 43-4, 46-8, 60,

73-5WHO 39, 41, 46-7York 39, 44-8, 74

Richardson HL 50Roholm K 49

Rousseau B 59Safe Drinking Water Act 61Schlesinger ER 49Seavey J 25sensitivity to fluoride 4sexual maturity 23Shelton TA 69silicofluorides 24skeletal fluorosis 43, 60skeletal muscle 27, 42sodium silicofluoride 10, 24Soriano M 29-32sources of fluoride 6Spencer J 64sperm morphology 29Spira L 33, 35Spittle BJ 2, 4, 18, 24-5, 27,

41, 46, 64, 66, 76Stannard JG 42Stecher PG 44Strunecká A 4Susheela vi, 3-4, 6-10, 22-

3, 27-9, 38, 40, 75-6tardive photopsia 27teeth, very good &

excellent 68-9thyroid function 60, 75thyroid hormone, TSH 4,

24, 44Tolstoy L 26-7tooth decay 70-1Truman H 65University of Otago 61uranium hexafluoride 65urine fluoride levels 7violent crime 24Waitaki District 60Waldbott GL 2, 4-10, 12-3,

33-8, 41, 44-8, 58, 75-6water disinfection agents

25WHO 40-1, 59Wilson B 39Zhao LB 47-8Zheng BS 7

I

Paua

“This book describes undeniable medical ill effects from fluoride added to

drinking water. … Those who deny reality and persist in discounting sensitivity to

fluoride in drinking water are like ostriches with their heads in the sand. They

would do well to heed what Dr Spittle has reported here and stop continuing to

promote and be misled by scientifically indefensible claims that do not hold up

under scrutiny.”

Albert W Burgstahler, PhD (Harvard, 1953)Professor Emeritus of ChemistryThe University of Kansas, USA.Editor, Fluoride (www.fluorideresearch.org)

ISBN 978-0-473-13092-3

Professor AK Susheela, PhD, FAMS (India), FASc, Ashoka Fellow

Executive Director

Fluorosis Research and Rural Development Foundation

Delhi, India.

“I am delighted with this book which very capably addresses a burning health

problem in many developed and developing countries that is afflicting millions of

men, women, and children. … I sincerely hope that, besides the general public,

policy makers and health officials, in the interest of the nation and the people they

are sworn to serve, will learn from reading this book to recognize and desist from

the “madness” being exercised by “fluoridation of drinking water.”

Bruce Spittle,

MB ChB (with distinction),

DPM (Otago), FRANZCP.

FLUORIDE FATIGUE outlines the chronic fatigue, not

relieved by extra sleep, and other various ill effects experienced by many when

they drink fluoridated water. The book notes how to test if fluoride is causing these

symptoms and, if it is, how they may often be cured.

Fluorides (as F)

IDLH Documentation

CAS number: Varies

NIOSH REL: 2.5 mg/m3 TWA

Current OSHA PEL: 2.5 mg/m3 TWA

1989 OSHA PEL: Same as current PEL

1993-1994 ACGIH TLV: 2.5 mg/m3 TWA

Description of Substance: Varies

Original (SCP) IDLH: 500 mg F/m3

Basis for original (SCP) IDLH: No data on acute inhalation toxicity are available on which to base the IDLH for fluorides. The chosen IDLH, therefore, has been estimated from the human acute lethal dose of 5 grams of sodium fluoride [Largent 1961 cited by AIHA 1965]. AIHA [1965] stated that the atmospheric concentration immediately hazardous to life is unknown, but "particulate fluorides are not likely to cause acute health problems among workmen unless large quantities are swallowed, or unless the more toxic decomposition products are involved. Exact concentrations producing immediate illness are unknown, but most likely are very high."

Short-term exposure guidelines: None developed

ACUTE TOXICITY DATA

Lethal concentration data:

Species

Reference

LC50

LCLo

Time

Adjusted 0.5-hr

LC (CF)

Derived value

SiF4 Rat

Carpenter et al. 1949

-----

69,220 mg/m3

4 hr

101,071 mg F/m3

10,107 mg F/m3

Lethal dose data:

Species

Reference

Route

LD50 (mg/kg)

LDLo (mg/kg)

Adjusted

LD

Derived

value

CaF2 G. pig Rat

Budavari 1989 Vest Akad Med Nk 1977

oral oral

----- -----

>5,000 4,250

>17,051 mg F/m3 14,488 mg F/m3

>1,705 mg F/m3 1,449 mg F/m3

AlF6·3Na Rabbit

Largent 1948

oral

-----

9,000

34,208 mg F/m3

3,421 mg F/m3

F6Si·2Na Mouse Rabbit

Gig Tr Prof Zabol 1988 Sine 1993

oral oral

----- -----

70 125

297 mg F/m3 530 mg F/m3

30 mg F/m3 53 mg F/m3

F6Si·Mg·6H2O G. pig

Frear 1969

oral

200

581 mg F/m3

58 mg F/m3

Human data: Skin rashes and complaints of the gastric, intestinal, circulatory, respiratory, and nervous systems have been reported in workers exposed chronically to concentrations ranging from 11 to 24 mg F/m3 [Roholm 1937]. Chronic exposures at concentrations greater than 24 mg F/m3 have been considered to be "elevated" and a concentration of 10 mg F/m3 was considered "excessive" [Collings et al. 1952]. It has also been stated that the atmospheric concentration immediately hazardous to life is unknown, and particulate fluorides are not likely to cause acute health problems among workers unless large quantities are ingested; concentrations producing immediate illness are unknown, but most likely are very high [AIHA 1965]. It has been stated that 5 grams of sodium fluoride is the probable lethal oral dose [Largent 1961]. [Note: An oral dose of 5 grams is equivalent to a worker being exposed to about 1,500 mg F/m3 for 30 minutes, assuming a breathing rate of 50 liters per minute and 100% absorption.]

Revised IDLH: 250 mg F/m3

Basis for revised IDLH: The revised IDLH for fluorides is 250 mg F/m3 based on toxicity data in humans [AIHA 1965; Largent 1961; Roholm 1937]. This may be a conservative value due to the lack of relevant acute toxicity data for workers exposed to concentrations above 250 mg F/m3.

REFERENCES:

1. AIHA [1965]. Fluoridebearing dusts and fumes (inorganic). In: Hygienic guide series. Am Ind Hyg Assoc J 26:426430.

2. Budavari S, ed. [1989]. 1669. Calcium fluoride. In: The merck index. 11th edition. Rahway, NJ: Merck & Co., Inc., p. 253.

3. Carpenter CP, Smyth HF Jr, Pozzani UC [1949]. The assay of acute vapor toxicity, and the grading and interpretation of results on 96 chemical compounds. J Ind Hyg Toxicol 31:343346.

4. Collings GH, Fleming RBL, May R, Bianconi WO [1952]. Absorption and excretion of inhaled fluorides. AMA Arch Ind Hyg Occup Med 6:368373.

5. Frear EH, ed. [1969]. Pesticide index. 4th ed. State College, PA: College Science Publishers, p. 265.

6. Gig Tr Prof Zabol [1988]; 53(11):80 (in Russian).

7. Largent EJ [1948]. The comparative toxicity of cryolite for rats and for rabbits. J Ind Hyg Toxicol 30:9297.

8. Largent EJ [1961]. Fluorosis, the health aspects of fluorine compounds. Columbus, OH: Ohio State University Press.

9. Roholm K [1937]. Fluorine intoxication. A clinical hygiene study with a review of the literature and some experimental investigations. London, England: H.K. Lewis & Co.

10. Sine C, ed. [1993]. Safsan®. In: Farm chemicals handbook '93, p. C302.

11. Vest Akad Med Nk [1977]; 2:2833 (in Russian).

Go back to the Documentation for Immediately Dangerous To Life or Health Concentrations (IDLHs)

This page was last updated 8/16/96:

Go back to the NIOSH home page or to the CDC home page.

FLUOTIC®

Hoechst Marion Roussel

Sodium Fluoride

Otospongiosis Therapy

http://www.rxmed.com/b.main/b2.pharmaceutical/b2.1.monographs/CPS-%20Monographs/CPS-%20(General%20Monographs-%20F)/FLUOTIC.html

Action And Clinical Pharmacology: Sodium fluoride acts partly by reducing bone resorption in the bone remodeling cycle and partly by increasing bone deposition. In organ culture of otospongiotic bone removed at operation, sodium fluoride increased radioactive calcium uptake. Analysis of the fluoride content of otospongiotic bone showed a higher fluoride content in untreated patients, than in the endochrondral bone of the noninvolved stapes, or the skeletal bone of the meatus. This is explained by the increased vascularity and bone remodeling activity, with increased opportunity of trace amounts of fluoride normally present in food and water, to contact the active focus. Following moderate dosage of sodium fluoride treatment for 6 months, the fluoride content of meatal bone and stapedial crura is barely perceptibly increased, but that of otospongiotic bone is increased nearly threefold compared to untreated conditions. Thus, otospongiotic bone has an affinity for circulating fluoride. The most convincing evidence of the effectiveness of sodium fluoride in reducing the activity of otospongiotic bone has been provided by enzyme studies in organ cultures of mature and immature specimens removed at surgery from treated and untreated patients. These investigations indicate a marked reduction in the enzyme activity of otospongiotic bone after treatment and during cultivation when fluoride is added to the culture medium. Of great significance has been the finding that cytotoxic enzymes, found in the majority of patients undergoing stapedectomy who had shown progression in sensorineural loss before operation, were very rarely found in similar patients after sodium fluoride treatment for 6 months. The toxic enzymes liberated by the active focus appear to be the mechanism of the sensorineural deterioration. Sodium fluoride acts partly as an enzyme inhibitor and partly to decrease osteoclastic resorption and to increase calcification of the focus, thus arresting its activity. Over 9 000 cases of otospongiotic patients treated with sodium fluoride have been reported in the medical literature since 1964. In most cases, between 40 to 60 mg of sodium fluoride a day was administered. The duration of treatment in these studies varied between 6 months to more

than 7 years in certain cases with no ill effects to the patients. The drug was generally well tolerated, especially in patients who received concomitantly a supplement of calcium and of vitamin D. The side effects most frequently reported were gastrointestinal complaints and musculoskeletal pain. There seems to be a relationship between therapeutic results and serum blood levels of fluoride and the optimum serum level appears to be from 8 to 12 µmol/L. The overall clinical results indicate a stabilization of the sensorineural loss of hearing in 80% of cases. Other symptoms such as tinnitus, vertigo and postural imbalance associated with otospongiosis may be improved in 50 to 80% of cases depending on the symptoms involved and the severity of the condition. Sodium fluoride is rapidly and almost completely absorbed from the gastrointestinal tract. Certain cations such as calcium, magnesium, aluminum and iron retard the absorption of fluoride ion by forming low solubility complexes in the gastrointestinal tract. Fluoride can be detected in all organs and tissues and especially in bones, thyroid, aorta and kidney. Fluoride is predominantly deposited in the skeleton and teeth and the degree of skeletal storage is related to age and intake. 50% of a given dose is excreted in the urine while the rest forms a chemical bond with bone. Indications And Clinical Uses: Nonsurgical cases: In patients with diagnosed neurosensorial hearing loss or tinnitus due to otospongiosis, especially if accompanied by a positive Schwartze sign indicating a vascular active focus. In patients with postural imbalance and/or vertigo caused by a lesion of the posterior labyrinth consecutive to otospongiosis and in patients with radiologically demonstrated demineralization of the cochlear capsule. Postsurgical cases: In patients where, following surgery, a soft vascular focus is encountered at the oval window or when the patient begins to experience progressive neurosensorial deterioration after successful stapedectomy. Contra-Indications: Pregnancy, Children and Adolescents: Since the safety of sodium fluoride has not been established in pregnant women, in children and adolescents up to 18 years old, the drug should not be used in these patients.

The drug is also contraindicated in severe renal insufficiency and in patients with an active peptic ulcer. Manufacturers' Warnings In Clinical States: Fluotic is not intended for dental use. The drug should preferably be prescribed with a daily supplement of calcium and vitamin D. Adverse Reactions: Sodium fluoride, at the recommended dosage, is usually well tolerated. Mild reactions consisting of gastrointestinal complaints, musculoskeletal pain and skin rash may occur. Symptoms And Treatment Of Overdose: Symptoms: Initial symptoms are secondary to the local action of sodium fluoride on the mucosa of the gastrointestinal tract. Salivation, nausea, abdominal pain, vomiting, and diarrhea are frequent. Systemic symptoms are varied and severe. The patient shows signs of increasing irritability of the nervous system, including paresthesias, a positive Chvostek sign, hyperactive reflexes, and tonic and clonic convulsions. These signs are related to the calcium binding effect of sodium fluoride. Hypocalcemia and hypoglycemia are frequent laboratory findings. The signs may be delayed for several hours. Pain in various muscle groups may occur. The blood pressure falls, presumably due to central vasomotor depression as well as a direct toxic action on cardiac muscle. The respiratory center is first stimulated and later depressed. Death usually results from either respiratory paralysis or cardiac failure. It is stated that the lethal dose of sodium fluoride for man is about 5 g; however, recovery has been reported in patients ingesting much larger doses, whereas a dose as low as 2 g has been fatal. In children as little as 500 mg of sodium fluoride may be fatal. Treatment: 1) Act quickly; 2) Start i.v. therapy with glucose in isotonic saline solution to maintain blood sugar and to have a venous channel available for transfusion in the event of shock; 3) Wash the stomach with limewater (0.15% calcium hydroxide solution) and then give limewater at frequent intervals; 4) Have calcium gluconate available for i.v. administration and watch closely for signs of tetany; 5) Maintain high urine volumes with parenteral fluid. Dosage And Administration: The average dose of Fluotic is 20 mg 3 times a day with meals. Clinical experience with sodium fluoride in osteoporosis, multiple myeloma and otospongiosis has shown that best results can be achieved by the addition of a calcium salt and of vitamin D. The addition of calcium, preferably calcium carbonate, 2 to 3 g a day, is

of prime importance since the use of sodium fluoride alone has been associated with a fall of serum calcium and hyper-parathyroidism. The net result is osteomalacia and increased bone resorption which may negate any beneficial effect that fluoride may have on bone formation. The effect of fluoride alone on bone is well known. Stimulation of osteoblastic bone formation occurs but in the absence of additional calcium, the bone is incompletely mineralized. Recalcification of the focus is the indication to reduce the dosage to a maintenance level, while continued or increased activity as shown by polytomography, positive Schwartze sign and neurosensorial loss progression are the indications to continue treatment or to increase the dosage. Control of patients: It is important to make periodic examinations of patients as follows: Clinical examination of patients should be made every 6 to 12 months along with a renal function test and a serum fluoride determination. Radiological examination to exclude the possibility of fluorosis should be made every 2 years. Clinical experience has shown that the optimum fluoride serum level should be between 8 to 12 µmol/L. Availability And Storage: Each red, enteric film-coated tablet contains: sodium fluoride 20 mg. Nonmedicinal ingredients: cellulose acetate phthalate, colloidal silicon dioxide, diethyl phthalate, FD&C red #40 aluminum lake, FD&C yellow #6 aluminum lake, hydroxypropyl methylcellulose, lactose, microcrystalline cellulose, polyethylene glycol, polysorbate, stearic acid and titanium dioxide. Gluten-free. Bottles of 100.

GERMAN CHEMICAL COMPANY TO PLEAD GUILTY

http://findarticles.com/p/articles/mi_pjus/is_200302/ai_3580832802/pg_1?tag=artBody;col1

US Department of Justice

WASHINGTON, D.C. -- Hoechst Aktiengesellschaft, an international

chemical conglomerate based in Germany, has agreed to plead guilty

and pay a $12 million fine for its participation in a conspiracy that

suppressed competition in the world markets for an industrial chemical

used in the production of commercial and consumer products,

including pharmaceuticals, herbicides, and plastic additives, the

Department of Justice announced today. The chemical,

monochloroacetic acid (MCAA), has annual U.S. sales of approximately

$50 million.

In a one-count felony case filed today in U.S. District Court in San

Francisco, Hoechst was charged with fixing prices and allocating

market shares of MCAA sold in the U.S. and elsewhere from

September 1995 until June 1997.

Hoechst will be the third company to plead guilty to participating in

this conspiracy. In Hoechst's plea agreement, which requires court

approval, the company has agreed to pay a $12 million fine and to

cooperate fully with the ongoing federal investigation of

anticompetitive behavior in the MCAA market.

In June 2001, the Dutch chemical giant Akzo Nobel Chemicals BV

pleaded guilty and was sentenced to pay a $12 million fine for its

involvement in this conspiracy. Elf Atochem of France pleaded guilty to

participating in the conspiracy and was fined $5 million in March 2002.

"The Antitrust Division has demonstrated its commitment to identifying

and prosecuting all companies, domestic or foreign, that harm

American businesses and consumers," said R. Hewitt Pate, Acting

Assistant Attorney General in charge of the Department's Antitrust

Division.

Hoechst is charged with conspiring, through its officers and

employees, to suppress and eliminate competition among MCAA

producers by:

participating in meetings and conversations to discuss the prices and

market shares of MCAA sold in the U.S. and elsewhere; agreeing,

during those meetings and conversations, to charge prices at certain

levels and otherwise to increase and maintain prices of MCAA sold in

the U.S. and elsewhere; agreeing, during those meetings and

conversations, to allocate among major MCAA producers the market

shares of MCAA to be sold in the U.S. and elsewhere; issuing price

announcements and price quotations in accordance with the

agreements reached; and exchanging information on sales of MCAA in

the U.S. and elsewhere, for the purpose of monitoring and enforcing

adherence to the agreed-upon prices and market shares.

James M. Griffin, the Antitrust Division's Deputy Assistant Attorney

General for Criminal Enforcement, stated, "Hoechst's decision to plead

guilty indicates the strength of the Antitrust Division's enforcement

powers against international cartels."

The charge against Hoechst was brought under Section 1 of the

Sherman Act, which carries a maximum fine of $10 million for

corporations. The maximum fine may be increased to twice the gain

derived from the crime or twice the loss suffered by the victims of the

crime if either of those amounts is greater than the statutory

maximum.

The charge announced today stems from continuing investigations

being conducted by the Antitrust Division's San Francisco Field Office

and the Federal Bureau of Investigation in San Francisco.

German firm fined under FD&C Act - Hoechst AG, federal Food, Drug, and Cosmetic Act

http://findarticles.com/p/articles/mi_m1370/is_/ai_11348640

FDA Consumer, Sept, 1991 by Paula Kurtzweil

A large German pharmaceutical and chemical company that does

business in the United States and one of its former research directors

have become the first foreign entities to be successfully prosecuted

under the Federal Food, Drug, and Cosmetic Act for conduct that

occurred overseas.

Hoechst Aktiengesellschaft, or Hoechst AG, of Frankfurt, Germany, and

Rainer Zapf, M.D., a former director of the company's clinical research

division, were sentenced last April in the U.S. District Court for the

District of New Jersey for failing to report in a timely manner the

deaths of two foreign patients associated with the use of the

company's antidepressant nomifensine maleate.

FDA regulations require drug manufacturers to report to FDA serious

and unexpected adverse drug reactions both before and after the drug

is approved for marketing in the United States. During clinical testing

before approval), such adverse drug reactions must be reported within

three days. After approval, significant adverse drug reactions must be

reported within 15 days after the manufacturer has received the

information.

These reports are required whether the adverse reactions occurred in

the United States or elsewhere. Until now, FDA has charged only U.S.

drug manufacturers with failing to file such reports.

In the Hoechst AG case, FDA determined that the deaths of an Italian

woman, age unknown, in 1980 and a 57-year-old French woman in

1984-before die drug was approved in the United States - were

associated with the use of nomifensine and that Hoechst AG had

known of the deaths but failed to report them until 1986, months after

the drug had been withdrawn from the market.

The drug was approved by FDA in 1984 and marketed in this country

as a prescription drug under the trade name Merital between 1985 and

1986 by the company's subsidiary, Hoechst-Roussel Pharmaceuticals

Inc., of Somerville, N.J.

Hoechst AG, which had marketed the drug in almost 80 countries,

voluntarily stopped selling it in January 1986 because of a rising

incidence of hemolytic anemia associated with its use. Hemolytic

anemia is a potentially fatal condition in which the oxygen-carrying red

blood cells break down faster than the body can replace them.

Nine other deaths involving hemolytic anemia - including three deaths

in the United States - were reported in people who used the drug.

(Most of these were promptly reported to FDA.) However, the agency

was able to confirm only the deaths of the two European women as

definitely associated with nomifensine.

In August 1986, shortly after Hoechst AG halted sales of nomifensine,

FDA began an investigation of the company's U.S. subsidiary, Hoechst-

Roussel. The investigation stemmed from a congressional hearing on

Merital earlier in the year.

The investigation, which lasted a year and a half, was lengthy because

officials of the U.S. company refused to allow personnel who had been

directly involved in analyzing and reporting adverse drug reactions to

speak to FDA investigators. In addition, months often passed before

they provided written answers to investigators' questions.

Despite the obstacles, investigators pieced together evidence showing

Hoechst AG and Zapf had been aware of the deaths of the two

European women shortly after they had occurred but had failed to

report them to FDA as required. FDA found no evidence that Hoechst-

Roussel had withheld such information from FDA.

In April 1989, FDA forwarded its evidence to the Department of

Justice. On Dec. 12, 1990, the U.S. attorney for the District of New

Jersey charged Hoechst AG with failing to report the deaths of the two

European women, first while Merital was being tested and then again

after it was approved. Zapf was charged with pre-approval violations.

No charges were filed against Hoechst-Roussel.

On April 26, 1991, Hoechst AG and Zapf pleaded guilty to the charges.

The company was fined $202,000, and Zapf, $2,200. Both fines were

the maximum allowed under then existing law.

Fluoride: The Ultimate Cluster Flux Folder 2A

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