VA Radiation & Physical Exposure Service

Depleted Uranium (DU) and Toxic Embedded

FragmentsMelissa A. McDiarmid, MD, MPH

Joanna Gaitens, PhD, MSN/MPH

Katherine S. Squibb, PhD

VA Maryland Health Care System

University of Maryland

Baltimore, USA

DisclaimerDisclaimer

The views expressed in this presentation are those of the author and do not necessarily represent the position of the Department of Veterans Affairs or the United States Government

I have no known conflicts of interest other than that I work for the Department of Veterans Affairs

Topics we will cover: Environmental exposures of concern to

Veterans: Depleted Uranium (DU), Toxic Embedded Fragments

The potential toxicity of DU and retained embedded fragments

Programs available through the VA for Veterans with concerns about these exposures

How Veterans enroll in these programs

What is Depleted Uranium?

By-product of uranium enrichment process through which 235U is extracted from natural uranium for use as nuclear fuel

Leftover is “depleted” with 235U/238U isotopic ratio = 0.245%

Isotopic Comparison of Natural and

Depleted Uranium

Radioactivity

Natural Uranium

Depleted Uranium

Isotope Ci/g Concentration

of isotopes Concentration

of isotopes

234U 6200.0 0.0058% 0.001%

235U 2.2 0.72% 0.2%

238U 0.33 99.28% 99.8%

Relative Radioactivity

1 0.6

*

Chemical vs Radiological Toxicity

Chemical toxicityU234 = U235 = U238

Radiological toxicitySpecific activity: U234 >>> U235 > U238

so Natural U > DU

Primary decay = alpha particles and gamma rays

Military Uses of DU

Tank armor for increased resistance to enemy projectiles

Munitions to increase penetrating power

Used in battle for first

time in Gulf War

Gulf War and OEF/OIF Exposures to DU

Friendly-fire incidents exposed US soldiers to: DU shrapnel Aerosolized DU oxides

Inhalation, ingestion, wound contamination

Burning of munitions storage facility Decontamination of military equipment

DU Embedded Fragment

Potential Toxicity of DU

Systemic effects due to release of U ions to circulation and uptake by organs Specific target organs of U

Kidney Bone

Primarily chemical toxicity of U

Local effects on tissue surrounding DU embedded fragments May be combination of chemical toxicity and

radioactivity of U

Mission of the DU Follow-Up Program

Since 1993:

To provide clinical surveillance for the ‘friendly fire’ DU-exposed GWI Veterans

Since 1998:

To provide biologic monitoring by mail for DU for all GWI and OIF Veterans

The next several slides will cover:

Depleted Uranium Follow-Up Program Purpose Surveillance protocol Findings

Depleted Uranium Mail-In Surveillance Program Purpose Findings

Purpose of DU Friendly Fire Victim Surveillance

Determine health effects, if any, in DU exposed populations (GWI, OEF, OIF)

Develop methods to measure DU exposure in this novel exposure mode (embedded fragments)

Examine surgical and medical management of embedded fragments– still an issue!

Surveillance Protocol during Biennial Inpatient Evaluation

Complete history (medical, social, family, reproductive, occupational exposure, partner)

Extensive laboratory studies (hematology, serum chemistry, neuroendocrine, urinalysis, urine, semen and blood uranium, renal markers, semen analysis)

Chromosomal analysis (mutations, chromosomal aberrations)

Neurocognitive testing Focus group/risk communication

Summary of Surveillance through 2009

Gulf War OIFYear DU-exposed Non-exposed DU-exposed Total

1993-4 33 33

1997 29 38 67

1999 21 + 29 new 50

2001 31 + 8 new 39

2003 32 32

2005 30 + 4 new 3 37

2007

2009

32 + 3 new

36 + 2 new

2 (1 new)

2

37

40

79 unique cases have been evaluated from Gulf War 4 Unique cases have been evaluated from OIF

Mean Urine Uranium Levels through 2007

for the 2009 Cohort

0.001

0.01

0.1

1

10

100

Samples Ranked from Low to High (n=36)

Uri

ne

Ura

niu

m (

μg

U/g

cre

atin

ine)

No shrapnel; No DU (n=19)

Shrapnel; No DU (n=2)

No shrapnel; DU (n=2)

Shrapnel; DU (n=13)

Thun 1975 = 65.1 µg/L

Occupational Decision Level = 0.8 µg/L

Dietary Limit = 0.365 g/L

DU Cut point = 0.1 µg/g creatinine

NHANES 95th% = 0.043 µg/g creatinine

Clinical Findings

No clinically significant differences detected between low and high uranium exposure groups Hematology Neuroendocrine Chemistries Neurocognitive

To provide urine uranium surveillance by mail for any Veteran requesting testing

Second Activity of DU Program:

Purpose of the DU Urine Biomonitoring Program

Determine urine uranium concentrations in Veterans from GWI and forward

Passively survey for exposure scenarios linked to DU exposure other than friendly fire

Provide assistance to Veterans’ primary care providers in interpreting results and answering Veterans questions

Summary of Mail-in Activity through May 31, 2010

Sampling kits requestedN > 4597

1682 > 2915

Samples tested as of 5/31/10

N = 3136

GWI OIFTOTAL

Total uraniumonly 476

Total uranium& DU 813

Total uranium& DU 1847

Positive for DUN = 4*

31

*All friendly fire

Toxic Embedded Fragment Surveillance Center (TEFSC)

and Registry

Background Traumatic injuries via contact with

improvised explosive devices (IEDs) are a major concern in Iraq, and increasingly in Afghanistan More than 40,000 soldiers with traumatic injuries

may have retained embedded fragments.

IEDs are packed with heterogeneous material that may lead to local and systemic adverse health effects.

VHA directed to address the issue of embedded fragments

Presidential Task Force Recommendation P-7 directed the VHA to establish a registry and medical surveillance program for Veterans with embedded fragments

Health concerns related to embedded fragments

Local effects Risk of the development of tumors at the

fragment sites

Systemic effects Risk of target organ effects arising from

chemicals released from fragments

Fate of DU Metal Fragments in Rat Muscle In Situ

Correlation of radiographic appearance with histologic appearance. (A) Thick fibrotic capsule with shards of corroded DU in lumen; (B) thick cellular capsule lined by squamous metaplasia, particles, and shards of corroded DU in wall and lumen; (C) particles and shards of disintegrated DU fragment scattered throughout a soft tissue sarcoma (Hahn et al, 2002).

1995 film 2001 filmChange in DU fragment appearance over time; suggests oxidation in situ and removal is warranted.

Embedded DU Fragment in 1991 Gulf War Veteran

New Alloy Used in Munitions: W/Ni/Co

Metastatic tumors caused by implanted tungsten alloy (W/Ni/Co) fragments in rats Rhabdomyosarcomas

rapidly metastasize to lung Survival time is

significantly reduced

Kalinich et al. Env. Hlth Perspec.113: 729-734, 2005

Evidence supports development of Toxic Embedded Fragment

Surveillance Center (TEFSC) Local Effects

Evidence from DU Program and medical device and fragment literature

New studies of metal implanted animals with new tungsten alloy (W, Co, Ni) demonstrating rapid carcinogenesis

Systemic Effects Known renal, reproductive and neurological

effects of metals (e.g. Pb, Cd, Ni, Mn, Cu)

The next several slides will cover:

Toxic Embedded Fragment Surveillance Center Mission Specific functions of TEFSC

VA’s Embedded Fragment Registry Purpose of the registry Eligibility criteria Screening process for identifying eligible

veterans Data captured in the registry

VA Toxic Embedded Fragment Surveillance Center

Established at Baltimore VA Medical Center

Mission: To provide care and active medical surveillance for Veterans with retained embedded fragments

Functions of TEFSC

Fragment Characterization

Biomonitoring & Medical Surveillance

Registry Development

Case Consultation

Chemical analysis of removed fragments Surface chemistry Total fragment composition

Analysis of tissue surrounding fragments Chemical analysis of tissue Characterization of tissue morphology

Histology- proliferative cells, neoplastic cells

Analyzing fragment composition is an essential

function of TEFSC

Summary of Composition of Fragments from

Military Personnel 2006-2008 (AFIP data)*407 fragments analyzed

1 radioactive

44 Organic materials 10 plastic & polymers 1 fabric and 1 wood26 Stones

336 non-radioactive alloys (steel & brass)

and non-alloyed metals

DU with traces ofAl, Cr, Cu, Ti, Zn

Fe, Cu, Al, Ni, Pb, Zn with traces of other elements

including Cr, Mn, Sn, Sb, Ti, W

*Division of Biophysical Toxicology, Armed Forces Institute of PathologyCenteno JA, et al. (2009)

70 Non-Metals337 Metals

Fragment data informs biomonitoring and medical

surveillance protocol

Fragment composition data helps: Identify a list of toxicants to include in

biomonitoring panels Identify outcomes of concern and means of

surveillance Identify potential biomarkers of early effect

Fragment Analysis Process

1. TEFSC sends fragment collection kit to requesting VA

2. VA obtains fragment from Veteran and mails completed kit to TEFSC

4. TEFSC sends result letters to Veteran and VA Provider

3. Fragment is analyzed

Biological Specimens also provide insight into exposure

Toxicants of interest Metals: Al, As, Cd, Cr, Co, Cu, Fe, Mn, Ni, Pb,

U, W, Zn Plastics/polymer components: Isocyanate,

Acrylics, Diethylhexylphthalates Others: Based on fragment analysis data

Biological Specimens Urine, blood, other body fluids when indicated

Biological Monitoring Process

1. TEFSC sends kit is sent to requesting VA

2. Veteran provides 24-hour urine sample and completes questionnaire

3. VA mails completed kit to Baltimore VA

5. TEFSC sends result letters to Veteran and VA Provider

4. Specimen and questionnaire are analyzed

Surveillance protocol involves periodic follow-up to identify

potential health outcomes Perform baseline urinalysis

based on chemical composition of removed fragment(s)

Perform periodic follow up urinalysis to identify specific biomarkers of exposure and effects

based on baseline results

Conduct periodic radiologic surveillance of embedded fragment location and shape

Consider target organ surveillance for toxicants of concern

Purpose of the VA Embedded Fragment Registry

To track, monitor and provide appropriate medical care and follow up for Veterans with embedded fragments resulting from injuries sustained during their tour of duty Identify Veterans who served in Iraq and Afghanistan

and who have embedded fragments Identify health concerns associated with embedded

fragments Develop medical and surgical management guidelines

for Veterans with embedded fragments

Any Veteran who served in Operation Enduring Freedom or

Operation Iraqi Freedom who has or likely has a retained fragment as

the result of an injury received while serving in the area of conflict

are eligible for inclusion into the registry.

Individuals with embedded fragments are identified by

both the VA and the DoD

The VA has created a process to screen Veterans for embedded fragments at their local VA facility

DoD is creating their own “Embedded Metal Fragment Registry”

The DoD and VA are collaborating to ensure that all Veterans who have embedded fragments are identified

and receive appropriate follow-up care.

The VA Screening process for Veterans with fragments uses the

“Clinical Reminder” system

Screening Questions Do you have or suspect you have a retained

fragment as the result of an injury received while serving in the area of conflict?- Were you injured by a bullet? - Were you injured as a result of a blast or explosion?

- Were you in or on a vehicle at the time of the blast or explosion? - Was the blast or explosion caused by: IED, RPG, land mine, grenade, enemy fire, friendly fire, don’t know, or other?

- Did you have shrapnel, fragments or bullets removed during surgery?

- If yes, were they sent to the lab for analysis? - Do you have retained shrapnel, fragments or bullets in your body?

- If yes, have they been documented by radiograph?

Screening information is automatically captured in the

VA’s Embedded Fragment Registry

Then TEFSC determines if the following services are needed: Fragment analysis Biological monitoring Clinical Consultation

The VA’s registry will also identify if the individual is in DoD’s registry AND if the individual had a

fragment removed and analyzed by DoD.

The Embedded Fragment Registry will capture “basic”

data Screening Details

Answers to screening question Local VA contact person

Referral Status Demographic Information Healthcare Information

Contact information for Primary Care Provider VA facility where Veteran receives care

…and Exposure/Health Details Injury and exposure information

Developed standardized exposure questionnaire

Biomonitoring data Tests ordered, analyses methods, results,

interpretation of results, tracking information

Fragment analysis data Analyses methods, results, interpretation of results,

tracking information

Health outcomes Results of specific clinical tests ICD-9 codes

Much of the registry data will come from existing data sources

Data Registry Sources

Screening data

Patient’s electronic medical record

Demographic information

Healthcare information

Health outcome data

Biomonitoring Data Baltimore VA Lab system

Fragment Data DoD electronic files

The registry will help the

VA and the DoD

refine how cases are identified

and

provide appropriate medical care for individuals with embedded fragments.

Conclusion

Toxic Embedded Fragment Surveillance Center

andDepleted Uranium Program

1-800-815-7533