Fluoride and Fluorosis Old and New

8/2/2019 Fluoride and Fluorosis Old and New

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Fluoride and Fluorosis

Old and New


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PREVELANCE OF FLOUROSIS

Prevalent all over the worldInternational Status

National Status


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FLUORIDEEXPOSURE

INTERNATIONAL STATUS


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FLUORIDEEXPOSURE

NATIONAL STATUS

People forced to consume water having even

up to 44mg/l FRural population is the major sufferer

17 states are endemic

4 States: 30% districts affected

8 States: 30-50% districts affected

5 states: 50-100% districts affected


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FLUORIDEEXPOSURE

RAJASTHAN STATE STATUS

All 32 districts are endemicWorst affected districts are

Nagaur, Tonk, Jaipur, Sikar, Barmer,

Jodhpur, Ajmer, Sirohi, Jhunjhunu,

Churu, Bikaner, Ganganagar


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Sources of fluoride insurface or ground waters

The sea

The atmosphere The earth's crust

Rock forming Minerals

Rocks

Commercial ores

Soils


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ROCK FORMING MINERAL

The rocks rich in fluoride are:

Flurospar CaF2 ( Sedimentary rocks, lime

stones, sand stones)

Cryolite Na3AlFPO6 ( Igneous, Granite)

Fluoroapatite Ca3(PO)2 Ca(FCl)2


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SOURCES OF FLUORIDE IN HUMANS

Water

Food

Drugs: Sodium fluoride, Niflumic acid,fluoride mouth rinse

Air : aluminum, phosphate fertilizers

Cosmetics:Toothpastes & Mouth Rinses Other : Bottled mineral water

Source - Villena-RS et al. 1998


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CHEMOBIOKINETICS & METABOLISM

Rapidly absorbed (GIT) & lungs (peaks after 30min)

Distributes in bloodExcreted via renal sys.( 50 - 90% over 4-6 h )

low conc. in saliva, sweat, and milk.

passes through the placenta also

90 % of remaining gets accumulated in calcifiedtissues (esp. skeleton and teeth).

Biological half-life of bound F is several years.Source:Ericsson, 1958; Weddle and Muhler, 1954;Hudge, 1965


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Excess fluoride damages

Teeth

Bones

Joints Muscles

IN FINAL STAGE Paralysis

Premature aging


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Effects on Teeth

Discoloration Delayed eruption

Chipping of Edges

Pitting


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Dental Fluorosis


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Dental Fluorosis


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Dental Fluorosis


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DENTAL FLUOROSIS

Effect on Developing Fully developed

Teeth Teeth Teeth

Systemic ++++ +

effect

Direct +++ +++

effect


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Bones and Joints

Heel Pain

Painful and restricted joint movement

Deformities in legs

Hunch back


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Painful and restricted joint movement

(Bones and Joints)


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Deformities in legs

(Bones and Joints)

Conditions like osteo arthritis due to damage of

Articular Cartilage (Basically structured by GAG

and Sialic acid)


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Hunch back

(Bones and Joints)


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Hunch back

(Bones and Joints)


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Skeletal fluorosis


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Skeletal fluorosis

Severe OsteopeniaNormal serum Calcium, PTH Hyper secretion, Elevated Osteocalcin, and,

normal 25 OHD and 1,25 (OH)2 D (Ref.: Srivastava RN et al, 1989)


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Calcification of interosseous membrane(Skeletal fluorosis)


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Clinical Fluorosis


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Extreme Cases

Paralysis

Muscular Wasting

Premature Aging


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Paralysis


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Bone and Muscle


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Premature Aging


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Neurological manifestation(NSM)

Nervousness & Depression

Tingling sensation in fingers and toes

Excessive thirst and tendency tourinate frequently (Polydypsia and

plyurea): The control by brain appears to

be adversely affected)

Headache Mental efficiency :reduced mental work

capacity (MWC); hair zinc content ;

decreased 5-hydroxy indole acetic acid

and increased norepinephrine in rat brain


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Muscular manifestations(NSM)

Muscle Weakness &

stiffness

Pain in the muscle and

loss of muscle power


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Skin manifestation(NSM)

Very painful skin rashes,

which are peri vascular

inflammation. Prevalent

in women and children

Pinkish red or bluish redspots, round or oval shape

on the skin that fade and

clear up with in 7-10 days.


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Gastro - intestinal problems(NSM)

Acute abdominal pain

Diarrhea

Constipation

Blood in stool

Bloated felling (Gas)

Tenderness in stomach Feeling of nausea

Mouth sores


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Gastro - intestinal problems(NSM)

Gastric manifestations are mediated by:

1. Local actionMediatedthrough formation of HF,which dissipates theBicarbonate gradient in visiblemucous (mucin)

2. Systemic ActionMediatedthrough PTH causing breakdown of Mucin layer ofStomach


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Urinary tract manifestations(NSM)

Urine may be much lessin volume

Yellow red in color

Itching in the region.

Kidney's


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PregnancyIn vivo effects

SGA new born babies

are more common Effects primary tooth

budding in infant


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T- CELL FUNCTION

Fluoride effects the cell mediatedimmunity by modifying T-cell functions

Clinically Important in

Immunization

may modify the immune responseto vaccination


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R.B.C;Ligament & Blood vessels:Thyroid(NSM)

RBC: Formation of eccynocytes. Eccynocytes

have less life span causing anemia

Ligaments and Blood Vessel Calcification

Fluoride and thyroid: Fluoride has inhibitoryeffect on iodine uptake causing manifestations of

hypothyroidism


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Cancer;Diabetes;Lactation(NSM)

Fluoride and Cancer: Sodium fluoride promotedthe growth of precancerous lesions of the liverinduced by DEN in rats.

Fluoride and diabetes: significant abnormalities inglucose tolerance which are reversible uponremoval of the excess fluoride. (Trivedi-N et al. ,1993)

Fluorosis and lactation: Inhibition of lactation in

lactating rats; During chronic fluorosis serum PRLlevel was decreased from pituitary lactotrophs andan enhanced function of dopaminergic system inhypothalamus (Yuan-SD et al., 1991)


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OTHER EFFECTS OFHIGH F INGESTION

Fluoride and SAP (F significantly increasedthe enzyme's activity in DP-1 and TE-85 by177 +/- 12% and 144 +/- 12.3%)


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Fluoride and Geno toxicity

Dose and time dependant effects

Increased chromosomal aberration

Sister chromatid exchangeThis iscontrolled by micro tubules, which shortenduring anaphase. This process is calcium

dependant. Unscheduled DNA synthesisMay cause

neoplastic transformation of embryo cells


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Fluoride and Fertility

Fluoride reduces the fertility (#) by causing (Zahvoronkov AA et al, Fluoride 1981)

Hypogonadism;

Decreased leydig cell function

Decreased testosterone levelsDecreased spermatogenesis

Disturbed Sertoli Cell function

Break down of blood testicular barrier

Decreased tRNA synthesisDecreased tRNA to spermatid

Decreased protein synthesis

Decreased intra testicular conc. of testosterone

Decreased spermatogenesis


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Fluoride and Fertility

Fluoride reduces the fertility (#) by causing(Zakrzewska H et al, Fluoride 2002)

Decreased spermatozoal motility Decreased activity of androgen dependant

enzymes ; Acid phosphatase, Lactate

dehydrogenase and gamma glutamyltransferase

Increased activity of Asperate transaminase


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Quantification of fluoride toxicity on

human health (Smith and Hodge)

Fluoride (mg/l)

Concentration

Source Effects

0.002 Air Destructive effect on plants

1.00 Water Prevention of Dental caries

>= 2 Water & Air effect dental enamel

>= 8 Water & Air effect Bones and muscles

>50 Food & Water Changes in Thyroid

>100 Food & Water defective development

>120 Food & Water Changes in Kidney


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Diagnosis

Endemicity of the disease in the area

Fluoride content in drinking water

Clinical manifestationsDental and Clinical

Clinical examination

Biochemical evaluations

Radiological evaluations


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Diagnosis


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PROPOSED PATHOPHYSIOLOGY OF FLUOROSIS

Fluoride ingestion INCREASED BLOODFLUORIDE

sequestration of calcium

Lowering of serum calcium(HYPOCALCEMIA)INCREASED PTH

increase in immatureosteoblast

increasedosteocalcin

Decreased Collagen synthesisand decreased in serum PICP

increased matrix formation increased osteoclastformation

increased collagenremoval

failure of mineralization Bone resorption

Decreased bone collagenHyperosteoidosis Restoration of serumcalcium

Increased Serum andBone GAG

Decreased bonecalcification

PROPOSEDPATHOPHYSIOLOGY OF

FLUOROSIS Pathophysiology


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Pathophysiology of fluorosis

(Brief Summary)

F ingestion Disturbs calcium homeostasis

Increased PTH

Changes in extra cellular Matrix, so

that calcium may be released from tissues

Maintains Calcium balance

Supplementcalcium andVit. D to avoid it

For restructuring ofgood quality of extracellular matrixSupplement Vit. C

with good proteinand Iron

Manifestationof fluorosis


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TREATMENT AND PREVENTION

Treatment : Possible in Children

Prevention : Avoid use of F rich

Diet and Water

Use diet rich in

Protein, Vitamin C and Calcium Changing dietary habits (e.g. cooking practices that

destroy Vitamin C during cooking) within their

available resources.

Rain Water Harvesting

TREATMENT


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TREATMENT

Fluorosis could be reversed, atleast in children by Calcium,

Vitamin C and Vitamin D

supplementationSource: Gupta et al. 1994,1996; NEERI 2002


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Delayed dentition(Reversal of fluorosis)


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Dental fluorosis(Reversal of fluorosis)


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Dental fluorosis(Reversal of fluorosis)


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Clinical fluorosis(Reversal of fluorosis)


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Skeletal fluorosis(Reversal of fluorosis)


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Role of calcium supplementation:

Improving serum calcium levels

Extra calcium in gut directly inhibits theabsorption of fluoride ions.

Inhibits the excessive release of PTH therebypreventing excessive activation of osteoblastsand osteoclasts, thus preventing

hyperosteoidosis and osteopenia (Tortora JG &Anagnostakas NP, 1990).

Also help in laying down of bones and teethmineralisation.


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Doses of Calcium

Doses of Calcium in terms of elemental Calcium

RDA 1000 mg per day

If F intake is 250 mg per day

10 mg per day

(25 mg elemental Ca/ mg of F)

One tablet of 500 mg calcium carbonate providesabout 200 mg elemental calcium

Doses of Vitamin D : 60,000 IU of Vitamin D

twice a week can be given safely

CALCIUM RICH DIETS


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CALCIUM RICH DIETS

(mg/100gm)

Ajwayan (1525) Til (1450)

Skimmed Milk Powder (1370) Mar (Agathi) (1130)

Jira (1080) Khoa (990)

Whole Milk Powder (950) Kantewali Chaulai (800)

Long Dry (740) Shalgam Ka Sag (710)

Hing (690) Dhania (630) Phool Gobhee (626)

Bathuva (520) Paneer (480) Kali Mirch (460)Coconut Dry (400) Chaulai Sag (397) Chukandar (380)

Methi Sag (395) Kaddu (392) Chumli (Arai) (364)

Chana Sag (340) Gajar Sag (340) Samp Machli (330)

Kala Til (300)


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Role of Vitamin D supplementation

Enhances calcium absorption andretention without causing hypercalcemia

Inhibits the excessive release of PTH byimproving hypocalcemia

And hence prevent excessive activation ofosteoblasts & osteoclasts thus preventinghyperosteoidosis and osteopenia.

Increases turnover of immature collegeninto more mature type that calcifies innormal manner

Inceases blood levels of both calcium andphosphorus, so more is available for


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Role of vitamin C in collagen synthesis

- Ketoglutarate [18O] Succinate

18O2Ascorbate

Pro Pro

18OH

Fe 2+


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Role of vitamin C supplementation

1. Induce massive and rapid collagen

synthesis by Inducing hydroxylation of

proline2. Making hyaluronic acid molecule

depolymerised and more diffusable.

3. Deficiency of Vitamin C is responsible forcreating acidic environment in the groundsubstance supplementation preventsthese changes

Ascorbic acid (Vitamin C)


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Ascorbic acid (Vitamin C)

rich diet (mg/100gm)

Amla (600) Shalgam (180) Mar (Agathi) (169)

Hara Dhania (135) Band Gobee (124) Mirch Green (111)

Chaulai Sag (99) Mooli Ka Sag (81) Gajar Sag (79)

Chotee Gobee (72) Chukandar (70) Neembu (63)

Phul Gobi (56) Malta (54) Methi Sag (52)

Mirch Dry (50) Mausambi (50) Guar Ki Phalli (49)

Shalgam (43) Nimbu Bada (39) Kalni Sag (37)Bathua Sag (35) Kantewali Chaulai (33)

Sarson-ka-sag (33) Raspberry (30) Palak (28)

Tomato (27) Pudina (27) Sem (27)

HIGH FLUORIDE CONTAINING


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HIGH FLUORIDE CONTAINING

FOOD

F Rich water Tea Fluoridated tooth paste

Pan Supari Tobacco

Green Garlic Onion Cabbage

Soya bean Carrot Corn

Potato Baking powder Egg

Cows liver and Kidney

Plant and vegetables grown in high fluoride containingwater



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(Some old methods and designs)



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(Some old methods and designs)


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DEFLUORIDATION

(ROL)

Adsorption

Ion Exchange Methods

Precipitation Methods

Miscellaneous Methods.

Source: Killedar et al.. 1988


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DEFLUORIDATION

Fluoride Removal Process based on adsorption

Commonly used techniques -

Nalgonda Activated Alumina

Recently Developed

KRASS Process


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DESIRABLE CHARACTERISTICS

Cost-effective

Independent of raw water Fluoride

concentration, alkalinity, pH, temperatureEasy to handle/operate by rural population -

the major sufferer

Should not affect taste of waterShould not add other undesirable

substances (eg. Aluminum) to treated water


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NALGONDA TECHNIQUE


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NALGONDA TECHNIQUE


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NALGONDA TECHNIQUE


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NALGONDA TECHNIQUE

Cost-effective

NOT independent of raw water Fluoride

concentration, alkalinity, pH NOT Easy to handle/operate by rural

population - the major sufferer

AFFECTS taste of water ADDS aluminum & TDS to treated water


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ACTIVATED ALUMINA

NOT Cost-effective

INDEPENDENT of raw water Fluoride

concentration, alkalinity, pH NOT easy to handle/operate by rural

population - the major sufferer

DOES NOT affect taste of water ADDS moderate aluminum to treated water


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ACTIVATED ALUMINA


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KRASS TECHNIQUE

Cost-effective

Independent of raw water Fluoride

concentration, alkalinity, pH, temperatureEasy to handle/operate by rural population -

the major sufferer

Does not affect taste of waterAdds other undesirable substances (eg.

Aluminum) only in traces.


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KRASS TECHNIQUE


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RESIDUAL ALUMINUM

In treated water

KRASS : Traces

Nalgonda : 2.01 - 6.86 mg/L (AAS+GF)

A. Alumina : 0.16 - 0.45 mg/L (Aluminon)


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ALUMINUM IN WATER

Desirable Limit : 0.03 mg/L

Permissible Limit : 0.2 mg/L

TOXIC EFFECTS OF


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TOXIC EFFECTS OF

ALUMINUM

CNS: Neuro-toxin-Alzheimers Disease, Enceph.

Impair Cognitive & motor function,

Peripheral Neuropathy , Myopathy,

BONES: Osteomalacia, Rickets, Pathological #

X-ray of BONE: Non healing #, Osteopenia,

Reduction in calcified tissue

ALLERGY : Itchy dermatitis axilla

RESP. TRACT: Pulm. Fibrosis, Asthma, Ch. Bron.

Blood: Microcytic Anemia


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Aluminofluoride complexes

Aluminofluoride complexes are formed spontaneouslyin a water solution containing fluoride and traceamounts of aluminum.

Affect G proteins (guanine nucleotide binding proteins).

G proteins have key role in all body system function(Specially liver, kidney, blood cells, bones cells ets)including brain where it causes neurotransmission andintercellular signaling in the brain.


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Summary of Al & F synergistics

Studies were conducted in two areas with similar

fluoride but different aluminum

Decreased MWC was observed in areas with higheraluminum. (Satyaprakash, 1999)

More severe presentations of fluorosis in areas with

higher aluminum (Sayal, 2000 and Jajoo, 2001)

Significant differences in neurological symptoms

like tremors, loss of co ordination, deterioration an

hand writing etc. (Sayal, 2000 and Jajoo, 2001)


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Is fluoridation practiced in

the west safe?


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THANK YOU

Fluoride and Fluorosis Old and New

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