Journal of Tissue Research Vol.

4 (2) 263-273 (2004)

ISSN: 0971 - 2283 (Printed in India) Review Article

FLUORIDE IN DRINKING WATER IN RAJASTHAN AND ITS ILL EF-

FECTS ON HUMAN HEALTH

?
HUSSAIN, J. , SHARMA, K. C.1 AND HUSSAIN, I2

Department of Environmental Studies, M.D.S. University, Ajmer 305 009. 1Vice-Chancellor, M.D.S. University,
Ajmer 305 009. 2Public Health Engineering Department, District Laboratory, Bhilwara 311 001 India.
E-mail: [email protected]; [email protected]
Received February 20, 2004 ; Accepted April 9, 2004

Fluorine is the ninth element of the periodic table. concentration may either inhibit or stimulates enzy-
Nevertheless, its applications and biological matic process and its interaction with other organic
significances were known only in the decades of and inorganic body components may cause disrup-
1920’s. It is the lightest member of the halogen fam- tion in normal physiological functions of human body.
ily and the most electronegative among all chemical The extent of caries reduction by various methods is
elements (Hodge and Smith, 1965). Fluorine has both influenced by the initial caries prevalence and the
notable chemical qualities and physiological proper- standard of health care in the community. Fluoride
ties, which are of great interest and significance to has been used in the treatment of osteoporosis for
human health. Fluorine is rarely or never found free two decades and, though beneficial effects have been
in the nature in elemental form. It has strong affinity reported, the dose-response relationships and efficacy
to combine chemically with other elements to form need further clarification. Fluoride containing com-
compounds called ‘fluoride’. Many workers and re- pounds are still used to increase the fluidity of metals
viewers used the word ‘Fluoride’ to donate the ion- and slugs in the glass and ceramic industries, fertil-
ized, physiologically available form of the element. izer industry. The fluoride tablets are effective as anti-
The chemical activity of the fluoride ion (E0 = -2.8 carcinogenic agent. Anhydrous hydrogen fluoride is
Volts) makes it physiologically more active than other used in the production of most fluorine-containing
elemental ion. Therefore, fluoride ions play an im- chemicals and in the production of refrigerants, her-
portant role in human physiology. Its presence in low bicides, pharmaceuticals, high octane gasoline, alu-

FLUORIDE

Beneficial Aspects Harmful Effects

Dental carries Dental Fluorosis

Medical Applications Skeletal Fluorosis
Essential Element Cardiovascular Effects
Glass & Ceramic Gastro Intestinal disorder
Industries Endocrine Effects
Fertilizer Industries Neurological Effects
Anti-cariogenic agent FLUORIDE TOXICITY Reproductive Effects
(Knife with Two Edges) Developmental Effects
Enzyme inhabitation
Genetic damage
Effect on the pineal gland

Fig. 1: Some beneficial and harmful effects of fluoride

 J. Tissue Research

Anthropogenic
Rivers, lakes & Air source
Groundwater

Sediments
Biota
Soil
Ocean
s
Dead organic
Volcanoes Rock matter / excreta

Fig. 2. Accumulation of fluoride in water (Biogeocycle)

minum, plastics, electrical components, and fluores- ing and leaching process, mainly by moving and per-
cent light bulbs. Aqueous hydrofluoric acid is used in colating water, play an important role in the incidence
stainless steel pickling, glass etching, and metal coat- of fluoride in groundwater. The features related to
ings. Volcanoes are the major natural source of hy- the release of fluoride into water by fluoride bearing
drogen fluoride. Sodium fluoride has been used as an minerals may be due to i) The chemical composition
insecticide, rodenticide, and fungicide.(Figure 1) of water ii) The presence and accessibility of fluo-
ride minerals to water or iii) The contact time be-
1. SOURCES OF FLUORIDE IN ENVIRON- tween the source minerals.
MENT:
Fluoride rich minerals, which are present in rocks and
The Cycle of fluoride through the biogeosphere is soil, when come in contact with water of high alka-
summarized in Figure 2 linity they release fluoride into groundwater through
hydrolysis replacing hydroxyl (OH) ion. The degree
2. SOURCE OF FLUORIDE IN WATER: of wreathing and leachable fluoride in a terrain is more
important in deciding the fluoride bearing minerals in
Fluorine always occurs in combined form of miner- the bulk rocks or soil. Due to weathering of rocks the
als as fluoride. It is high reactivity and represents Ca-Mg / carbonate concentration which form in arid
about 0.06 to 0.09% of the earth crust (WHO, report and semi arid areas appears to be good sink for the
1994). The presence of fluorine in ground water is fluoride ion (Jack et al., 1980). The factors that con-
mainly a natural phenomenon, and mainly influenced trol the leachability to fluoride from carbonate con-
by local and regional geological conditions, as the fluo- centration from carbonate concentration or from the
ride minerals are nearly insoluble in water. Hence topsoil horizon may be (1) pH of the draining solution
fluorine is present in ground water only when the (2) Alkalinity and (3) the dissolved CO2 in water and
conditions favor their solution. The main source of in features in the soil. Besides these factors, the to-
fluorine in groundwater is basically from the mafic pographic features also play an important role in the
minerals shown in table 1 and concentration of fluo- control of fluoride content as suggested by Rameshan
ride in these rocks given in table 2. These minerals and Rajagopalan (1985). The existence of some of
are commonly associated with the country rocks the basis dykes such as doleritic intrusions normally
through which the ground water percolates under acts as natural barriers against the flow of under-
variable temperature conditions. ground water making the groundwater stagnated in
fractures and pores. If the groundwater is more al-
Besides these minerals, alkali rocks, hydrothermal kaline and stagnant for longer time, all the fluoride
solutions may also contribute to higher concentration minerals in basic dyke rocks, and the overlying soil
of fluoride in groundwater. Robinson and Edington that are rich in mafic minerals undergoes greater ion-
(1946) reported that the main source of fluorine in ization facilitating the ground water to get enriched
ordinary soil consists of clay minerals. The weather- with fluoride. The degree of ionization increases with
 Hussain et al.
Table 1: Source of fluoride in ground water
Minerals Chemical Composition Rocks of these minerals
1. Fluorite (Fluorspar) CaF2 Pegmatite Pneumatolitic deposits as vein deposit
2. Fluorapatite (Apatite) Ca5(F,Cl)PO4 Pegmatite & metamorphosed limestone.
3. Micas
a. Biotite K(MgFe+2)3(AlSi3)O10(OHF) 2 Basalts
b. Muscovite KAl2(AlSi3O10)(OHF)2 Permatites, Amphiboites,
4. Amphiboles
a. Hornblende NaCa2(MgFe+2)4(AlFe+3)(SiAl) 8O22(OHF)2 Gneisses, schists, shales,
b.Tremolite Actinolite Ca2(MgFe+2)5(Si8O22) (OHF)2 Clay, Alkaline rocks etc.
5. Topaz Al2SiO4(OH.F)2 Acid Igneous rocks, Schists, gneisses etc.
6. .Rock Phosphate NaCa2(MgFe+2)4(AlFe+3)(SiAl) 8O22(OHF)2 Limestone, Fossils etc.
Table 2: The value of fluoride in various rock types.
Fluoride range Average 3. FLUORIDE DISTRIBUTION IN RAJAS-
Rocks
(in ppm) (in ppm) THAN:
Basalt 20-1060 360
Granites & Gneisses 20-2700 870
Shales & Clay 10-7600 800 Rajasthan is the largest state, which covers 10% of
Lime stones 0-1200 220 the country area but receives only 1/100 of the total
Sandstones 10-880 180
Phosphorite 24000-41500 31000
rains. It shares only 1/10 of the average share of
Coals(ash) 40-480 80 water than rest of the country. The geographical and
geological setup leads to deterioration of water qual-
ity. Therefore, state faces acute water crisis. The
great Indian Thar Desert covers most of the area
affected by fluoride. Thus extremely arid and dry cli-
mate conditions prevail, receiving 5 mm to 20 mm
annual rainfall. Groundwater is deeper and contains
high mineral concentrated chemicals which makes
the water unfit to drink. The eastern part of the state
is semi desert and hilly, therefore the water availabil-
ity in this region is also limited (Fig.3).

Due to arid and semi arid climate and insufficient

surface water resources, Rajasthan is indebt heavily
on ground water for drinking and for agriculture pur-
Fig. 3: Categorization of fluoride affected districts of Rajasthan pose. Unfortunately, the groundwater quality in a large
Category A: 50% and above villages have excess of fluoride (very number of districts is not according prescribed stan-
serious). Category B: 25-50 % villages having excess fluoride
(serious). Category C: 10-25 % villages having excess fluoride dards. Rajasthan is the only state where almost all
(less serious). Category D: Below 10% villages having excess the districts are affected by high fluoride (beyond the
fluoride (insignificant). permissible limit). In 23 districts the fluorosis prob-
Table 3: Fluoride concentration and affected population of vil- lem can be visualized at various intensity level i.e.
lages in Rajasthan Dental fluorosis, skeletal fluorosis, nonskeletal mani-
Fluoride Number of festation etc. The studies made by Rajasthan Volun-
Total population
S. No. concentration affected tary Health Association in 1994 has showed that the
under threat
mg/l Village
1. 1.2 to 2.9 1467 1643542 total number of villages having fluoride problem in
2. 3.0 to 4.9 668 719309 Rajasthan is 2433 covering nearly 2.6 million popula-
3. 5.0 to 9.9 255 238447 tion. Moreover, nearly 30,000 people are drinking
4. Above 10 43 35477
Total 2433 water with concentration of 10.0 mg/l of fluoride.
Data on number of population in affected villages and
depth resulting an increase in total dissolved salts and fluoride concentration is shown in Table 3.
alkalinity. The rocks are the natural aggregation of
minerals and contain fluoride in abundant quantity. In order to actuate the proper coverage of water sup-
Soil is also rich in fluoride bearing minerals (Keller, ply schemes in rural area and to identify the quality
1976). Rameshan and Rajagopalan (1985) summa- of water a survey was conducted in the year 1973-
rized the ingestion of fluoride concentration in the arid 74. Public Health Engineering Department conducted
and semi arid drought prone areas of Karnataka. the district wise surrey under a program Rajeev
 J. Tissue Research
Table 4. Detail of Fluoride Affected Villages in Rajasthan
No. of Villages/ No. of Villages/
Total Number of
S.No. Name of District Habitation Where F> 1.5 Habitation Where F> 3.0
Villages Habitation Total Villages Habitation Total Villages Habitation Total
1 Ajmer 985 952 1931 654 371 1025 352 232 584
2 Alwar 1946 2449 4395 537 342 879 155 68 223
3 Banswara 1431 3175 4606 293 551 844 35 60 95
4 Bharatpur 1345 549 1894 529 81 610 152 11 163
5 Barmer 1623 2780 4403 597 221 818 181 68 249
6 Bhilwara 1566 963 2534 678 318 996 392 227 619
7 Bikaner 580 366 946 84 2 86 7 0 7
8 Bundi 826 332 1158 42 9 51 3 0 3
9 Chittorgarh 2173 904 3077 115 48 163 14 9 23
10 Churu 926 199 1125 240 8 248 27 1 28
11 Dholpur 551 983 1534 142 157 299 22 18 40
12 Dungarpur 846 681 1527 127 225 362 30 55 85
S. Ganga nagar
13 4437 4190 8627 425 418 844 149 129 273
/Hanumangarh
14 Jaipur/ Dausa 3140 7518 10758 1187 1795 3172 491 739 1230
15 Jaisalmer 518 1172 1690 300 184 484 96 65 161
16 Jalore 666 823 1489 369 107 476 115 45 160
17 Jhalawar 1448 124 1572 42 5 47 15 3 18
18 Jhunjhuinu 824 208 1032 96 3 99 15 1 16
19 Jodhpur 860 2801 3661 314 99 413 59 8 67
20 Kota / Baran 1881 288 2169 44 0 44 17 0 22
21 Nagaure 1374 1972 3346 778 147 925 322 42 364
22 Pali 904 651 1555 242 83 330 69 34 103
23 Swaimadhopur/ Karoli 1464 2191 3655 452 263 725 121 69 190
24 Sikar 931 2401 3332 331 471 792 125 144 269
25 Sirohi 446 92 544 176 5 181 43 1 44
26 Tonk 1019 881 1900 516 209 724 199 71 270
27 Udaipur/Raj Samand 3179 5561 8740 431 497 923 74 81 155
Total 37889 45311 8200 9741 6619 16560 3280 2181 5461
Source: Public Health Engineering Department Rajasthan, (1991) and Hussain et al. (2002)

Gandhi National Drinking Water Mission. The per- 4. EFFECT OF FLUROIDE ON HUMAN HEALTH:
missible limit is 1.5 mg/l according to the CPHED,
Government of India and the World Health Organi- Fluoride contamination is a major health hazard in
zation. The district wise number of villages and other many parts of the world. Fluoride is considered ben-
habitations having excessive concentration of fluoride eficial to human health if taken in limited quantity (0.5
(> 1.5 & 3.0 mg/l ) is shown in table 4. Total 9741 to 1.5 mg/l). Fluoride prevents tooth decay by en-
villages and 6819 other habitations are having fluoride hancing the remineralization of enamel that is under
level over 1.5 mg/l in groundwater. Similarly 3280 vil- attack, as well as inhibiting the production of acid by
lages and 2181 habitations are having fluoride concen- decay causing bacteria in dental plaque. Fluoride is
tration more than 3.0 mg/l. A district wise categoriza- also a normal constituent of the enamel itself, incor-
tion is shown in the following Map -1. The survey indi-
Table 5. Concentration of fluoride and Biological effects
cates that the degree of fluoride problem is very seri-
Fluoride in
ous in 7 districts (Ajmer, Bhilwara, Nagaure, Dausa, S. No Effect
drinking water mg/l
Jaipur, Tonk, Jalore) and a serious in 10 districts (Alwar, 1. 0.002 mg/l in air Injury to vegetation
2. 1 mg/l in water Dental caries reduction
Barmer, Bharatpur, Dungarpur, Jaisalmer, Sikar, Pali, 3. 2 mg/l or more in water Mottled enamel
Swaimadhopur, Karoli, Sirohi), less serious in 9 dis- 4. 3.1 to 6.0 mg/l in water Osteoporosis
tricts (Banswara, Jhunjhuinu, Udaipur, Churu, Dholpur, 5. 8 mg/l in water 10%osteoporosis
6. 20 – 80 mg/day or more Crippling skeletal fluorosis
Ganga nagar, Raj Samand, Jodhpur, Hanumangarh) and in water or air
insignificant in 6 districts (Baran, Bundi, Bikaner, 7. 50 mg/l in food or water Thyroid change
Chittorgarh, Jhalawar and Kota,). Fluoride level in 8. 100 mg/l in food or water Growth retardation
9 More than 125 mg/l Kidney change
ground water is spread in all the 32 districts and be- in food or water
come a health hazard in 25 districts. 10 2.5 – 5.0 gm in actual dose Death
 Hussain et al.
porated into the crystalline structure of the develop- Aoba, 1997; Whitford, 1997). Experimental animal
ing tooth and enhancing its resistance to acid dissolu- studies suggest that this hypomineralization results
tion. But it is also known to cause dental, skeletal from fluoride disturbance of the process of enamel
fluorosis, osteosclerosis, thyroid, kidney changes and maturation (Richards et al., 1986).
cardiovascular, gastrointestinal, endocrine, neurologi-
cal, reproductive, developmental, molecular level, In India, Viswanathan (1951) first reported a disease
immunity effects. If concentration is higher than 1.5 similar to mottled enamel, which is prevalent in hu-
mg/l in drinking water (WHO, 1996). Smith and man beings in Madras presidency. Mahajan (1934)
Hodge, (1959) have shown the correlation between reported a similar disease in cattle in certain parts of
fluoride and biological effect (Table 5). old Hyderabad state. However, Shortt et al. (1937)
was the first to identify the disease as fluorosis. Sub-
Effect on dental enamel: Dental fluorosis is a con- sequent to these findings, cases of fluorosis were
dition that results from the intake of excess levels of reported from several other parts of the country.
fluoride during the period of tooth development, usu- Dental fluorosis is caused in human being consuming
ally from birth to approximately 6–8 years of age. It water containing 1.5 mg/l or more of fluorides, par-
has been termed a hypoplasia or hypomineralization ticularly from birth to the age of eight. Mottled enamel
of dental enamel and dentine and is associated with usually takes the shape of modification to produce
the excessive incorporation of fluoride into these struc- yellow brown stains or an unnatural opaque chalky
tures. The severity of this condition, generally char- white appearance with occasional striations patting.
acterized as ranging from very mild to severe, is re- The incidence and severity of mottling was found to
lated to the extent of fluoride exposure during the increase with increasing concentration of fluoride in
period of tooth development. Mild dental fluorosis is drinking water. In extensive studies, Dean and co-
usually typified by the appearance of small white ar- workers (Dean, 1942; Dean and Elvove, 1937) have
eas in the enamel; individuals with severe dental fluo- correlated the appearance and severity of dental fluo-
rosis have teeth that are stained and pitted (“mottled”) rosis to different fluoride levels in the drinking water
in appearance. In human fluorotic teeth, the most with the aid of a special classification and weighing
prominent feature is a hypomineralization of the of severity of the lesion (Table 6).
enamel. In contrast to many animal species, fluoride-
induced enamel hypoplasia (indicating a severe fluo- Distribution of dental fluorosis at different levels of
ride disturbance of enamel matrix production) seems fluoride in drinking water may be assessed by a
to be rare in affected human enamel. The staining mottled enamel index of the community, which is de-
and pitting of fluorosed dental enamel are both post fined in terms of the degree of severity of mottled
eruptive phenomena (i.e., acquired after tooth erup- enamel observed clinically. Since no such data avail-
tion and occur as a consequence of the enamel able in India to evaluate community index of fluoro-
hypomineralization). The incorporation of excessive sis and in the absence of this permissive or excessive
amounts of fluoride into enamel is believed to inter- limits of fluoride in drinking water are only arbitrary.
fere with its normal maturation, as a result of alter-
ations in the rheologic structure of the enamel matrix Osteoporosis: Fluoride above 4 mg/l in drinking wa-
and/or effects on cellular metabolic processes asso- ter may cause a condition of dense and brittle bones
ciated with normal enamel development (WHO, 1984; known as osteoporosis. It affects tens of million of

Table 6. Dental fluorosis categorization (Dean, 1942)

The enamel presents translucent, semi-vitriform type of structure. The surface is smooth, glossy and
Normal
usually pale creamy white colour.
Seen in area of relatively high endemicity, occasional cases are borderline and one would hesitate to
Questionable
classify them as apparently normal or very mild.
Very Mild Small, opaque paper-white area seen, scattering irregularly over the labial and buccal tooth surfaces.
The white opaque areas involve at least half of the tooth surface and faint brown stains are sometimes
Mild
apparent
Generally all tooth surfaces are involved and minute pitting is often present on the labial and buccal
Moderately
surfaces. Brown stain is frequently a disfiguring complication.
Pitting is marked, more frequent and generally observed on all tooth surfaces. Brown stains if present
Moderately Severe
are generally of greater intensity.
The severe hypeoplasic affect the form of the teeth and stains are wide spread, and vary in intensity
Severe
from deep brown to black.
 J. Tissue Research

people worldwide and is responsible for as many as stage of crippling fluorosis. However, radiological
75% of all fractures in people over the age of 45. changes are discernible in the skeleton at a much
Costly and disabling fractures of spine, hip, wrist and earlier stage and provide the only means of diagnos-
other bones can be preceded by years of undetected ing the early and relatively asymptomatic stages of
bone loss. It is found that as many as 20% of those fluorosis (Connett, 2002; Lavy, 2003).
who suffer from osteoporosis related hip fractures
die within 6 months. Women are at four times greater Such early cases are usually in young adults whose
risk of developing osteoporosis than males (Bezerra only complaints are vague pains noted most frequently
et al., 2003). in the small joints of the hands and feet, in the knee
joints and in the joint of spine. These cases are fre-
Skeleton fluorosis: The chronic toxic effects of fluo- quent in the endemic areas and may be misdiagnosed
ride on the skeletal system have been described from as rheumatoid or osteoarthritis. In later stages, there
certain geographical regions of the world where drink- is an obvious stiffness of the spine with limitation of
ing water contains excessive quantities of natural fluo- movements and still later, the development of kypho-
ride. This form of chronic intoxication was first de- sis. There is difficulty in walking due partly to stiff-
scribed in India from the state of Madras as early as ness and limitation of the movements of various joints
1937 (Shortt et al., 1937). Subsequently cases of en- and partly to the neurological lesions of advanced
demic fluorosis have been reported from other parts cases. Similarly, some of the patients complain of
of India, particularly from Punjab (Singh et al., dyspnoea on exertion because of the rigidity of the
1962a,b, 1963) and sporadically from other parts of thoracic cage. In Roholm’s series of industrial fluo-
the world, notably Ceylon (Clark, 1942), China (Lyth, rosis cases, the gastrointestinal symptoms of lack of
1946), Japan (Hamamoto et al., 1954), Saudi Arabia appetite, nausea and constipation were as frequent
( El, Tannir, 1959), USA, (Leone et al., 1954; Zipkin as the symptoms of stiffness of joints, but the former
et al., 1958) Canada ( Kilborn et al., 1950) and Eu- have not been described in the different studies of
rope (Odenthal and Wieneke, 1959). Besides endemic endemic fluorosis.
fluorosis, chronic toxic effects of fluoride on the skel-
etal system have also been observed in relation to According to an early estimate, the number of per-
industrial exposure to fluorides such as cryolite and sons at risk of developing skeletal fluorosis was 5
in fact it is the pioneer studies of Roholm (1937) that million in Punjab and more in Andhra Pradesh and
have paved the way for further contributions on the Madras, India (Siddiqui, 1970). The frequency of skel-
subject. etal fluorosis (as identified by the clinical picture)
among children 3–10 years of age was 39% (18/46)
At higher levels of ingestion from 2 to 8 mg daily in a village in India, where the fluoride concentra-
when signs of fluorosis appear in teeth mineralized tions in the three wells were 0.6, 4.0 and 1.34 mg/l
during the ingestion period, certain other factors (cli- (Shivashankara et al., 2000). It was not possible to
matic conditions, malnutrition, age, storage, other con- discern, from the information available, the contribu-
stituents of water and possibly individual variations in tion of each well to the drinking water of the resi-
absorption) may be involved. Under such conditions dents.
and over a number of years, skeletal fluorosis may
arise characterized by an increased density of bone In a clinical survey for fluorosis in a random sample
and demonstrated in adults radiographically (Yildiz et of residents in five areas in Tamil Nadu, South India,
al., 2003). The data put forward by McClure et al. the drinking-water fluoride concentration was directly
(1945), although no longer regarded as accurate indi- related to the prevalence of dental fluorosis in chil-
cate that the limit of total fluoride which may be in- dren (8–15 years of age) and adults. Among chil-
gested daily without hazardous body storage is of the dren, no skeletal fluorosis (no information on diag-
order of 4-5mg daily. nostic criteria provided) was observed; among adults,
the prevalence of fluorosis was 34% (157 individuals
Fluoride replaces hydroxides and deposited in bones surveyed) in the area with the highest drinking-water
causing chronic effect known as skeleton fluorosis. fluoride concentration (summer month average 6.8
The dental and skeletal changes in endemic fluorosis mg/l, non-summer month average 5.6 mg/l) (estimated
provide important clinical diagnostic criteria. Whereas total daily fluoride intake 20 mg), while no skeletal
dental fluorosis is easily recognized but the skeletal fluorosis was observed in the other areas, where the
involvement is not clinically obvious until the advanced mean fluoride concentrations were 2.2 (summer
 Hussain et al.
months) and 1.8 (non-summer months) mg/l or lower, nomic nervous systems. Hypocalcemia can cause
with estimated total daily fluoride intakes less than tetany, decreased myocardial contractility, and possi-
10 mg (Karthikeyan et al., 1996). bly cardiovascular collapse (Bayless and Tinanoff,
1985). Hyperkalemia has been suggested as the cause
A correlation between average water fluoride con- of the repeated episodes of ventricular fibrillation and
centration and prevalence of skeletal fluorosis (as- eventual death that are often encountered in cases
sessed by X-ray) was found among adults in 15 vil- of fluoride poisoning (Baltazar et al., 1980).
lages in Dungapur district in Rajasthan, India
(Choubisa et al., 1997). The prevalence ranged from Gastrointestinal effects: The primary gastrointes-
4.4% at a water fluoride level of 1.4 mg/l to 63.0% at tinal effects following both acute and chronic oral
the level of 6.0 mg/l. Crippling fluorosis was consis- exposure to fluoride consist of nausea, vomiting, and
tently observed in villages with fluoride concentra- gastric pain. The irritation of the gastric mucosa is
tions of >3 mg/l. In a survey carried out by Hussain attributed to fluoride (as sodium fluoride) forming
et al. (2004) in Bhilwara district of Rajasthan, 825 hydrofluoric acid in the acidic environment of the
individual were examined for fluorosis due to intake stomach (Hoffman et al., 1980; Waldbott, 1981). The
of fluoride above 5.0 mg/l in drinking water. In the uncharged hydrogen fluoride molecule can then pen-
skeletal fluorosis positive individuals maximum indi- etrate cell membranes and enter the neutral environ-
vidual (194 no’s, 23.52%) have Grade I skeletal fluo- ment of the cytoplasm.
rosis, which is characterized by bone and joint pain.
Only 4 individual (0.48%) have Grade III type of skel- A study by Susheela et al. (1993) assessed the preva-
etal fluorosis in which bone and joint pain, stiffness lence and severity of gastrointestinal disturbance in
and rigidity of dorso-lumber spine and restricted move- an area of endemic skeletal and dental fluorosis in
ments at spine and joints are general symptom inclu- India. The highest prevalence (52.4%) of non-ulcer
sive deformities of spine and limbs, knock knees, dyspeptic symptoms was found among 288 individu-
crippled or bed ridden state, kyphosis, invalidism, genu- als (69 families) living in a village where the mean
varum and genu-valgum. Prevalence and severity of fluoride concentration in the 36 separate water
skeletal fluorosis were found also increasing with in- sources was 3.2 ppm (range 0.25 to 8.0 ppm). Eleven
creasing fluoride concentration. of these water sources were defined by the authors
as safe (i.e., with fluoride levels of 1.0 ppm or less).
Deformities and crippling fluorosis: The ad- The authors noted that in patients who reverted to
vanced stage of fluoride intoxication results from the safe water, dyspeptic symptoms and complaints dis-
continuous exposure of an individual to 20-80 mg of appeared within 2-3 weeks.
fluoride ion daily over a period of 10 - 20 years. Such
heavy exposure is associated with a level of at least Endocrine effects: In the endocrine system where
10 mg/l in the drinking water supply. The crippling the intermediary metabolism and synthesis of highly
fluorosis is seen in such numbers in endemic areas of sensitive hormones involves enzymatic action, it is
Rajasthan, Punjab and Southern India. The Crippling expected that interferences with the mechanism by
deformities are due partly to mechanical factors and chemical agents would produce early and pronounced
partly to the immobilization necessitated by pain and clinical effects. Considerable attention has conse-
paraplegia. The commonest deformities are kypho- quently been given of recent years to the behavior of
sis, flexion deformity of the hips, flexion deformity of fluoride in hormone chemistry and to the possible and
the knees and fixation of the chest in the position of to the possible clinical disturbances of endocrine func-
inspiration due to calcification of cartilages. The quad- tion, particularly the thyroid gland Robinson et al.,
riplegic patient bent with kyphosis and with restricted 2002). Significant increases in serum thyroxin levels
movements of his spine, with contractures of hips were observed in residents of North Gujarat, India
and knees (Kaminsky et al., 1990) 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
Cardiovascular effects: The cardiovascular effects al., 1996). No significant changes in serum triiodot-
of fluoride have been attributed to hypocalcemia and hyronine or thyroid stimulating hormone levels were
hypercalemia caused by high fluoride levels. Fluo- found. Increases in serum epinephrine and norepi-
ride can bind with serum calcium if the dose is suffi- nephrine levels were also observed. It is unclear if
cient and cause hypocalcemia. Calcium is necessary nutritional deficiencies played a contributing role to
for the functional integrity of the voluntary and auto- the observed endocrine effects.
 J. Tissue Research

vulsions), studies tend to indicate that hypocalcemia

Immunological and lymphoreticular effects: A caused by fluoride binding of calcium causes these
request to the American Academy of Allergy was symptoms (Eichler et al., 1982). The decreases in
made by the U.S. Public Health Service for an evalu- intelligence were reported in children living in areas
ation of suspected allergic reactions to fluoride as of China with high levels of fluoride in the drinking
used in the fluoridation of community water supplies water, as compared to matched groups of children
(Austen et al., 1971). The response to this request living in areas with low levels of fluoride in the drink-
included a review of clinical reports and an opinion ing water (Li et al., 1995; Lu et al., 2000), but these
as to whether these reports constituted valid evidence studies are weak inasmuch as they do not address
of a hypersensitivity reaction to fluoride exposure of important confounding factors.
types I, II, III, or IV (Austen et al., 1971), which are,
respectively, anaphylactic or reaginic, cytotoxic, toxic Reproductive effects: There are limited data on
complex, and delayed-type reactivity. The Academy the potential of fluoride to induce reproductive ef-
reviewed the wide variety of symptoms presented fects in humans following oral exposure. A meta-
(vomiting, abdominal pain, headaches, scotomata analysis found a statistically significant association
[blind, or partially blind areas in the visual field], per- between decreasing total fertility rate and increasing
sonality change, muscular weakness, painful numb- fluoride levels in municipal drinking water (Freni,
ness in extremities, joint pain, migraine headaches, 1994). Annual county birth data (obtained from the
dryness in the mouth, oral ulcers, convulsions, mental National Center for Health Statistics) for over 525,000
deterioration, colitis, pelvic hemorrhages, urticaria, women aged 10–49 years living in areas with high
nasal congestion, skin rashes, epigastric distress, and fluoride levels in community drinking water were
hematemesis) and concluded that none of these symp- compared to a control population approximately
toms were likely to be immunologically mediated re- 985,000 women) living in adjacent counties with low
actions of types I–IV. No studies were located that fluoride drinking water levels. The fluoride-exposed
investigated alterations in immune response follow- population lived in counties reporting a fluoride level
ing fluoride exposure in humans. No studies were of 3 ppm or higher in at least one system. The
located that investigated alterations in immune re- weighted mean fluoride concentration (county mean
sponse following fluoride exposure in human. In a fluoride level weighted by the 1980 size of the popu-
study with rabbits administered 4.5 mg fluoride/kg/ lation served by the water system) was 1.51 ppm
day as sodium fluoride for 18 months, decreased an- (approximately 0.04 mg fluoride/kg/day), and 10.40%
tibody titers were observed (Jain and Susheela, 1987). of the population was served by water systems with
These results were observed after 6 months of treat- at least 3 ppm fluoride. The mean weighted mean
ment; the authors hypothesized that a threshold level fluoride concentration in the control population was
is reached at which time the immune system is im- 1.08 ppm (approximately 0.03 mg fluoride/kg/day).
paired. However, as only one dose level (4.5 mg fluo- However, this meta-analysis relied on a comparison
ride/kg/day) was tested, no dose-effect. of two quite disparate data sets, inasmuch as the fluo-
ridation population often did not correlate well with
Neurological effects: The neurological manifesta- the population for whom health statistics was avail-
tions have been exclusively reported from India. able. Furthermore, other studies have not found a
Credit for the earliest description of neurological com- similar correlation. Another study found significantly
plications in fluorosis must be given to Shortt et al. decreased serum testosterone levels in 30 men diag-
(1937), who reported ten such cases from the Nellore nosed with skeletal fluorosis and in 16 men related to
district of Madras. A few sporadic cases have also men with fluorosis and living in the same house as
been described from other parts of India (Chuttani et the patient (Susheela and Jethanandani, 1996). The
al., 1962; Janardhanan and Venkaswamy, 1957; mean drinking water fluoride levels were 3.9 ppm
Murthi et al., 1953). Fluoride has been shown to in- (approximately 0.11 mg fluoride/kg/day), 4.5 ppm
terfere with glycolysis. Because the central nervous (0.13 mg fluoride/kg/day), and 0.5 ppm (0.014 mg
system relies heavily on this energy source, hypoth- fluoride/kg/day) in the patients with skeletal fluoro-
eses have been advanced as to a mechanism for fluo- sis, related men, and a control group of 26 men living
ride effects on the central nervous system. Although in areas with low endemic fluoride levels. No corre-
effects on glycolytic enzymes could explain the neu- lations between serum testosterone and urinary fluo-
romuscular symptoms seen frequently in cases of fluo- ride levels or serum testosterone and serum fluoride
ride poisoning (e.g., tetany, paresthesia, paresis, con- levels were found. One limitation of this study is that
 Hussain et al.
the control men were younger (28.7 years) than the ages occur in a cell, producing a sperm or egg it will
men with skeletal fluorosis (39.6 years) and the re- be replicated in every cell of the offspring body and
lated men (38.7 years). In addition, the groups are leads to birth defects. Irreparable damage of a seg-
small and potentially confounding factors are not well ment of DNA is responsible for control of cell growth
addressed (Mychreest et al., 2002). and may cause tumors or cancer.

Developmental effects: Fluoride crosses the pla- Effect on immune system: Fluoride interacts with
centa in limited amounts and is found in fetal and the bonds of protein molecular required to maintain
placental tissue (Gedalia et al., 1961; Theuer et al., the normal shape of proteins. The fluoride effect the
1971). The available human data suggest that fluo- immune system by i) Damage the immune system by
ride has the potential to be developmentally toxic at inhibiting the migration rate of white blood cells to
doses associated with moderate to severe fluorosis. infected means, ii) Interferes with phagcytosis (de-
The human and animal data suggest that the devel- struction of bacteria and other foreign agents by white
oping fetus is not a sensitive target of fluoride toxic- blood cells or iii) Induces the release of super oxide
ity. Analysis of birth certificates and hospital records free radicals in resting white blood cell. The fluoride-
for over 200,000 babies born in an area with fluori- induced interference leads to an increased and more
dated water and over 1,000,000 babies born in a low prolonged exposure of the body to foreign materials
fluoride area found no difference in the incidence of and releases free radicals damaging the body.
birth defects attributable to fluoride (Erickson et al.,
1976). Exposure to high levels of fluoride has been Fluoride as carcinogen: Fluoride was found to be
described together with an increased incidence of an equivocal carcinogen by the National Cancer In-
spina bifida (Gupta et al., 1995). The occurrence of stitute. Toxicological effects due to excess of fluo-
spina bifida was examined in a group of 50 children ride is 6.9 fold and cause bone cancer in young males.
aged 5–12 years living in an area of India with high Several epidemiological studies are available on the
levels of fluoride in the drinking water (4.5–8.5 ppm) possible association between fluoride in drinking wa-
and manifesting either clinical (bone and joint pain, ter and cancer rates among the population IACR
stiffness, and rigidity), dental, or skeletal fluorosis. evaluated these studies on fluoride and
An age- and weight-matched group of children living carcinogenticity in humans. (IARC, 1987; Maurer et
in areas with lower fluoride levels (#1.5 ppm) served al., 1990). Numerous epidemiological studies have
as a control group. Spina bifida was found in 22 (44%) examined the issue of a connection between fluori-
of the children in the high fluoride area and in six dated water and cancer. The weight of evidence in-
(12%) children in the control group. This study did dicates that no such connection exists. However, all
not examine the possible role of potentially important of the investigations were ecologic studies, and the
nutrients such as folic acid, however, and had other sensitivity limit of even the most sensitive analysis in
study design flaws. these studies appears to be a 10–20% increase. Since
any carcinogenic effect of fluoride at the levels found
Effect at molecular level: The acceleration of the in water supplies would probably be below this level
aging process by fluoride occurs at the bio-chemical of sensitivity, a National Toxicology Program (NTP)
level through enzyme inhabitation, collagen break cancer bioassay was conducted to assess the effect
down, genetic damage or disruption of the immune of fluoride on cancer incidence in animals (Bucher et
system. Fluoride damage enzymes, and results in a al. 1991; NTP report, 1990). The NTP study found
wide range of chronic disease. Fluoride as low as 1 equivocal evidence of a fluoride-related increase in
mg/l causes breakdown of collagen, the most abun- osteo-sarcomas in male rats, and no evidence of any
dant of the body protein at 30%. It leads to irregular fluoride-related neoplasm in female rats or male or
formation of collagen, which serves as a major struc- female mice. A study sponsored by Proctor and
tural component of skin, ligaments, tendons, muscles, Gamble (Maurer et al., 1990) found no evidence of
cartilage, bone and teeth. A number of studies re- fluoride carcinogenicity in either male or female rats.
vealed that fluoride causes genetic damage. The Both studies contain limitations that preclude strong
mechanism cannot be exactly pinpointed because conclusions. The NTP is presently carrying out addi-
fluoride interferes with a number of physiological pro- tional experiments on the relationship, if any, between
cesses. Most evidence indicates that it acts on the fluoride and cancer. The International Agency for
DNA Repair Enzyme system. It may also interfere Research on Cancer (IARC) reviewed the literature
with DNA synthesis. If the unprepared DNA dam- on fluoride carcinogenicity in 1982. It concluded that
 J. Tissue Research

Table 7. Defluoridation Techniques

Technique Description Limitations
Using bone Char Water is filtered through crushed bone char in Material is costly & continued availability is not
column. Fluoride is taken up by the bone char. guaranteed, not accepted by Hindu population
Contact Precipitation of fluoride with Ca & PO4-2 in contact
with an appropriate surface.
Nalgonda techniques Aluminum sulphate and lime are mixed slowly then Fluoride removed as CaF2, but the solubility of CaF2,
left for setting. Fluoride is removed with is such that fluoride below 8 mg/l remains in drinking
precipitates water.
Yttrium Loaded Poly Yttrium loaded Poly (Hydroxamic acid) ion It absorbs only in the pH range of 2.8 to 4.2, but the
(hydroxamic acid) resin exchange resin absorbs fluoride ion in the pH range drinking water range is generally 6.5 to 7.5
of 2.8 to 4.2
Reverse osmosis Membrane filtration based technology, which Costly and requires electricity which is not available
removes all dissolved solids including fluoride. all the time in rural areas
Marble Slurry Marble slurry is mixed slowly then left for settling. -
Fluoride is removed with precipitates
Activated Alumina Fluoride can be removed by adsorption on alumina. Alumina should be pretreated
This method is widely used.

there is no evidence from epidemiological studies of Austen, K.F., Dworetzky, M. and Farr R.S.: J. Allergy, 47:
an association between fluoride ingestion and human 347-348 (1971).
cancer mortality, and the available data are inadequate Baltazar, R.F., Mower, M. M. and Funk, M.: Chest, 78(4):
for an evaluation of the carcinogenicity of sodium 660-663 (1980).
Balusu, K.R.: J. Inst. Engg., 60: 1 (1979).
fluoride in experimental animals (IARC, 1982). Sev-
Bayless, J.M. and Tinanoff, N.: J. Am. Dent. Assoc., 110:
eral major cancer bioassays of fluoride have been 209-211 (1985).
conducted since the IARC review. Bezerra, de Menezes, L.M., Volpato, M.C. and Rosalen,
P.L. and Cury, J.A.: Forensic Sci. Int., 137(2-3): 209-214
5. DEFLUORIDATION METHODS: (2003).
Bucher, J.R., Hejtmancik, M.R. and Toft, J.D.: Int. J. Cancer,
Wide range of treatment systems have been reported 48: 733-737 (1991).
for controlling excess fluoride in water. Some are very Choubisa, S.L., Choubisa, D.K., Joshi, S.C. and Choubisa,
expensive, where as some are ineffective with cer- L.: Fluoride, 30: 223–228 (1997).
tain type of water quality and only laboratory studies Chuttani, P.N., Wahi, P.L. and Singh, S.: J. Indian Med.
Ass., 39: 61 (1962).
are available for some systems. Defluoridation meth-
Clark, A.: J. Trop. Med. Hyg., 45: 49 (1942).
ods can be broadly divided into three categories i) Connett, P.: Fluoride, 35(4): 245-24 (2002).
precipitation, ii) adsorption / ion exchange or iii) elec- Dean, H.T. and Elvove, E.: Public Health Rep., 52: 1249
trochemical methods and membrane technique. Sev- (1937).
eral reviews are available on the various defluoridation Dean, H.T.: Am. Assoc. Adv. Sci., 19: 23-31(1942).
methods (Balusu, 1979; Killedar and Bhargava, Eichler, H.G., Lenz, K. and Fuhrmann, M.: Int. J. Clin.
1988). Precipitation methods involve the addition of Pharmacol. Ther. Toxicol., 20: 334-338 (1982).
a soluble chemical to the water, which leads to the El Tannir, M.D.: Amer. J. Publ. Hith, 49: 45-52 (1959).
fluoride precipitation or adsorption of fluoride on Erickson, J. D., Oakley, G.P. Jr. and Flynt, J.W. Jr.: J. Am.
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Freni, S.C.: J. Toxicol. Environ. Health, 42: 109-121 (1994).
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defluoridating material. Some of these defluoridation Biol. Med., 106: 147-149 (1961).
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Hamamoto, E., Fujiwara, H., Kimoto, H., Furutani, A.,
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