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Year : 2009  |  Volume : 20  |  Issue : 3  |  Page : 350-355
Physiology and toxicity of fluoride

1 Department of Pediatric Dentistry, Darshan Dental College and Hospital, Udaipur, Rajasthan, India
2 Faculty of Science, M.L. Sukhadia University, Udaipur, Rajasthan, India

Click here for correspondence address and email

Date of Submission09-Aug-2008
Date of Decision30-Apr-2009
Date of Acceptance23-Jun-2009
Date of Web Publication30-Oct-2009


Fluoride has been described as an essential element needed for normal development and growth of animals and extremely useful for human beings. Fluoride is abundant in the environment and the main source of fluoride to humans is drinking water. It has been proved to be beneficial in recommended doses, and at the same time its toxicity at higher levels has also been well established. Fluoride gets accumulated in hard tissues of the body and has been know to play an important role in mineralization of bone and teeth. At high levels it has been known to cause dental and skeletal fluorosis. There are suggested effects of very high levels of fluoride on various body organs and genetic material. The purpose of this paper is to review the various aspects of fluoride and its importance in human life.

Keywords: Dental, fluoride, fluorosis, skeletal, toxicity

How to cite this article:
Dhar V, Bhatnagar M. Physiology and toxicity of fluoride. Indian J Dent Res 2009;20:350-5

How to cite this URL:
Dhar V, Bhatnagar M. Physiology and toxicity of fluoride. Indian J Dent Res [serial online] 2009 [cited 2019 Nov 12];20:350-5. Available from:
Fluoride has been described as an essential nutrient and fluorine has also been included in the list of 14 elements recognized to be physiologically essential for the normal development and growth of human beings.

The fluoride ion comes from the element fluorine. Fluorine, the 17 th most abundant element in the earth's crust, is a gas and never occurs in a free state in nature. Fluorine exists only in combination with other elements as fluoride compounds, which are constituents of minerals in rocks and soil.

   Fluoride From the Air Top

The atmosphere normally contains negligible concentrations of airborne fluorides. Studies reporting the levels of fluoride in air in the United States suggest that ambient fluoride contributes little to an individual's overall fluoride intake. [1],[2]

   Fluoride in Food Top

Fish, such as sardines, may contribute to higher dietary fluoride intake if the bones are ingested. Brewed teas may also contain fluoride concentrations of 1-6 ppm depending on the amount of dry tea used, the water fluoride concentration and the brewing time. [3]

The average daily dietary intake of fluoride (expressed on a body weight basis) by children residing in optimally fluoridated (1 ppm) communities is 0.05 mg/kg/day; in communities without optimally fluoridated water, average intakes for children are about 50% lower. Dietary fluoride intake by adults in optimally fluoridated (1 ppm) areas averages 1.4-3.4 mg/day, and in nonfluoridated areas averages 0.3-1.0 mg/day. [4]

   Water Fluoridation Top

Based on extensive research, the U.S. Public Health Service (USPHS, 1986) established the optimum concentration for fluoride in the water in the United States in the range of 0.7-1.2 ppm. This range effectively reduces tooth decay while minimizing the occurrence of dental fluorosis. The optimum level is dependent on the annual average of the maximum daily air temperature in the geographic area. [5]

   Indian Scenario Top

In India, fluoride level in ground water varies substantially in different regions.

High concentrations of fluoride (>1.5 mg/l) have been reported in the states of Haryana, Delhi, Rajasthan, Karnataka, Uttar Pradesh, Maharastra, Gujarat, Madhya Pradesh, Andhra Pradesh, Tamil Nadu, Kerala, Jammu and Kashmir, Punjab, Orissa, Himachal Pradesh, and Bihar. [6]

Due to lack of central water supply in most of the country, groundwater is being used for drinking purposes. Fluoride levels in drinking water are also found to be low or normal in certain areas. Unfortunately, proper fluoride mapping has not been carried in India so as to locate areas with normal, low, or high levels of fluoride. Dietary fluoride supplements are available only by prescription and are intended for use by children living in nonfluoridated areas to increase their fluoride exposure so that it is similar to that by children who live in optimally fluoridated areas. [7],[8],[9] Dietary fluoride supplements are available in two forms: Drops for infants aged six months and up, and chewable tablets for children and adolescents. [10] The correct amount of a fluoride supplement is based on the child's age and the existing fluoride level in the drinking water [Table 1] and [Table 2]. [11],[12] While total costs for the purchase of supplements and administration of a program are small (compared with the initial cost of the installation of water fluoridation equipment), the overall cost of supplements per child is much greater than the per capita cost of community fluoridation. [13] In addition, community water fluoridation provides decay prevention benefits for the entire population regardless of age, socioeconomic status, educational attainment, or other social variables. [14] This is particularly important for families who do not have access to regular dental services.

   Metabolism of Fluoride Top

After ingestion of fluoride, such as drinking a glass of optimally fluoridated water, the majority of the fluoride is absorbed from the stomach and small intestine into the blood stream. [15] This causes a short-term increase of fluoride levels in the blood. The fluoride levels increase quickly and reach a peak concentration within 20-60 min. [16] The concentration declines rapidly, usually within 3-6 h following the peak levels, due to the uptake of fluoride by hard tissue and efficient removal of fluoride by the kidneys. [3] Approximately, 50% of the fluoride absorbed each day by young or middle- aged adults becomes associated with hard tissues within 24 h while virtually all of the remainder is excreted in the urine. Approximately, 99% of the fluoride present in the body is associated with hard tissues. [15]

Fluoride exists in both ionic and bound forms in plasma, with the bound form being present in larger quantity. Fluoride concentrations in human saliva are slightly less than those found in plasma, ranging from less than 0.01 to 0.05 ppm.

Ingested or systemic fluoride becomes incorporated into forming tooth structures. Fluoride ingested regularly during the time when teeth are developing is deposited throughout the entire surface of the tooth and contributes to long lasting protection against dental decay. [17]

An individual's age and stage of skeletal development will affect the rate of fluoride retention. The amount of fluoride taken up by bone and retained in the body is inversely related to age. More fluoride is retained in young bones than in the bones of older adults. [3],[14],[15]

According to generally accepted scientific knowledge, the ingestion of optimally fluoridated water does not have an adverse effect on bone. [18],[19],[20],[21],[22]

The kidneys play the major role in the removal of fluoride from the body. Normally kidneys are very efficient and excrete fluoride very rapidly. However, decreased fluoride removal may occur among persons with severely impaired renal function who may not be on renal dialysis. [23] No cases of dental fluorosis or symptomatic skeletal fluorosis have been reported among persons with impaired renal function; however, the overall health significance of reduced fluoride removal is uncertain and continued follow-up is recommended especially for children with impaired renal function. [12]

   Fluoride in Hard Tissues Top


Simply put, fluoride is obtained in two forms: Topical and systemic. Topical fluorides strengthen teeth already present in the mouth. In this method of delivery, fluoride is incorporated into the surface of teeth making them more decay resistant. Topically applied fluoride provides local protection on the tooth surface. Topical fluorides include toothpastes, mouth rinses, and professionally applied fluoride gels and rinses.

Systemic fluorides are those that are ingested into the body and become incorporated into forming tooth structures. In contrast to topical fluorides, systemic fluorides ingested regularly during the time when teeth are developing are deposited throughout the entire surface and provide longer lasting protection than those applied topically. [17] Systemic fluorides can also give topical protection because ingested fluoride is present in saliva, which continually bathes the teeth providing a reservoir of fluoride that can be incorporated into the tooth surface to prevent decay. Fluoride also becomes incorporated into dental plaque and facilitates further remineralization. [24] Sources of systemic fluorides include water, dietary fluoride supplements in the forms of tablets, drops or lozenges, and fluoride present in food and beverages.

Researchers have observed fluoride's decay preventive effects through three specific mechanisms: [25],[26]

  1. It reduces the solubility of enamel in acid by converting hydroxyapatite into less soluble fluorhydroxyapatite/fluorapatite.
  2. It exerts an influence directly on dental plaque by reducing the ability of plaque organisms to produce acid.
  3. It promotes the remineralization or repair of tooth enamel in areas that have been demineralized by acids.

The remineralization effect of fluoride is of prime importance. Fluoride ions in and at the enamel surface result in fortified enamel that is not only more resistant to decay, but enamel that can repair or remineralize early dental decay caused by acids from decay-causing bacteria. [27],[28],[29],[30],[31]

Maximum decay reduction is produced when fluoride is available for incorporation during all stages of tooth formation (systemically) and by topical effect after eruption. [32]


The quantity of fluoride accumulation by the skeleton is closely related to the concentration of fluoride in drinking water, although it would be influenced by large deviations from normal levels of fluoride in the diet. Numerous studies have established that fluoride is bound within the bone replacing hydroxyl or bicarbonate groups normally associated with hydroxyapatite structures and it increases the crystallinity or crystal structure of the apatite.

   Fluoride Toxicity Top

It is well established that prolonged use of fluoride at recommended levels does not produce any harmful physiological effects in the human. However, there are safe limits for fluoride beyond which harmful effects can occur. These effects can be classified as acute and chronic toxicity.

Acute toxicity

This can occur due to a single ingestion of a large amount of fluoride. Ingestion of an acute fatal dose of fluoride is very rare. The amount of fluoride considered lethal when taken orally is 35-70 mg F per kg body weight. This is equivalent to 5-10 g sodium fluoride for a 70-kg adult and 1-2 g sodium fluoride for a 15-kg child. [33]

Symptoms of acute toxicity occur rapidly. There is diffuse abdominal pain, diarrhea, vomiting, excess salivation, and thirst. Rapid measures to reduce fluoride absorption should be started by inducing vomiting and administrating large volume of calcium as in lime water or milk. Because alkaline urine prevents fluoride reabsorption, it is suggested that expeditious manipulation of urinary pH by diuresis with an alkalinizing agent might favorably affect the clinical outcome in such cases. Due to rapid elimination of fluoride in the urine, a patient surviving the first 24 h has a good prognosis. [3]

Chronic toxicity

This is caused due to long-term ingestion of smaller amounts of fluoride in drinking water. Excessive fluoride more than 8 ppm in drinking water daily for many years can lead to skeletal fluorosis. Severe cases are normally found only in warm climates where drinking water contains very high levels of fluoride. Due to chronic toxicity, bone density slowly increases; the joints stiffen and becomes painful.

At higher levels of ingestion-from 2 to 8 mg daily, skeletal fluorosis may arise. Whereas dental fluorosis is easily recognized, the skeletal involvement is not clinically obvious until the advanced stage and early cases may be misdiagnosed as rheumatoid or osteoarthritis. [33]

Fluoride increases the stability of the crystal lattice in bone, but makes bone more brittle. The total quantity of fluoride ingested is the single most important factor in determining the clinical course of skeletal fluorosis; the severity of symptoms correlates directly with the level and duration of exposure.

Bone changes observed in human skeletal fluorosis are structural and functional, with a combination of osteosclerosis, osteomalacia, osteoporosis and exostosis formation, and secondary hyperparathyroidism in a proportion of patients. At very high fluoride concentrations, stages 2 and 3 of skeletal fluorosis are likely to occur. The clinical signs of these stages are chronic joint pain, dose related calcification of ligaments, osteosclerosis, possible osteoporosis of long bones, and in severe cases, muscle wasting and neurological defects. Because some of the clinical symptoms mimic arthritis, the first two clinical phases of skeletal fluorosis could be easily misdiagnosed.

Dental fluorosis

It can be described as a diffuse symmetric hypomineralization disorder of ameloblasts. Fluorosis is irreversible and only occurs with exposure to fluoride when enamel is developing.

Instead of being a normal creamy-white translucent color, fluorosed enamel is porous (objectionable secondary staining often occurs) and opaque; teeth can resemble a ghastly white chalk color (light refractivity is greatly reduced because the enamel's prism structure is defective). Cloudy striated (lines of demarcation) enamel, white specks or blotches, 'snow- capping', yellowish-brown spots, or brown pits on teeth are all characteristic of fluorosis. In its more severe form, fluorosed enamel is structurally weak (brittle) and prone to erosion and breakage, especially when drilled and filled. Even in the milder forms, there is increased enamel attrition. Fluorotic lesions are not just confined to enamel but can be seen by microscope in dentin as well. Because fluoride is a powerful bone and tooth seeking element, it also deposits bone or bone-like material externally on the roots of teeth, and internally in the tooth's pulp chamber; the calcified material narrows the pulp chamber, and thereby interferes with tooth nutrition. Fluorosis is a toxic manifestation of chronic (low-dose, long-term) fluoride intake. To prevent fluorosis from occurring in the most prominent and/or most susceptible teeth, the most critical time to avoid fluoride exposure is the first three to six years of a child's life.

Fejerskov et al. (1977) stated that the effect of fluoride on enamel formation can follow several possible pathogenic pathways: [29]

  1. Effect on ameloblasts

    1. Secretory phase

      • Diminished matrix production
      • Change of matrix composition
      • Change in ion transport mechanism

    2. Maturation phase

      • Diminished withdrawal of protein and water

  2. Effect on nucleation and crystal growth in all stages of enamel formation
  3. Effect on calcium homeostasis generally with dental fluorosis as an indirect result

During tooth formation, the cells of the dental tissues, particularly the ameloblasts, are very sensitive to fluoride. At relatively low doses, e.g., 2 ppm of fluoride in the water, small spots, or mottling, vary in color from paper white to dark brown. The brown stain of the latter condition usually accumulates after eruption. These doses affect only the appearance and not the structure of the tooth. At higher doses, the cells may be affected and the tooth structure severely altered, so that the normally smooth surface shows hypoplastic corrugations. These effects, mottled appearance and altered form, are produced only when excessive amounts of fluoride are ingested during the period of formation and calcification, i.e., during the first eight years of life in man. After the tooth erupts and calcification has been completed, ingested fluoride does not have adverse dental consequences. Fluorosis is seen to affect mainly permanent dentition and very high fluoride levels (>10 ppm) are required in drinking water for it to cross placental barrier and affect primary dentition.

Dental fluorosis might be more than a cosmetic defect if enough fluorotic enamel is fractured and lost to cause pain, adversely affect food choices, compromise chewing efficiency, and require complex dental treatment.

   Genotoxicity of Fluoride Top

Many studies have examined the possible effects of fluoride on chromosome damage. While there are no published studies on the genotoxic (damage to DNA) effect of fluoride in humans, numerous studies have been done on mice. [23] These studies have shown no evidence of effect of fluoride on chromosomes in bone marrow or sperm cells even at fluoride levels 100 times higher than that in fluoridated water. [34],[35],[36],[37],[38],[39],[40] Another independent group of researchers reported a similar lack of fluoride-induced chromosomal damage to human white blood cells, which are especially sensitive to agents that cause genetic mutations. Not only did fluoride fail to damage chromosomes but it also protected them against the effect of a known mutagen. [41] The genotoxic effects of fluoride were also studied in hamster bone marrow cells and cultured hamster ovarian cells. Again, the results supported the conclusion that fluoride does not cause chromosomal damage, and therefore, was not a genetic hazard. [42] In further tests, fluoride has not caused genetic mutations in the most widely used bacterial mutagenesis assay (the Ames test) over a wide range of fluoride levels. [43],[44],[45]

Occasional questions arise regarding fluoride's effects on human reproduction, fertility and birth rates. Very high levels of fluoride intake have been associated with adverse effects on reproductive outcomes in many animal species. Based on these findings, it appears that fluoride concentrations associated with adverse reproductive effects in animals are far higher (100-200 ppm) than those to which human populations are exposed. Consequently, there is insufficient scientific basis on which to conclude that ingestion of fluoride at levels found in community water fluoridation (0.7-1.2 ppm) would have adverse effects on human reproduction. [23]

The National Research Council (NRC) of the National Academy of Sciences 1993 [23] supports the conclusion that drinking optimally fluoridated water is not a genetic hazard. In a statement summarizing its research, the NRC states that:

  1. The genotoxicity of fluoride is limited primarily to doses much higher than those to which humans are exposed.
  2. Even at high doses, genotoxic effects are not always observed.
  3. The preponderance of the genotoxic effects that have been reported are of the types that probably are of no or negligible genetic significance.

The lowest dose of fluoride reported to cause chromosomal changes in mammalian cells was approximately 170 times than normally found in human cells in areas where drinking water is fluoridated, which indicates a very large margin of safety.

   Others Top

Fluoride toxicity at high levels has been associated with thyroid changes, growth retardation, kidney changes, and even urolithiasis.

Existing data indicate that some subsets of the population may be unusually susceptible to the toxic effects of fluoride and its compounds. These populations include the elderly, people with deficiencies of calcium, magnesium, and/or vitamin C, and people with cardiovascular and kidney problems.

   Conclusions Top

It is very clear that fluoride in recommended concentrations is definitely beneficial to health. So as to capitalize on the beneficial effects of fluoride, judicious use of fluoride supplements is mandatory. The need to mark out areas with low, recommended, and high levels of fluoride in drinking water or food cannot be underestimated. Measures should be taken to use fluoride to our advantage in achieving optimal health.

   References Top

1.Hodge HC, Smith FA. Occupational fluoride exposure. J Occup Med 1977;19:12-39.   Back to cited text no. 1  [PUBMED]  [FULLTEXT]  
2.Committee on Biologic Effects of Atmospheric Pollutants. Biologic effects of atmospheric pollutants: Fluorides. Washington DC: National Academy of Sciences; 1971.p. 5-9.   Back to cited text no. 2      
3.Whitford GM. The metabolism and toxicity of fluoride. 2 nd rev. ed. Monographs in oral science. Vol. 16. Basel, Switzerland: Karger; 1996.   Back to cited text no. 3      
4.Institute of Medicine, Food and Nutrition Board. Dietary reference intakes for calcium, phosphorus, magnesium, vitamin D and fluoride. Report of the Standing Committee on the Scientific Evaluation of Dietary Reference Intakes. Washington, DC: National Academy Press;(In press).   Back to cited text no. 4      
5.US Department of Health and Human Services, Centers for Disease Control, Dental Disease Prevention Activity. Water fluoridation: A manual for engineers and technicians. Atlanta; 1986.  Back to cited text no. 5      
6.Susheela AK. Fluorosis: Indian scenario. A Treatise on Fluorosis. Fluorosis Research and Rural Development Foundation; 2001. p. 13-5.  Back to cited text no. 6      
7.Largent E. The supply of fluorine to man: 1. Introduction. Fluorides and human health. Geneva: World Health Organization Monograph Series No. 59; 1970. p. 17-8.   Back to cited text no. 7      
8.Rugg-Gunn AJ. Nutrition and dental health. New York: Oxford University Press; 1993.   Back to cited text no. 8      
9.Safe Drinking Water Committee, National Research Council. Drinking water and health. Washington, DC; National Academy of Sciences; 1977.   Back to cited text no. 9      
10.American Dental Association, Council on Access Prevention and Interprofessional Relations. Caries diagnosis and risk assessment: A review of preventive strategies and management. J Am Dent Assoc 1995;126.   Back to cited text no. 10      
11.Levy SM, Kiritsy MC, Warren JJ. Sources of fluoride intake in children. J Public Health Dent 1995;55:39-52.   Back to cited text no. 11      
12.US Department of Health and Human Services, Public Health Service. Review of fluoride: Benefits and risks. Washington, DC; Report of the Ad Hoc Subcommittee on Fluoride; 1991.   Back to cited text no. 12      
13.Garcia AI. Caries incidence and costs of prevention programs. J Public Health Dent 1989;49:259-71.  Back to cited text no. 13      
14.Horowitz HS. The effectiveness of community water fluoridation in the United States. J Public Health Dent 1996;56:253-8.  Back to cited text no. 14      
15.Whitford GM. The physiological and toxicological characteristics of fluoride. J Dent Res 1990;69:539-49.   Back to cited text no. 15      
16.Whitford GM. Intake and metabolism of fluoride. Adv Dent Res 1994;8:5-14.  Back to cited text no. 16      
17.Newbrun E. Fluorides and dental caries. 3 rd ed. Springfield, Illinois: Charles C. Thomas, publisher; 1986.   Back to cited text no. 17      
18.Cauley JA, Murphy PA, Riley TJ, Buhari AM. Effects of fluoridated drinking water on bone mass and fractures: The study of osteoporotic fractures. J Bone Min Res 1995;10:1076-86.   Back to cited text no. 18      
19.Gordon SL, Corbin SB. Summary of workshop on drinking water fluoridation influence on hip fracture on bone health. (National Institutes of Health, 10 April, 1991) Osteoporos Int 1992;2:109-17.   Back to cited text no. 19      
20.Jacobsen SJ, O'Fallon WM, Melton LJ 3 rd . Hip fracture incidence before and after the fluoridation of the public water supply, Rochester, Minnesota. Am J Public Health 1993;83:743-5.   Back to cited text no. 20      
21.Karagas MR, Baron JA, Barrett JA, Jacobsen SJ. Patterns of fracture among the United States elderly: Geographic and fluoride effects. Ann Epidemiol 1996;6:209-16.   Back to cited text no. 21      
22.Suarez-Almazor ME, Flowerdew G, Saunders LD, Soskolne CL, Russell AS. The fluoridation of drinking water and hip fracture hospitalization rates in two Canadian communities. Am J Public Health 1993;83:689-93.   Back to cited text no. 22      
23.National Research Council. Health effects of ingested fluoride. Report of the Subcommittee on Health Effects of Ingested Fluoride. Washington, DC: National Academy Press;1993.   Back to cited text no. 23      
24.Lambrou D, Larsen MJ, Fejerskov O, Tachos B. The effect of fluoride in saliva on remineralization of dental enamel in humans. Caries Res 1981;15:341-5.   Back to cited text no. 24      
25.DePaola PF, Kashket S. Prevention of dental caries. In: Fluorides, effects on vegetation, animals and humans. Schupe JL, Peterson HB, Leone NC, editors. Salt Lake City: Paragon Press; 1983. p. 199-211.   Back to cited text no. 25      
26.Mellberg JR, Ripa LW. Fluoride in preventive dentistry: Theory and clinical applications. Chicago: Quintessence; 1983. p. 41-80.   Back to cited text no. 26      
27.Backer-Dirks O, Kunzel W, Carlos JP. Caries-preventive water fluoridation. In: Progress in caries prevention. Ericsson Y, editor. Caries Res 1978;12:7-14.   Back to cited text no. 27      
28.Featherstone JD. The mechanism of dental decay. Nutrition Today; 1987. p. 10-6.   Back to cited text no. 28      
29.Fejerskov O, Thylstrup A, Larsen MJ. Rational use of fluorides in caries prevention. A concept based on possible cariostatic mechanisms. Acta Odontol Scan 1981;39:241-9.   Back to cited text no. 29      
30.Silverstone LM, Wefel JS, Zimmerman BF, Clarkson BH, Featherstone MJ. Remineralization of natural and artificial lesions in human dental enamel in vitro. Effect of calcium concentration of the calcifying fluid. Caries Res 1981;15:138-57.   Back to cited text no. 30      
31.Silverstone LM. Remineralization and enamel caries: New concepts. Dental Update 1993;10:261-73.   Back to cited text no. 31      
32.Hargreaves JA. The level and timing of systemic exposure to fluoride with respect to caries resistance. J Dent Res 1992;71:1244-8.   Back to cited text no. 32      
33.Mellberg JR, Ripa LW. Flouride metabolism. Fluorides in Preventive Dentistry-Theory and clinical Applications. Quintessence Publishing Co Limited; 1983. p. 81-102.  Back to cited text no. 33      
34.Dunipace AJ, Zhang W, Noblitt TW, Li Y, Stookey GK. Genotoxic evaluation of chronic fluoride exposure: Micronucleus and sperm morphology studies. J Dent Res 1989;68:1525-8.   Back to cited text no. 34      
35.Kram D, Schneider EL, Singer L, Martin GR. The effects of high and low fluoride diets on the frequencies of sister chromatid exchanges. Mutat Res 1978;57:51-5.   Back to cited text no. 35      
36.Li Y, Dunipace AJ, Stookey GK. Effects of fluoride on the mouse sperm morphology test. J Dent Res 1987;66:1509-11.   Back to cited text no. 36      
37.Li Y, Dunipace AJ, Stookey GK. Lack of genotoxic effects of fluoride in the mouse bone-marrow micronucleus test. J Dent Res 1987;66:1687-90.   Back to cited text no. 37      
38.Li YM, Heerema NA, Dunipace AJ, Stookey GK. Genotoxic effects of fluoride evaluated by sister-chromatid exchange. Mutat Res 1987;192:191-201.   Back to cited text no. 38      
39.Li YM, Zhang W, Noblitt TW, Dunipace AJ, Stookey GK. Genotoxic evaluation of chronic fluoride exposure: Sister-chromatid exchange study. Mutat Res 1989;227:159-65.   Back to cited text no. 39      
40.Zeiger E, Gulati DK, Kaur P, Mohamed AH, Revazova J, Deaton TG. Cytogenetic studies of sodium fluoride in mice. Mutagenesis 1994;9:467-71.   Back to cited text no. 40      
41.Obe G, Slacik-Erben R. Suppressive activity by fluoride on the induction of chromosome aberrations in human cells and alkylating agents in vitro. Mutat Res 1973;19:369-71.   Back to cited text no. 41      
42.Martin GR, Brown KS, Singer L, Ophaug R, Jacobson-Kram D. Cytogenic and mutagenic assays on fluoride. In: Fluorides, effects on vegetation, animals and humans. Schupe JL, Peterson HB, Leone NC, editors. Salt Lake City: Paragon Press; 1983. p. 271-80.   Back to cited text no. 42      
43.Li Y, Dunipace AJ, Stookey GK. Absence of mutagenic and antimutagenic activities of fluoride in Ames salmonella assays. Mutut Res 1987;120:229-36.   Back to cited text no. 43      
44.Martin GR, Brown KS, Matheson DW, Lebowitz H, Singer L, Ophaug R. Lack of cytogenetic effects in mice or mutations in salmonella receiving sodium fluoride. Mutat Res 1979;66:159-67.  Back to cited text no. 44      
45.Tong CC, McQueen CA, Brat SV, Williams GM. The lack of genotoxicity of sodium fluoride in a battery of cellular tests. Cell Biol Toxicol 1988;4:173-86.   Back to cited text no. 45      

Correspondence Address:
Vineet Dhar
Department of Pediatric Dentistry, Darshan Dental College and Hospital, Udaipur, Rajasthan
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0970-9290.57379

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14 Prevalence of dental fluorosis in eight cohorts of Mexicans born in the establishment of the national domestic salt fluoridation [Prevalencia de fluorosis dental en ocho cohorts de mexicanos nacidos durante la instauración del programa nacional de fluoruración de la sal doméstica]
Casanova-Rosado, A.J. and Medina-Soĺs, C.E. and Casanova-Rosado, J.F. and Vallejos-Sánchez, A.A. and de la Rosa-Santillana, R. and Mendoza-Rodríguez, M. and Villalobos-Rodelo, J.J. and Maupomé, G.
Gaceta Medica de Mexico. 2013; 149(1): 27-35
15 The effects of fluorine on antioxidant system and apoptosis of brain tissue in carp (cyprinus carpio L.)
Cao, J. and Chen, J. and Wang, J. and Luo, Y.
Huanjing Kexue Xuebao/Acta Scientiae Circumstantiae. 2013; 33(3): 861-866
16 Effects of fluoride on liver apoptosis and Bcl-2, Bax protein expression in freshwater teleost, Cyprinus carpio
Jinling Cao,Jianjie Chen,Jundong Wang,Ruhui Jia,Wenjuan Xue,Yongju Luo,Xi Gan
Chemosphere. 2013; 91(8): 1203
[Pubmed] | [DOI]
17 The toxicity mechanism of sodium fluoride on fertility in female rats
Yongjiang Zhou,Yiwen Qiu,Junlin He,Xuemei Chen,Yubing Ding,Yingxiong Wang,Xueqing Liu
Food and Chemical Toxicology. 2013; 62: 566
[Pubmed] | [DOI]
18 Effect of sodium fluoride on neuroimmunological parameters, oxidative stress and antioxidative defenses
Y. P. Reddy,S. K. Tiwari,A. P. Shaik,A. Alsaeed,A. Sultana,P. K. Reddy
Toxicology Mechanisms and Methods. 2013; : 1
[Pubmed] | [DOI]
19 Assessment of relationship on excess fluoride intake from drinking water and carotid atherosclerosis development in adults in fluoride endemic areas, China
Hui Liu,Yanhui Gao,Liyan Sun,Mang Li,Bingyun Li,Dianjun Sun
International Journal of Hygiene and Environmental Health. 2013;
[Pubmed] | [DOI]
20 The Relationship of PTH Bst BI Polymorphism, Calciotropic Hormone Levels, and Dental Fluorosis of Children in China
Shibao Wen,Anqi Li,Liuxin Cui,Qi Huang,Hongyang Chen,Xiaoyi Guo,Yixin Luo,Qianyun Hao,Jiaxiang Hou,Yue Ba
Biological Trace Element Research. 2012; 147(1-3): 84
[Pubmed] | [DOI]
21 Effect of Fluoride on Insulin Level of Rats and Insulin Receptor Expression in the MC3T3-E1 Cells
Chun-yan Hu,Li-qun Ren,Xi-ning Li,Nan Wu,Guang-sheng Li,Qin-yi Liu,Hui Xu
Biological Trace Element Research. 2012; 150(1-3): 297
[Pubmed] | [DOI]
22 Excessi{dotless
Lütfioǧlu, M. and Sakallioǧlu, E.E. and Sakallioǧlu, U. and Gülbahar, M.Y. and Muǧlali, M. and Baş, B. and Aksoy, A.
Clinical Oral Investigations. 2012; 16(6): 1563-1570
23 Effect of fluoride on insulin level of rats and insulin receptor expression in the MC3T3-E1 cells
Hu, C.-Y. and Ren, L.-Q. and Li, X.-N. and Wu, N. and Li, G.-S. and Liu, Q.-Y. and Xu, H.
Biological Trace Element Research. 2012; 150(1-3): 297-305
24 The relationship of PTH Bst BI polymorphism, calciotropic hormone levels, and dental fluorosis of children in China
Wen, S. and Li, A. and Cui, L. and Huang, Q. and Chen, H. and Guo, X. and Luo, Y. and Hao, Q. and Hou, J. and Ba, Y.
Biological Trace Element Research. 2012; 147(1-3): 84-90
25 Prevalence of dental fluorosis & dental caries in association with high levels of drinking water fluoride content in a district of Gujarat, India
Kotecha, P.V. and Patel, S.V. and Bhalani, K.D. and Shah, D. and Shah, V.S. and Mehta, K.G.
Indian Journal of Medical Research. 2012; 135(6): 873-877
26 Molecular Mechanisms of Cytotoxicity and Apoptosis Induced by Inorganic Fluoride
Natalia Ivanovna Agalakova, Gennadii Petrovich Gusev
ISRN Cell Biology. 2012; 2012: 1
[VIEW] | [DOI]
27 Perinatal exposure to sodium fluoride with emphasis on territorial aggression, sexual behaviour and fertility in male rats
Kamel, M.M., El-lethey, H.S., Shaheed, I.B.
Life Science Journal. 2011; 8(2): 686-694
28 Toxicity effects and action mechanism of fluoride
Chai, L., Jiang, L., Shi, Y., Wang, H.
ISWREP 2011 - Proceedings of 2011 International Symposium on Water Resource and Environmental Protection 4,. 2011; art(5893495): 2946-2950
29 Acute toxicity and DNA damage of fluoride to larval big toad Bufo gargarizans
Chai, L., Liu, X., Jiang, L., Dong, S., Wang, H.
ISWREP 2011 - Proceedings of 2011 International Symposium on Water Resource and Environmental Protection 1,. 2011; art(5893036): 430-433
30 Studies on the comparative effect of sodium fluoride on collagen content in various rat organs
Siddiqi, N.J.
African Journal of Biotechnology. 2011; 10(79): 18252-18255
31 Effects of fluoride on expression of bone-specific genes in developing Xenopus laevis larvae
Nair, M. and Belak, Z.R. and Ovsenek, N.
Biochemistry and Cell Biology. 2011; 89(4): 377-386
32 Effects of the fluoride on the central nervous system [Efectos del flúor sobre el sistema nervioso central]
Valdez-Jiménez, L. and Soria Fregozo, C. and Miranda Beltrán, M.L. and Gutiérrez Coronado, O. and Pérez Vega, M.I.
Neurologia. 2011; 26(5): 297-300
33 Effects of fluoride on expression of bone-specific genes in developingXenopus laevislarvae
Manoj Nair,Zachery R. Belak,Nick Ovsenek
Biochemistry and Cell Biology. 2011; 89(4): 377
[Pubmed] | [DOI]
34 Effect of inorganic fluoride on living organisms of different phylogenetic level
N. I. Agalakova, G. P. Gusev
Journal of Evolutionary Biochemistry and Physiology. 2011; 47(5): 393
[VIEW] | [DOI]
35 Effect of sodium fluoride with and without ginseng on the submandibular gland of adult male albino rat
Amany Mohamed Mousa
The Egyptian Journal of Histology. 2011; 34(2): 291
[Pubmed] | [DOI]
36 Efectos del flúor sobre el sistema nervioso central
L. Valdez-Jiménez,C. Soria Fregozo,M.L. Miranda Beltrán,O. Gutiérrez Coronado,M.I. Pérez Vega
Neurología. 2011; 26(5): 297
[Pubmed] | [DOI]
37 Effects of the fluoride on the central nervous system
L. Valdez-Jiménez,C. Soria Fregozo,M.L. Miranda Beltrán,O. Gutiérrez Coronado,M.I. Pérez Vega
Neurología (English Edition). 2011; 26(5): 297
[Pubmed] | [DOI]
38 Excessıve fluorıde ıntake alters the MMP-2, TIMP-1 and TGF-β levels of perıodontal soft tıssues: an experımental study ın rabbıts
Müge Lütfioğlu, Elif Eser Sakallıoğlu, Umur Sakallıoğlu, M. Yavuz Gülbahar, Mehtap Muğlalı, Burcu Baş, Abdurrahman Aksoy
Clinical Oral Investigations. 2011;
[VIEW] | [DOI]
39 Fluoride-induced death of rat erythrocytes in vitro
Natalia I. Agalakova, Gennadii P. Gusev
Toxicology in Vitro. 2011;
[VIEW] | [DOI]
40 Interactive effect of arsenic and fluoride on cardio-respiratory disorders in male rats: possible role of reactive oxygen species
S. J. S. Flora, Vidhu Pachauri, Megha Mittal, Deo Kumar
BioMetals. 2011;
[VIEW] | [DOI]
41 Cell death or survival: The double-edged sword of environmental and occupational toxicity
Rodrigo Franco, Mihalis I. Panayiotidis
Chemico-Biological Interactions. 2010; 188(2): 265
[VIEW] | [DOI]
42 Fluoride-Induced Oxidative Stress in Three-Dimensional Culture of OS732 Cells and Rats
Hui Liu, Jing-chun Sun, Zhi-tao Zhao, Jin-ming Zhang, Hui Xu, Guang-sheng Li
Biological Trace Element Research. 2010;
[VIEW] | [DOI]


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