Essay: Effects of Fluoride Pollution

Abstract
An estimated 200 million people from 29 countries including India are severely affected due to fluoride pollution. Ingestion of fluoride beyond the WHO recommended permissible level (1.5 mg/l) is associated with dental and skeletal fluorosis and other toxic responses while inadequate intake of fluoride is associated with dental caries. Natural weathering of various minerals (like apatite, fluorite, topaz, fluorspar, and mica) provides fluoride to soils. In site-specific cases some industries (mainly phosphorous fertilizer plants; steel, aluminum, zinc, smelting industries; glass and ceramic industries, etc) are also responsible for fluoride contamination of soils. Fluoride gets transferred from contaminated irrigation water to cultivated crops, vegetables and fruits. This bioaccumulation of fluoride contributes further fluoride to the human food chain in addition to the drinking water pathway, and thus it is causing larger risk to the already fluoride-contamination affected population. Moreover, this new avenue of fluoride highly endangers the most susceptible infants and children towards dental fluorosis. The ‘Nalgonda’ and ‘activated alumina’ processes are the most commonly used defluoridation techniques of drinking water. But, a suitable, efficient, user-friendly and cost-effective technique for defluoridation is yet to be developed. Equal emphases are to be given on creation of awareness in people regarding fluorosis and restriction of usage of fluoride-contaminated groundwater for irrigation purpose.
Key words Fluorosis; Fluoride pollution; Fluoride bioaccumulation; Fluoride in food chain
Introduction
Moderate to high concentration of fluoride in groundwater is reported to be one of the major environmental issues of Algeria, Brazil, Canada, China, Ethiopia, Ghana, India, Iran, Italy, Japan, Jordan, Kenya, Korea, Malawi, Mexico, Norway, Pakistan, Sri Lanka, Thailand, Turkey, and the USA (WHO 2006a; Brindha and Elango 2011) threatening an estimated 200 million people (Bhattacharya and Chakrabarti 2011). Fluoride can be found in different environmental components originated from mineral sources, atmospheric sources, and geothermal sources. After its dissolution from weathered rock it becomes mobile, and it enters soil, groundwater, cultivated crops, fruits and vegetables depending on the prevailing geological agents. The natural cause which leads to high fluoride concentration in groundwater is the dissolution of fluorite, apatite, and topaz from bedrocks (Suthar et al. 2008). Moreover, different anthropogenic influences like usage of phosphate fertilizers and pesticides, discharge of untreated or partially treated sewage and sludge in groundwater, overexploitation of groundwater for irrigation, etc., are also responsible for the increase of fluoride concentration in groundwater (EPA 1997; Ramanaiah et al. 2006). Fluoride in groundwater is mostly of geological origin. Waters with high levels of fluoride content are mostly found at the foot of high mountains and in areas where the sea has made geological deposits. Ingestion of excess fluoride, most commonly via drinking water (other sources are food, industrial gas and excessive use of toothpaste), can cause ‘fluorosis’ which affects the teeth and bones (WHO 2006b). Moderate amounts of fluoride lead to dental effects, but long-term ingestion of large amounts of fluoride can lead to potentially severe skeletal and other adverse problems. Paradoxically, low levels of fluoride intake help to prevent dental caries. The control of drinking water quality is therefore critical in preventing fluorosis. The associated human health risks from fluoride can be broadly categorized as: dental effects, skeletal effects, reproductive effects, developmental effects, renal effects, neurological effects, endocrine effects, and carcinogenic effects. Thus, the World Health Organization (WHO) has made 1.5 mg/l as the permissible limit for fluoride in drinking water (WHO 2006a).
Fluorosis is endemic in 20 out of total 29 states of India, spreading over 65% of the total rural habitations of the country (UNICEF 1999). More than 65 million Indians including six million children are at risk due to the presence of fluoride beyond the desirable 1.5 mg/l level in drinking water (Andezhath et al. 1999; UNICEF 1999). High concentration of fluoride in groundwater has been mainly reported from different regions of Assam, Andhra Pradesh, Bihar, Chhattisgarh, Gujarat, Karnataka, Madhya Pradesh, Maharashtra, Odisha, Rajasthan, Telangana, Uttar Pradesh and West Bengal (PHED Report 2007; Chatterjee et al. 2008; Salve et al. 2008; Sankararamakrishnan et al. 2008; Suthar et al. 2008; Mishra et al. 2009; Kundu and Mandal 2009a; Bhattacharya and Chakrabarti 2011; Brindha et al. 2011; Dar et al. 2011; Chakrabarti and Bhattacharya 2013; Samal et al. 2015; Bhattacharya 2016). The present review focuses on the assimilation of relevant data and information on past and present status of fluoride contamination in India, mobility of fluoride in ecosystems, and the related human health issues.
Fluoride contamination in water—sources, essentiality vs. toxicity
Fluoride is present in almost all groundwater, but the percentage of total fluoride that is leachable varies widely with rock types (Lirong et al. 2006). The types of minerals, residence time, and climate primarily control dissolution of fluoride from bedrock (Hem 1985). The pH, hardness, ionic strength, and other water quality parameters also have important roles in site-specific cases influencing mineral solubility, complexation, and sorption/exchange reactions (Apambire et al. 1997). The common fluoride-bearing minerals being sparingly soluble release fluoride to water slowly with the exception of villiaumite (Saxena and Ahmed 2003). Dissolution of fluorapatite gets enhanced in the presence of microbes which seek to separate phosphorus from the solid phase (Allen-Long 2001). Similar is the case of fast fluorite dissolution in sodium-bicarbonate waters (Apambire et a1. 1997) while the release of fluoride from clay minerals depends strongly on pH (Saxena and Ahmed 2003). The maximum concentration of fluoride in groundwater is usually controlled by the solubility of fluorite (Edmunds and Smedley 2005). Hence the groundwater fluoride concentration is not linearly correlated to the percentage of fluoride-bearing minerals in the geologic substrate. The influence of climate on fluoride concentrations in groundwater is largely dependent on the recharge of groundwater through rainfall and subsequent groundwater flow (IGRAC 2003; Edmunds and Smedley 2005). Humid tropical regions with high rainfall are less likely to have high fluoride concentrations in groundwater. This is because soluble ions such as fluoride are leached out and diluted due to heavy rainfall. On the opposite side arid environments normally have high fluoride contents due to the low rates of groundwater recharge. Low rainfall leads to prolonged water-mineral interaction and higher salinities in the arid environment, which further enhance mineral dissolution (Smedley et al. 2002). Temperature also regulates the solubility of fluorine-bearing minerals. The presence of high pH, and low calcium and magnesium contents in water had been reported to be the two major factors responsible for rapid leaching of fluoride and consequently resulting into elevated concentration of it in water (Rao et al. 1993).
Drinking water has been established to be the major contributor for entry of fluoride in the human food chain (Susheela 1999). According to Wood (1974) the intake of fluoride within the range of 0.5–1 mg/l in water is beneficial for human health. This permitted range of fluoride helps in the production and maintenance of healthy teeth and bones. Later, the United States Environment Protection Agency (USEPA) revised the recommended range of fluoride as 0.7–1.2 mg/l (USEPA 2010). Thus, any water sample with fluoride contents <0.7 or > 1.5 mg/l should not to be utilized as a source of potable water. Fluoride may be added at low levels during treatment of drinking water in places which are devoid of adequate quantity of fluoride to aid in dental and skeletal health of the residents, especially children. Again, excessive intake of fluoride causes chronic dental and skeletal fluorosis, which is manifested by mottling of teeth in mild cases, softening of bones and neurological damages in severe cases (Steinberg et al. 1955). In India the Bureau of Indian Standards (BIS) and Indian Council of Medical Research (ICMR) have prescribed 0.6–1.2 mg/l and 1.5 mg/l as the desirable range and permissible limit for fluoride, respectively (ICMR 1975; BIS 2003). Consumption of fluoride in excess of 2 mg/l was reported to cause dense and brittle bone, and also dental problems (Chatterjee et al. 2008). However, the United States Public Health Service (USPHS) has advocated following a range of allowable concentrations for fluoride in drinking water for different regions depending on prevailing climatic conditions (USPHS 1962). The USPHS argued that the amount of water consumed and consequently the amount of fluoride ingested being influenced primarily by the air temperature of that region. Thus, presence of fluoride in drinking water is often metaphoric as two-edged sword−prolonged ingestion in excess of the permissible fluoride level is associated with dental, and skeletal fluorosis and other toxic responses while inadequate intake of fluoride is associated with dental caries.
Fluoride contamination in soil−sources and significances
Fluoride is the 13th most abundant element of the earth’s crust representing ~0.3 g/kg of the earth’s crust. It is mainly present as NaF or HF, which can be found in minerals fluorspar, fluorapatite, topaz and cryolite. In most of the rocks fluorine is present normally in the range of 100−1,300 mg/kg (Faure 1991), but in soils fluoride contents generally vary in the range 20−500 mg/kg (Edmunds and Smedley 2005). Exceptionally higher presence of fluoride (>1,000 mg/kg) was observed in soils derived from rocks with high fluorine contents (Cronin et al. 2003) or in cultivated soils affected by anthropogenic inputs, like application of phosphate fertilizers (Kabata-Pendias and Pendias 2001), intrusion of sewage sludge, and industrial contamination (Cronin et al. 2003). According to Bhat et al. (2015) fluoride contamination of soil is fundamentally because of phosphorous fertilizers containing <1% to >1.5% fluorine. The sorption capacity of soil (which varies with soil pH), types of sorbents present in soil, and soil salinity largely regulate the mobility of fluoride in soil (Pickering 1985; Cronin et al. 2003). In comparison to sandy soils, fine-grained soils have higher clay and oxyhydroxide contents, and thus retain more fluoride. High salinity (ionic strength) affects fluoride mobility by enhancing the potential for fluoride complexes to form and by increasing the number of ions that compete for soil sorption sites. Edmunds and Smedley (2005) suggested that evapotranspiration was able to raise the salinity of soil solutions leading to higher content of fluoride ultimately reaching groundwater. The primary anthropogenic sources of fluoride pollution in soil are different chemical industries (like phosphorous fertilizer plants, steel, aluminum, zinc, smelting industries, etc), glass and ceramic industries, and power plants. The soil of the areas in vicinity of the above said industrial units contain medium to high content of fluoride (Bhat et al. 2015).
Agriculture is also responsible for disposal of fluoride in soil. This is due to the facts that irrigation and application of fertilizers normally increase the sodicity of soils which ultimately result into high fluoride content in soils (Brindha et al. 2011). A significant correlation (r = 0.56) was detected by Samal et al. (2015) between the fluoride content in deep tube wells and that in agriculture field soils. In a fluoride affected area if fluoride-contaminated groundwater is used for irrigation then there is a high possibility of bioaccumulation of fluoride into irrigated crops. This would further endanger human health due to augmented fluoride consumption through cultivated crops, fruits and vegetables in addition to drinking water pathway. Soils polluted with fluoride negatively impact human wellbeing through direct contact with soil, through inhalation of vaporized soil contaminants, through ingestion of contaminated foods, and through intake of contaminated groundwater (Blagojevic et al. 2002; Begum 2012; Bhat et al. 2015). Fluorine can penetrate deep soil layers of <80 cm, and when present in high concentrations it can oppress biological activities operating in soil medium (Polonskij 2013).
Transfer of fluoride from contaminated irrigation water to cultivated crops
Plants via xylematic flow transport fluoride to different organs, mainly the leaves (Davison and Weinstein 1998). Bioconcentration of fluoride in plants at various levels was shown by different researchers (Fornasiero 2001; Kalinic et al. 2005; Kozyrenko et al. 2007; Saini et al. 2013). The bioaccumulation of fluoride had been established to cause chronic toxicity in grazing animals and humans (Clark and Stewart 1983). The chronic toxicity may finally lead to bone damage as well as tooth wear. Extensive monitoring in fluoride affected areas has to be thus conducted to assess the degree of bioaccumulation of fluoride by locally cultivated crops and vegetables. Leafy vegetables are susceptible to air borne fluoride and shows wide variations in the fluoride level cultivated in different areas. According to Gupta and Banerjee (2011) the higher fluoride contents in leafy vegetables were due to the increased metabolism and/or photosynthesis rate in leafy shoots in comparison to seeds/grains or other storage organs (tubers). In another study leafy vegetables (like radish, spinach, cabbage and cauliflower) were reported to bioconcentrate fluoride more preferably (BCF>1) indicating higher rate of photosynthesis in leafy vegetables associated with higher intake of irrigation water (Pal et al. 2012). Cereals were usually found to accumulate <1 mg/kg fluoride as fluoride mostly gets accumulated in the outer layer of the grain and in the embryo (Kumpulainen and Kovistoinen 1977). In many studies especially in areas adjacent to industries spinach has been reported to be unusually enriched in fluoride (Haidouti et al. 1993; Saini et al. 2013). Tea is one of the most popular refreshment drinks of many countries of the world including India. But, at the same time tea had been established to be one of the most fluoride-enriched conventional beverages as ~67% of the total fluoride in leaves gets solubilised in the drink (Fung et al. 1999). Fluoride-contaminated irrigation water (7.4−14 mg/l) had been shown to transfer fluoride (mg/kg) in the cultivated crops of Rajasthan (spinach: 26, methi: 19, etc) (Gautam et al. 2010). Lower translocation of fluoride in edible parts was observed for the grain-yielding crop plant (mustard), fruiting vegetables (tomato, brinjal), and tubers (potato), with an exception of beans while higher translocation was seen for leafy vegetables like spinach, coriander leaves, and marsilea (Gupta and Banerjee 2011).
High fluoride levels produce different negative impacts on plants like inhibition of germination, malformations of ultrastructures, reduction of photosynthetic capacity, alteration in permeability of membranes, bringing down productivity as well as biomass, and production of other physiological and biochemical disorders (Gautam et al. 2010). Certain physiological processes are known to be significantly affected by fluoride which results into chlorosis, leaf tip burn, leaf necrosis, change in biochemical ratio of plant body, etc (Mcnulty and Newman 1961; Miller et al. 1999). Fluoride was observed to produce toxic effects on chlorophyll pigment and on secondary metabolites like sugar, ascorbic acid, amino acids and proteins (Mcnulty and Newman 1961; Kundu and Mondal 2010). Table 1 summarizes concentrations of fluoride in different environmental components as well as in cultivated crops and vegetables.
Entry of fluoride into the human food chain and its consequences
Drinking of fluoride-contaminated water has been long established to be the major factor for entrance of fluoride in human beings. Moreover, the transfer of fluoride from contaminated irrigation water to the cultivated crops may ultimately enter the human food chain through consumption of rice, wheat, pulses, vegetables and fruits. The dose of fluoride exposure through drinking of fluoride-contaminated deep tube well water of the Bankura and Purulia districts of West Bengal was evaluated by Samal et al. (2015) for infants, children and adults. The results showed that for infants the doses of fluoride exposure were 0.02−0.53 mg/kg-day. The standard dose of fluoride exposure is 0.05 mg/kg-day. This is the Agency for Toxic Substances and Disease Registry (ATSDR) recommended the minimum risk level (MRL) value (Ortiz et al. 1998). In children and adults of the studied area the doses of fluoride exposure were observed in the ranges 0.01–0.24 and 0.01–0.14 mg/kg-day, respectively. The estimated values in infants, children and adults were evaluated to be around 11, 5 and 3 times higher than the ATSDR’s MRL value (Samal et al. 2015). The authors on the basis of the obtained results predicted that infants and children of the studied area would be very much affected by dental fluorosis and thus suggested immediate mitigation of the situation.
In a similar study at Unnao district of Uttar Pradesh the toxicological risk from fluoride exposure by different age groups due to consumption of vegetables and cereal crops was estimated (Jha et al. 2011). The results showed that the cumulative estimated daily intake (EDI) of fluoride (mg/kg-day) in contaminated areas were 0.065–0.082 for 3-14 year children, 0.026–0.032 for 15-18 years, and 0.031–0.039 for 19-70 years adults, respectively. Thus, the cumulative EDI values in children of 3–14 years were found to be higher as compared to the other age groups. As children are more prone to dental fluorosis, the obtained results were of deep concern. The same was further reinforced with the evaluated higher hazard index (HI) values for this age group (HI>1). The authors also reported that the dose of fluoride exposure from rice and wheat in all the age groups was more (≥95%) than the dose of fluoride exposure due to the consumption of locally grown vegetables.
The average daily intake of fluoride via all possible exposure pathways contributing to risk of fluorosis in infants and children was estimated by Erdal and Buchanan (2005). The authors considered intake of fluoride through drinking water, beverages, cow’s milk, foods, and fluoride supplements, consumption of infant formula (by infants only), inadvertent swallowing of toothpaste (by children only) and incidental ingestion of soil (by children only) as the possible exposure pathways. The results showed that drinking water and infant formula contributed the most (52% and 39%, respectively) towards the cumulative daily fluoride intake for infants. Similarly, for children toothpaste (57%), drinking water (22%), and food (9%) were found to be the major contributor for cumulative EDI. According to the literature for the reasonable maximum exposure (RME) scenario intake of fluoridated drinking water and consumption of infant formula for infants and incidental ingestion of toothpaste during brushing by children resulted the HI values >1. The findings raised concerns that a segment of the infants and children living in the US might be exposed to amounts of fluoride greater than required for prevention of dental caries. Additionally the children might increase their fluoride intake by using mouth rinses, gels, and specially flavored toothpastes. As tea is a good accumulator of fluoride children who consume tea frequently are hypothesized to have higher intake of fluoride (Cao et al. 1997).
Fluoride exposure and its health risk assessment in drinking water and staple food in the population of Dayyer, Iran were reported by Keshavarz et al. (2015). The authors found that the daily fluoride intake from drinking water varied with the season: 0.07−0.08 mg/kg-day in spring to 0.09−0.1 mg/kg-day in summer for adults and children, respectively. The total estimated oral intake of fluoride for children in summer and spring were 0.12 and 0.15 mg/kg-day, respectively, and the values for adults were 0.1 and 0.11 mg/kg-day, respectively. The results established that drinking water of the region was the most important contributor of dietary intake of fluoride in the studied population. Potential health risk of fluorosis was concluded by estimating the HI values (>1).
Effects of fluoride on human health
The effect of fluoride on human health was first identified in the late 19th century when significant fluoride content was found in bones and teeth of human beings (Edmunds and Smedley 2005). During the early 20th century it was observed that residents living in certain areas of the US had developed brown stains on their teeth. The prevalence and severity of this condition were later shown to be correlated directly to the fluoride content of drinking water of those regions (Smith et al. 1931). Interestingly at the same time it was established that the ingestion of fluoride in optimal amounts provided protection against the development of dental caries without staining the teeth (Dean 1938). During the 1940s, it was suggested that public drinking water supplies were to be fluoridated with an optimal level of 0.7−1.2 mg/l depending on the ambient air temperature of the region (Yiming et al. 2001; Ozsvath 2006).
Absorption of fluoride in the body: Fluoride is electronegative in nature and it can form strong complexes with aluminum, boron, beryllium, ferric iron, silica, sodium, uranium, and vanadium. But, these constituents are usually absent in natural water bodies (Hem 1985). The magnesium-fluoride complex is typically the most prevalent form in potable water (Edmunds and Smedley 2005). Different epidemiological studies suggested that the ingestion of fluorosilicates might have different biological effects from those via the intake of NaF or fluoride from natural waters (Urbansky and Schock 2000).
The absorption of soluble inorganic fluoride in body is mostly controlled by acidity in the stomach while the absorption of less soluble inorganic and organic fluorides is more complicated. The absorption depends on various dietary factors e.g. when calcium, magnesium and aluminum salts are amended in diet, some fluoride is incorporated into less soluble compounds that are eliminated through excretory process. Likewise the addition of phosphates, sulphates and molybdenum to diet ensures increased absorption of fluoride from the gastrointestinal tract. Within the stomach, low pH gastric acid favors the formation of the HPO complex, comprising of >90% of the total fluoride at pH 2 (Doull et al. 2006). HPO is readily absorbed from both the stomach and small intestine by simple diffusion process. Once it enters the less acidic mucosa; it dissociates to release fluoride (Whitford et al. 1999). Almost 50% of the absorbed fluoride is quickly integrated in the development of bones and teeth where nearly all of the body’s fluoride is found. The remaining fluoride is excreted via urination (Cerklewski 1997). The uptake of fluoride by the skeleton is most efficient in children, and the rate decreases with age (Whitford et al. 1999). The process mostly continues up to the age 55 (Rao 2003). Once incorporated into hard tissues, fluoride is retrievable, but this entails an extremely slow process of ‘osteoclastic resorption’ that occurs over many years (Doullet al. 2006).
Beneficial effects of fluoride: By the year 1930 it was established that moderate level of fluoride ingestion could reduce the incidence of dental caries and, also promote the development of strong bones (Rao 2003; Edmunds and Smedley 2005; Doull et al. 2006). The sharpest decline in dental caries was found for fluoride concentrations between 0.7 and 1.2 mg/l, and little additional benefit was observed for presence of fluoride beyond the above range (Doull et al. 2006). Clinical research and epidemiological studies showed that fluoride ingestion supplemented with appropriate doses of calcium and Vitamin D could improve bone mineralization, but did not necessarily reduce the number of fractures. Rather it appeared that the potential of fluoride to reduce bone fractures followed a ‘U’-shaped curve, with the maximum benefits achieved at ~1mg/l (Yiming et al. 2001). Increase in fracture cases were noticed when the fluoride content of drinking water was ≥ 4 mg/l (Sowers et al. 2005). Therefore, although fluoride may hold promise for the treatment of osteoporosis, much remains to be learned about the optimal levels for maximizing the benefits while minimizing the risks (Aoba 1997).
Adverse effects of fluoride: The acute effects of fluoride toxicity from accidental overdoses or due to the ingestion of NaF and dental products are vomiting, hemoptysis, cramping of the arms and legs, bronchospasm, cardiac arrest, ventricular fibrillation, fixed and dilated pupils, hyperkalemia, hypocalcemia, and sometimes death (Whitford 1992; Shulman and Wells 1997). The chronic effects due to long term fluoride exposure in human beings are genetic mutations, birth defects, hypersensitivity reactions, allergic illnesses, repetitive bone injury, Alzheimer’s disease, etc.
 Dental effects of fluoride: Dental fluorosis guided the discovery of a relationship between fluoride intake and human health. It is characterized by mottling of the tooth surface, or enamel. As enamel develops, there is increased mineralization within the developing tooth accompanied by a loss of matrix proteins. Exposure to fluoride during this process causes a dose-related disruption of enamel mineralization which results in anomalously large gaps in its crystalline structure, excessive retention of enamel proteins, and increased porosity (Aoba and Fejerskov 2002). Mild forms of dental fluorosis are evidenced by the appearance of white horizontal striations on the tooth surface or opaque patches of chalky white discolorations (Susheela 2003; Rao 2003). In moderate to severe forms of dental fluorosis, the opaque patches become stained yellow to brown or even black, and eventually the increased tooth porosity leads to structural damages, such as pitting or chipping (Rao 2003).
 Skeletal effects of fluoride: The increased bone mass and density, accompanied by a range of skeletal and joint symptoms are collectively called the ‘skeletal fluorosis’. The threshold level of fluoride ingestion needed to cause skeletal fluorosis varies on water quality, intake of water, and other dietary factors. The stages of development of skeletal fluorosis are well established but, the mechanisms are not well understood yet (Edmunds and Smedley 2005). In early stages the symptoms include pain and stiffness in the backbone, hip region, and joints, accompanied by increased bone density (‘osteosclerosis’). The stiffness increases steadily until the entire spine becomes one continuous column of bone (‘poker back’). As this condition progresses, various ligaments of the spine can also become calcified and ossified. In its most advanced stages, skeletal fluorosis produces neurological defects, muscle wasting, paralysis, crippling deformities of the spine and major joints, and compression of the spinal cord.
 Reproductive effects of fluoride: The reproductive effects of fluoride on humans are not well studied yet. Freni (1994) examined the relationship between increase of fluoride concentrations in drinking water (>3 mg/l) and decrease in birth rates by the US population. The results of other studies suggested that high fluoride ingestion had negative reproductive effects on males. The effects include morphology and mobility of sperm, or the levels of testosterone, follicle-stimulating hormones and inhibin B (Ortiz-Perez et al. 2003).
 Developmental effects of fluoride: Some studies have reported about the existence of a positive correlation between the fluoride concentrations in maternal and umbilical cord blood plasma, suggesting that the placenta allows passive diffusion of fluoride from mother to fetus (Gupta et al. 1993; Malhotra et al. 1993). Experiments on laboratory animals indicated that adverse developmental outcomes were possible at very high doses of fluoride; but in case of human populations the results were inconclusive (Doull et al. 2006). There is a possible link between fluoride ingestion and the prevalence of Down’s syndrome (Whiting et al. 2001), especially for children born to mothers of age <30. Gupta et al. (1995) had reported that the incidence of ‘spina bifida occulta’ was abnormally high in fluorosis-prone regions.
 Neurological effects of fluoride: The effects of dietary fluoride ingestion on the intelligence of children were reported (Xiang et al. 2003; Wang et al. 2007). The results showed that the children who ingested high levels of fluoride (>2 mg/l) scored more poorly on intelligence tests than by the children who were exposed to lower levels of fluoride (<1 mg/l). Trivedi et al. (2007) established a statistically significant inverse relationship between the IQ and urinary fluoride levels of school-aged children in India. Spittle et al. (1998) concluded that the threshold fluoride level required for a neurotoxicity response in children was in the range 2−4 mg/l. Spittle (1994) previously had described several types of biochemical changes that fluoride might cause in proteins and enzymatic systems which could interfere with normal brain functioning, and cause impaired cognition and memory.
 Endocrine effects of fluoride: Studies conducted on the effect of fluoride on normal endocrine function and responses were inconclusive. Doull et al. (2006) found that the primary effects of fluoride exposure on the endocrine system were decreased thyroid function, increased calcitonin activity, increased parathyroid activity, secondary hyperparathyroidism, and impaired glucose tolerance (Type II diabetes). However, these effects were observed to vary in degree and kind in different individuals. Many subjects could be classified as subclinical, i.e., they were not considered as adverse health effects.
 Gastrointestinal effects of fluoride: Acute fluoride toxicity induces a variety of gastrointestinal effects like nausea, vomiting, diarrhea and abdominal pain. Animal studies revealed that fluoride can stimulate the secretion of stomach acid, reduce blood flow away from the stomach lining, and even cause the death of gastrointestinal tract epithelium cells (Doull et al. 2006). The level of chronic f1uoride ingestion required to cause these types of responses in humans is not established yet. The adverse gastrointestinal symptoms are common in areas of endemic fluorosis where nutrition is generally poor (Dasarathy et al. 1996), although similar levels of fluoride exposure in the US and Britain did not produce the same response (Jenkins 1991). According to Doull et al. (2006) if fluoride in water is <4 mg/l, the gastrointestinal hypersensitive people (<1% of the population) would experience gastrointestinal symptoms.
 Renal effects of fluoride: Excess fluoride from different organs is excreted through the renal system (Whitford 1992), and thus it might be at higher risk of fluoride toxicity than most of the soft tissues of the body. The chronic ingestion of fluoride was shown to have non-carcinogenic effects on the kidneys (Doull et al. 2006). Juuti and Heinonen (1980) found that residents living in areas with groundwater fluoride level exceeding 1.5 mg/l experienced higher hospital admission rates for ‘urolithiasis’ (process of forming kidney stones) than did residents living in other areas. Singh et al. (2001) by studying a fluoride-contaminated area of India (fluoride concentrations in drinking water: 3.5−4.9 mg/l) reported that patients with clear signs of skeletal fluorosis were 4.6 times more likely to develop kidney stones.
 Carcinogenic effects of fluoride: A few studies have found evidence of a relationship between fluoride exposure and specific cancers for which no biological causal mechanism is known. These include possible associations between fluoride in drinking water and the prevalence of uterine and colon cancer (Yang et al. 2000; Takahashi et al. 2001). Some animal studies showed evidence of increased ‘osteosarcoma’ (bone cancer) and ‘osteoma’ (noncancerous bone tumors), although there is uncertainty in the application of these findings to humans (Doull et al. 2006). Evidence of association between fluoride exposure and the incidence of kidney and bladder cancer was reported by some researchers (Takahashi et al. 2001, Grandjean and Olsen 2004). Assessment of the epidemiological studies to identify the carcinogenic potential of chronic fluoride exposure is very much difficult as there is large diversity of cancers and potential causal factors, which necessitates that each type of cancer is to be evaluated separately (McDonagh et al. 2000; Steiner 2002; Harrison 2005).
Management and mitigations of fluoride contamination
The fluoride contamination has spread in many parts of India causing both health and social problems. Thus, mitigation and management of this burning issue are urgently needed. Since fluorosis is irreversible, its prevention is the only appropriate measure, and can be done by using various intervention steps. Fluoride poisoning can be prevented or minimized by using alternative sources of safe drinking water, by removing excess fluoride from drinking water, and by improving the overall nutritional status of populations at risk. The simplest remedial option for fluoride poisoning is the use of safe surface water sources and consumption of groundwater having fluoride content <1.5 mg/l. The other effective measures of minimizing fluoride are defluoridation of water through flocculation and adsorption processes, creation of awareness in people about fluorosis, providing health education, etc. The presently used defluoridation processes have their own merits and demerits in terms of their use, effectiveness and costing. Some defluoridation techniques are discussed below:
 Nalgonda process: This process involves direct addition of lime in water to maintain the pH and also direct addition of a known quantity of alum in water depending on the fluoride content of raw water. Therefore, it is difficult to standardize the alum dose as it is different for each source of water. The cumbersome technique is unsuitable for operation by laymen, thus has limited rural applications. Further, the process can only be used for water sources having fluoride content of <10 mg/l. High content of free residual aluminum (2−7 mg/l) which is beyond the IS 10500 recommended maximum permissible limit (0.2 mg/l; BIS 2003) is usually present in output water. Moreover, when this treated water is boiled in aluminum utensils it further aggravates the free aluminum concentration in water. The taste of the treated water is also generally not acceptable. It is relevant to note that aluminum is a neurotoxin and the concentration as low as 0.08 mg/l of aluminum in drinking water was reported to cause Alzheimer’s disease.
 Activated alumina process: Activated alumina filters can easily reduce fluoride levels from ~10 mg/l to <1 mg/l. The amount of fluoride removal largely depends on how long the water is actually in contact with the alumina filter media. Basically, the more alumina in the filter, the less fluoride will be in the final filtered water. Lower temperature water and lower pH water (acidic water) are filtered more effectively in this technique. Ideal pH for this treatment is 5.5, which allows up to 95% fluoride removal. But, the reactivation of filter material (treatment of filter bed by acid and alkali) is cumbersome, and it can be done only by trained personnel, who are generally unavailable in most of the fluoride affected villages of India. This process also results in moderately high (0.1−0.3 mg/l) residual aluminum in output water. Overall it is an expensive process of defluoridation of drinking water.
 Some other defluoridation techniques: Venkatramanan et al. (1951) developed a technique for separating fluoride by using paddy husk carbon impregnated with alum. The process involved autoclaving paddy husk carbon by 1% NaOH and soaking overnight in 1% alum solution. Fluoride can be reduced from water by precipitation using CaSO4 or Fe2(SO4)3 solution. But elimination of excess Ca2+ is difficult and if iron is taken regularly, it will have adverse effect to body because it does not have any metabolic exit. Sarkar and Banerjee (2003) had developed a simple, low cost and techno-feasible method for removal of fluoride from drinking water. The locally available natural material ‘laterite’ (or red soil) was used as the adsorbent. Processes like electrodialysis, reverse osmosis, etc. require special equipments, especially trained persons to operate, and need constant maintenance. These processes are very expensive also.
A suitable, efficient, user-friendly and cost-effective technique for defluoridation is yet to be developed. The process should be such that it would be suitable for any fluoride concentration, pH, TDS, alkalinity and temperature of input water, and can be handled by rural population.
Conclusions
The past and present status of fluoride contamination in water, soil, crops, and vegetables are reviewed in this article. Fluoride exposure to humans through consumption of drinking water and other dietary routes is one of the alarming global problems. Irrespective of some beneficial effects fluoride is responsible for dental and skeletal fluorosis, and other adverse reproductive, developmental, neurological, renal, carcinogenic, endocrine and gastrointestinal effects. To improve the scenario of fluoride pollution on long-term basis an efficient fluorosis risk management plan should involve identification of all potential exposure pathways, mapping of affected zones, supplying of defluoridated drinking water, restriction in usage of contaminated water for irrigation, health education, improving the nutritional status of populations at risk, encouragement for utilizing surface water, harvesting of rainwater, etc. Provision for adequate nutrition of people comprising of calcium, iodized salt, vitamin C and antioxidants in the fluoride-contaminated areas should be arranged by the government to protect the residents from early and severe fluorosis, which is an irreversible and untreatable disease.