Ambient Water Quality Criteria for Fluoride

Water Quality

3.0 Fluoride Metabolism

Table 2.1 gives the solubilities of some fluoride salts in cold water. This information should be referred to when reviewing papers on the effects of various doses and concentrations of fluoride on organisms. For example, Simonin and Pierron (1937), in Table 5.2, report effects of fluoride at concentrations in excess of the solubility of the salt at physiological temperatures. It is not always clear in some papers whether the concentration referred to is the concentration of the salt or only of the fluoride component. Table 2.1 also gives the percentage of fluoride in the common fluoride salts used in physiological experiments.

Dietary Intake

All food contains some fluoride, generally between 0.1 and 10 mg/kg (Nommik, 1953). Some examples are given in Table 3.1. Fish, tea and some vegetables have much higher fluoride levels than other common foods. Some fish can reach 100 mg/kg and tea generally ranges from 8-400 mg/kg (McClure, 1949; Anon, 1970; Nommik, 1953; Matuura et al.., 1954 ; Reid, 1936; Wang et al.., 1949); however, considerably higher levels of 1758 to 1900 mg/kg are reported in some teas (Matuura et al.., 1954; Reid, 1936). About two-thirds of the fluoride in tea leaves dissolves in tea so that one cup of tea made from 100 mg/kg tea leaves would add about 0.1 to 0.2 mg of fluoride to the daily fluoride intake (Tarzwell, 1957; Underwood, 1971; and Reid, 1936). Two cups of tea made from the highest fluoride level tea leaves would exceed the recommended daily fluoride intake. The use of fluoridated water supplies in food preparation can double the level of fluoride in prepared foods. Vitamins, toothpaste and pharmaceuticals also add to the daily fluoride dose. The use of bone meal supplements, more common in pet and livestock feeds, can add quite large amounts of fluoride to the diet.

Estimates of the daily dietary intake of fluoride by adults are 0.2 to 3.1 mg (Anon, 1980; Rose and Marier, 1977; and Anon, 1970), in areas where the water is not fluoridated, but 3.5 to 5.5 mg (Rose and Marier, 1977), when water is fluoridated at 1.0 mg/L. For children, the estimates are 0.5 mg (Anon, 1970), and <2.0 mg (Anon, 1980), respectively. Table 3.2 gives more specific examples. Daily intake levels will be exceeded in hot climates where fluoridated water is available, and by those individuals who drink tea (Rose and Marier, 1977). Assuming a 70 kg adult, the estimates of acceptable daily fluoride intake are 0.033 to 0.073 mg/kg (Rose and Marier, 1977; Farkas, 1975b; Farkas, 1975a; Toth, 1975), based on levels in bones and 0.053 to 0.076 mg/kg (Rose and Marier, 1977), based on levels in blood plasma. The 3.5 to 5.5 mg/d intake estimates in areas with fluoridated water corresponds to a 0.05 to 0.08 mg/kg daily intake. Thus, to remain within the acceptable daily intake levels of fluoride from all sources, the water supplies should not exceed 1.0 mg/L.

Hard water confers some protection from fluorosis (Herbert and Shurben, 1964; and Neuhold and Sigler, 1960). Chronic fluoride intake increases the need for calcium, magnesium, manganese and vitamin C (Rose and Marier, 1977).

Fluoride as an Essential Element

Due to the ubiquitous nature of fluoride it is very difficult to prepare fluoride-free diets to test the hypothesis that fluorine is an essential element. If it is essential only very low levels are required (Anon, 1980). In 1972 it was claimed that fluoride was essential for the growth of rats (Schwarz, 1973), and fluoride was shown to enhance fertility and growth of rats in small doses (Underwood, 1971). There are other studies claiming that fluorine is essential for animals (Messer et al., 1972; and Underwood, 1975); however, there is no consensus yet on its status as an essential element, since other studies did not find any effects over several generations, when fluoride levels in diets were as low as 5 µg/kg of fluoride (Weber, 1966; Doberanz et al., 1963; and Maurer and Day, 1957).

Metabolism

The general systemic effects of fluoride are remarkably similar from species to species; only dose rates and the time required to achieve any effect vary. Thus the fluoride ion must exert its effect upon some basic physiologic process common to mammalian life. Enzyme systems and the central nervous system are affected very early in the process of fluorosis. Due to rapid excretion and active scavenging by bones and teeth, soft tissue damage is relatively difficult to achieve and requires repetitive high doses (Davis, 1961).

Fluoride ingested in water is almost completely absorbed. Up to 97% of a dose of 12 to 25 mg/day will be absorbed (Sargent and Heyroth, 1949). Absorption efficiency of fluoride from foods is somewhat lower, but still quite high, with the exception of fish and some meats which may have absorption efficiencies as low as 25%. Fluoride passes via the placenta to the fetus and passes through the milk to nursing young (Zipkin and Likins, 1957; Wallace, 1953; and Anon, 1974). Distribution of absorbed fluoride is rapid with most retained in the skeleton and the teeth (Underwood, 1971). While the fluoride retention rate decreases with age (Anon., 1980), bone fluoride increases up to about age 55 (Jackson and Weidmans, 1958). Excretion of fluoride is primarily in the urine and is affected by health and previous fluoride history.

At high doses, fluoride interferes with carbohydrate, lipid, protein, vitamin, enzyme and mineral metabolism (Anon, 1970). Many symptoms of acute fluoride intoxication are a result of the calcium in the body being bound as CaF₂. The body attempts to prevent accumulation of toxic fluorides in the tissues by increased renal excretion of 52 to 63% of the absorbed fluoride (Pantucek, 1975; and Sargent and Heyroth, 1949), or permanent sequestration in the bones and teeth. The acute lethal doses for humans cited in the literature are 2 g of fluoride or 5 g of NaF (Anon, 1980), 0.5 g/kg (Greenwood, 1940), 2.5 g (Forrest et al., 1957), or 4.0 g (Anon, 1960). Severe symptoms occur at 250 to 450 mg (Anon, 1960). Initial signs and symptoms of fluoride intoxication include vomiting, nausea, abdominal pain, diarrhea and convulsions (Anon, 1977). Pathological changes due to high doses include gastric hemorrhaging, kidney damage and injury to the liver and heart (Anon, 1970). Gastric and intestinal mucosa are severely affected by large oral doses of fluoride (Suttie, 1977). High fluoride levels cause cell damage and necrosis which affect organ function. Enzymes, including cholinesterase, are inhibited, and hyperglycemia may occur. The decrease in plasma calcium may be responsible for the effects on the nervous system, blood clotting and membrane permeability.

In spite of various prior claims to the contrary, it is generally agreed that there is no acceptable evidence that fluoride in water is carcinogenic to people (Anon, 1980; Anon, 1970; Clemmesen, 1983; and Anon, 1982. Suggestions that fluoride is mutagenic, teratogenic or in any way related to birth defects has also been reviewed and proven to be groundless (Anon, 1970). It is probable, but not proven, that it is the gross disturbance of calcium metabolism that leads to death in acute fluoride intoxication (Davis, 1961). Adults, not subject to occupational high fluoride levels, may use drinking and cooking water with up to 5 mg/L without cosmetic or harmful effects. Generally, if urinary excretion rates do not exceed 5 to 8 mg/day (5 to 10 mg/L of urine), there is no deleterious effect on health (Princi, 1960).

Teeth and Bones

Fluoride, when incorporated into the teeth, reduces the solubility of the enamel under acidic conditions and prevents dental caries. The incidence of caries decreases as fluoride in the water rises to about 1 mg/L (Anon, 1980). Mottling of teeth may occur when fluoride levels rise to about 1.5 to 2.0 mg/L or at 1.0 mg/L under long-term consumption by children up to 7 years old with kidney diseases. Once teeth have matured and mineralization has ceased, mottling will not occur (Anon, 1977; and Anon, 1968). Thus adults can be exposed to higher fluoride levels than young children without risk of tooth mottling. Skeletal fluorosis occurs at about 3 to 6 mg/L depending upon additional sources of fluoride intake (Anon, 1977).

Bone damage in children and adults is reported to occur when fluoride levels reach 8 to 20 mg/L over long periods of time or when intakes reach 20 to 40 mg/day. The damage consists of depressed collagen formation, bone resorption and an increase in bone crystal (Anon, 1977; Anon, 1970; Hodge and Smith, 1954; and Neer et al., 1966).

High Risk Groups

Some portions of the population are more at risk from high fluoride levels than others; they include: workers in welding, aluminum smelter and phosphate fertilizer industries; people living near such industries where water and air are subject to pollution: people living in areas where goiter is endemic; people with kidney disfunction, polydipsia or diabetes insipidus; those whose diets are deficient in iodine, calcium, manganese or vitamin-C; and those with low calcium to phosphorus ratios in their diet (Rose and Marier, 1977). Hemodialysis treatments require very low fluoride water since increased plasma fluoride levels may occur in patients when water containing as little as 1.0 mg/L is used. Such increases in plasma fluoride may be as much as 2 to 4 times normal at a 1.0 mg/L fluoride concentration. Such patients tend to already have higher than normal plasma fluoride levels due to their kidney insufficiency, and can ill-afford further increases (Posen et al., 1971; Cordy et al., 1974; Seidenberg et al., 1976; and Hahijarvi, 1971).

Table 3.3 gives some effects of various fluoride doses on mammals, including man. The effects are arranged in increasing dose size. The fluoride dose given is expressed in several ways and a separate increasing dose section of the table is provided for doses on a mg/kg, mg/day, mg/animal and mg/litre basis.

Synergistic Responses

When Chlorella vulgaris is grown in 759 mg/L fluoride and 635 mg/L copper (as NaF and CuS0₄ respectively), respiration is almost completely arrested, while neither compound alone had much affect on respiration. These copper levels are three orders of magnitude higher than those reported to affect growth, photosynthesis and respiration in algae and Chlorella in particular (Singleton, 1987). If, instead of simultaneous treatment, the algal cells were pretreated with copper before adding fluoride, respiratory inhibition was found to increase with pretreatment time. Pretreating with fluoride produces less inhibition as the pretreatment time increases. Presumably fluoride blocks the main respiratory pathway and copper blocks the hexose monophosphate shunt (Hassel, 1969). The significance of these responses at very high copper and fluoride levels, compared to normal metabolic responses found in other organisms at much lower copper and fluoride levels, is not known.


	Water Quality Ambient Water Quality Criteria for Fluoride 3.0 Fluoride Metabolism Table 2.1 gives the solubilities of some fluoride salts in cold water. This information should be referred to when reviewing papers on the effects of various doses and concentrations of fluoride on organisms. For example, Simonin and Pierron (1937), in Table 5.2, report effects of fluoride at concentrations in excess of the solubility of the salt at physiological temperatures. It is not always clear in some papers whether the concentration referred to is the concentration of the salt or only of the fluoride component. Table 2.1 also gives the percentage of fluoride in the common fluoride salts used in physiological experiments. Dietary Intake All food contains some fluoride, generally between 0.1 and 10 mg/kg (Nommik, 1953). Some examples are given in Table 3.1. Fish, tea and some vegetables have much higher fluoride levels than other common foods. Some fish can reach 100 mg/kg and tea generally ranges from 8-400 mg/kg (McClure, 1949; Anon, 1970; Nommik, 1953; Matuura et al.., 1954 ; Reid, 1936; Wang et al.., 1949); however, considerably higher levels of 1758 to 1900 mg/kg are reported in some teas (Matuura et al.., 1954; Reid, 1936). About two-thirds of the fluoride in tea leaves dissolves in tea so that one cup of tea made from 100 mg/kg tea leaves would add about 0.1 to 0.2 mg of fluoride to the daily fluoride intake (Tarzwell, 1957; Underwood, 1971; and Reid, 1936). Two cups of tea made from the highest fluoride level tea leaves would exceed the recommended daily fluoride intake. The use of fluoridated water supplies in food preparation can double the level of fluoride in prepared foods. Vitamins, toothpaste and pharmaceuticals also add to the daily fluoride dose. The use of bone meal supplements, more common in pet and livestock feeds, can add quite large amounts of fluoride to the diet. Estimates of the daily dietary intake of fluoride by adults are 0.2 to 3.1 mg (Anon, 1980; Rose and Marier, 1977; and Anon, 1970), in areas where the water is not fluoridated, but 3.5 to 5.5 mg (Rose and Marier, 1977), when water is fluoridated at 1.0 mg/L. For children, the estimates are 0.5 mg (Anon, 1970), and <2.0 mg (Anon, 1980), respectively. Table 3.2 gives more specific examples. Daily intake levels will be exceeded in hot climates where fluoridated water is available, and by those individuals who drink tea (Rose and Marier, 1977). Assuming a 70 kg adult, the estimates of acceptable daily fluoride intake are 0.033 to 0.073 mg/kg (Rose and Marier, 1977; Farkas, 1975b; Farkas, 1975a; Toth, 1975), based on levels in bones and 0.053 to 0.076 mg/kg (Rose and Marier, 1977), based on levels in blood plasma. The 3.5 to 5.5 mg/d intake estimates in areas with fluoridated water corresponds to a 0.05 to 0.08 mg/kg daily intake. Thus, to remain within the acceptable daily intake levels of fluoride from all sources, the water supplies should not exceed 1.0 mg/L. Hard water confers some protection from fluorosis (Herbert and Shurben, 1964; and Neuhold and Sigler, 1960). Chronic fluoride intake increases the need for calcium, magnesium, manganese and vitamin C (Rose and Marier, 1977). Fluoride as an Essential Element Due to the ubiquitous nature of fluoride it is very difficult to prepare fluoride-free diets to test the hypothesis that fluorine is an essential element. If it is essential only very low levels are required (Anon, 1980). In 1972 it was claimed that fluoride was essential for the growth of rats (Schwarz, 1973), and fluoride was shown to enhance fertility and growth of rats in small doses (Underwood, 1971). There are other studies claiming that fluorine is essential for animals (Messer et al., 1972; and Underwood, 1975); however, there is no consensus yet on its status as an essential element, since other studies did not find any effects over several generations, when fluoride levels in diets were as low as 5 µg/kg of fluoride (Weber, 1966; Doberanz et al., 1963; and Maurer and Day, 1957). Metabolism The general systemic effects of fluoride are remarkably similar from species to species; only dose rates and the time required to achieve any effect vary. Thus the fluoride ion must exert its effect upon some basic physiologic process common to mammalian life. Enzyme systems and the central nervous system are affected very early in the process of fluorosis. Due to rapid excretion and active scavenging by bones and teeth, soft tissue damage is relatively difficult to achieve and requires repetitive high doses (Davis, 1961). Fluoride ingested in water is almost completely absorbed. Up to 97% of a dose of 12 to 25 mg/day will be absorbed (Sargent and Heyroth, 1949). Absorption efficiency of fluoride from foods is somewhat lower, but still quite high, with the exception of fish and some meats which may have absorption efficiencies as low as 25%. Fluoride passes via the placenta to the fetus and passes through the milk to nursing young (Zipkin and Likins, 1957; Wallace, 1953; and Anon, 1974). Distribution of absorbed fluoride is rapid with most retained in the skeleton and the teeth (Underwood, 1971). While the fluoride retention rate decreases with age (Anon., 1980), bone fluoride increases up to about age 55 (Jackson and Weidmans, 1958). Excretion of fluoride is primarily in the urine and is affected by health and previous fluoride history. At high doses, fluoride interferes with carbohydrate, lipid, protein, vitamin, enzyme and mineral metabolism (Anon, 1970). Many symptoms of acute fluoride intoxication are a result of the calcium in the body being bound as CaF₂. The body attempts to prevent accumulation of toxic fluorides in the tissues by increased renal excretion of 52 to 63% of the absorbed fluoride (Pantucek, 1975; and Sargent and Heyroth, 1949), or permanent sequestration in the bones and teeth. The acute lethal doses for humans cited in the literature are 2 g of fluoride or 5 g of NaF (Anon, 1980), 0.5 g/kg (Greenwood, 1940), 2.5 g (Forrest et al., 1957), or 4.0 g (Anon, 1960). Severe symptoms occur at 250 to 450 mg (Anon, 1960). Initial signs and symptoms of fluoride intoxication include vomiting, nausea, abdominal pain, diarrhea and convulsions (Anon, 1977). Pathological changes due to high doses include gastric hemorrhaging, kidney damage and injury to the liver and heart (Anon, 1970). Gastric and intestinal mucosa are severely affected by large oral doses of fluoride (Suttie, 1977). High fluoride levels cause cell damage and necrosis which affect organ function. Enzymes, including cholinesterase, are inhibited, and hyperglycemia may occur. The decrease in plasma calcium may be responsible for the effects on the nervous system, blood clotting and membrane permeability. In spite of various prior claims to the contrary, it is generally agreed that there is no acceptable evidence that fluoride in water is carcinogenic to people (Anon, 1980; Anon, 1970; Clemmesen, 1983; and Anon, 1982. Suggestions that fluoride is mutagenic, teratogenic or in any way related to birth defects has also been reviewed and proven to be groundless (Anon, 1970). It is probable, but not proven, that it is the gross disturbance of calcium metabolism that leads to death in acute fluoride intoxication (Davis, 1961). Adults, not subject to occupational high fluoride levels, may use drinking and cooking water with up to 5 mg/L without cosmetic or harmful effects. Generally, if urinary excretion rates do not exceed 5 to 8 mg/day (5 to 10 mg/L of urine), there is no deleterious effect on health (Princi, 1960). Teeth and Bones Fluoride, when incorporated into the teeth, reduces the solubility of the enamel under acidic conditions and prevents dental caries. The incidence of caries decreases as fluoride in the water rises to about 1 mg/L (Anon, 1980). Mottling of teeth may occur when fluoride levels rise to about 1.5 to 2.0 mg/L or at 1.0 mg/L under long-term consumption by children up to 7 years old with kidney diseases. Once teeth have matured and mineralization has ceased, mottling will not occur (Anon, 1977; and Anon, 1968). Thus adults can be exposed to higher fluoride levels than young children without risk of tooth mottling. Skeletal fluorosis occurs at about 3 to 6 mg/L depending upon additional sources of fluoride intake (Anon, 1977). Bone damage in children and adults is reported to occur when fluoride levels reach 8 to 20 mg/L over long periods of time or when intakes reach 20 to 40 mg/day. The damage consists of depressed collagen formation, bone resorption and an increase in bone crystal (Anon, 1977; Anon, 1970; Hodge and Smith, 1954; and Neer et al., 1966). High Risk Groups Some portions of the population are more at risk from high fluoride levels than others; they include: workers in welding, aluminum smelter and phosphate fertilizer industries; people living near such industries where water and air are subject to pollution: people living in areas where goiter is endemic; people with kidney disfunction, polydipsia or diabetes insipidus; those whose diets are deficient in iodine, calcium, manganese or vitamin-C; and those with low calcium to phosphorus ratios in their diet (Rose and Marier, 1977). Hemodialysis treatments require very low fluoride water since increased plasma fluoride levels may occur in patients when water containing as little as 1.0 mg/L is used. Such increases in plasma fluoride may be as much as 2 to 4 times normal at a 1.0 mg/L fluoride concentration. Such patients tend to already have higher than normal plasma fluoride levels due to their kidney insufficiency, and can ill-afford further increases (Posen et al., 1971; Cordy et al., 1974; Seidenberg et al., 1976; and Hahijarvi, 1971). Table 3.3 gives some effects of various fluoride doses on mammals, including man. The effects are arranged in increasing dose size. The fluoride dose given is expressed in several ways and a separate increasing dose section of the table is provided for doses on a mg/kg, mg/day, mg/animal and mg/litre basis. Synergistic Responses When Chlorella vulgaris is grown in 759 mg/L fluoride and 635 mg/L copper (as NaF and CuS0₄ respectively), respiration is almost completely arrested, while neither compound alone had much affect on respiration. These copper levels are three orders of magnitude higher than those reported to affect growth, photosynthesis and respiration in algae and Chlorella in particular (Singleton, 1987). If, instead of simultaneous treatment, the algal cells were pretreated with copper before adding fluoride, respiratory inhibition was found to increase with pretreatment time. Pretreating with fluoride produces less inhibition as the pretreatment time increases. Presumably fluoride blocks the main respiratory pathway and copper blocks the hexose monophosphate shunt (Hassel, 1969). The significance of these responses at very high copper and fluoride levels, compared to normal metabolic responses found in other organisms at much lower copper and fluoride levels, is not known.