This summarizes current knowledge of the benefits and risks of fluoride ingestion. The preponderance of evidence indicates that fluoride can reduce the incidence of dental caries and that fluoridation of drinking water can provide such protection. Due to the ubiquitous nature of exposures to fluoride sources other than drinking water, it is currently impossible to draw firm conclusions regarding the independent effect of fluoride in drinking water on caries prevalence using an ecologic study design. Moderate dental fluorosis occurs in 1 to 2% of the population exposed to fluoride at 1 mg/l in drinking water and in about 10% of the population at 2 mg/l; moderate/severe fluorosis occurs in variable percentages ranging up to 33% of the population exposed to fluoride at 2.4 to 4.1 mg/l in drinking water. The issue of whether moderate or severe dental fluorosis represents an adverse health effect is still controversial. There is no evidence of skeletal fluorosis among the general U.S. population exposed to drinking water fluoride concentrations lower than 4 mg/l. Radiographically detected osteosclerosis after chronic exposure to fluoride in drinking water at 8 mg/l was not associated with clinical symptoms. Reports of crippling skeletal fluorosis associated with low concentrations of fluoride in drinking water in tropical countries have been attributed to other dietary factors. The available data suggest that some individuals may experience hypersensitivity to fluoride-containing agents. Further studies on hypersensitivity are required. There is no evidence of increased incidence of renal disease or renal dysfunction in humans exposed to up to 8 mg fluoride per liter in drinking water. Structural changes in kidneys of experimental animals have been detected at doses exceeding 1 to 5 mg fluoride per kilogram per day. Based on four case reports, individuals with renal insufficiency who consume large volumes of naturally fluoridated water at 2 to 8 mg/l are possibly at increased risk of developing skeletal fluorosis. Studies on the effects of fluoride in individuals with renal insufficiency are needed. There is no evidence that chronic exposure to concentrations of fluoride reported to be greater than 2 mg/l in drinking water increases human cancer mortality or incidence. A study of lifetime exposure to fluoride on cancer incidence in rats and mice has been completed, but assessment for cancer has not been completed. There is no evidence that fluoride is genotoxic except in some in vitro assays at cytotoxic concentrations. There is no in vivo evidence that fluoride affects human cellular enzyme activities.(ABSTRACT TRUNCATED AT 400 WORDS)

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