Data Selection. Although some recent recommendations have been made for additional research in the areas of intake, dental fluorosis, bone strength, and carcinogenicity, extensive reviews of the scientific literature revealed no adverse effects unless fluoride intakes were greater than 10 mg/day for 10 or more years (Kaminsky et al., 1990; NRC, 1993; USPHS, 1991). At these high, chronic intake levels, the risk of skeletal changes consistent with preclinical or stage 1 skeletal fluorosis increases. Therefore, the data deemed most appropriate for identifying a NOAEL (or LOAEL) for older children and adults are provided by studies on skeletal fluorosis.
Identification of a NOAEL (or LOAEL) and Critical Endpoint. Epidemiological studies reported no detectable radiographic changes in bone density in persons in the United States exposed to drinking water containing less than 4 mg/liter of fluoride (McCauley and McClure, 1954; Schlesinger et al., 1956; Sowers et al., 1986; Stevenson and Watson, 1957). Leone et al. (1955) compared bone x-rays of long-term residents of Bartlett and Cameron, Texas, which had water supplies with fluoride concentrations of 8.0 and 0.4 mg/liter, respectively. In this study, osteosclerosis was detected radiographically in 10 to 15 percent of individuals exposed to water containing 8.0 mg/liter of fluoride for an average of 37 years. However, no clinical symptoms of skeletal fluorosis were reported. Another report dealing with a variety of other medical conditions among residents of Bartlett and Cameron revealed no significant differences except for a slightly higher rate of cardiovascular abnormalities in Cameron residents (Leone et al., 1954). Therefore, based on the available data addressing the association between fluoride intake and skeletal fluorosis in North America, a NOAEL of 10 mg/day of fluoride was identified. This level of intake for some individuals would occur in areas where the drinking water has a fluoride concentration of 5 mg/liter and the diet is the main source of fluoride.
Uncertainty Assessment. Based on the fact that the NOAEL derives from human studies and the lack of evidence for symptomatic skeletal fluorosis observed at this level of fluoride intake, a UF of 1 was selected.
Derivation of the UL. The risk of developing early signs of skeletal fluorosis is associated with a fluoride intake greater than 10 mg/