Hara (1980) found elevated T3 and T4 at the lowest dose (approximately 0.1 mg/kg/day), decreased T3 and normal T4 at intermediate doses (3-4 mg/kg/day), and decreased TSH and growth hormone (indicating possible effects on pituitary function) at the highest doses (10-20 mg/kg/day). This was the only animal study of fluoride effects on thyroid function to measure TSH concentrations; however, full details (e.g., iodine intake) are not available in English.

Other studies have shown no effect of fluoride on the end points examined (Gedalia et al. 1960; Siebenhüner et al. 1984; Clay and Suttie 1987; Choubisa 1999; Table E-1). Choubisa (1999) looked only for clinical evidence of goiter in domestic animals (cattle and buffaloes) showing signs of enamel or skeletal fluorosis; no hormone parameters (e.g., T4, T3, TSH) were measured. Gedalia et al. (1960) also did not measure T4, T3, or TSH; radioiodine uptake, protein-bound iodine, and total blood iodine were all normal in rats receiving fluoride doses up to approximately 1 milligram per kilogram of body weight per day (mg/kg/day). Clay and Suttie (1987) reported no significant differences from control values for T4 concentration and T3 uptake in heifers fed up to 1.4 mg/kg/day; iodine intake is not stated but probably was adequate, and TSH was not measured.

Siebenhüner et al. (1984) carried out a special experiment involving iodine depletion of the thyroid before 6 days of fluoride treatment. No effects were seen on the parameters measured, including T3 and T4 concentrations; however, TSH was not measured. In addition, propylthiouracil (PTU), the agent used to deplete the thyroid of iodine, also has an inhibitory effect on deiodinases (Larsen et al. 2002; Larsen and Davies 2002); Siebenhüner et al. (1984) did not mention this second action of PTU and its relevance to the interpretation of the experimental results, and there was no control group without the PTU treatment.

Human Studies

Several authors have reported an association between endemic goiter and fluoride exposure or enamel fluorosis in human populations in India (Wilson 1941; Siddiqui 1960; Desai et al. 1993), Nepal (Day and Powell-Jackson 1972), England (Wilson 1941; Murray et al. 1948), South Africa (Steyn 1948; Steyn et al. 1955; Jooste et al. 1999), and Kenya (Obel 1982). Although endemic goiter is now generally attributed to iodine deficiency (Murray et al. 1948; Obel 1982; Larsen et al. 2002; Belchetz and Hammond 2003), some of the goitrogenic areas associated with fluoride exposure were not considered to be iodine deficient (Steyn 1948; Steyn et al. 1955; Obel 1982; Jooste et al. 1999). Obel (1982) indicated that many cases of fluorosis in Kenya occur concurrently with goiter. Several authors raise the possibility that the goitrous effect, if not due to fluoride, is due to some other substance



The National Academies | 500 Fifth St. N.W. | Washington, D.C. 20001
Copyright © National Academy of Sciences. All rights reserved.
Terms of Use and Privacy Statement