so affected (McKay 1933); however, there seems to have been no further report on thyroid conditions in the village.

More recently, Demole (1970) argued that a specific toxicity of fluoride for the thyroid gland does not exist, because (1) fluoride does not accumulate in the thyroid; (2) fluoride does not affect the uptake of iodine by thyroid tissue; (3) pathologic changes in the thyroid show no increased frequency in regions where water is fluoridated (naturally or artificially); (4) administration of fluoride does not interfere with the prophylactic action of iodine on endemic goiter; and (5) the beneficial effect of iodine in threshold dosage to experimental animals is not inhibited by administration of fluoride, even in excessive amounts. Bürgi et al. (1984) also stated that fluoride does not potentiate the consequences of iodine deficiency in populations with a borderline or low iodine intake and that published data fail to support the hypothesis that fluoride has adverse effects on the thyroid (at doses recommended for caries prevention). McLaren (1976), however, pointed out the complexity of the system, the difficulties in making adequate comparisons of the various studies of fluoride and the thyroid, and evidence for fluoride accumulation in the thyroid and morphological and functional changes (e.g., changes in activity of adenylyl cyclase), suggesting that analytical methods could have limited the definitiveness of the data to date. His review suggested that physiological or functional changes might occur at fluoride intakes of 5 mg/day.

Although fluoride does not accumulate significantly in most soft tissue (as compared to bones and teeth), several older studies found that fluoride concentrations in thyroid tissue generally exceed those in most other tissue except kidney (e.g., Chang et al. 1934; Hein et al. 1954, 1956); more recent information with improved analytic methods for fluoride was not located. Several studies have reported no effect of fluoride treatment on thyroid weight or morphology (Gedalia et al. 1960; Stolc and Podoba 1960; Saka et al. 1965; Bobek et al. 1976; Hara 1980), while others have reported such morphological changes as mild atrophy of the follicular epithelium (Ogilvie 1953), distended endoplasmic reticulum in follicular cells (Sundström 1971), and “morphological changes suggesting hormonal hypofunction” (Jonderko et al. 1983).

Fluoride was once thought to compete with iodide for transport into the thyroid, but several studies have demonstrated that this does not occur (Harris and Hayes 1955; Levi and Silberstein 1955; Anbar et al. 1959; Saka et al. 1965). The iodide transporter accepts other negatively charged ions besides iodide (e.g., perchlorate), but they are about the same size as iodide (Anbar et al. 1959); fluoride ion is considerably smaller and does not appear to displace iodide in the transporter.