DEVELOPMENTAL TOXICITY EVALUATION OF SODIUM-FLUORIDE ADMINISTERED TO RATS AND RABBITS IN DRINKING-WATER

Sodium fluoride (NaF; Cas No. 7681-49-4) is used in fluoridating munic ipal water supplies, resulting in chronic exposure of millions of peop le worldwide. Because of a lack of pertinent developmental toxicity st udies in the literature, sodium fluoride was administered ad libitum i n deionized/filtered drinking water (to mimic human exposure) to Sprag ue-Dawley-derived rats (26/group) on Gestation Days (GD) 6 through 15 at levels of 0, 50, 150, or 300 ppm and New Zealand White rabbits (26/ group) on GD 6 through 19 at levels of 0, 100, 200, or 400 ppm. Higher concentrations via drinking water were not practicable due to the poo r palatability of sodium fluoride. Drinking water (vehicle) contained less than 0.6 ppm sodium fluoride (limit of detection) and sodium fluo ride content of the feed was 12.4 ppm fluoride (rats) and 15.6 ppm flu oride (rabbits). Maternal food, water, body weights, and clinical sign s were recorded at regular intervals throughout these studies. Animals were killed on GD 20 (rats) or 30 (rabbits) and examined for implant status, fetal weight, sex, and morphological development. In the high- dose group of both studies there was an initial decreased maternal bod y weight gain which recovered over time and a decreased water consumpt ion-attributed to decreased palatability. No clear clinical signs of t oxicity were observed. Maternal exposure to sodium fluoride during org anogenesis did not significantly affect the frequency of postimplantat ion loss, mean fetal body weight/litter, or external, visceral or skel etal malformations in either the rat or the rabbit. The NOAEL for mate rnal toxicity was 150 ppm sodium fluoride in drinking water (similar t o 18 mg/kg/day) for rats, and 200 ppm (similar to 18 mg/kg/day) for ra bbits. The NOAEL for developmental toxicity was greater than or equal to 300 ppm sodium fluoride (similar to 27 mg/kg/day) for rats and grea ter than or equal to 400 ppm (similar to 29 mg/kg/day) for rabbits adm inistered during organogenesis in drinking water. The total exposure t o fluoride (mg F/kg body weight/day from food and drinking water combi ned) in the mid- and high-dose groups for both species was >100-fold h igher than the range at 0.014-0.08 mg F/kg/day estimated for a 70-kg p erson from food and fluoridated (1 ppm) drinking water. (C) 1996 Socie ty of Toxicology