Developmental toxicity of sodium fluoride in rats.
Despite the chronic exposure of the US population to fluoridated drinking water since the 1940s, existing studies have been judged inadequate to determine any potential reproductive or developmental hazard. This study was conducted to determine the effects of sodium fluoride (NaF) on foetal development. Sperm-positive female rats were given 0, 10, 25, 100, 175 or 250 ppm NaF daily throughout gestation. They were dosed by drinking water to mimic human exposure to fluoridated water. No dose-related behavioural changes or maternal clinical signs were noted. Fluid consumption by females in the 175- and 250-ppm groups was significantly less than that of the control females. Because of this decreased fluid consumption, the daily amount of NaF ingested (0, 1.4, 3.9, 15.6, 24.7 and 25.1 mg/kg body weight) was less than expected at the two high levels. Feed consumption decreased significantly at 250 ppm, and body weights of pregnant females reflected feed consumption trends. The mean number of viable foetuses per female in all treated groups was similar to that of the control group. The significant decrease in the mean number of implants per litter in the 250-ppm group is probably linked to the lower mean number of corpora lutea in this group. The occurrence of in utero deaths was similar in the control and treated groups. Foetal growth (in terms of foetal body weight and crown-rump length) was not affected by NaF, despite the fact that the dams in the 250-ppm group ate significantly less feed and drank significantly less fluid. There was no dose-related increase in the number of external anomalies in foetuses due to NaF ingestion. At the doses given, NaF had no effect on the development of specific bones, including sternebrae. A significant increase was seen in the average number of foetuses with three or more skeletal variations in the 250-ppm group; the number of litters with foetuses with three or more skeletal variations was increased in the 250-ppm group also, but the increase was not significant. There was no dose-related effect of NaF on the incidence of soft tissue variations.
Collins
T F
TF
Center for Food Safety and Applied Nutrition, US Food and Drug Administration, Laurel, MD 20708, USA.
Sprando
R L
RL
Shackelford
M E
ME
Black
T N
TN
Ames
M J
MJ
Welsh
J J
JJ
Balmer
M F
MF
Olejnik
N
N
Ruggles
D I
DI
D000014:Abnormalities, Drug-Induced; D000284:Administration, Oral; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D005260:Female; D005460:Fluorides, Topical / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D011247:Pregnancy; D051381:Rats; D012969:Sodium Fluoride / Q000008:administration & dosage / Q000633:toxicity*; D015430:Weight Gain / Q000187:drug effects
D005460:Fluorides, Topical; D012969:Sodium Fluoride