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Administrative data

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
18.5 mg/kg bw/day
Additional information

Collins, et al. (2001) reported that sodium fluoride in drinking water of Sprague-Dawley rats at levels up to 250 ppm the highest concentration tested. This cocentration, equivalent to 28.4 mg sodium fluoride/kg body weight/day or 12.8 mg fluoride/kg body weight/day, had no adverse effects on reproduction throughout three generations. Mating, fertility and survival indices were not affected.


Short description of key information:
Fluoride salts are not considered to have detrimental effects on fertility.The key study reports a NOAEL of 28.4 mg/kg/day based on NaF, which is converted to 18.5 mg/kg/bw based on H2TiF6, based on the fluoride content of both substances.

Justification for selection of Effect on fertility via oral route:
Key study. Comment: The key study reports a NOAEL of 28.4 mg/kg/day based on NaF, which is converted to 18.5 mg/kg/bw based on H2TiF6, based on the fluoride content of both substances.

Effects on developmental toxicity

Description of key information
Fluoride salts are not considered developmental toxins based on a lack of developmental effects in several reported developmental toxicity studies in pregnant rats and rabbits exposed to drinking water containing high levels of sodium fluoride, including levels causing maternal toxicity.  The key study reports a NOAEL of 27 mg/kg/day based on NaF, which is converted to 17.6 mg/kg/bw based on H2TiF6,  based on the fluoride content of both substances.
Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
17.6 mg/kg bw/day
Additional information

The developmental toxicity study of sodium fluoride conducted in Sprague-Dawley CD rats by the U.S. National Toxicology Program (NTP, 1994; Heindel, et al., 1996) determined that maternal exposure to conentrations up to 300 ppm (approximately 27 mg NaF/kg/day) during organogenesis (gestation days 6 to 15) did not significantly affect the frequency of postimplantation loss, mean fetal body weight/litter, or external, visceral or skeletal malformations. In the rat, the NOAEC for maternal toxicity was 150 ppm sodium fluoride and the NOAEC for developmental toxicity was 300 ppm sodium fluoride (the highest concentration tested).

The developmental toxicity study of sodium fluoride conducted in New Zealand white rabbits by the U.S. National Toxicology Program (NTP, 1993; Heindel, et al., 1996) determined that maternal exposure to conentrations up to 400 ppm (approximately 29 mg NaF/kg/day) during organogenesis (gestation days 6 to 19) did not significantly affect the frequency of postimplantation loss, mean fetal body weight/litter, or external, visceral or skeletal malformations in the rabbit. In the rabbit, the NOAEC for maternal toxicity was 200 ppm sodium fluoride and the NOAEC for developmental toxicity was at least 400 ppm sodium fluoride.

Collins, et al. (1995) conducted a developmental toxicity in rats in which pregnant rats were given drinking water with sodium fluoride concentrations of 0, 10, 25, 100, 175 or 250 ppm throughout gestation (days 0 to 20). Pregnant rats drinking water with 250 ppm sodium fluoride drank significantly less fluid and ate less food than did controls thoughout gestation (the amount of sodium fluoride ingested daily was 25.1 mg/kg/day). These findings were reflected by significant decreases in body weight gain at 250 ppm. No definative treatment-related effects on foetal growth or on the incidence of external, visceral, or skeletal abnormalities at levels of sodium fluoride up to and including 250 ppm (25.1 mg/kg/day) were found.

Collins, et al. (2001) evaluated the developmental effects of continous exposure to 0, 25, 100, 175 or 250 ppm sodium fluoride in drinking water over three generations of rats. Parental (P) generation rats were treated for 10 weeks and mated within groups. At gestation day 20, caesarean sections were performed and eight P females per group and their litters (F1) were observed for implant status, fetal weight and length, sex and morphological development. The remaining P females were allowed to litter. F1 offspring were mated within groups, and caesarian sections were performed at gestation day 20. The F1 females and their litters (F2) were oberved for implant status, fetal weight and length, sex and morphological development. In addition, F2 fetuses were evaluated for internal (soft-tissue) and skeletal development.A concentration of 175 ppm sodium fluoride in drinking water of a parental (P) and two filial generations (F1 and F2) of rats did not produce developmental effects and is considered a NOEC for developmental toxicity. A concentration of 250 ppm sodium fluoride in drinking water of a parental (P) and two filial generations (F1 and F2) of rats caused statistically significant decreased ossification of the hyoid bone in F2 fetuses and is considered an effect concentration for developmental toxicity.


Justification for selection of Effect on developmental toxicity: via oral route:
Key study. Comment: The key study reports a NOAEL of 27 mg/kg/day based on NaF, which is converted to 17.6 mg/kg/bw based on H2TiF6, based on the fluoride content of both substances.

Justification for classification or non-classification

No adverse effects on reproduction or development were observed in rat or rabbit teratology studies or in a 3 generation study in mice. No classification is proposed.

Additional information