Table 5.

Reproductive toxicity in experimental animals (selected high-quality studies)

Species, strain, number of animals	Exposure duration, chemical form, route	NaF-concentration in DW (mg/L)	Doses (mg/kg/d)	NOAEL (mg/L) (mg/kg/d)	LOAEL (mg/L) (mg/kg/d)	Outcome (as stated by the authors)	Comment	References
Rat, CD, 48/sex/group	Continuously during three generations F0 rats were treated for 10 weeks and mated within groups Investigations of F0, F1 and F2 fetuses at GD 20 Sodium fluoride (DW)	0, 25, 100, 175, 250	NaFa: 0, 2.8–3.8, 11.0–14.6, 18.0–21.8, 23.1–28.0 0, F–a: 1.3–1.7, 5.0–6.6, 8.1–9.9, 10.5–12.7	250 mg/L NaF 23.1–28.0 mg NaF/kg/d 10.5–12.7 mg F–/kg/d	–	NaF up to 250 mg/L did not affect reproduction in rats. No cumulative effects were observed in the three generations Mating, fertility and survival indices were not affected	Diet: NIH-07 low fluoride (7.95 mg/kg F–) Concentration of F– in the Pico system treated water:  < 0.2 mg/L	Collins et al. (2001a)
Rat, CD, 48/sex/group	Continuously during three generations F0 rats were treated for 10 weeks and mated within groups Investigations of F0, F1 and F2 fetuses at GD 20 Sodium fluoride (DW)	0, 25, 100, 175, 250	NaFa: 0, 2.8–3.0, 11.0–11.3, 18.0–18.6, 23.1–24.1 F–a: 0, 1.3–1.4, 5.0–5.1, 8.1–8.4, 10.5–10.9	250 mg/L NaF 23.1–24.1 mg NaF/kg/d 10.5–10.9 mg F–/kg/d	–	Effects on male reproduction: prolonged exposure to NaF in drinking water up to 250 mg/L did not adversely affect spermatogenesis or endocrine function in the F0 or F1 generation of male rats	Diet: NIH-07 low fluoride (7.95 mg/kg F–) Concentration of F– in the Pico system treated water: < 0.2 mg/L	Sprando et al. (1997, 1998)

DW drinking water, GD gestation day, NaF sodium fluoride

^aAs reported by the authors of the study