Table 1.

Chronic toxicity studies; selected studies investigating primarily systemic effects

Species, strain, number of animals	Exposure duration, chemical form, route	NaF concentration in DW (mg/L)	NaF dosesa (mg/kg b.w./day)	Effects	NOAEL F– (mg/kg b.w./day)	LOAEL F– (mg/kg b.w./day)	Comment	References
Rat F-344 N 50–80 sex/group	103 weeks Sodium fluoride (DW)	0, 25, 100, 175 (0, 11.3, 45.3, 79.3 mg F–/L) Control: deionized water	0, 1.3, 5.2–5.5, 8.6–9.5 (corresponding to 0, 0.6, 2.4–2.5, 3.9–4.3 mg F–/kg b.w./day)	Resp, cardio, gastro, hemato, hepatic, renal, bd wt	3.9		Diet: NIH-07 low fluoride	NTP (1990)
				Musc/skel (osteosclerosis)	2.5	4.3
Mouse B6C3F1 50–80 sex/group	103 weeks Sodium fluoride (DW)	0, 25, 100, 175 (0, 11.3, 45.3, 79.3 mg F–/L) Control: deionized water	0, 2.4–2.8, 9.6–11.3, 16.7–18.8 (corresponding to 0,1.1–1.3, 4.3–5.1, 7.6–8.5 mg F–/kg b.w./day)	Resp, cardio, gastro, hemato, hepatic, renal, bd wt	7.6		Diet: NIH-07 low fluoride	NTP (1990)
				Musc/skel (dentine dysplasia)	4.3, M	7.6
Rabbit 9/group	24 month Sodium fluoride (GW)		10 (corresponding to 4.5 mg F–/kg b.w./day)	Gastro (roughened duodena mucosa)		4.5	Standard animal diet; DW: fluoride content less than 0.5 mg/L	Susheela and Das (1988)
Rabbit 5/group	7–12 month Sodium fluoride (G)		10 (corresponding to 4.5 mg F–/kg b.w./day)	Hemato (decreased leucocyte and hemoglobin levels)		4.5		Susheela and Jain (1983)

Bd wt body weight, Cardio cardiovascular, DW drinking water, F females, G gavage, Gastro gastrointestinal, GW gavage in water, Hemato hematological, LOAEL lowest-observed-adverse-effect level, M males, Musc/skel muscular/skeletal, NaF sodium fluoride, NOAEL no-observed-adverse-effect level, Resp respiratory

^aAs reported by the authors