Formamide (FORM), a high production, industrial solvent with likely human exposure in industrial and laboratory settings, was evaluated for reproductive toxicity in CD-1 (Swiss) mice using the Reproductive Assessment by Continuous Breeding Protocol (RACB). Male and female mice were exposed to FORM in drinking water at doses of 0, 100, 350, and 750 ppm (~20 to 200 mg/kg/day).
A Maximum Tolerated Dose (MTD) of FORM, based on indices of generalized toxicity, was not reached for F0 animals. However, reproductive toxicity. including reduced fertility and litter size, was observed at 750 ppm FORM. F0 females at 750 ppm FORM exhibited an increase in the average days to litter, and tended to spend more time in diestrus than in another stage of the cycle. FORM caused no detectable change in the histopathology of kidney, liver, or reproductive organs. Estimated exposure for the F0 generation was 24, 80, and 195 mg/kg/day for the 100, 350, and 750 ppm FORM groups, respectively. Females tended to have higher relative exposure (mg/kg/day) compared to males.
F1 postnatal survival was unaffected by treatment. The MTD for the F1 generation was 750 ppm FORM, based on reduced body weight. Mild reproductive toxicity, observed as reduction in litter size and increased days to litter, occurred at 750 ppm. No significant histopathologic changes were observed in either males or females. Estimated exposure to FORM was 26, 87, and 190 mg/kg/day for F1 animals.
In summary, the MTD for generalized toxicity was not reached for the F0 generation, but was established at 750 ppm for the F1 generation. The No-Observed-Adverse-Effect-Level (NOAEL) for generalized toxicity was 750 ppm for the F0 generation and 350 ppm for the generation. Reproductive toxicity was observed at 750 ppm in both generations.
NTIS # PB93-109213