Teratogenicity Study of N-methylformamide (mmf) in the Rat with Cover Letter dated 013189.

摘要

Teratogenicity was evaluated in groups of 25 pregnant female Crl:CDBT rats exposed to nominal concentrations of 0, 15, 50, or 150 ppm of N-methylformamide (MMF) on days 7-16 of gestation. Mortality was observed in one rat in the high dose group on gestation day 14. Clinical observations in rats in the 50 and 150 ppm dose groups included mild respiratory distress, wheezing, and rattling. Maternal toxicity was evidenced by significant decreases (p≤0.05) in body weight, feed consumption and absolute and relative thymus weights. Statistically significant differences (P≤0.05) were observed in mean number of resorptions per litter (increase) and mean number of live fetuses per litter (decrease) in high dose females, and mean fetal body weight (decrease) for exposure levels of 50 ppm and above. The incidence of structural malformations was significantly increased in fetuses from the high dose group. An exposure-related response in the incidence of fetuses with variations (external, visceral, head and skeletal) was observed. While overall incidence of developmental variations was not significant across treated groups, significance was detected for total skeletal variations as compared to controls. The NOAEL (no-observable-adverse effect level) for both dam andfetus was 15 ppm MMF per day.