Abstract |
In a range-finding study, groups of 5 pregnant Charles River COBS CD rats each were administered dimethylacetamide (DMAC) at dose levels of 200, 400, 800, 1800, or 3500 mg/kg/day orally by gavage as a single daily dose on gestation days 6 through 19 at a constant volume of 10 ml/kg bw. Maternal toxicity and death were increased over vehicle (deionized water) controls at dosages of 1800 mg/kg/day and above. Decreased maternal body weight, increased postimplantation loss, and a decrease in the mean number of viable fetuses were seen in the 400 and 800 mg/kg/day groups. No effects on observed parameters were seen in the 200 mg/kg/day group. In the full teratology study, groups of 25 females were administered single daily doses (10 ml/kg volume) of 65, 160, or 400 mg/kg/day orally by gavage on gestation days 6 through 19. A treatment-related decreased mean maternal body weight gain occurred during the treatment period. Fetal body weight was reduced in the 160 mg/kg/day animals, and at 400 mg/kg/day, a significant increase was noted in postimplantation loss, an increase in variations (mainly decreased ossification) which was correlated with fetal weight reduction in this group. Malformations (heart and/or vessel anomalies, cleft palate and anasarca) were increased in the 400 mg/kg/day dose group. |