[Toxicological studies on a new cephamycin, MT-141 IX. Its teratogenicity test in rats and rabbits]

A teratogenicity study of MT-141 was performed in SD rats and Japanese white rabbits. The pregnant rats were administered intramuscularly (i.m.) with MT-141 at the dose levels of 200, 400, 800 and 1,600 mg/kg/day from the day 7 up to the day 17 of gestation. The pregnant rabbits were administered intravenously (i.v.) with the drug at the dose levels of 10, 20 and 40 mg/kg/day from the day 6 up to the day 18 of gestation. The results are summarized as follows. Rats: Though the administrations with MT-141 at all dose levels did not change body weight gain and water intake of treated dams, a slight suppression in the food consumption was produced by MT-141 at the dose of 1,600 mg/kg/day. The examinations on cesarean section revealed no effect of MT-141 on teratological parameters such as external malformation and frequency of visceral and skeletal anomalies in the fetuses. MT-141 at all dose levels exerted no toxic effect on developmental, functional and behavioral parameters in F1 rats and on mating, fertility and pregnancy of F1 rats. Furthermore, there was no effect of MT-141 on the findings in cesarean section of F1 rats. The fetuses from F1 rats had no malformation of external appearance, viscera and skeleton. Rabbits: MT-141 had no significant effect on body weight gain and food consumption of dams at the all dose levels, but caused a slight suppression in the water intake at the doses more than 20 mg/kg/day. One rabbit aborted in each group given 20 or 40 mg/kg/day. One rabbit died in the group given 20 mg/kg/day. Examinations on cesarean section showed that MT-141 at the dose of 40 mg/kg/day produced a decrease in body weights of females and an increase in dead or resorbed fetuses followed by a decrease in live fetuses. MT-141 is no effect malformation of external appearance, viscera and skeleton in the fetuses of all treated groups. The above-mentioned results suggest that MT-141 has no teratogenic effect on pregnant rats and rabbits. It is concluded from these results that the maximal "no effective" dose of MT-141 on fetal toxicity is above 1,600 mg/kg/day i.m. for pregnant rats and 10 mg/kg/day i.v. for pregnant rabbits.