Effects of chlordiazepoxide on the pre- and postnatal development of rats

Chlordiazepoxide HCl, a widely used tranquilizer, was evaluated for pre- and postnatal effects in rats by dosing orally on days 1--21 of gestation. In the prenatal study, maternally tolerated doses of 10, 25, 50 or 100 mg/kg/day of chlordiazepoxide produced a dose-related decrease in fetal weight and an increased incidence of skeletal anomalies. The latter consisted of retarded calvarial ossification and miscellaneous sternal defects. In the postnatal study, the parturition was delayed for 24 h in a few dams from the 25 and 50 mg/kg groups. There was a reduction in the pup survival and mean pup weight, an increase in the number of runts, an impairment in locomotion and a delay in hair growth and opening of vagina. The 12-week-old female offspring in the 50 mg/kg group manifested a marked prolongation of hexobarbital sleeping time; suggesting that the hepatic microsomal enzymes have been suppressed in these animals.