Teratogenic effects of nitrazepam in rats

The teratogenicity of nitrazepam, a benzodiazepine-type drug, was investigated in Sprague-Dawley rats. Nitrazepam was administered to pregnant females at levels of 100, 200 or 300 mg/kg in a single dose on one of gestation days 10-14. Fetuses were examined for external and skeletal malformations on day 20 of gestation. Nitrazepam was found to produce various types of malformations, i.e., exencephaly, cleft palate, micrognathia, short or kinky tail and limb reduction defects. The predominant malformation was limb reduction defects, which were produced at high frequency by treatment on day 12 or 13 of gestation. Microscopic examination of limb buds revealed hemorrhage and mesenchymal cell necrosis at 24 hours after nitrazepam treatment.