Teratogenic effect of extended administration of N-nitrosoethylurea and ethylurea/nitrite in rats

N-Nitrosoethylurea (ENU) and ethylurea (EU) with sodium nitrite (NaNO2) were administered daily by mouth to Hooded Wistar rats. Doses ranged from 1-50 mg ENU/kg body weight (day-1) and from 20-70 mg EU/kg body weight day-1 and extended over days 7 to 16 inclusive of pregnancy. Severe teratogenesis occurred in animals which received from 10 mg ENU/kg day-1. Fetal death predominated at intakes above 12.5 mg ENU/kg body wt. Many organ systems were affected by ENU, but developmental anomalies of the nervous system were most common, especially anophthalmia and hydrocephalus. With EU and nitrite severe teratogenesis was noted at levels above 50 mg EU/kg body weight. Maximum teratogenic potency was obtained when nitrite was administered at approximately 50% of the level of the EU dose. Terata arising from treatment with EU/nitrite were similar to those caused by ENU. However, unlike ENU-treated animals, litters from the EU/nitrite study were either severely malformed or barely affected at all. The erratic nature of the teratogenesis following treatment with EU/nitrite was not influenced by the presence of food in the stomach at the time of dosing. For both substances administered over a 10-day period, the threshold dose needed for obvious teratogenicity was considerably less than in all previously reported single-dose studies.