Teratogenic effect of extended administration of N-nitrosoethylurea and ethylurea/nitrite in rats. 1983

I E Dreosti, and A J McMichael, and T M Bridle

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.

UI MeSH Term Description Entries
D009573 Nitrites Salts of nitrous acid or compounds containing the group NO2-. The inorganic nitrites of the type MNO2 (where M Nitrite
D009607 Nitrosourea Compounds A class of compounds in which the core molecule is R-NO, where R is UREA. Compounds, Nitrosourea
D011247 Pregnancy The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH. Gestation,Pregnancies
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D005038 Ethylnitrosourea A nitrosourea compound with alkylating, carcinogenic, and mutagenic properties. Nitrosoethylurea,N-Ethyl-N-nitrosourea,N Ethyl N nitrosourea
D005260 Female Females
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013723 Teratogens An agent that causes the production of physical defects in the developing embryo. Embryotoxins,Fetotoxins,Teratogen
D014508 Urea A compound formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. Basodexan,Carbamide,Carmol
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus

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