The Comparison of Teratogenic and Carcinogenic Effects of Some Carbamate Compounds

Summary Ethyl carbamate and a series of related compounds were given in single intraperitoneal doses to pregnant Syrian hamsters on Day 8 of gestation, and fetuses were examined for malformations on Day 13 of gestation. Urethan produced a variety of malformations and growth retardation. Of the compounds modified in the carboethoxy end, n -propyl carbamate was as teratogenic as the ethyl carbamate, and β-hydroxyethyl carbamate had only borderline effect, while allyl carbamate and n -butyl carbamate were completely negative. Four compounds modified in the cabamyl portion of the molecule were tested. Three of these, ethyl N -methylcarbamate, ethyl N -hydroxycarbamate, and diethylcarbonate, were teratogenic; a fourth, ethyl N,N -dimethylcarbamate was not teratogenic. The ethyl N -hydroxycarbamate was the most potent teratogen tested. Although no qualitative differences were found among the various compounds tested, ethyl N -hydroxycarbamate produced a quantitatively greater number of fetuses with malformed extremities and anophthalmia. The diethylcarbonate was as potent as urethan, the ethyl N -methylcarbamate was more teratogenic than urethan, while the ethyl N,N -dimethylcarbamate was negative. The similarity of abnormalities produced by these teratogens suggests a common mechanism of action for these compounds. Striking positive correlations were found between the teratogenic effects in hamsters and skin tumor initiation and lung adenomas in mice.