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The Comparison of Teratogenic and Carcinogenic Effects of Some Carbamate Compounds

Etiology, Biology Branch, National Cancer Institute, NIH, Bethesda, Maryland 20014

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 ß-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.

¹ Lalor Foundation Fellow. Permanent address: Institute of Pharmacology, Czechoslovak Academy of Sciences, Prague, Czechoslovakia.

Received 12/29/66. Accepted 5/ 2/67.