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Abstract

Comparative in vitro metabolic activity of human and rat liver fractions toward 5 ring-substituted methylcarbamates are reported. Human liver appeared to be less metabolically active than rat liver toward 4-dimethylamino-3,5-xylyl methylcarbamate (Zectran), 4-dimethylamino-3-cresyl methylcarbamate (Matacil), 4-methylthio-3,5-xylyl methylcarbamate (Mesurol), and 1-naphthyl methylcarbamate (carbaryl). In these studies the human liver metabolized 2-chloro-4,5-xylyl methylcarbamate (Banol) as well as did the rat. Both species produced esssentially the same major metabolites from the carbamates although quantitative differences were observed. Ring hydroxylation and N-dealkylation are the main oxidative metabolic pathways of carbamate metabolism studied in both the human and rat. The human liver produced a few metabolites not seen with the rat liver. The human liver had more difficulty oxidizing the N-methylcarbamate side chain to form the N-hydroxymethylcarbamate derivative of all the carbamates except Mesurol. In both species the major metabolic products from the carbamates retained the OC(O)NC group necessary for acetylcholinesterase inhibition.