Studies on in vitro metabolism of acrylamide and related compounds.

The in vitro biotransformations of acrylamide and ten related compounds in the hepatic enzyme system of the mouse were studied in order to learn more about their toxic actions in vivo. Of nine analogues, which could be analyzed quantitatively by gas chromatography, seven compounds--N-tert-butylacrylamide, diacetone acrylamide, N,N-dimethylacrylamide, N-isobutoxymethylacrylamide,--were metabolized in microsomal enzymes with NADPH generating system. One or two metabolites from each of the seven compounds, except for N-isobutoxymethylacrylamide were detected by gas chromatography. The metabolite of N-isopropylacrylamide was identified as acrylamide by gas chromatography-mass spectrometry. The metabolite of N,N-dimethylacrylamide showed a RT value identical with and a mass spectrum similar to N-methylacrylamide. No metabolites from the other four compounds have yet been identified. Acrylamide and crotonamide did not seem to be metabolized in the same system. Phenobarbital pretreatment of mice enhanced the metabolic reactions of the seven compounds, but did not elevate those of acrylamide and crotonamide. The Km value of N-isopropylacrylamide was 0.35 mM, which was the smallest of all the test analogues. All of the eleven analogues studied were found to be metabolized by hepatic glutathione S-transferases as well. This reaction was also elevated by the phenobarbital treatment of mice. The relationships between the in vitro metabolisms and the in vivo toxicities of acrylamide analogues are discussed.