Formation of mercapturic acids from acrylonitrile, crotononitrile, and cinnamonitrile by direct conjugation and via an intermediate oxidation process
van Bladeren, P.J.; Delbressine, L.P.; Hoogeterp, J.J.; Beaumont, A.H.; Breimer, D.D.; Seutter-Berlage, F.; van der Gen, A.
Drug Metabolism and Disposition the Biological Fate of Chemicals 9(3): 246-249
1981
ISSN/ISBN: 0090-9556 PMID: 6113934 Document Number: 168836
After administration of acrylonitrile, crotononitrile and cinnamonitrile to rats, 2 types of mercapturic acids were isolated from urine and identified by mass and NMR spectroscopy as N-acetyl-S-(2-cyanoethyl)-L-cysteine (I) and N-acetyl-S-(2-hydroxyethyl)-L-cysteine (II) (methyl-substituted in the case of crotonitrile and phenyl-substituted in the case of cinnamonitrile). After pretreatment of rats with the cytochrome P-450 inhibitor 1-phenylimidazole, no trace of mercapturic acid II was found; a higher amount of mercapturic acid I was excreted. The 1st type of products may result from direct addition of glutathione; the 2nd group of metabolites (II), in which the cyano group has been replaced by a hydroxyl group, may be formed via an intermediate epoxide. Substituents on the double bond had a considerable influence on the ratio of the 2 mercapturic acids formed, and thus presumably on the amount metabolized via an oxidative process: the ratio of the cyano (I) to hydroxy (II) mercapturic acid was 72:28 for AN; introduction of a methyl or a phenyl group resulted in ratios of 91:9 and 98:2, respectively. [Acrylonitrile is an industrial mutagen structurally similar to the carcinogen vinyl chloride.].