Metabolism of methacrylonitrile to cyanide: in vitro studies

In liver fractions from male Sprague-Dawley rats, the metabolism of methacrylonitrile (MeAN) to cyanide (CN-) was localized in microsomal fraction and required reduced nicotinamide adenine dinucleotide phosphate (NADPH) and oxygen for maximal activity. The biotransformation of MeAN to CN- was characterized with respect to time, microsomal protein concentration, pH, and temperature. Metabolism of MeAN was increased in microsomes obtained from phenobarbital-treated rats (310% of control) and decreased with CoCl2 and SKF 525 A treatments (55% and 61%, respectively). Addition of the epoxide hydratase inhibitor, 1,1,1-trichloropropane 2,3-oxide, decreased the formation of CN- from MeAN. Addition of glutathione, cysteine, D-penicillamine, and 2-mercaptoethanol enhanced the released of CN- from MeAN. These findings indicate that MeAN is metabolized to CN- via a cytochrome P-450-dependent mixed-function oxidase system.