Metabolism and disposition of alpha-methylstyrene in rats

alpha -Methylstyrene (AMS) is a volatile hydrocarbon used primarily in the production of specialty polymers and resins. In the present study, the tiss ue distribution, metabolism, and excretion of [C-14] AMS was investigated i n male rats after i.v. administration (11 mg/kg). Over 90% of AMS administe red intravenously to rats was excreted in 72 h. Urinary excretion accounted for 86% of the administered dose, volatile breath and feces accounted for 2.2 and 1.9%, respectively, and elimination as carbon dioxide was negligibl e. Metabolites were isolated from rat urine following a high oral dose of A MS (1000 mg/kg) and characterized using gas chromatography/mass spectrometr y and NMR spectrometry. The metabolites were 2-phenyl-1,2-propanediol (3% o f urinary radioactivity) and its glucuronide (50%), atrolactic acid (27%), S-(2-hydroxy-2-phenylpropyl)-N-acetylcysteine (13%), and 2-phenylpropionic acid (1%); the glucuronides and mercapturates were each conjugated on the m ethylene carbon beta to the ring. The presence of both of the diastereomeri c isomers of the mercapturates and of the glucuronides suggested that the i nitial epoxidation of AMS was not stereoselective and proceeded with additi on of active oxygen to yield enantiomeric epoxides. Incubation of AMS with human liver slices produced the same metabolites as those excreted in rat u rine, with 2-phenyl-1,2-propanediol present as the predominant metabolite a fter 5 h of incubation.