Studies on metabolism and toxicity of styrene. V. The metabolism of styrene, racemic, (R)-(+)-, and (S)-(--)-phenyloxiranes in the rat.

Metabolism of styrene, racemic phenyloxirane, (R)-(+)-, and (S)-(--)-phenyloxiranes in rats has been described. The animals excreted phenylethanediol, mandelic acid, phenylglyoxylic acid, and two regioisomeric mercapturic acids in their urine after the intraperitoneal injection of the phenyloxiranes as well as styrene. The mercapturic acids were identified as N-acetyl-S-(1-phenyl-2-hydroxyethyl)cysteine (MA-1) and N-acetyl-S-(2-phenyl-2-hydroxyethyl)cysteine (MA-2). The ratios of the mercapturic acids to the other metabolites excreted in the urine were 1 to 1.8 and 1 to 1.5 for styrene and racemic phenyloxirane, respectively. A remarkable stereoselectivity was observed in the excretion of both types of the metabolites when optically active phenyloxiranes were administered. The rate of excretion of the mercapturic acids was 2.5 times higher than that of the other metabolites when the (R)-oxirane was injected, but the reverse was the case in the (S)-oxirane. The mercapturic acid, MA-1, was excreted at higher rate than the isomer, MA-2, on the administration of styrene and the phenyloxiranes. The most significant regioselectivity in the excretion of MA's was observed when styrene and (S)-phenyloxirane were administered.