PNEUMOTOXICITY AND HEPATOTOXICITY OF STYRENE AND STYRENE OXIDE

The purpose of this study was to investigate the toxicity of styrene a nd styrene oxide in the lung in comparison to the toxicity in the live r. Pneumotoxicity caused by styrene or styrene oxide was measured by e levations in the release of gamma-glutamyltranspeptidase (GGT) and lac tate dehydrogenase (LDH) into bronchoalveolar lavage fluid (BALF), whi le hepatotoxicity was measured by increases in serum sorbitol dehydrog enase (SDH) in non-Swiss Albino (Hsd:NSA) mice. Intraperitoneal admini stration of styrene at doses of 500-1000 mg/kg caused consistent dose- dependent increases in both sets of biomarkers with the hepatic effect appearing earlier than the pulmonary effect. Pyridine, phenobarbital, and beta-naphthoflavone, inducers of CYP2E1, CYP2B, and CYP1A, respec tively, increased the toxicity of styrene. Pyridine and phenobarbital treatments increased mortality due to styrene. Styrene oxide exists in two enantiomeric forms: (R)- and (S)-styrene oxide, and the different ial toxicities of the two enantiomers and racemic styrene oxide were c ompared. In all studies, (R)-styrene oxide caused greater toxicity tha n the (S) enantiomer, especially in the liver. Trichloropropene oxide, an epoxide hydrolase inhibitor, was used to inhibit styrene oxide det oxification and increased its hepatotoxicity, while buthionine sulfoxa mine, a glutathione depletor, did not There results demonstrated the g reater role of epoxide hydrolase in styrene oxide detoxification.