Subacute Toxicity of Vinyltoluene Vapour: Effects on the Hepatic and Renal Drug Biotransformation and the Urinary Excretion of Thioether

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Abstract
Male rats were exposed by inhalation to vinyltoluene at 50, 100 or 300 ppm for 8, 12 or 15 wk. Vinyltoluene was metabolized to glutathione conjugates via the formation of electrophilic intermediates. This metabolic pathway was suggested by the decreased hepatic nonprotein SH content, with a concomitant increase in the urinary excretion of thioethers. The excretion of thioethers showed no saturation phenomena, suggesting that the formation of electrophilic intermediates capable of conjugating with glutathione was fairly linear, at least with exposure to vinyltoluene vapor up to 300 ppm. The slight increase in the activities of hepatic drug biotransformation enzymes (7-ethoxycoumarin O-deethylase, UDP-glucuronosyltransferase) observed after 8 wk of exposure to vinyltoluene vapor disappeared by wk 15 irrespective of the continued intermittent inhalation of vinyltoluene. Histological study revealed that cell size had decreased in the rats exposed to vinyltoluene.