Subacute toxicity of vinyltoluene vapour: effects on the hepatic and renal drug biotransformation and the urinary excretion of thioether.

Male rats were exposed by inhalation to vinyltoluene at concentrations of 50, 100, or 300 p.p.m. for 8, 12 or 15 weeks. Vinyltoluene was found to be metabolized to glutathione conjugates via the formation of electrophilic intermediates. This metabolic pathway was suggested by the decreased hepatic non-protein sulfhydryl 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 is fairly linear, at least with exposure to vinyltoluene vapour up to 300 p.p.m. The slight increase in the activities of hepatic drug biotransformation enzymes (7-ethoxycoumarin 0-deethylase. UDPglucuronosyltransferase) observed after 8 weeks of exposure to vinyltoluene vapour disappeared by week 15 irrespective of the continued intermittent inhalation of vinyltoluene. Histological study revealed that cell size had decreased in the rats exposed to vinyltoluene.