Dose Dependent Induction of Rat Liver Microsomal Cytochrome P‐450 and Microsomal Enzymatic Activities after Inhalation of Toluene and Dichloromethane

Sprague-Dawley rats were exposed, by inhalation, to toluene and dichloromethane (500, 1,500 or 3,000 p.p.m.) and to benzene (1,500 p.p.m.) for three days. Toluene and benzene increased the concentration of liver microsomal cytochrome P-450. A dose dependent increase in the in vitro liver microsomal formation of several metabolites of biphenyl and benzo(a)pyrene was observed for both dichlormethane and toluene. At the highest dose-level the increase in the in vitro formation of benzo(a)pyrene-7,8-dihydrodiol was more than three-fold for both dichloromethane and toluene whereas the formation of benzo(a)pyrene-4,5-dihydrodiol increased more than five-fold following exposure to toluene but less than two-fold after exposure to dichloromethane. Our results suggest that dichloromethane and toluene can modify the metabolism and thereby the toxicity of other environmental contaminants.