Potentiation of toluene toxicity by hepatic enzyme inhibition in mice

The toxicity of toluene was evaluated in male mice by the narcotic effects and lethality. The i.p. LD50 of toluene for male mice was calculated to be 1.15g/kg according to the method of Weil. Pretreatment with phenobarbital, produced a marked decrease in the number of sleep induced by a test dose (0.96 g/kg i.p.) of toluene. By contrast, pretreatment with a variety of hepatic enzyme inhibitors such as CCl4, SKF 525A, pyrazole and cyanamide was found to produce an increase in the number of sleep and death, accompanied with the prolongation of sleeping time. The present results suggest that the toxicity of toluene is enhanced by the inhibition of any step of metabolism.