Toxicity-related changes in benzene metabolism in vivo.

1. The influence of microsomal enzyme inducers and inhibitors on the metabolism of [U-14C]benzene in the rat was examined. 2. Pre-treatment of animals with the inhibitors piperonyl butoxide and cobaltous chloride tended to reduce the urinary excretion of metabolites in 24 h but increase the overall urinary excretion. Piperonyl butoxide tended to increase expired benzene. 3. Pre-treatment of animals with the inducer phenobarbital tended to increase urinary excretion of metabolites but decrease expired benzene, as did pre-treatment with benzene itself. 4. All pre-treatments appeared to increase the excretion of phenolic glucuronides, particularly benzene pre-treatment. Phenobarbital and benzene pre-treatment tended to increase phenylmercapturic acid excretion and benzene pre-treatment markedly increased excretion of quinol. 5. The results are discussed in relation to the effect of microsomal enzyme inhibitors and inducers on benzene-induced bone marrow toxicity.