Effects of pretreatment with toluene, phenobarbital and 3-methylcholantrene on the in vivo metabolism of toluene and on the excretion of hippuric acid in the rat.

The limit of the capacity of male adult Sprague-Dawley rats to metabolize toluene and excrete it as hippuric acid was reached at a dose of 10 mmol toluene/kg. At this dose of benzoic acid or hippuric acid, the excretion of hippuric acid was 1.5-fold and 4-fold, respectively, greater than that following this dose of toluene. When toluene was given after phenobarbital pretreatment the excretion rate of hippuric acid increased 3-4-fold, but 3-methylcholanthrene pretreatment had no effect. Consecutive toluene exposures increased hippuric acid excretion on the third day by about 2-fold. It seems that the side-chain oxidation is the rate-limiting step in toluene metabolism of uninduced rats, and toluene accelerates its own metabolism by inducing cytochrome P-450 dependent microsomal monooxygenases.