INFLUENCE OF PHENOBARBITAL ON XYLENE METABOLISM IN MAN AND RATS

Retention of inhaled m-xylene vapors and the amount of the excreted metabolite, i.e., conjugated m-methylbenzoic acid (MBA), was measured in five volunteers before and after hepatic microsomal enzyme induction by phenobarbital. During exposure to m-xylene vapors at a concentration of 400 mg/m3 air, phenobarbital pretreatment did not affect either retention of xylene vapors or the amount of excreted MBA. Higher concentrations of m-xylene were studied in rats. At 400 and 800 mg/m3, respectively, the result was the same as in humans, i.e., the amount of excreted MBA did not differ in pretreated and control animals. A rise in the concentration of m-xylene vapors to 2000 and 4000 mg/m3, respectively, increased fourfold the amount of excreted MBA in phenobarbital pretreated rats compared with control rats. It is assumed that during inhalation of low concentrations of xylene vapors, the normal biotransformation capacity of the liver is sufficient to metabolize the total portion of the absorbed substance entering the liver and, therefore, enzyme induction does not increase the amount of the metabolite formed. Only at high concentrations does the amount of the supplied xenobiotic surpass the normal biotransformation capacity of the liver and, in this case, can the higher capacity, due to enzyme induction, assert itself. © 1979 Springer-Verlag.