Changes in rat liver microsomal cytochrome P-450 and enzymatic activities after the inhalation of n-hexane, xylene, methyl ethyl ketone and methylchloroform for four weeks.

Abstract

Groups of Sprague-Dawley rats were exposed, by inhalation, to n-hexane (900 ppm, 3240 mg/m3), xylene (600 ppm, 2625 mg/m3), methyl ethyl ketone (800 ppm, 2345 mg/m3) and methylchloroform (800 ppm, 4345 mg/m3) for 4 wk. Increased liver weights and liver to body weight ratios were observed for all solvents except n-hexane. An increased in vitro formation of certain metabolites of all substrates was found in rats exposed to xylene. The in vitro microsomal metabolism of biphenyl, benzo[a]pyrene, 4-androstene-3,17-dione and 5.alpha.-androstane-3.alpha.,17.beta.-diol in combination with sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that n-hexane was without effect on rat liver microsomal cytochrome P-450 and that methyl ethyl ketone and methylchloroform depressed the formation of 2 metabolites of androstenedione but did not alter the concentration of cytochrome P-450. Xylene was a phenobarbital-like inducer of rat liver microsomal cytochrome P-450.