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. (1975). British Journal of Induistrial Medicine, 32, 42-48. Effect of repeated exposure to aniline, nitrobenzene, and benzene on liver microsomal metabolism of the rat. Exposure of rats to aniline at daily doses of 50 mg/kg of body weight over a month stimulated the microsomal metabolism as manifested by (1) acceleration of p-hydroxylation of aniline and N-demethylation of aminopyrine in 9000 x g postmitochondrial supernatant of the liver, (2) shortening the sleeping time after hexobarbital, and (3) reduction of the antipyretic effect of phenacetin.In the rats exposed to nitrobenzene in a similar manner to aniline, nitroreduction of nitrobenzene and p-hydroxylation of aniline remained unaffected; the antipyretic effect of phenacetin was decreased, whereas hexobarbital sleeping time remained unchanged.Exposure of rats to benzene (50 mg/kg of body weight daily for a month) had no effect on the rate of hydroxylation of benzene and N-demethylation of aminopyrine. In benzeneexposed rats hexobarbital sleeping time was prolonged whereas the antipyretic effect of phenacetin was unaffected.Microsomal metabolism of aniline, nitrobenzene, and benzene was stimulated and inhibited when the rats were pretreated with phenobarbital and SKF 525-A, respectively.

1. The rates of aniline metabolism have been studied in vitro using rat liver homogenates, and in vivo by determination of the unchanged aniline remaining in the cadaver. 2. Metabolism of aniline in vivo is stimulated by phenobarbital and 3,4-benzpyrene, and inhibited by SKF 525-A. 3. Cyclobarbital and phenacetin stimulate aniline metabolism both in vitro and in vivo. 4. Pre-treatment with aniline impaired the metabolism of aniline in vivo but increased the in vitro metabolism to p-aminophenol. Pre-treatment of rats with phenobarbital and aniline did not accelerate metabolism of aniline in vivo but the stimulating effect of phenobarbital on protein synthesis in microsomes was maintained. In contrast, pre-treatment with 3,4-benzpyrene and aniline stimulated metabolism of aniline in vivo. The possible mechanism of changes in aniline metabolism due to previous exposure to aniline is discussed.