Hepatic effects of xylidine isomers in rats

The effect of repeated (4 weeks) oral administration of 2,4-, 2,5- or 2,6-xylidine (at dose levels of 400--500 mg/kg/day) on the morphology and microsomal drug metabolising enzyme activity of the liver was studied in rats. All 3 isomers caused hepatomegaly which was considered to be due to proliferation of the smooth endoplasmic reticulum. Decreases in glycogen content and glucose-6-phosphatase activity were demonstrated histochemically. Biochemical investigations showed increases in microsomal protein and cytochrome P-450 content in rats dosed with 2,4- or 2,5-xylidine and in glucuronyltransferase activity in rats given 2,4-, 2,5- or 2,6-xylidine. Aniline hydroxylase activity was increased in all treated rats except males dosed with 2,6-xylidine. The results of the study indicate that all isomes of xylidine can be inducers of microsomal drug-metabolising enzyme activity, that they may be metabolised by oxidation and that the xylidine molecule may be eliminated as a conjugate with glucuronic acid.