Age related effects of di(2-ethylhexyl)phthalate on hepatic cytochrome P450 monooxygenases in Wistar rats.

Age related response of di(2-ethylhexyl)phthalate (DEHP) was studied by administering the plasticizer (2000 mg/kg, orally) to 3, 6 and 10 week old wistar rats for 1, 7 or 15 days and determining the activity of hepatic P450 monooxygenases. Single administration of DEHP decreased the cytochrome P450 contents and activity of arylhydrocarbon hydroxylase, aniline hydroxylase and ethylmorphine N-demethylase at all the age groups while repeated exposure induced them with maximum alterations occurring in 3 week old rats. Repeated administration for 15 days, on the other hand, caused a decrease in the cytochrome P450 content and the activity of arylhydrocarbon hydroxylase, aniline hydroxylase and ethylmorphine N-demethylase only in the 3 week old rats. The 6 and 10 week old rats exposed to the same schedule of DEHP showed an inhibition in the activity of arylhydrocarbon hydroxylase and an increase in the activity of aniline hydroxylase and ethylmorphine N-demethylase, which was however lower than that seen after 7 days of exposure to DEHP in the respective age group of animals. Our data have indicated the differences in the sensitivity of the P450 monooxygenases towards DEHP and its metabolites amongst 3, 6 and 10 week old animals.