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 b y administering the plasticizer (2000 mg/kg, orally) to 3, 6 and 10 we ek 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 hydroxyla se, aniline hydroxylase and ethylmorphine N-demethylase at all the age groups while repeated exposure induced them with maximum alterations occuring in 3 week old rats. Repeated administration for 15 days, on t he other hand. caused a decrease in the cytochrome P450 content and th e activity of arylhydrocarbon hydroxylase, aniline hydroxylase and eth ylmorphine N-demethylase only in the 3 week old rats. The 6 and 10 wee k old rats exposed to the same schedule of DEHP showed an inhibition i n the activity of arylhydrocarbon hydroxylase and an increase in the a ctivity of aniline hydroxylase and ethylmorphine N-demethylase, which was however lower than that seen after 7 days of exposure to DEHP in t he respective age group of animals. Our data have indicated the differ ences in the sensitivity of the P450 monooxygenases towards DEHP and i ts metabolites amongst 3, 6 and 10 week old animals.