Hepatic peroxisome proliferation and hypolipidemic effects of di(2-ethylhexyl)phthalate in neonatal and adult rats

Abstract

To determine the relative sensitivity of suckling rats as compared to adults to the effects of di(2-ethylhexyl) phthalate (DEHP), five daily oral doses of 0, 10, 100, 1000, or 2000 mg DEHP/kg body weight were given to male Sprague-Dawley rats beginning at 6, 14, 16, 21, 42, and 86 days of age. Twenty-four hours after the last dose, rats were sacrificed and plasma cholesterol and triglyceride levels and the activities of the hepatic peroxisomal enzymes, palmitoyl CoA oxidase and carnitine acetyltransferase, were determined. Suckling rats (1-3 weeks of age) suffered severe growth retardation at doses of 1000 mg/kg and death at 2000 mg/kg while older rats only showed decreased weight gain at 2000 mg/kg. Of particular interest was the lethality at doses of 1000 mg/kg at 14 days of age but not at 16 days or at other ages. Increases in relative liver weight and hepatic peroxisomal enzyme activities were similar in all age groups except the 14-day old group in which the increases were greater. Relative kidney weight was increased in 21-, 42-, and 86-day-old rats at the highest doses but not in younger rats. Hypolipidemia was observed only in 21-, 42-, and 86-day-old rats at doses of 1000 and 2000 mg/kg, while elevated plasma cholesterol levels were observed in 6- and 14-day-old rats at the 1000 mg/kg dose, possibly due to the dietary differences between suckling and weaned rats. The results suggest that neonatal and suckling rats are more sensitive to the lethal and growth retardation effects of DEHP than are adult rats, but the hepatic peroxisome proliferation is similar at all ages with the exception of a greater increase at 14 days of age.