Effects of prolonged treatment with phthalate ester on rat liver.

Rats were fed a diet containing 2%, 0.2% or 0.02% di(2-ethylhexyl)phthalate (DEHP) for a period of 102 weeks. Only the 2% diet caused a substantial decrease in body weight. Both peroxisomal palmitoyl-CoA dehydrogenase and mitochondrial carnitine acetyltransferase activities were greatly induced by exposure to the highest dose of phthalate ester, reaching maximal plateau values after about 20 weeks of treatment. The diet containing 0.2% DEHP increased both activities slowly, but continuously, and at the end of the two-year period these increases were almost comparable to those obtained with the highest dose. Even the lowest dose gave a slowly increase in these activities. Both microsomal NADPH-cytochrome c reductase activity and the level of cytochrome P-450 were increased initially by exposure to 2% DEHP, but returned almost or completely to the control level after about 30 weeks of exposure. Depending on the dose of DEHP in the diet, peroxisomal catalase activity was elevated above the control level during the first year of treatment but was about the same as in the control animals during the second year. A substantial decrease in peroxisomal urate oxidase activity was observed throughout the entire experimental period. When treatment was ceased after one year, all activities returned to the control values within 2-3 weeks. These results demonstrate the complex nature of the effects caused by prolonged treatment with DEHP with cumulative increases at low doses.