Toxicological investigation of Di(ethyl-hexyl) phthalate in rats. The determination of doses-without-effect for various enzyme parameters

Two animal experiments are described in which male rates have been exposed to di(2-ethyl-hexyl)phthalate (DEHP) for 2 and 4 weeks. A number of enzyme parameters in liver homogenates have been determined which have a relation with the proliferation of peroxisomes in hepatocytes, such as palmitoyl coenenzyme-A oxidase (PCO), enoyl coenzyme-A hydratase (ECH), carnitine acetyl transferase (CAT), catalase (cat) and lauric acid hydroxylase (LAH). In addition, the induction of ECH has been detected with Western blotting. Glutamate dehydrogenase (GlDH) was measured as a control enzyme for mitochondria. For all enzymes, except GlDH, a dose-response relationship was observed. There were not many differences between the 2 and 4 weeks exposed animals. In the 2 weeks exposure experiment, the enzyme parameters appeared to be slightly more sensitive, therefore the parameters from this experiment were taken for determination of the doses-without-effect (DWE). CAT appeared to be the most sensitive parameter. Because the lowest dose group showed a significant difference from to control group, no DWE could be established. Since CAT from mitochondria also contribute to the measured activity, CAT can not be seen as a specific parameter for perxoisome proliferation. The induction of the other enzymes, such as PCO, ECH, cat and LAH are considered to be specific for peroxisome proliferation. The most sensitive parameter was the LAH and ECH activity (DWE = 5 mg/kg b.w./day) followed by PCO (DWE 18 mg/kg b.w./day). Catalase was the least sensitive parameter (52 mg/kg b.w./day). An overal no-observed-effect level for DEHP was established as 5 mg/kg b.w./day, based on peroxisome proliferation.<br&gt