Hepatic effects of phthalate esters and related compounds--in vivo and in vitro correlations

Environmental Health Perspectives
B G LakeS D Gangolli

Abstract

The hepatic effects of phthalate esters and related compounds on peroxisomal and microsomal enzyme activities were investigated in the intact animal and in primary hepatocyte cultures. In vitro studies with a series of phthalate monoesters demonstrated structure activity differences in the induction of the specific peroxisomal marker KCN-insensitive palmitoyl-CoA oxidation and also of carnitine acetyltransferase. These effects could be reproduced in vivo, and potency differences were also observed between di(2-ethylhexyl) phthalate (DEHP) and its straight-chain isomer, di-n-octyl phthalate. In in vivo studies, DEHP, mono(2-ethylhexyl) phthalate, and clofibrate/clofibric acid produced large increases in liver size and peroxisomal enzyme activities in Sprague-Dawley rats and Chinese hamsters, but had less effect in Syrian hamsters. These effects could be largely reproduced in vitro where good responses were obtained with rat and Chinese hamster hepatocytes, but either little or no effect with Syrian hamster and Dunkin-Hartley guinea pig hepatocytes. Both DEHP and clofibrate appeared to induce similar form(s) of microsomal cytochrome P-450 which exhibited a high specificity towards lauric acid hydroxylation. With a range of hypoli...Continue Reading

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Citations

Feb 17, 1998·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·N O Mocchiutti, C A Bernal
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