Comparative Studies of the Hepatic Effects of Di‐ and Mono‐n‐Octyl Phthalates, Di‐(2‐Ethylhexyl) Phthalate and Clofibrate in the Rat

Abstract
The oral administration of di-n-octyl phthalate (DNOP), mono-n-octyl phthalate (MNOP), di-(2-ethylhexyl) phthalate (DEHP) and clofibrate to young male Sprague-Dawley rats for 14 days resulted in liver enlargement. Morphological examination of liver sections from DEHP and clofibrate treated rats, but not from DNOP or MNOP treated animals, revealed increased numbers of peroxisomes (microbodies). DEHP and clofibrate treatment markedly stimulated the activities of certain peroxisomal marker enzymes; DNOP and MNOP produced only marginal effects. DEHP and clofibrate, but not DNOP or MNOP, increased microsomal cytochrome P-450 content and markedly stimulated microsomal lauric acid hydroxylation activity. While the branched chain phthalate ester DEHP induced peroxisomal proliferation, the straight chain analog DNOP and its metabolite ester MNOP were essentially inactive. DEHP treatment appeared to induce similar form(s) of cytochrome P-450 in rat liver to those previously described after clofibrate administration.