Studies on the effects of orally administered dicyclohexyl phthalate in the rat

Abstract: The oral administration of 500–2500 mg/kg/day dicyclohexyl phthalate (DCHP) to young male Sprague-Dawley rats for 7 days resulted in liver enlargement and induction of some parameters of hepatic xenobiotic metabolism. Additional studies indicated that the hepatic enzyme induction resembled that of sodium phenobarbitone rather than that of polycyclic hydrocarbons. Morphological examination of the livers of DCHP treated rats revealed centrilobular cell hypertrophy and ultrastructural examination demonstrated marked proliferation of the smooth endoplasmic reticulum. Mitochondrial structure and numbers of peroxisomes (microbodies) were not affected. DCHP treatment did not affect kidney and testes weights but some histological evidence of testicular damage was obtained with 2500 mg/kg/day of DCHP. The metabolites of DCHP, namely monocyclohexyl phthalate (MCHP) and cyclohexanol, also induced certain parameters of hepatic xenobiotic metabolism. MCHP, but not cyclohexanol also produced marked testicular atrophy. It is concluded that DCHP is a weak drug-type inducer of hepatic xenobiotic metabolism in the rat and the hepatic effects of this phthalate diester are different from those of di-(2-ethylhexyl) phthalate.