Phthalate esters I: Effects on cytochrome P-450 mediated metabolism in rat liver and lung, serum enzymatic activities and serum protein levels.

Dimethylphthalate (DMP), dibutylphthalate (DBP) and di(2-ethylhexyl)phthalate (DEHP) were given i.p. (3.8 mM/kg) to Sprague Dawley rats for 5 days. DBP increased significantly the liver concentration of cytochrome P-450, but decreased the lung concentration by about 40%. DBP decreased the lung concentration of cytochrome b5 and NADPH-cytochrome-c-reductase activity by about 30%. Only minor effects were seen after treatment with DMP and DEHP. The direction of B(a)P metabolism was changed and the formation of 2- and 3-hexanol metabolites were increased in liver microsomes after DBP treatment. All phthalate esters decreased the lung metabolism of B(a)P. The cytochrome P-450 enzyme system in the lung was ten times more effective than that in the liver as far as metabolism of n-hexane was concerned. Only minor effects were observed in serum enzyme activities, but a significant decrease in the serum level of albumin was observed after treatment with DBP. No relationship was found between the carbon chain length of the investigated chemicals and effects on microsomal enzymatic activities.