Di-(2-propylheptyl) phthalate (DPHP) and its metabolites in blood of rats upon single oral administration of DPHP

Abstract

Di-(2-propylheptyl) phthalate (DPHP) does not act as a reproductive toxicant or endocrine disruptor in contrast to other phthalates. Considering adverse effects of phthalates to be linked to their metabolism, it was the aim of the present study to investigate in the rat the blood burden of DPHP and its metabolites as a basis for understanding the toxicological behavior of DPHP. Rats were administered single oral doses of DPHP of 0.7 and 100mg/kg body weight. Concentration-time courses of DPHP and metabolites were monitored in blood. The areas under the concentration-time curves in blood (AUCs), normalized for the dose of DPHP, showed the following order: DPHP<mono-(2-propyl-6-oxoheptyl) phthalate<mono-(2-propyl-6-hydroxyheptyl) phthalate=mono-(2-propylheptyl) phthalate<mono-(2-propyl-6-carboxyhexyl) phthalate (cx-MPHP). Glucuronidation of the monoesters accounted for less than 5% of total compounds. The elimination half-lives of the compounds ranged from 2.3h (DPHP) to 8.2h (cx-MPHP). The normalized AUCs of the metabolites were lower at the high dose of DPHP than at the low one indicating saturation kinetics of intestinal DPHP hydrolysis. The absence of toxicity to reproduction of DPHP may be related to the comparatively low bioavailability of the parent compound and its metabolites.