Metabolism of di (2-ethylhexyl) phthalate (DEHP): comparative study in juvenile and fetal marmosets and rats

Abstract

We compared the metabolic profile of di (2-ethylhexyl) phthalate (DEHP) in juveniles and fetus between rats and marmosets. STUDY-I: (14)C-DEHP (100 and 2,500 mg/kg) was singly administered to juvenile and adult marmosets by gavage. C(max) of the radioactivity in juvenile marmosets was 6.45 and 31 µg eq./g, respectively. The radioactivity excreted mainly into feces; however, at least 10% of the radioactivity was absorbed even at 2,500 mg/kg. No abnormal accumulation was observed in the male reproductive organs. STUDY-II: (14)C-DEHP (100 mg/kg) was singly administered to juveniles of rat and marmoset. The plasma radioactivity in marmosets was about 5% to 9% of that in rats. Free forms of mono-2-ethylhexyl phthalate (MEHP) and its oxidized metabolites such as oxo-, OH-, and COOH-MEHP were detected as the main compositions in rat plasma. In marmosets, free form of MEHP was also detected as a major composition, but not for oxidized MEHP metabolites. In rats, oxidized MEHP metabolites were excreted into urine as unconjugated forms. MEHP and its oxidized metabolites were also detected in marmoset urine; however, they were mostly glucuronized. No specific accumulation of the radioactivity was noted in the testes of either species; however, the radioactivity concentration in the marmoset testes was much lower than that in rats. STUDY-III: (14)C-DEHP (100 mg/kg) was singly administered to dams on gestation day 130 for marmosets and day 20 for rats. In either species, no specific accumulation of radioactivity was noted in the testis of fetuses from the dams treated with (14)C-DEHP; however, the radioactivity in the rat testis was about 20-times higher than that in the marmoset. Major metabolite components in rat whole fetal tissue were free forms of MEHP, OH-MEHP, and oxo-MEHP. Free form of MEHP was also detected as only a peak in the marmoset fetal tissue.