Metabolite profiling and identification in human urine after single oral administration of DEHP

Di(2-ethylhexyl)phthalate (DEHP) is known to be a reproductive toxicant in male rodents, and its primary or secondary metabolites seem to be causative agents. To identify and quantify urinary metabolites of DEHP in humans, urine samples collected from healthy male and female volunteers following oral administration of deuterium labeled DEHP (d(4)-DEHP) at 3mg/person were analyzed by a high performance liquid chromatograph/mass spectrometer (LC-MS), and the excretion behavior of orally taken DEHP was evaluated. Mono(2-ethylhexyl)phthalate (MEHP), OH-MEHP, oxo-MEHP, COOH-MEHP, and their glucuronides were identified as metabolites in the male and female urine. The ratios of the conjugate forms in the total urinary metabolites were remarkably high from immediately after administration (0 to 4-hr post-dose), which were approximately 69% to 86% (male) and 80% to 89% (female) until 36-hr post-dose. It was suggested that DEHP taken orally was promptly converted to MEHP and its oxidative metabolites such as OH-MEHP, oxo-MEHP, and COOH-MEHP, and most of these metabolites received the conjugation reaction and were excreted as glucuronides. Remarkable differences from rodents, in which most of these metabolites were excreted as free forms, were demonstrated.