Kinetics of di(2-ethylhexyl) phthalate (DEHP) and mono(2-ethylhexyl) phthalate in blood and of DEHP metabolites in urine of male volunteers after single ingestion of ring-deuterated DEHP.

Abstract The plasticizer di(2-ethylhexyl) phthalate (DEHP) is suspected to induce antiandrogenic effects in men via its metabolite mono(2-ethylhexyl) phthalate (MEHP). However, there is only little information on the kinetic behavior of DEHP and its metabolites in humans. The toxikokinetics of DEHP was investigated in four male volunteers (28–61 y) who ingested a single dose (645 ± 20 μg/kg body weight) of ring-deuterated DEHP (DEHP-D 4 ). Concentrations of DEHP-D 4 , of free ring-deuterated MEHP (MEHP-D 4 ), and the sum of free and glucuronidated MEHP-D 4 were measured in blood for up to 24 h; amounts of the monoesters MEHP-D 4 , ring-deuterated mono(2-ethyl-5-hydroxyhexyl) phthalate and ring-deuterated mono(2-ethyl-5-oxohexyl) phthalate were determined in urine for up to 46 h after ingestion. The bioavailability of DEHP-D 4 was surprisingly high with an area under the concentration-time curve until 24 h (AUC) amounting to 50% of that of free MEHP-D 4 . The AUC of free MEHP-D 4 normalized to DEHP-D 4 dose and body weight (AUC/D) was 2.1 and 8.1 times, that of DEHP-D 4 even 50 and 100 times higher than the corresponding AUC/D values obtained earlier in rat and marmoset, respectively. Time courses of the compounds in blood and urine of the volunteers oscillated widely. Terminal elimination half-lives were short (4.3–6.6 h). Total amounts of metabolites in 22-h urine are correlated linearly with the AUC of free MEHP-D 4 in blood, the parameter regarded as relevant for risk assessment.