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 (28-61y) who ingested a single dose (645±20μg/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 24h; 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 46h after ingestion. The bioavailability of DEHP-D(4) was surprisingly high with an area under the concentration-time curve until 24h (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 (4.3-6.6h). 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.

• Authors: Winfried Kessler, Wanwiwa Numtip, Wolfgang Völkel, Elcim Seckin, György A Csanády, Christian Pütz, Dominik Klein, Hermann Fromme, Johannes G Filser
• Journal: Toxicology and applied pharmacology (Toxicol Appl Pharmacol) Vol. 264 Issue 2 Pg. 284-91 (Oct 15 2012) ISSN: 1096-0333 [Electronic] United States
• PMID: 22963843 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• Glucuronides
• Indicators and Reagents
• Deuterium
• Diethylhexyl Phthalate
• mono-(2-ethylhexyl)phthalate

Topics

• Adult
• Area Under Curve
• Biotransformation
• Body Weight
• Deuterium
• Diethylhexyl Phthalate (analogs & derivatives, blood, pharmacokinetics, urine)
• Dose-Response Relationship, Drug
• Glucuronides (blood, urine)
• Half-Life
• Humans
• Indicators and Reagents
• Kinetics
• Male
• Middle Aged