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

Winfried Kessler, Wanwiwa Numtip, Wolfgang Völkel, Elcim Seckin, György A. Csanády, Christian Pütz, Dominik Klein, Hermann Fromme, Johannes G. Filser

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86 Scopus citations

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-D4). Concentrations of DEHP-D4, of free ring-deuterated MEHP (MEHP-D4), and the sum of free and glucuronidated MEHP-D4 were measured in blood for up to 24h; amounts of the monoesters MEHP-D4, 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-D4 was surprisingly high with an area under the concentration-time curve until 24h (AUC) amounting to 50% of that of free MEHP-D4. The AUC of free MEHP-D4 normalized to DEHP-D4 dose and body weight (AUC/D) was 2.1 and 8.1 times, that of DEHP-D4 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-D4 in blood, the parameter regarded as relevant for risk assessment.

Original languageEnglish
Pages (from-to)284-291
Number of pages8
JournalToxicology and Applied Pharmacology
Volume264
Issue number2
DOIs
StatePublished - 15 Oct 2012

Keywords

  • Blood
  • Di(2-ethylhexyl) phthalate (DEHP)
  • Mono(2-ethylhexyl) phthalate (MEHP)
  • Monoesters human
  • Urine

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