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Kessler, W. ; Numtip, W. ; Völkel, W.* ; Seckin, E.* ; Csanády, G.A. ; Pütz, C. ; Klein, D. ; Fromme, H.* ; Filser, J.G.

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.

Toxicol. Appl. Pharmacol. 264, 284-291 (2012)
DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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 mu g/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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Di(2-ethylhexyl) Phthalate (dehp) ; Mono(2-ethylhexyl) Phthalate (mehp) ; Monoesters Human ; Blood ; Urine; TANDEM MASS-SPECTROMETRY; DEUTERIUM-LABELED DEHP; N-BUTYL PHTHALATE; MONO-(2-ETHYLHEXYL) PHTHALATE; DI-(2-ETHYLHEXYL) PHTHALATE; EXPOSURE ASSESSMENT; COMMON MARMOSETS; RISK-ASSESSMENT; SERUM; RAT
ISSN (print) / ISBN 0041-008X
e-ISSN 1096-0333
Zeitschrift Toxicology and Applied Pharmacology
Quellenangaben Band: 264, Heft: 2, Seiten: 284-291 Artikelnummer: , Supplement: ,
Verlag Elsevier
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Molecular Toxicology and Pharmacology (TOXI)