In vitro metabolism of 2-ethylhexyldiphenyl phosphate (EHDPHP) by human liver microsomes.

Autor: Ballesteros-Gómez A; Toxicological Center, University of Antwerp, Universiteitsplein 1, Antwerp, Wilrijk 2610, Belgium; Institute for Environmental Studies (IVM), VU University, De Boelelaan 1087, Amsterdam 1081 HV, The Netherlands. Electronic address: a.m.ballesterosgomez@gmail.com., Erratico CA; Toxicological Center, University of Antwerp, Universiteitsplein 1, Antwerp, Wilrijk 2610, Belgium., Eede NV; Toxicological Center, University of Antwerp, Universiteitsplein 1, Antwerp, Wilrijk 2610, Belgium., Ionas AC; Toxicological Center, University of Antwerp, Universiteitsplein 1, Antwerp, Wilrijk 2610, Belgium., Leonards PE; Institute for Environmental Studies (IVM), VU University, De Boelelaan 1087, Amsterdam 1081 HV, The Netherlands., Covaci A; Toxicological Center, University of Antwerp, Universiteitsplein 1, Antwerp, Wilrijk 2610, Belgium.
Jazyk: angličtina
Zdroj: Toxicology letters [Toxicol Lett] 2015 Jan 05; Vol. 232 (1), pp. 203-12. Date of Electronic Publication: 2014 Nov 11.
DOI: 10.1016/j.toxlet.2014.11.007
Abstrakt: 2-ethylhexyl diphenyl phosphate (EHDPHP) is used as flame retardant and plasticizer additive in a variety of consumer products. Since EHDPHP is toxic to aquatic organisms and has been detected in environmental samples, concerns about human exposure and toxicity are emerging. With the aim of identifying human-specific metabolites, the biotransformation of EHDPHP was investigated using human liver microsomes. Using an in silico program (Meteor) for the prediction of metabolites, untargeted screening tools (agilent Mass Hunter) and a suitable analysis platform based on ultra-high performance liquid chromatography (UPLC) and quadrupole time-of-flight high resolution mass spectrometer (QTOF-MS), for the first time a wide variety of phases-I and II metabolites of EHDPHP were identified. Mono- and di-hydroxylated metabolites, keto metabolites, mixed keto and hydroxylated metabolites and diphenyl phosphate were the major phase-I metabolites of EHDPHP. Glucuronidated metabolites of phase-I metabolites of EHDPHP were also formed by human liver microsomes. Using these results, we propose a general metabolism pathway for EHDPHP in humans and a number of candidate biomarkers for assessing the human exposure to this ubiquitous phosphate flame retardant and plasticizer in future biomonitoring studies. Furthermore, we provide a template analytical approach based on the combination of untargeted and targeted screening and UPLC-QTOF-MS analysis suitable for use in future metabolism studies.
(Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)
Databáze: MEDLINE
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