Title
In vitro metabolism of 2-ethylhexyldiphenyl phosphate (EHDPHP) by human liver microsomesIn vitro metabolism of 2-ethylhexyldiphenyl phosphate (EHDPHP) by human liver microsomes
Author
Faculty/Department
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences. Pharmacy
Research group
Toxicological Centre
Publication type
article
Publication
Amsterdam,
Subject
Pharmacology. Therapy
Source (journal)
Toxicology letters. - Amsterdam
Volume/pages
232(2015):1, p. 203-212
ISSN
0378-4274
ISI
000346175100023
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
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. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
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https://repository.uantwerpen.be/docman/iruaauth/01d7b9/93a122736.pdf
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