Title
First insights in the metabolism of phosphate flame retardants and plasticizers using human liver fractions
Author
Faculty/Department
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences. Pharmacy
Publication type
article
Publication
Amsterdam ,
Subject
Pharmacology. Therapy
Source (journal)
Toxicology letters. - Amsterdam
Volume/pages
223(2013) :1 , p. 9-15
ISSN
0378-4274
ISI
000326108100002
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
Phosphate flame retardants and plasticizers (PFRs) are additives used in a wide range of polymers. Important representatives, such as tris(2-butoxyethyl) phosphate (TBOEP), triphenyl phosphate (TPHP), tris(2-chloroethyl) phosphate (TCEP), tris(1-chloro-2-propyl) phosphate (TCIPP), tris(1,3-dichloro-2propyl) phosphate (TDCIPP), have been found in the indoor environment at high levels. Biotransformation of these PFRs needs to be investigated because it can be a major determinant of their bioavailability and toxicity in humans. TBOEP, TPHP, TCEP, TCIPP and TDCIPP were incubated with human liver S9 fraction and microsomes. Supernatants were analyzed using a liquid chromatography coupled to a quadrupoletime-of-flight mass spectrometer. Chromatograms were scanned for the presence of Phase-I and Phase-II metabolites and tentatively identified based on mass accuracy of the molecular formula, isotopic pattern, and MS/MS spectra. The two major metabolites of TBOEP were products of O-dealkylation and of hydroxylation, respectively. TPHP was mainly transformed to its diester metabolite by O-dearylation and to a hydroxylated metabolite. TCEP was poorly metabolized into its diester and a product of oxidative dehalogenation. The major metabolite of TCIPP was a product of oxidative dehalogenation. TDCIPP was mainly transformed into its diester and a glutathione S-conjugate. The metabolites identified in the present study are candidate biomarkers for future human biomonitoring studies. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
E-info
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