Publication
Title
Mass spectrometric identification of in vitro-generated metabolites of two emerging organophosphate flame retardants : V6 and BDP
Author
Abstract
The aim of the present study was to investigate the in vitro metabolism of two emerging organophosphate flame retardants, namely tetrekis(2-chlorethyl)dichloroisopentyldiphosphate (V6) and bisphenol-A bis-diphenyl phosphate (BDP) in human liver microsomes (HLMs), HLM S9 fractions and in human serum. In particular, the role of cytochrome P450 (CYPs) enzymes and/or paraoxonases (PONs) in the formation of V6 and BDP phase I metabolites was studied. Mono-, di-hydroxylated and hydrolytic phase I metabolites of V6 were mainly formed by CYPs in HLMs, while hydrolytic and O-dealkylated phase I metabolites of BDP were generated by PONs mainly in serum experiments. Limited number of glucuronidated and sulfated phase II metabolites were also identified for the two chemicals. The activity of seven recombinant CYPs (rCYPs) including rCYP1A2, rCYP2B6, rCYP2C9, rCYP2C19, rCYP2D6, rCYP2E1 and rCYP3A4 in the in vitro phase I metabolism of V6 and BDP was investigated. The formation of V6 metabolites was catalyzed by several enzymes, especially rCYP1A2 that was responsible for the exclusive formation of two metabolites, one primary (M1) and its secondary metabolite (M9). For BDP, only one phase I metabolite (MM1) was catalyzed by the seven rCYPs. Collectively, these results indicate that CYPs have a predominant role in the metabolism of V6, while PONs have a predominant role in BDP in vitro metabolism. These results are a starting point for future studies involving the study of the toxicity, bioaccumulation and in vivo biomonitoring of V6 and BDP.
Language
English
Source (journal)
Chemosphere. - Oxford, 1972, currens
Chemosphere. - Oxford, 1972, currens
Publication
Oxford : 2018
ISSN
0045-6535 [print]
1879-1298 [online]
Volume/pages
212 (2018) , p. 1047-1057
ISI
000447478100113
Pubmed ID
30286534
Full text (Publisher's DOI)
Full text (open access)
Full text (publisher's version - intranet only)
UAntwerpen
Faculty/Department
Research group
Project info
Advanced tools for exposure assessment and biomonitoring (A-TEAM).
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identification
Creation 09.10.2018
Last edited 20.11.2021
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