Publication
Title
Kinetics of tris (1-chloro-2-propyl) phosphate (TCIPP) metabolism in human liver microsomes and serum
Author
Abstract
Tris(1-chloro-2-propyl) phosphate (TCIPP) is an emerging contaminant which is ubiquitous in the indoor and outdoor environment. Moreover, its presence in human body fluids and biota has been evidenced. Since no quantitative data exist on the biotransformation or stability of TCIPP in the human body, we performed an in vitro incubation of TCIPP with human liver microsomes (HLM) and human serum (HS). Two metabolites, namely bis(2-chloro-isopropyl) phosphate (BCIPP) and bis(1-chloro-2-propyl) 1-hydroxy-2-propyl phosphate (BCIPHIPP), were quantified in a kinetic study using HLM or HS (only BCIPP, the hydrolysis product) and LC-MS. The Michaelis-Menten model fitted best the NADPH-dependent formation of BCIPHIPP and BCIPP in HLM, with respective V-MAX of 154 +/- 4 and 1470 +/- 110 pmol/min/mg protein and respective apparent K-m of 80.2 +/- 4.4 and 96.1 +/- 14.5 mu M. Hydrolases, which are naturally present in HLM, were also involved in the production of BCIPP. A HS paraoxonase assay could not detect any BCIPP formation above 38.6 +/- 10.8 pmol/min/mu L serum. Our data indicate that BCIPP is the major metabolite of TCIPP formed in the liver. To our knowledge, this is the first quantitative assessment of the stability of TCIPP in tissues of humans or any other species. Further research is needed to confirm whether these biotransformation reactions are associated with a decrease or increase in toxicity. (C) 2015 Elsevier Ltd. All rights reserved.
Language
English
Source (journal)
Chemosphere. - Oxford, 1972, currens
Publication
Oxford : 2016
ISSN
0045-6535 [print]
1879-1298 [online]
Volume/pages
144(2016), p. 1299-1305
ISI
000367774400162
Full text (Publishers DOI)
Full text (open access)
The author-created version that incorporates referee comments and is the accepted for publication version Available from 01.02.2018
Full text (publishers version - intranet only)
UAntwerpen
Faculty/Department
Research group
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identification
Creation 16.02.2016
Last edited 23.05.2017
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