Kinetics of tris (1-chloro-2-propyl) phosphate (TCIPP) metabolism in human liver microsomes and serum

Nele Van den Eede, Gregg Tomy, Fang Tao, Thor Halldorson, Stuart Harrad, Hugo Neels, Adrian Covaci

Research output: Contribution to journalArticlepeer-review

42 Citations (Scopus)
218 Downloads (Pure)

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 VMAX of 154 ± 4 and 1470 ± 110 pmol/min/mg protein and respective apparent Km of 80.2 ± 4.4 and 96.1 ± 14.5 μM. 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/μL 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.

Original languageEnglish
Pages (from-to)1299-1305
Number of pages7
JournalChemosphere
Volume144
Early online date23 Oct 2015
DOIs
Publication statusPublished - Feb 2016

Bibliographical note

Copyright © 2015 Elsevier Ltd. All rights reserved.

Fingerprint

Dive into the research topics of 'Kinetics of tris (1-chloro-2-propyl) phosphate (TCIPP) metabolism in human liver microsomes and serum'. Together they form a unique fingerprint.

Cite this