title: First insights in the metabolism of phosphate flame retardants and plasticizers using human liver fractions.
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-2-propyl) 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 quadrupole-time-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.
authors.affiliation: Toxicological Center, University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Wilrijk, Belgium.
authors.forename: Nele
authors.initials: N
authors.lastname: Van den Eede
authors.forename: Walid
authors.initials: W
authors.lastname: Maho
authors.forename: Claudio
authors.initials: C
authors.lastname: Erratico
authors.forename: Hugo
authors.initials: H
authors.lastname: Neels
authors.forename: Adrian
authors.initials: A
authors.lastname: Covaci
mesh_terms: D002853:Chromatography, Liquid; D005260:Female; D005411:Flame Retardants / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008297:Male; D009943:Organophosphorus Compounds / Q000378:metabolism*; D010968:Plasticizers / Q000378:metabolism*; D053719:Tandem Mass Spectrometry
chemical_list: D005411:Flame Retardants; D009943:Organophosphorus Compounds; D010968:Plasticizers
keywords: Human liver enzymes; In vitro; Metabolism; Phosphate flame retardants