title: High-resolution mass spectrometry provides novel insights into products of human metabolism of organophosphate and brominated flame retardants.
abstract: The high resolution, accurate mass, and fast scanning features of the Orbitrap(TM) mass spectrometer, combined with the separation power of ultrahigh-performance liquid chromatography were applied for the first time to study the metabolic profiles of several organic flame retardants (FRs) present in indoor dust. To mimic real-life exposure, in vitro cultured HepG2 human hepatocyte cell lines were exposed simultaneously to various FRs in an indoor dust extract for 24 h. Target parent FRs, hexabromocyclododecanes (α-, β-, and γ-HBCDs), tris-2-chloroethyl phosphate (TCEP), tris(1-chloro-2-propyl) phosphate (TCIPP), and tris(1,3-dichloro-2-propyl) phosphate (TDCIPP), were separated in a single run for the first time using alternating positive and negative heated ESI source. Further metabolite separation and identification was achieved using full scan (70,000 full width at half maximum (FWHM)), accurate mass (up to 1 ppm) spectrometry. Structural confirmation was performed via all ion fragmentation (AIF) spectra using the optional higher collisional dissociation (HCD) cell and MS/MS analysis. First insights into human metabolism of HBCDs revealed several hydroxylated and debrominated phase I metabolites, in addition to conjugated phase II glucuronides. Furthermore, various hydroxylated, oxidized, and conjugated metabolites of chlorinated phosphorous FRs were identified, leading to the suggestion of α-oxidation as a significant metabolic pathway for these compounds.
authors.affiliation: Division of Environmental Health and Risk Management, School of Geography, Earth and Environmental Sciences, University of Birmingham, Birmingham, B15 2TT, UK, mae_abdallah@yahoo.co.uk.
authors.forename: Mohamed Abou-Elwafa
authors.initials: MA
authors.lastname: Abdallah
authors.forename: Jinkang
authors.initials: J
authors.lastname: Zhang
authors.forename: Gopal
authors.initials: G
authors.lastname: Pawar
authors.forename: Mark R
authors.initials: MR
authors.lastname: Viant
authors.forename: J Kevin
authors.initials: JK
authors.lastname: Chipman
authors.forename: Kyle
authors.initials: K
authors.lastname: D'Silva
authors.forename: Maciej
authors.initials: M
authors.lastname: Bromirski
authors.forename: Stuart
authors.initials: S
authors.lastname: Harrad
mesh_terms: D000818:Animals; D001966:Bromine / Q000378:metabolism*; D005411:Flame Retardants / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D009943:Organophosphorus Compounds / Q000378:metabolism*; D051381:Rats
chemical_list: D005411:Flame Retardants; D009943:Organophosphorus Compounds; D001966:Bromine