title: Quantification of tetrabromo benzoic acid and tetrabromo phthalic acid in rats exposed to the flame retardant Uniplex FPR-45.
abstract: The first withdrawal of certain polybrominated diphenyl ethers flame retardants from the US market occurred in 2004. Since then, use of brominated non-PBDE compounds such as bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate (BEH-TEBP) and 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EH-TBB) in commercial formulations has increased. Assessing human exposure to these chemicals requires identifying metabolites that can potentially serve as their biomarkers of exposure. We administered by gavage a dose of 500 mg/Kg bw of Uniplex FRP-45 (>95 % BEH-TEBP) to nine adult female Sprague-Dawley rats. Using authentic standards and mass spectrometry, we positively identified and quantified 2,3,4,5-tetrabromo benzoic acid (TBBA) and 2,3,4,5-tetrabromo phthalic acid (TBPA) in 24-h urine samples collected 1 day after dosing the rats and in serum at necropsy, 2 days post-exposure. Interestingly, TBBA and TBPA concentrations correlated well (R (2) = 0.92). The levels of TBBA, a known metabolite of EH-TBB, were much higher than the levels of TBPA both in urine and serum. Because Uniplex FRP-45 was technical grade and EH-TBB was present in the formulation, TBBA likely resulted from the metabolism of EH-TBB. Taken together, our data suggest that TBBA and TBPA may serve as biomarkers of exposure to non-PBDE brominated flame retardant mixtures. Additional research can provide useful information to better understand the composition and in vivo toxicokinetics of these commercial mixtures.
authors: Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA, 30341, USA. zca2@cdc.gov.
authors: Manori J
authors: MJ
authors: Silva
authors: Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA, 30341, USA.
authors: Donald
authors: D
authors: Hilton
authors: Reproductive Toxicology Branch, Toxicity Assessment Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC, 27709, USA.
authors: Johnathan
authors: J
authors: Furr
authors: Reproductive Toxicology Branch, Toxicity Assessment Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC, 27709, USA.
authors: L Earl
authors: LE
authors: Gray
authors: Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA, 30341, USA.
authors: James L
authors: JL
authors: Preau
authors: Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA, 30341, USA.
authors: Antonia M
authors: AM
authors: Calafat
authors: Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA, 30341, USA.
authors: Xiaoyun
authors: X
authors: Ye
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000652:urine; D004781:Environmental Exposure / Q000032:analysis; D005260:Female; D005411:Flame Retardants / Q000032:analysis* / Q000493:pharmacokinetics; D006842:Hydrocarbons, Brominated / Q000652:urine*; D010795:Phthalic Acids / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity / Q000652:urine*; D017207:Rats, Sprague-Dawley
chemical_list: C000612045:2,3,4,5-tetrabromo benzoic acid; D015415:Biomarkers; D005411:Flame Retardants; D006842:Hydrocarbons, Brominated; D010795:Phthalic Acids; C016132:tetrabromophthalic acid; C576262:bis(2-ethylhexyl) 2,3,4,5-tetrabromophthalate
keywords: 2-Ethylhexyl-2,3,4,5-tetrabromobenzoate; BEH-TEBP; Bis-(2-ethylhexyl)-2,3,4,5-tetrabromophthalate; EH-TBB; Flame retardant; Tetrabromo benzoic acid; Tetrabromo phthalic acid