title: Determination of glucuronide conjugates of hydroxyl triphenyl phosphate (OH-TPHP) metabolites in human urine and its use as a biomarker of TPHP exposure.
abstract: In vitro studies using avian hepatocytes or human liver microsomes suggest that hydroxylation is an important pathway in the metabolism of triphenyl phosphate (TPHP), a chemical used as a flame retardant and plasticizer. TPHP metabolism can lead to the formation of para(p)- and meta(m)-hydroxyl-(OH-)TPHP products as well as their glucuronide conjugates. To determine whether the TPHP hydroxylation and depuration pathway also occurs in vivo in humans, the present study developed a sensitive method for quantification of p- and m-OH-TPHP glucuronides in human urine samples. In n = 1 pooled urine sample and n = 12 individual urine samples collected from four human volunteers from Ottawa (ON, Canada), p- and m-OH-TPHP glucuronides were detectable in 13 and 9 of the 13 analyzed samples and at concentrations ranging from <MLOQ-25 pg/mL and nd-4 pg/mL, respectively. A strong, positive correlation (p = 0.02, r = 0.6569) was observed between p-OH-TPHP glucuronide and diphenyl phosphate concentrations (DPHP, a known dealkylated metabolite of TPHP). To our knowledge, this is the first report demonstrating that TPHP hydroxylation and conjugation occurs in vivo in humans, and further suggests that p-OH-TPHP glucuronide can be used as a specific biomarker of TPHP exposure in humans.
authors.affiliation: Department of Chemistry, Carleton University, Ottawa, ON, K1S 5B6, Canada; Ecotoxicology and Wildlife Health Division, Environment and Climate Change Canada, National Wildlife Research Centre, Carleton University, Ottawa, ON, K1A 0H3, Canada. Electronic address: guanyong.su85@gmail.com.
authors.forename: Guanyong
authors.initials: G
authors.lastname: Su
authors.affiliation: Department of Chemistry, Carleton University, Ottawa, ON, K1S 5B6, Canada; Ecotoxicology and Wildlife Health Division, Environment and Climate Change Canada, National Wildlife Research Centre, Carleton University, Ottawa, ON, K1A 0H3, Canada.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Letcher
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse & School of the Environment, Nanjing University, Nanjing, China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Yu
authors.affiliation: Duke University, Department of Chemistry, P.O. Box 90354, Durham, NC, 27708, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Gooden
authors.affiliation: Nicholas School of the Environment, Duke University, Durham, NC, USA.
authors.forename: Heather M
authors.initials: HM
authors.lastname: Stapleton
mesh_terms: D015415:Biomarkers / Q000378:metabolism / Q000652:urine*; D002170:Canada; D004781:Environmental Exposure / Q000032:analysis*; D004785:Environmental Pollutants / Q000652:urine*; D005411:Flame Retardants / Q000378:metabolism; D020719:Glucuronides / Q000378:metabolism / Q000652:urine*; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D017665:Hydroxyl Radical / Q000378:metabolism / Q000652:urine; D006900:Hydroxylation; D008862:Microsomes, Liver / Q000378:metabolism; D010755:Organophosphates / Q000652:urine*; D010968:Plasticizers / Q000378:metabolism
chemical_list: D015415:Biomarkers; D004785:Environmental Pollutants; D005411:Flame Retardants; D020719:Glucuronides; D010755:Organophosphates; D010968:Plasticizers; D017665:Hydroxyl Radical; C005445:triphenyl phosphate
keywords: Biomarker; Flame retardant; Glucuronidation; Human urine; Hydroxylation; Metabolism; Triphenyl phosphate