Determination of glucuronide conjugates of hydroxyl triphenyl phosphate (OH-TPHP) metabolites in human urine and its use as a biomarker of TPHP exposure. (April 2016)

• Record Type: Journal Article
• Authors: Su, Guanyong; Letcher, Robert J.; Yu, Hongxia; Gooden, David M.; Stapleton, Heather M.
• Is Part Of: Chemosphere. Volume 149(2016)
• Page Start: 314
• Page End: 319
• Publication Date: 2016-04
• Subjects: Triphenyl phosphate -- Flame retardant -- Metabolism -- Hydroxylation -- Glucuronidation -- Human urine -- Biomarker; Pollution -- Periodicals; Pollution -- Physiological effect -- Periodicals; Environmental sciences -- Periodicals; Atmospheric chemistry -- Periodicals; 551.511
• DOI: 10.1016/j.chemosphere.2016.01.114
• Languages: English
• ISSNs: 0045-6535

Abstract

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. Graphical abstract: Highlights: A method was developed for determination of para ( p )- and meta ( m )-OH TPHP glucuronides in urine. Both p- and m -OH-TPHP glucuronides were detected in urine samples. Concentration ranges of p - and m -OH-TPHP glucuronides were <MLOQ-25 and nd-4 pg/mL. p -OH-TPHP glucuronide and DPHP concentrations in urine were strongly and positively correlated. This is first known report demonstrating TPHP hydroxylation occurs in TPHP exposed humans.