title: Does Biotransformation of Aryl Phosphate Flame Retardants in Blood Cast a New Perspective on Their Debated Biomarkers?
abstract: Aryl phosphate flame retardants (aryl-PFRs), such as triphenyl phosphate (TPHP) and 2-ethylhexyl diphenyl phosphate (EHDPHP), are emerging contaminants that can exhibit toxic properties, including severe aquatic toxicity and endocrine disruptive effects. Monitoring exposure to aryl-PFRs through specific biomarkers is necessary to assess the health risk associated with chronic exposure. Hydrolytic serum enzymes could play an important role in the formation of the hydrolysis product diphenyl phosphate (DPHP), the seemingly most abundant in vivo biomarker of TPHP in urine. Here, we assess whether serum enzymes have an impact on the toxicokinetics of TPHP and EHDPHP and on the contribution of both aryl-PFRs to in vivo DPHP levels. TPHP and EHDPHP were incubated separately with pooled human serum to measure the formation of hydrolysis products DPHP and 2-ethylhexyl phenyl phosphate (EHPHP) by liquid chromatography-tandem mass spectrometry. Clearance of TPHP and EHDPHP was 70 and 8.6 mL/min/L serum (as measured by formation of DPHP and EHPHP, respectively). No discernible amount of DPHP was produced from EHDPHP by serum hydrolases. Our results suggest that serum hydrolases can significantly contribute to the in vivo levels of DPHP formed from TPHP and can play an important role in the toxicokinetics, toxicity, and selection of biomarkers for aryl-PFRs.
authors: University of Antwerp, Toxicological Center , Universiteitsplein 1, 2610 Wilrijk, Belgium.
authors: Nele
authors: N
authors: Van den Eede
authors: University of Antwerp, Toxicological Center , Universiteitsplein 1, 2610 Wilrijk, Belgium.|VU University Amsterdam, Institute for Environmental Studies , De Boelelaan 1087, 1081 HV Amsterdam, The Netherlands.
authors: Ana
authors: A
authors: Ballesteros-Gómez
authors: University of Antwerp, Toxicological Center , Universiteitsplein 1, 2610 Wilrijk, Belgium.
authors: Hugo
authors: H
authors: Neels
authors: University of Antwerp, Toxicological Center , Universiteitsplein 1, 2610 Wilrijk, Belgium.
authors: Adrian
authors: A
authors: Covaci
mesh_terms: D015415:Biomarkers; D001711:Biotransformation; D005411:Flame Retardants; D006801:Humans; D010755:Organophosphates / Q000097:blood*; D010710:Phosphates
chemical_list: D015415:Biomarkers; D005411:Flame Retardants; D010755:Organophosphates; D010710:Phosphates