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Biotransformation of three phosphate flame retardants and plasticizers in primary human hepatocytes: untargeted metabolite screening and quantitative assessment


, : Biotransformation of three phosphate flame retardants and plasticizers in primary human hepatocytes: untargeted metabolite screening and quantitative assessment. Journal of Applied Toxicology 36(11): 1401-1408

Tris(2-butoxyethyl) phosphate (TBOEP), triphenyl phosphate (TPHP) and tris(1-chloro-2-propyl) phosphate (TCIPP) are current high-volume organophosphate flame retardants/plasticizers (PFRs) and are abundant in the indoor environment. While recent in vitro research has indicated potential toxic effects in the endocrine system, biotransformation of these compounds is still underexplored. In this study, we aimed to characterize the metabolite formation for three PFRs in primary human hepatocytes, an in vitro system that mimics in vivo liver metabolism more closely than hepatic subcellular fractions or cell lines. Cryopreserved human hepatocytes were thawed and suspended in media with 50 μm TBOEP or TCIPP, or 20 μm TPHP up to 2 h. Extracts were analyzed by liquid chromatography-quadrupole-time-of-flight-mass spectrometry. Quantification of biotransformation products in hepatocytes exposed for 2 h revealed that bis(1-chloro-2-propyl) phosphate and diphenyl phosphate corresponded to less than half of the depletion of TCIPP and TPHP, respectively, while bis(2-butoxyethyl) 2-hydroxyethyl phosphate compared to 40-66% of the depletion of TBOEP. Other metabolite structures of these PFRs were produced at 4- to 10-fold lower rates. These findings help interpret biological levels of the major metabolites and relate it to levels of their parent PFR. Percentage of substrate depletion was largest for TBOEP followed by comparable values for TPHP and TCIPP, indicating that hepatic clearance of TPHP and TCIPP would be slower than that of TBOEP. The resulting higher levels and longer presence of TPHP in the circulation after exposure, would allow TPHP a larger time window to exert its suspected adverse effects compared to TBOEP. Copyright © 2016 John Wiley & Sons, Ltd.

US$19.90

PMID: 26889657

DOI: 10.1002/jat.3293


Other references

Flint, S.D.; Searles, P.S.; Caldwell, M.M., 2004: Field testing of biological spectral weighting functions for induction of UV-absorbing compounds in higher plants. Action spectra are typically used as biological spectral weighting functions (BSWF) in biological research on the stratospheric ozone depletion issue. Despite their critical role in determining the amount of UV supplied in experiments, there has b...

Derenne, J.; Martel, A., 2016: A Model CSMH Curriculum for Child and Adolescent Psychiatry Training Programs. Child and adolescent psychiatrists (CAP) care for high school students preparing to enter college. They also may continue to see students while on school vacations and may care for college students in various settings (emergency room, inpatient ho...

Okono, A.; Monneveux, P.; Ribaut, J-Marcel., 2013: Facing the challenges of global agriculture today: what can we do about drought?. Frontiers in Physiology 4: 289-289

Santos-Martinez, J.; Selkurt, E.E., 1969: Renal lymph and its relationship to the countercurrent multiplier system of the kidney. American Journal of Physiology 216(6): 1548-1555

Gagne, J.M.; Armstrong, P.J.; Weiss, D.J.; Lund, E.M.; Feeney, D.A.; King, V.L., 1999: Clinical features of inflammatory liver disease in cats: 41 cases (1983-1993). 25 cats with lymphocytic portal hepatitis (LPH) and 16 cats with acute (7 cats) or chronic (9) cholangiohepatitis (CH) were selected by evaluating records from liver biopsy specimens submitted to the University of Minnesota Veterinary Teaching Hos...

Anonymous, 2012: Successful use of allopurinol in a patient on dialysis. We report the case of a man with chronic tophaceous gout who had end-stage renal failure secondary to the Alport syndrome. Following a failed kidney transplant, where urate deposition was a suspected contributor, the patient responded positively t...

Perea, G.; Araque, A., 2006: Synaptic information processing by astrocytes. Glial cells were classically considered as supportive cells that do not contribute to information processing in the nervous system. However, considerable amount of evidence obtained by several groups during the last few years has demonstrated the...

Stein, G.H.W., 1962: Vertikalrassen europaseher Sauge-tiere. Symposium Theriologicum. Unknown

Kim, E-Soo.; Ros-Freixedes, R.; Pena, R.N.; Baas, T.J.; Estany, J.; Rothschild, M.F., 2016: Identification of signatures of selection for intramuscular fat and backfat thickness in two Duroc populations. Intramuscular fat (IMF) content is an important trait affecting the quality of pork. Two Duroc populations, one under positive selection for IMF and the other selected for decreased backfat but under stabilizing selection for IMF, were used to ide...

Osztovics, M.; Bühler, E.M.; Müller, H.; Stalder, G.R., 1973: Banding techniques in the evaluation of human chromosomal variants. Humangenetik 18(2): 123-128