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In Vitro Metabolism of the Flame Retardant Triphenyl Phosphate in Chicken Embryonic Hepatocytes and the Importance of the Hydroxylation Pathway
journal contribution
posted on 2015-04-14, 00:00 authored by Guanyong Su, Robert J. Letcher, Doug Crump, David
M. Gooden, Heather M. StapletonWe report for the first time either in vitro or in vivo the phase I hydroxylation
and phase II conjugation
metabolic pathways of an organophosphate flame retardant, triphenyl
phosphate (TPHP), in addition to diphenyl phosphate (DPHP) metabolite
formation. Using a chicken embryonic hepatocyte (CEH) assay, TPHP
was phase I metabolized to p- and m-hydroxy-TPHP metabolites, which were largely present in the assay
medium and cells as phase II conjugates with glucuronic acid. After
treatment with β-glucuronidase, deconjugated p-OH-TPHP was present in both the medium and cells at increasing concentrations
of 0.073 ± 0.003, 1.95 ± 0.03, and 2.10 ± 0.09 nmol/well
at CEH incubation time points of 0, 12, and 36 h, respectively. Similarly,
after β-glucuronidase treatment, there were increasing m-OH-TPHP concentrations of 0.0050 ± 0.0005, 0.18 ±
0.01, and 0.18 ± 0.01 nmol/well. p-OH-TPHP at
36 h accounted for 60% of the initial TPHP treatment concentration,
which was 3.5- or 12-fold greater than that of the DPHP or m-OH-TPHP metabolites, respectively. Overall, in TPHP-exposed
organisms, this study demonstrates the importance of phase I and II
metabolic processes in the biological fate of TPHP.