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• W2965658839 endingPage "124474" @default.
• W2965658839 startingPage "124474" @default.
• W2965658839 abstract "The present study investigated the metabolism of the flame retardant and plasticizer chemical, triphenyl phosphate (TPHP), in a rat liver microsome-based in vitro assay with glutathione (GSH) in order to elucidate metabolic pathways leading to formation of conjugates. A highly sensitive and efficient method was developed for the detection and characterization of GSH reactive metabolites using LC-Q-TOF-MS/MS both in the negative and positive electrospray ionization modes. Seven GSH conjugates formed as a result of microsomal incubation, which were identified as S-conjugates based on MS/MS spectra, and confirmed by subsequent time-dependent incubation assays. With the exception of hydrolysis reactions leading to formation of a diester metabolite, diphenyl phosphate (DPHP), the results demonstrated that Phase I epoxidation on phenyl ring of TPHP leading to mono- and di-hydroxylated TPHP metabolites, which can further conjugate with GSH. Depending on hydroxylated TPHP formation, an o-hydroquinone intermediate formed in vitro via Phase I metabolism, and the o-benzoquinone form reacted with GSH and also formed GSH conjugates. The present study showed that via hydroxylated TPHP Phase I formation that GSH conjugates are important Phase II metabolites for TPHP metabolism in vitro. Some GSH conjugates may be valuable candidate biomarkers for monitoring TPHP exposure in biota." @default.
• W2965658839 created "2019-08-13" @default.
• W2965658839 creator A5028326798 @default.
• W2965658839 creator A5066265469 @default.
• W2965658839 date "2019-12-01" @default.
• W2965658839 modified "2023-09-27" @default.
• W2965658839 title "In vitro metabolic activation of triphenyl phosphate leading to the formation of glutathione conjugates by rat liver microsomes" @default.
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• W2965658839 doi "https://doi.org/10.1016/j.chemosphere.2019.124474" @default.
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