Metabolism of phosphoric acid triesters by rat liver homogenate

Sasaki, Kumiko; Suzuki, Takashi; Takeda, Masayuki; Uchiyama, Mitsuru

doi:10.1007/bf01625544

Cited by 90 publications

(85 citation statements)

References 3 publications

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“…This is not surprising as TPHP was shown to be readily metabolized by rat and human liver microsomes (Van den Eede et al, 2013a;Sasaki et al, 1984). These compounds were also not detected in any of the serum samples tested above MDL levels (<5.4 ng/mL), although serum analysis was limited by low volumes ($250 ll).…”

Section: Organophosphate Componentsmentioning

confidence: 92%

Editor’s Highlight: Transplacental and Lactational Transfer of Firemaster® 550 Components in Dosed Wistar Rats

Phillips¹,

Chen²,

Rock³

et al. 2016

Toxicol. Sci.

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FiremasterV R 550 (FM 550) is a commercial mixture of organophosphate and brominated flame retardants currently in use as a replacement for pentaBDE. Its organophosphate components include triphenyl phosphate (TPHP) and a suite of isopropylated triarylphosphate isomers (ITPs); its brominated components include 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EH-TBB) and bis (2-ethylhexyl)-2,3,4,5-tetrabromophthalate (BEH-TEBP). Taken together, these chemicals have been shown to be endocrine disrupting and potentially toxic, and human exposure to them is widespread. In this study, maternal transfer of FM 550 components, and in some cases their metabolites, was investigated in dosed Wistar rats. Gestational and lactational transfer were examined separately, with dams orally exposed to 300 or 1000 mg of FM 550 for 10 consecutive days during gestation (gestational day [GD] 9-18) or lactation (postnatal day [PND] 3-12). Levels of parent compounds were measured in fetus and whole pup tissue homogenates, and in dam and pup serum, and several metabolites were measured in dam and pup urine. EH-TBB body burdens resulting from lactational transfer were approximately 200-to 300-fold higher than those resulting from placental transfer, whereas low levels of BEH-TEBP were transferred during both lactation and gestation. TPHP and ITPs were rapidly metabolized by the dams and were not detected in whole tissue homogenates. However, diphenyl phosphate (DPHP) and mono-isopropylphenyl phenyl phosphate (ip-PPP) were detected in urine from the dosed animals. This study is the first to confirm ip-PPP as a urinary metabolite of ITPs and establish a pharmacokinetic profile of FM 550 in a mammalian model.

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Section: Organophosphate Componentsmentioning

confidence: 92%

Editor’s Highlight: Transplacental and Lactational Transfer of Firemaster® 550 Components in Dosed Wistar Rats

Phillips¹,

Chen²,

Rock³

et al. 2016

Toxicol. Sci.

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show abstract

“…Nomeir et al (1981) identified a glutathione-conjugated TDCIPP as a Phase-II metabolite in rat livers in vitro. TCEP can also metabolize to bis (2-chloroethyl) hydrogen phosphate (BCEP), bis (2-chloroethyl) carboxymethyl phosphate and glucuronide of bis (2-chloroethyl) 2-hydroxyethyl phosphate in rats (Burka et al, 1991;Sasaki et al, 1984).…”

Section: Chlorinated Opfrsmentioning

confidence: 99%

“…Although CYPs appear to be the main family of enzymes responsible for the formation of Phase-I metabolites, some hydrolysed metabolites may be catalyzed by NADPH independent liver microsomal phosphatase enzymes, such as, for example, paraoxonases and aryl esterases (Van den Eede et al, 2013a). However, the role of CYPs is likely to be more significant than that of the hydrolases in the these processes, such as O-dealkylationhase-II reactions via the hydroxylation metabolic pathway (Chapman et al, 1991;Sasaki et al, 1984;Van den Eede et al, 2013a). In Phase-II reactions, the conjugating enzymes consist of many superfamilies of enzymes, including glucuronyl transferases (UGTs), sulfotransferases (SULTs) and gluathione S-transferases (GSTs) (Van den Eede et al, 2013a).…”

Section: Enzymes In Metabolismmentioning

confidence: 99%

Review of OPFRs in animals and humans: Absorption, bioaccumulation, metabolism, and internal exposure research

2016

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h i g h l i g h t sThe absorption, bioaccumulation, metabolism and internal exposure of OPFRs are reviewed. Inhalation, ingestion and dermal contact are the main OPFRs absorptionpathways for humans. General in vivo and in vitro metabolic pathways of three different types of OPFRs are proposed. DAPs and MAPs are considered as putative biomarkers for the assessment of internal exposure of OPFRs in humans. a r t i c l e i n f o t r a c tDue to their widespread use, organophosphate flame retardants (OPFRs) are commonly detected in various environmental matrices and have been identified as emerging contaminants. Considering the adverse effects of OPFRs, many researchers have paid their attention on the absorption, bioaccumulation, metabolism and internal exposure processes of OPFRs in animals and humans. In this article, we first review the diverse absorption routes of OPFRs by animals and humans (e.g., inhalation, ingestion, dermal absorption and gill absorption). Bioaccumulation and biomagnification potentials of OPFRs in different types of organisms and food webs are also summarized, based on quite limited available data and results. For metabolism, we review the Phase-I and Phase-II metabolic processes for each type of OPFRs (chlorinated OPFRs, alkyl-OPFRs and aryl-OPFRs) in the animals and humans, as well as toxicokinetic information and putative exposure biomarkers on OPFRs. Finally, we highlight gaps in our knowledge and critical directions for future internal exposure studies of OPFRs in animals and humans.

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“…The organophosphorus triesters are hydrolysed in blood and urine spontaneously or enzymatically by ␣-esterases and phosphorylphosphatases [25]. Hence the main metabolites of the trialkyl-and triarylphosphates in animal experiments and in in vitro studies are the corresponding dialkyl-and diarylphosphates [26][27][28]. Fig.…”

Section: Introductionmentioning

confidence: 99%

Determination of human urinary organophosphate flame retardant metabolites by solid-phase extraction and gas chromatography–tandem mass spectrometry

Schindler

Förster

Angerer

2009

Journal of Chromatography B

112

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Metabolism of phosphoric acid triesters by rat liver homogenate

Cited by 90 publications

References 3 publications

Editor’s Highlight: Transplacental and Lactational Transfer of Firemaster® 550 Components in Dosed Wistar Rats

Editor’s Highlight: Transplacental and Lactational Transfer of Firemaster® 550 Components in Dosed Wistar Rats

Review of OPFRs in animals and humans: Absorption, bioaccumulation, metabolism, and internal exposure research

Determination of human urinary organophosphate flame retardant metabolites by solid-phase extraction and gas chromatography–tandem mass spectrometry

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