Environmentally relevant organophosphate triesters in herring gulls: In vitro biotransformation and kinetics and diester metabolite formation using a hepatic microsomal assay

Greaves, Alana K.; Su, Guanyong; Letcher, Robert J.

doi:10.1016/j.taap.2016.08.007

Cited by 97 publications

(77 citation statements)

References 23 publications

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“…Hallanger et al, 2015). The in vitro metabolism of these same six OPEs were reported in a herring gull bird model system (Greaves et al, 2016b) and thus a comparison between the present Arctic mammals and that of a bird model system was possible. Finally, we have robust and validated analytical methods for the determination of these six OPE (triesters) as well as their OP diester metabolites (Chu and Letcher, 2015;Letcher et al, 2018).…”

Section: In Vitro Op Triester Metabolism and Op Diester Formationmentioning

confidence: 77%

“…OPEs have been shown to be degraded through abiotic processes such as pHdependent hydrolysis as well as biotic processes such as enzymatic metabolism (Greaves et al, 2016b;Su et al, 2016b). Abiotic degradation should lead to consideration of effective controls in experiments to determine the contribution of enzymatic metabolism.…”

Section: Ope Metabolismmentioning

confidence: 99%

“…Polar bear and ringed seal liver tissue was processed into microsomal suspensions following procedures published previously (Greaves et al, 2016b; Figure 2-2). Briefly, liver tissue was thawed on ice, and the microsomes were prepared for each individual by homogenization and centrifugation using previously cooled microcentrifuge tubes and a Beckman TLA 100.4 rotor.…”

Section: Liver Microsome Preparation and Poolingmentioning

confidence: 99%

“…The in vitro metabolism biotransformation assay for OP triesters was conducted according to previously published methods for rat and herring gull liver microsomes (Chu et al, 2011;Chu and Letcher, 2015;Greaves et al, 2016b). Briefly, liver microsomes and NADPH regenerating solutions were thawed slowly on ice and the dosing OP triester solution (see These aliquots were placed in a methanol quenching solution containing internal standard mixture (25 ppb).…”

Section: In Vitro Metabolism Assay For Op Triester Depletion and Op Dmentioning

confidence: 99%

“…Therefore, this thesis project aims to provide degradation, respective metabolite formation, and internal fate data in the representative Arctic wildlife predator-prey relationship between polar bear and ringed seal. OPE metabolic rate was determined utilizing the established ultra-high performance liquid chromatography-electrospray ionization (+) triple quadrupole mass spectrometry (UPLC-ESI(+)-QQQ-MS/MS) method (Chu et al, 2011) along with some modifications (Greaves et al, 2016b).…”

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confidence: 99%

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Fate of organophosphate esters (OPEs) in East Greenland polar bears and their ringed seal prey using in vitro lab- and field-based studies to investigate metabolism

Strobel¹

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Arctic wildlife can be exposed to environmental chemical contamination due to longrange transport and subsequent deposition. Organophosphate esters (OPEs) are emerging chemicals of concern, found at high concentration in Arctic abiota but low levels in biota, including in polar bear and ringed seal adipose tissue currently under study. OPE metabolism was investigated in East Greenland polar bears and ringed seals using enzymatically-active liver microsomes. Organophosphate triester metabolism rate and extent were found to be greater in polar bears than ringed seals. Chemical structure and physical properties of OPEs affected metabolism; notably, bulkier, alkyl-substituted triphenyl phosphates had decreased metabolism in both species. The degradation of OPEs with aryl and alkyl substituents occurred at a greater rates in polar bears and ringed seals respectively. The structure-dependent metabolism of eleven OPEs have important implications for regulatory and risk assessments, as some compounds have little to no toxicokinetics data available in the current literature.

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Section: In Vitro Op Triester Metabolism and Op Diester Formationmentioning

confidence: 77%

Section: Ope Metabolismmentioning

confidence: 99%

Section: Liver Microsome Preparation and Poolingmentioning

confidence: 99%

Section: In Vitro Metabolism Assay For Op Triester Depletion and Op Dmentioning

confidence: 99%

mentioning

confidence: 99%

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Fate of organophosphate esters (OPEs) in East Greenland polar bears and their ringed seal prey using in vitro lab- and field-based studies to investigate metabolism

Strobel¹

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Uptake, Deposition, and Metabolism of Triphenyl Phosphate in Embryonated Eggs and Chicks of Japanese Quail (Coturnix japonica)

Marteinson

Guigueno

Fernie

et al. 2020

Enviro Toxic and Chemistry

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The toxicokinetics of triphenyl phosphate (TPHP) in vivo including the uptake, deposition, and biotransformation into the metabolite diphenyl phosphate (DPHP) is presently reported in embryonated eggs and chicks of Japanese quail. Quail were dosed with TPHP at 3 concentrations by air cell egg injection on embryonic day 0, followed by daily oral dosing after chicks hatched (5 d). Vehicle‐only exposed controls were also used. In dosed eggs, only 33% of the TPHP remained 2 d after injection (no hepatic development); after 10 d (post‐hepatogenesis), only 2% remained. The estimated TPHP half‐lives in the eggs ranged from 1.1 to 1.8 d for the 3 dosed groups. In all exposed eggs and chicks, DPHP significantly increased with dose (0.001 < p < 0.044). It appears that DPHP is an important metabolite in quail, making up 41 to 74% of all metabolites formed in embryonated eggs. In chicks, at medium and high doses, DPHP concentrations significantly exceeded those of TPHP (p ≤ 0.007), making up 67 and 76% of the total burden, respectively. Our findings suggest that rapid TPHP metabolism occurred in chicks and embryonated quail eggs but that this may vary with the age of the embryonated egg and the stage of embryo development, which should be considered when evaluating concentrations of TPHP and DPHP measured in eggs of wild birds. Environ Toxicol Chem 2020;39:565–573. © 2019 Her Majesty the Queen in Right of Canada. Environmental Toxicology and Chemistry © 2019 SETAC

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Determination of In Vivo Biotransformation Kinetics Using Early‐Time Biota Concentrations

Kuo

Toro

2021

Enviro Toxic and Chemistry

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Technical challenges have hampered the characterization of biotransformation kinetics-a critical link in understanding and predicting the toxicokinetics and ecotoxicology of organic compounds. A shortcut approach to characterize the in vivo biotransformation rate constant (k M ) with incomplete pathway or metabolite details was proposed. The value of k M can be derived as ( ), with f PC (t) being the molar equivalent fraction of the parent compound (PC) at an early time t in both constant exposure and decay source chemical uptake scenarios. The approximation-based k M values agreed well with k M values derived from rigorous fitting or toxicokinetic modeling (n = 42, root mean square error = 0.30) with accuracy exceeding those of typical toxicokinetic or partitioning models. The method is accurate when sampling time is adequately resolved (i.e., t < ln(2)/k M ) but will likely produce biased k M values with improper time-averaging. The approximate equation yields consistent theoretical expectations for fast and slow biotransformation reactions and is fully compatible with standard bioaccumulation and toxicity testing protocols. The simplification strategy circumvents statistical complications and numerical issues inherent in regressing or modeling the toxicokinetics of multimetabolite systems and may be adapted to similar problems at other physiological scales or ecotoxicological contexts. The method can help advance interspecies comparison of chemical metabolism and support the development of in vitro-in vivo extrapolations and in silico models needed for building next-generation ecological and health risk-assessment practices.

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Environmentally relevant organophosphate triesters in herring gulls: In vitro biotransformation and kinetics and diester metabolite formation using a hepatic microsomal assay

Cited by 97 publications

References 23 publications

Fate of organophosphate esters (OPEs) in East Greenland polar bears and their ringed seal prey using in vitro lab- and field-based studies to investigate metabolism

Fate of organophosphate esters (OPEs) in East Greenland polar bears and their ringed seal prey using in vitro lab- and field-based studies to investigate metabolism

Uptake, Deposition, and Metabolism of Triphenyl Phosphate in Embryonated Eggs and Chicks of Japanese Quail (Coturnix japonica)

Determination of In Vivo Biotransformation Kinetics Using Early‐Time Biota Concentrations

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