Hepatic metabolism of chlorinated derivatives of bisphenol A (ClxBPA) and interspecies differences between rats and humans

Plattard, N.; Venisse, Nicolas; Carato, Pascal; Dupuis, Antoine; Haddad, Sami

doi:10.1007/s00204-021-03217-7

Cited by 4 publications

(6 citation statements)

References 40 publications

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“…Interspecies differences and variable routes of administration may explain these different metabolic patterns. Interestingly, similar relative abundances of 3,3′-Cl 2 BPA-G over 3,3′-Cl 2 BPA-S were found in vitro after incubation with rat and human hepatocytes, 35 suggesting that there were no major interspecies differences in hepatic metabolism.…”

Section: Discussionmentioning

confidence: 78%

“…Nevertheless, these conjugated metabolites have already been identified in vitro in the incubation medium of rat and human hepatocyte suspensions. 35…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, these conjugated metabolites have already been identified in vitro in the incubation medium of rat and human hepatocyte suspensions. 35 The concentrations of 3,3 0 -Cl 2 BPA-G and 3,3 0 -Cl 2 BPA-S in human and rat plasma were measured at 2…”

Section: Discussionmentioning

confidence: 99%

“…28 Toxicokinetics are a major component of the risk assessment of environmental pollutants, contributing to the identification of the main routes of absorption, distribution to target organs, and elimination pathways. The toxicokinetics of ClxBPA remain mostly unknown, but a recent article by Plattard et al (2022) reported the metabolic constants of Cl x BPA (Vmax, Km, and intrinsic clearance). Moreover, phase II metabolites (glucuronide and sulfate) of Cl 2 BPA were identified by UHPLC-MS/MS.…”

Section: Introductionmentioning

confidence: 99%

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Quantification of the Conjugated Forms of Dichlorobisphenol A (3,3′-Cl2BPA) in Rat and Human Plasma Using HPLC-MS/MS

Plattard

Gnanasegaran

Krekesheva

et al. 2023

Therapeutic Drug Monitoring

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Background: Bisphenol A (BPA) is a ubiquitous contaminant that has endocrine-disrupting effects. Chlorinated derivatives of BPA are formed during chlorination of drinking water and have higher endocrine-disrupting activity. Dichlorobisphenol A (Cl 2 BPA) is the most abundant chlorinated BPA derivative found in several human biological matrices. Recent in vitro experiments have shown that Cl 2 BPA is metabolized in sulpho-and glucuro-conjugated compounds. To date, no assay has been developed to quantify the sulfoand glucuro-conjugates of 3,3 0 -Cl 2 BPA (3,3 0 -Cl 2 BPA-S and 3,3 0 -Cl 2 BPA-G, respectively).Methods: A high-performance liquid chromatography-tandem mass spectrometry assay for the determination of 3,3 0 -Cl 2 BPA conjugated forms in plasma samples was developed and validated according to the European Medicines Agency guidelines. Quantification was performed in the multiple reaction monitoring mode for all target analytes using a SCIEX 6500 + tandem mass spectrometer with an electrospray source operating in the negative ionization mode. Chromatographic separation was achieved using a C18 column maintained at 408C and a binary mobile phase delivered in the gradient mode at a flow rate of 0.35 mL/min. Sample was prepared via simple precipitation using acetonitrile. The assay was validated and applied to rat and human plasma samples.Results: Linearity was demonstrated over the range of 0.006-25 ng/mL for 3,3 0 -Cl 2 BPA-G and 0.391-100 ng/mL for 3,3 0 -Cl 2 BPA-S. Intraday and interday bias values were in the 95%-109% range, and the imprecision ,9%. Internal standard corrected matrix effects were also investigated. This method enabled quantification of the conjugated forms of 3,3 0 -Cl 2 BPA in plasma samples.Conclusions: This is the first report on the development and validation of an analytical method for the quantification of 3,3 0 -Cl 2 BPA-G and 3,3 0 -Cl 2 BPA-S in the plasma matrix. This study is also the first report on the in vivo occurrence of these metabolites.

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Section: Discussionmentioning

confidence: 78%

“…Nevertheless, these conjugated metabolites have already been identified in vitro in the incubation medium of rat and human hepatocyte suspensions. 35…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Quantification of the Conjugated Forms of Dichlorobisphenol A (3,3′-Cl2BPA) in Rat and Human Plasma Using HPLC-MS/MS

Plattard

Gnanasegaran

Krekesheva

et al. 2023

Therapeutic Drug Monitoring

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“…Evaluating the metabolism of xenobiotics through in vitro systems is critical for characterizing toxicokinetics; however, determining the formation of metabolites is equally important, especially when extrapolating results to in vivo predictions. Traditional methods to assess in vitro metabolite formation involve targeted analytical methods [ 26 , 27 , 28 ]. However, targeted analyses may not detect the presence of metabolites due to sensitivity issues.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Metabolism of a Defined Pesticide Mixture through Multiple In Vitro Liver Models

Valdiviezo

Kato

Baker

et al. 2022

Toxics

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The evaluation of exposure to multiple contaminants in a mixture presents a number of challenges. For example, the characterization of chemical metabolism in a mixture setting remains a research area with critical knowledge gaps. Studies of chemical metabolism typically utilize suspension cultures of primary human hepatocytes; however, this model is not suitable for studies of more extended exposures and donor-to-donor variability in a metabolic capacity is unavoidable. To address this issue, we utilized several in vitro models based on human-induced pluripotent stem cell (iPSC)-derived hepatocytes (iHep) to characterize the metabolism of an equimolar (1 or 5 µM) mixture of 20 pesticides. We used iHep suspensions and 2D sandwich cultures, and a microphysiological system OrganoPlate® 2-lane 96 (MimetasTM) that also included endothelial cells and THP-1 cell-derived macrophages. When cell culture media were evaluated using gas and liquid chromatography coupled to tandem mass spectrometry methods, we found that the parent molecule concentrations diminished, consistent with metabolic activity. This effect was most pronounced in iHep suspensions with a 1 µM mixture, and was lowest in OrganoPlate® 2-lane 96 for both mixtures. Additionally, we used ion mobility spectrometry–mass spectrometry (IMS-MS) to screen for metabolite formation in these cultures. These analyses revealed the presence of five primary metabolites that allowed for a more comprehensive evaluation of chemical metabolism in vitro. These findings suggest that iHep-based suspension assays maintain higher metabolic activity compared to 2D sandwich and OrganoPlate® 2-lane 96 model. Moreover, this study illustrates that IMS-MS can characterize in vitro metabolite formation following exposure to mixtures of environmental contaminants.

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Hepatic glucuronidation of tetrabromobisphenol A and tetrachlorobisphenol A: interspecies differences in humans and laboratory animals and responsible UDP-glucuronosyltransferase isoforms in humans

Hanioka,

Isobe,

Saito

et al. 2024

Arch Toxicol

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Hepatic metabolism of chlorinated derivatives of bisphenol A (ClxBPA) and interspecies differences between rats and humans

Cited by 4 publications

References 40 publications

Quantification of the Conjugated Forms of Dichlorobisphenol A (3,3′-Cl2BPA) in Rat and Human Plasma Using HPLC-MS/MS

Quantification of the Conjugated Forms of Dichlorobisphenol A (3,3′-Cl2BPA) in Rat and Human Plasma Using HPLC-MS/MS

Evaluation of Metabolism of a Defined Pesticide Mixture through Multiple In Vitro Liver Models

Hepatic glucuronidation of tetrabromobisphenol A and tetrachlorobisphenol A: interspecies differences in humans and laboratory animals and responsible UDP-glucuronosyltransferase isoforms in humans

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