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Article ; Online: A PBPK model to evaluate zebrafish eleutheroembryos’ actual exposure: bisphenol A and analogs’ (AF, F, and S) case studies [Correction: Jan. 2023, 30(3), p. 7654]

Billat, Pierre-André / Brochot, Céline / Brion, François / Beaudouin, Rémy

Environ Sci Pollut Res. 2023 Jan., v. 30, no. 3, p. 7640-7653

2023 , Page(s) 7640–7653

Abstract: The zebrafish eleutheroembryo model is increasingly used to assess the toxicity and developmental adverse effects of xenobiotics. However, the actual exposure is seldom measured (poorly accessible), while a predictive model could estimate these ... ...

Abstract	The zebrafish eleutheroembryo model is increasingly used to assess the toxicity and developmental adverse effects of xenobiotics. However, the actual exposure is seldom measured (poorly accessible), while a predictive model could estimate these concentrations. The predictions with a new eleutheroembryo physiologically based pharmacokinetic (PBPK) model have been evaluated using datasets obtained from literature data for several bisphenols. The model simulated the toxicokinetics of bisphenols A (BPA), AF, F, and S through the eleutheroembryo tissues while considering the body and organ growth. We further improved the predictions by adding dynamic flows through the embryo and/or its chorion, impact of experimental temperature, metabolic clearance, and saturation of the absorption by Bayesian calibration. The model structure was determined using the BPA dataset and generalized to the other bisphenols. This model revealed the central role of the chorion in the compound uptake in the first 48 h post-fertilization. The predictions for the BPA substitutes estimated by our PBPK model were compared to available toxicokinetics data for zebrafish embryos, and 63% and 88% of them were within a twofold and fivefold error intervals of the corresponding experimental values, respectively. This model provides a tool to design new eleutheroembryo assays and evaluate the actual exposure.
Keywords	Bayesian theory ; Danio rerio ; absorption ; bisphenol A ; chorion ; data collection ; models ; pharmacokinetics ; temperature ; toxicity ; xenobiotics
Language	English
Dates of publication	2023-01
Size	p. 7640-7653
Publishing place	Springer Berlin Heidelberg
Document type	Article ; Online
ZDB-ID	1178791-0
ISSN	1614-7499 ; 0944-1344
ISSN (online)	1614-7499
ISSN	0944-1344
DOI	10.1007/s11356-022-22741-2
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Correction to: A PBPK model to evaluate zebrafish eleutheroembryos' actual exposure: bisphenol A and analogs' (AF, F, and S) case studies.

Billat, Pierre-André / Brochot, Céline / Brion, François / Beaudouin, Rémy

Environmental science and pollution research international

2022 Volume 30, Issue 3, Page(s) 7654

Language	English
Publishing date	2022-09-09
Publishing country	Germany
Document type	Published Erratum
ZDB-ID	1178791-0
ISSN	1614-7499 ; 0944-1344
ISSN (online)	1614-7499
ISSN	0944-1344
DOI	10.1007/s11356-022-22994-x
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Article ; Online: A PBPK model to evaluate zebrafish eleutheroembryos' actual exposure: bisphenol A and analogs' (AF, F, and S) case studies.

Billat, Pierre-André / Brochot, Céline / Brion, François / Beaudouin, Rémy

Environmental science and pollution research international

2022 Volume 30, Issue 3, Page(s) 7640–7653

Abstract	The zebrafish eleutheroembryo model is increasingly used to assess the toxicity and developmental adverse effects of xenobiotics. However, the actual exposure is seldom measured (poorly accessible), while a predictive model could estimate these concentrations. The predictions with a new eleutheroembryo physiologically based pharmacokinetic (PBPK) model have been evaluated using datasets obtained from literature data for several bisphenols. The model simulated the toxicokinetics of bisphenols A (BPA), AF, F, and S through the eleutheroembryo tissues while considering the body and organ growth. We further improved the predictions by adding dynamic flows through the embryo and/or its chorion, impact of experimental temperature, metabolic clearance, and saturation of the absorption by Bayesian calibration. The model structure was determined using the BPA dataset and generalized to the other bisphenols. This model revealed the central role of the chorion in the compound uptake in the first 48 h post-fertilization. The predictions for the BPA substitutes estimated by our PBPK model were compared to available toxicokinetics data for zebrafish embryos, and 63% and 88% of them were within a twofold and fivefold error intervals of the corresponding experimental values, respectively. This model provides a tool to design new eleutheroembryo assays and evaluate the actual exposure.
MeSH term(s)	Animals ; Zebrafish/metabolism ; Bayes Theorem ; Benzhydryl Compounds/toxicity ; Benzhydryl Compounds/metabolism ; Phenols/toxicity ; Phenols/metabolism
Chemical Substances	bisphenol A (MLT3645I99) ; Benzhydryl Compounds ; Phenols
Language	English
Publishing date	2022-08-31
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1178791-0
ISSN	1614-7499 ; 0944-1344
ISSN (online)	1614-7499
ISSN	0944-1344
DOI	10.1007/s11356-022-22741-2
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Embryonic exposures to chemicals acting on brain aromatase lead to different locomotor effects in zebrafish larvae.

Blanc-Legendre, Mélanie / Sire, Sacha / Christophe, Armelle / Brion, François / Bégout, Marie-Laure / Cousin, Xavier

Environmental toxicology and pharmacology

2023 Volume 102, Page(s) 104221

Abstract: Pathways underlying neurodevelopmental effects of endocrine disruptors (EDs) remain poorly known. Expression of brain aromatase (aroB), responsible for estrogen production in the brain of teleosts, is regulated by estrogenic EDs and could play a role in ... ...

Abstract	Pathways underlying neurodevelopmental effects of endocrine disruptors (EDs) remain poorly known. Expression of brain aromatase (aroB), responsible for estrogen production in the brain of teleosts, is regulated by estrogenic EDs and could play a role in their behavioral effects. We exposed zebrafish eleutheroembryos (0-120 h post-fertilization) to various concentrations of 16 estrogenic chemicals (incl. bisphenols and contraceptives), and of 2 aroB inhibitors. Behavior was monitored using a photomotor response test procedure. Both aroB inhibitors (clotrimazole and prochloraz) and a total of 6 estrogenic EDs induced significant behavioral alterations, including DM-BPA, BPC and BPS-MPE, three bisphenol substitutes which behavioral effects were, to our knowledge, previously unknown. However, no consensus was reported on the effects among tested substances. It appears that behavioral changes could not be linked to groups of substances defined by their specificity or potency to modulate aroB expression, or by their structure. Altogether, behavioral effects of estrogenic EDs in 120 h post-fertilization larvae appear unrelated to aroB but are nonetheless not to be neglected in the context of environmental safety.
MeSH term(s)	Animals ; Zebrafish/metabolism ; Aromatase/metabolism ; Larva/metabolism ; Estrogens/pharmacology ; Brain ; Benzhydryl Compounds/toxicity ; Endocrine Disruptors/metabolism
Chemical Substances	Aromatase (EC 1.14.14.1) ; Estrogens ; Benzhydryl Compounds ; Endocrine Disruptors
Language	English
Publishing date	2023-07-13
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1318302-3
ISSN	1872-7077 ; 1382-6689
ISSN (online)	1872-7077
ISSN	1382-6689
DOI	10.1016/j.etap.2023.104221
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Article ; Online: Interlaboratory prevalidation of a new in vitro transcriptional activation assay for the screening of (anti-)androgenic activity of chemicals using the UALH-hAR cell line.

Garoche, Clémentine / Grimaldi, Marina / Michelin, Erwan / Boulahtouf, Abdelhay / Marconi, Anthony / Brion, François / Balaguer, Patrick / Aït-Aïssa, Selim

Toxicology in vitro : an international journal published in association with BIBRA

2023 Volume 88, Page(s) 105554

Abstract: We report an interlaboratory evaluation of a recently developed androgen receptor (AR) transactivation assay using the UALH-hAR reporter cell line that stably expresses the luciferase gene under the transcriptional control of androgen receptor elements ( ... ...

Abstract	We report an interlaboratory evaluation of a recently developed androgen receptor (AR) transactivation assay using the UALH-hAR reporter cell line that stably expresses the luciferase gene under the transcriptional control of androgen receptor elements (AREs) with no glucocorticoid receptor (GR) crosstalk. Herein, a two-step prevalidation study involving three laboratories was conducted to assess performance criteria of the method such as transferability as well as robustness, sensitivity, and specificity. The first step consisted in the validation of the transfer of the cell line to participant laboratories through the testing of three reference chemicals: the AR agonist dihydrotestosterone, the AR antagonist hydroxyflutamide and the glucocorticoid dexamethasone. Secondly, a blinded study was conducted by screening a selection of ten chemicals, including four AR agonists, five AR antagonists, and one non-active chemical. All test compounds yielded the same activity profiles in all laboratories. The logEC
MeSH term(s)	Humans ; Androgen Antagonists/pharmacology ; Androgen Receptor Antagonists/pharmacology ; Androgens ; Cell Line ; Receptors, Androgen/genetics ; Receptors, Androgen/metabolism ; Reproducibility of Results ; Transcriptional Activation ; Drug Evaluation, Preclinical
Chemical Substances	Androgen Antagonists ; Androgen Receptor Antagonists ; Androgens ; Receptors, Androgen
Language	English
Publishing date	2023-01-11
Publishing country	England
Document type	Journal Article
ZDB-ID	639064-x
ISSN	1879-3177 ; 0887-2333
ISSN (online)	1879-3177
ISSN	0887-2333
DOI	10.1016/j.tiv.2023.105554
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Zs.A 2223: Show issues

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Article ; Online: PBTK modeled perfluoroalkyl acid kinetics in zebrafish eleutheroembryos suggests impacts on bioconcentrations by chorion porosity dynamics.

Billat, Pierre-André / Vogs, Carolina / Blassiau, Clément / Brochot, Céline / Wincent, Emma / Brion, François / Beaudouin, Rémy

Toxicology in vitro : an international journal published in association with BIBRA

2023 Volume 89, Page(s) 105588

Abstract: The zebrafish eleutheroembryo (zfe) is widely used as a model to characterize the toxicity of chemicals. However, analytical methods are still missing to measure organ concentrations. Therefore, physiologically-based toxicokinetic (PBTK) modeling may ... ...

Abstract	The zebrafish eleutheroembryo (zfe) is widely used as a model to characterize the toxicity of chemicals. However, analytical methods are still missing to measure organ concentrations. Therefore, physiologically-based toxicokinetic (PBTK) modeling may overcome current limitations to help understand the relationship between toxic effects and internal exposure in various organs. A previous PBTK model has been updated to include the chorionic transport barrier and its permeabilization, hatching dynamics within a zfe population over development, and active mediated transport mechanisms. The zfe PBTK model has been calibrated using measured time-dependent internal concentrations of PFBA, PFHxS, PFOA, and PFOS in a zfe population and evaluated using external datasets from the literature. Calibration was successful with 96% of the predictions falling within a 2-fold range of the observed concentrations. The external dataset was correctly estimated with about 50% of the predictions falling within a factor of 3 of the observed data and 10% of the predictions are out of the 10-fold error. The calibrated model suggested that active mediated transport differs between PFAS with a sulfonic and carboxylic acid functional end groups. This PBTK model predicts well the fate of PFAS with various physicochemical properties in zfe. Therefore, this model may improve the use of zfe as an alternative model in toxicokinetic-toxicodynamic studies and help to refine and reduce zfe-based experiments, while giving insights into the internal kinetics of chemicals.
MeSH term(s)	Animals ; Zebrafish ; Bioaccumulation ; Kinetics ; Porosity ; Fluorocarbons/toxicity
Chemical Substances	Fluorocarbons
Language	English
Publishing date	2023-03-21
Publishing country	England
Document type	Journal Article
ZDB-ID	639064-x
ISSN	1879-3177 ; 0887-2333
ISSN (online)	1879-3177
ISSN	0887-2333
DOI	10.1016/j.tiv.2023.105588
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Article: A comparison of behavioral and reproductive parameters between wild-type, transgenic and mutant zebrafish: Could they all be considered the same “zebrafish” for reglementary assays on endocrine disruption?

De Oliveira, Julie / Chadili, Edith / Turies, Cyril / Brion, François / Cousin, Xavier / Hinfray, Nathalie

Comparative biochemistry and physiology. 2021 Jan., v. 239

2021

Abstract: Transgenic zebrafish models are efficiently used to study the effects of endocrine disrupting chemicals (EDC); thereby informing on their mechanisms of action. However, given the reported differences between zebrafish strains at the genetical, ... ...

Abstract	Transgenic zebrafish models are efficiently used to study the effects of endocrine disrupting chemicals (EDC); thereby informing on their mechanisms of action. However, given the reported differences between zebrafish strains at the genetical, physiological and behavioral levels; care should be taken before using these transgenic models for EDC testing. In the present study, we undertook a set of experiments in different transgenic and/or mutant zebrafish strains of interest for EDC testing: casper, cyp19a1a-eGFP, cyp19a1a-eGFP-casper, cyp11c1-eGFP, cyp11c1-eGFP-casper. Some behavioral traits, and some biochemical and reproductive physiological endpoints commonly used in EDC testing were assessed and compared to those obtained in WT AB zebrafish to ensure that transgene insertion and/or mutations do not negatively modify basal reproductive physiology or behavior of the fish.Behavioral traits considered as anxiety and sociality have been monitored. Sociality was evaluated by monitoring the time spent near congeners in a shuttle box while anxiety was evaluated using the Novel tank diving test. No critical difference was observed between strains for either sociality or anxiety level. Concerning reproduction, no significant difference in the number of eggs laid per female, in the viability of eggs or in the female circulating VTG concentrations was noted between the 5 transgenic/mutants and the WT AB zebrafish studied.In summary, the transgene insertion and the mutations had no influence on the endpoints measured in basal conditions. These results were a prerequisite to the use of these transgenic/mutant models for EDC testing. Next step will be to determine the sensitivity of these biological models to chemical exposure to accurately validate their use in existing fish assays for EDC testing.
Keywords	Danio rerio ; anxiety ; biochemistry ; females ; fish ; genetically modified organisms ; mutants ; reproduction ; social behavior ; transgenes ; viability
Language	English
Dates of publication	2021-01
Publishing place	Elsevier Inc.
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	189285-x
ISSN	0306-4492 ; 0742-8413 ; 1532-0456
ISSN	0306-4492 ; 0742-8413 ; 1532-0456
DOI	10.1016/j.cbpc.2020.108879
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: ReadEDTest: A tool to assess the readiness of in vitro test methods under development for identifying endocrine disruptors

Crouzet, Thibault / Grignard, Elise / Brion, François / Blanc, Etienne B. / Podechard, Normand / Langouet, Sophie / Alonso-Magdalena, Paloma / Hubert, Philippe / Kim, Min-ji / Audouze, Karine

Environment International. 2023 Apr., v. 174 p.107910-

2023

Abstract: Growing evidence shows that endocrine disruptors (EDs), known to affect the reproductive system, may also disturb other hormone-regulated functions leading to cancers, neurodevelopmental defects, metabolic and immune diseases. To reduce exposure to EDs ... ...

Abstract	Growing evidence shows that endocrine disruptors (EDs), known to affect the reproductive system, may also disturb other hormone-regulated functions leading to cancers, neurodevelopmental defects, metabolic and immune diseases. To reduce exposure to EDs and limit their health effects, development of screening and mechanism-based assays to identify EDs is encouraged. Nevertheless, the crucial validation step of test methods by regulatory bodies is a time- and resource-consuming process. One of the main raisons of this long duration process is that method developers, mainly researchers, are not fully aware of the regulatory needs to validate a test. We propose an online self-assessment questionnaire (SAQ) called ReadEDTest easy to be used by all researchers. The aim of ReadEDTest is to speed up the validation process by assessing readiness criteria of in vitro and fish embryo ED test methods under development. The SAQ is divided into 7 sections and 13 sub-sections containing essential information requested by the validating bodies. The readiness of the tests can be assessed by specific score limits for each sub-section. Results are displayed via a graphical representation to help identification of the sub-sections having sufficient or insufficient information. The relevance of the proposed innovative tool was supported using two test methods already validated by the OECD and four under development test methods.
Keywords	environment ; fish ; questionnaires ; reproductive system ; Endocrine disrupting chemicals ; Zebrafish embryo ; OBERON ; Pepper ; Validation process ; IATA ; OECD
Language	English
Dates of publication	2023-04
Publishing place	Elsevier Ltd
Document type	Article ; Online
ZDB-ID	554791-x
ISSN	1873-6750 ; 0160-4120
ISSN (online)	1873-6750
ISSN	0160-4120
DOI	10.1016/j.envint.2023.107910
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Zs.A 3131: Show issues

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Article: Hypericum lanceolatum

Gence, Laura / Fernezelian, Danielle / Bringart, Matthieu / Veeren, Bryan / Christophe, Armelle / Brion, François / Meilhac, Olivier / Bascands, Jean-Loup / Diotel, Nicolas

Frontiers in pharmacology

2022 Volume 13, Page(s) 832928

Abstract: Hypericum ... ...

Abstract	Hypericum lanceolatum
Language	English
Publishing date	2022-03-11
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2022.832928
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Article: A comparison of behavioral and reproductive parameters between wild-type, transgenic and mutant zebrafish: Could they all be considered the same "zebrafish" for reglementary assays on endocrine disruption?

De Oliveira, Julie / Chadili, Edith / Turies, Cyril / Brion, François / Cousin, Xavier / Hinfray, Nathalie

Comparative biochemistry and physiology. Toxicology & pharmacology : CBP

2020 Volume 239, Page(s) 108879

Abstract	Transgenic zebrafish models are efficiently used to study the effects of endocrine disrupting chemicals (EDC); thereby informing on their mechanisms of action. However, given the reported differences between zebrafish strains at the genetical, physiological and behavioral levels; care should be taken before using these transgenic models for EDC testing. In the present study, we undertook a set of experiments in different transgenic and/or mutant zebrafish strains of interest for EDC testing: casper, cyp19a1a-eGFP, cyp19a1a-eGFP-casper, cyp11c1-eGFP, cyp11c1-eGFP-casper. Some behavioral traits, and some biochemical and reproductive physiological endpoints commonly used in EDC testing were assessed and compared to those obtained in WT AB zebrafish to ensure that transgene insertion and/or mutations do not negatively modify basal reproductive physiology or behavior of the fish. Behavioral traits considered as anxiety and sociality have been monitored. Sociality was evaluated by monitoring the time spent near congeners in a shuttle box while anxiety was evaluated using the Novel tank diving test. No critical difference was observed between strains for either sociality or anxiety level. Concerning reproduction, no significant difference in the number of eggs laid per female, in the viability of eggs or in the female circulating VTG concentrations was noted between the 5 transgenic/mutants and the WT AB zebrafish studied. In summary, the transgene insertion and the mutations had no influence on the endpoints measured in basal conditions. These results were a prerequisite to the use of these transgenic/mutant models for EDC testing. Next step will be to determine the sensitivity of these biological models to chemical exposure to accurately validate their use in existing fish assays for EDC testing.
MeSH term(s)	Animals ; Animals, Genetically Modified/physiology ; Animals, Wild/physiology ; Endocrine Disruptors/pharmacology ; Female ; Male ; Models, Animal ; Reproduction/drug effects ; Zebrafish/genetics ; Zebrafish/physiology
Chemical Substances	Endocrine Disruptors
Language	English
Publishing date	2020-08-30
Publishing country	United States
Document type	Comparative Study ; Journal Article
ZDB-ID	189285-x
ISSN	1532-0456 ; 0306-4492 ; 0742-8413
ISSN	1532-0456 ; 0306-4492 ; 0742-8413
DOI	10.1016/j.cbpc.2020.108879
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