Assays for the identification of Thyroid Hormone axis-disrupting chemicals: Elaborating Novel Assessment strategies

Leistungen

Report on effects of thyroid hormone axis-disrupting chemicals on human-specific thyroid physiology including thyroidal stimulation by hCG

Report on the effects of thyroid hormone axis disruptingchemicals on humanspecific thyroid physiology including thyroidal stimulation by hCG We will detail the outcome of activities in Task 92

Policy briefing no 2 to the European Commission and JRC
Provisional list of identified transmembrane transporters in placenta, BBB and BCSFB

Provisional list of identified transmembrane transporters in placenta BBB and BCSFB prioritized as candidate proteins for new screening assays month 30 ERASMUS STICHTING VUVUA This will detail known transporters to be selected as candidate proteins for new screening assays

Qualitative AOP network of the thyroid hormone axis for adverse neurodevelopmental outcomes

Qualitative AOP network of the thyroid hormone axis for adverse neurodevelopmental outcomes This deliverable will describe the outcome of Task 101

Risk assessment procedure
Concept for interaction with other H2020 projects on EDC test method development

Concept for interaction with other H2020 projects on EDC test method development This will detail a series of activities with the other 7 projects funded under this call

Policy briefing no 1 to the European Commission and JRC

Policy briefing no 1 to the European Commission and JRC: These policy briefing will summarise relevant work in ATHENA, together with policy implications

Initial setup of DEHAL1 screening assay and pilot screen cellular membrane transporter with an EDC compound library

A stable cell line clone recombinantly overexpressing human DEHAL1 at sufficient activity levels required for implementation of the HTS will be used in the DEHAL1 enzyme activity test based on the nonradioactive SandellKolthoff reaction A specific DEHAL1 inhibitor will be used for quality control in assay development A small EDC compound library will be tested as a pilot screen for the cellular membrane transporter MCT8 in a 96 well format The aim is to identify potent MCT8 inhibitors

Analysis of commonalities and differences in screening, testing and hazard/risk assessment of substances covered by case studies

Analysis of commonalities and differences in screening testing and hazardrisk assessment of substances covered by case studies

Policy briefing no 3 to the European Commission and JRC
Pilot DEHAL1 screen with an EDC compound library and final HTS of cellular membrane transporter with large chemical libraries for small molecules

A small EDC compound library will be tested as a pilot screen DEHAL1 in a 96 well format The aim is to identify potent DEHAL1 inhibitors The final HTS MCT8 of the cellular membrane transporter MCT8 with large libraries for small molecules in the 384 well format will be implemented together with subcontractor FMP We expect completion of this final MCT8 T3 transporter HTS by month 45 and expect identification of new potent and specific MCT8 inhibitors Curated data of the completed final MCT8 T3 transport HTS will be transferred to our WP2 partners for development of QSAR models by month 45

Document inventory of screening and testing activities specifically for thyroid hormone axis-disrupting chemicals, including priority setting principles and risk assessments

Document inventory of screening and testing activities specifically for thyroid hormone axisdisrupting chemicals including priority setting principles and risk assessments and overview summary of the document inventory D 111

Identification of thyroid hormone axis-disrupting chemicals for which consequences on gestational thyroid function are influenced by iodine status

Identification of thyroid hormone axisdisrupting chemicals for which consequences on gestational thyroid function are influenced by iodine status This deliverable will describe the outcome of Task 93

Preliminary plan for exploitation and dissemination

Release of a preliminary plan for exploitation and dissemination

Report on cellular and molecular data on consequences of the interactions between iodine deficiency and thyroid hormone axis-disrupting chemicals on brain development

Report on cellular and molecular data on consequences of the interactions between iodine deficiencyhypothyroidism and THADCs on brain development in two vertebrate models mouse and xenopus This deliverable will describe the activities in Task 91

High through-put cell based screening assay with overexpressed OATP1C1

High throughput cellbased screening assay with overexpressed OATP1C1 month 36 VUA CHARIT A description of HTP screening assay with overexpressed OATP1C1

Policy briefing no 4 to the European Commission and JRC
Data on associations of exposure to major EDC subgroups with maternal thyroid function during pregnancy

Provide data on the association of exposure to major EDCs subgroups with maternal thyroid function during pregnancy (month18) (ERASMUS): We will leverage epidemiological studies with information on EDC exposures and T4 levels in pregnancy to provide criteria for test compound selection in the subsequent WP

Reporting templates and project handbook

Reporting templates and project handbook: we will create reporting templates and a project handbook, to be delivered to all partners to ease the reporting on finances and deliverables

Report on the calibration and identification of thyroid specific and sensitive endpoints in 3D cell models

Report on the calibration and identification of thyroid hormone specific and sensitive endpoints in each of the 3D cell based models month 24 CNRS and CHARIT We will provide a description of new thyroid sensitive endpoints in 3D cell culture models

Preliminary testing protocol for inclusion of measurement endpoints of thyroid hormone action that can be incorporated into relevant OECD test guidelines

Preliminary testing protocol for inclusion of measurement endpoints of thyroid hormone action that can be incorporated into relevant OECD test guidelines month 36 This will describe endpoints for downstream effects of thyroid disruption on the brain together with a preliminary testing protocol

Data Management plan

Submission of a first version of a Data Management Plan (DMP) at month 6 of the project. The DMP will be updated over the course of the project whenever significant changes arise, such as (but not limited to): - new data - changes in consortium policies (e.g. new innovation potential, decision to file for a patent) - changes in consortium composition and external factors (e.g. new consortium members joining or old members leaving).

Project website

Project website The site will link to a portal of all projects funded under this call and will detail the work programme and partners in ATHENA

Release of new QSARs in free public websites

Release of the new QSARs in free public websites month 54 The new models will be released in websites

Veröffentlichungen

A Mixture of Chemicals Found in Human Amniotic Fluid Disrupts Brain Gene Expression and Behavior in Xenopus laevis.

Autoren: Leemans M, Spirhanzlova P, Couderq S, Le Mével S, Grimaldi A, Duvernois-Berthet E, Demeneix B, Fini JB
Veröffentlicht in: International Journal of Molecular Sciences, Issue 24, 2023, ISSN 1422-0067
Herausgeber: Multidisciplinary Digital Publishing Institute (MDPI)
DOI: 10.3390/ijms24032588

Developmental thyroid disruption permanently affects the neuroglial output in the murine subventricular zone.

Autoren: Vancamp, P., Le Blay, K., Butruille, L., Sébillot, A., Boelen, A., Demeneix, B. A., & Remaud, S
Veröffentlicht in: Stem Cell Reports, Issue 17, 2022, ISSN 2213-6711
Herausgeber: Cell Press
DOI: 10.1016/j.stemcr.2022.01.002

Association of urinary bisphenols and triclosan with thyroid function during early pregnancy

Autoren: Arash Derakhshan, Huan Shu, Robin P. Peeters, Andreas Kortenkamp, Christian H. Lindh, Barbara Demeneix, Carl-Gustaf Bornehag, Tim I.M. Korevaar
Veröffentlicht in: Environment International, Issue 133, 2019, Page(s) 105123, ISSN 0160-4120
Herausgeber: Pergamon Press Ltd.
DOI: 10.1016/j.envint.2019.105123

Perinatal exposure to the thyroperoxidase inhibitors methimazole and amitrole perturbs thyroid hormone system signaling and alters motor activity in rat offspring.

Autoren: Ramhøj L, Svingen T, Frädrich C, Rijntjes E, Wirth EK, Pedersen K, Köhrle J, Axelstad M
Veröffentlicht in: Toxicology Letters, 2021, ISSN 0378-4274
Herausgeber: Elsevier BV
DOI: 10.1016/j.toxlet.2021.10.010

Mechanistic insights into the synergistic activation of the RXR-PXR heterodimer by endocrine disruptor mixtures.

Autoren: Delfosse V, Huet T, Harrus D, Granell M, Bourguet M, Gardia-Parège C, Chiavarina B, Grimaldi M, Le Mével S, Blanc P, Huang D, Gruszczyk J, Demeneix B, Cianférani S, Fini JB, Balaguer P, Bourguet W.
Veröffentlicht in: Proceedings of the National Academy of Sciences, Issue 118, 2020, ISSN 1091-6490
Herausgeber: National Academy of Sciences
DOI: 10.1073/pnas.2020551118

Association of endocrine disrupting chemicals exposure with human chorionic gonadotropin concentrations in pregnancy.

Autoren: Derakhshan A, Shu H, Broeren MAC, Kortenkamp A, Lindh CH, Demeneix B, Peeters RP, Bornehag CG, Korevaar TIM
Veröffentlicht in: Environment International, Issue 178, 2023, ISSN 0160-4120
Herausgeber: Pergamon Press Ltd.
DOI: 10.1016/j.envint.2023.108091

Testing for thyroid hormone disruptors, a review of non-mammalian in vivo models

Autoren: Stephan Couderq, Michelle Leemans, Jean-Baptiste Fini
Veröffentlicht in: Molecular and Cellular Endocrinology, Issue 508, 2020, Page(s) 110779, ISSN 0303-7207
Herausgeber: Elsevier BV
DOI: 10.1016/j.mce.2020.110779

Transient developmental exposure to low doses of bisphenol F negatively affects neurogliogenesis and olfactory behaviour in adult mice,

Autoren: Vancamp, P., Butruille, L., Herranen, A., Boelen, A., Fini, J. B., Demeneix, B. A., & Remaud, S.
Veröffentlicht in: Environment International, Issue 172, 2023, ISSN 0160-4120
Herausgeber: Pergamon Press Ltd.
DOI: 10.1016/j.envint.2023.107770

Removing Critical Gaps in Chemical Test Methods by Developing New Assays for the Identification of Thyroid Hormone System-Disrupting Chemicals—The ATHENA Project

Autoren: Andreas Kortenkamp, Marta Axelstad, Asma H. Baig, Åke Bergman, Carl-Gustaf Bornehag, Peter Cenijn, Sofie Christiansen, Barbara Demeneix, Arash Derakhshan, Jean-Baptiste Fini, Caroline Frädrich, Timo Hamers, Lina Hellwig, Josef Köhrle, Tim I.M. Korevaar, Johan Lindberg, Olwenn Martin, Marcel E. Meima, Philipp Mergenthaler, Nikolai Nikolov, David Du Pasquier, Robin P. Peeters, Bjorn Platzack, Lou
Veröffentlicht in: International Journal of Molecular Sciences, Issue 21/9, 2020, Page(s) 3123, ISSN 1422-0067
Herausgeber: Multidisciplinary Digital Publishing Institute (MDPI)
DOI: 10.3390/ijms21093123

Association of phthalate exposure with thyroid function during pregnancy

Autoren: Arash Derakhshan, Huan Shu, Maarten A.C. Broeren, Christian H. Lindh, Robin P. Peeters, Andreas Kortenkamp, Barbara Demeneix, Carl-Gustaf Bornehag, Tim I.M. Korevaar.
Veröffentlicht in: Environment International, Issue 157, 2021, Page(s) 106795, ISSN 0160-4120
Herausgeber: Pergamon Press Ltd.
DOI: 10.1016/j.envint.2021.106795

Association of per- and polyfluoroalkyl substances with thyroid homeostasis during pregnancy in the SELMA study

Autoren: Derakhshan A, Kortenkamp A, Shu H, Broeren MAC, Lindh CH, Peeters RP, Bornehag CG, Demeneix B, Korevaar TIM
Veröffentlicht in: Environment International, Issue 167, 2022, ISSN 0160-4120
Herausgeber: Pergamon Press Ltd.
DOI: 10.1016/j.envint.2022.107420

Testing for heterotopia formation in rats after developmental exposure to selected in vitro inhibitors of thyroperoxidase.

Autoren: Ramhøj L, Frädrich C, Svingen T, Scholze M, Wirth EK, Rijntjes E, Köhrle J, Kortenkamp A, Axelstad M.
Veröffentlicht in: Environmental Pollution, 2021, ISSN 0269-7491
Herausgeber: Pergamon Press Ltd.
DOI: 10.1016/j.envpol.2021.117135

Asymmetrical Transport of Thyroxine Across Human Term Placenta

Autoren: Chen Z, Peeters RP, Leeuwenburgh S, Broekhuizen M, Neuman RI, Hitzerd E, Tan L, Jongejan RMS, de Rijke YB, Reiss IKM, Danser AHJ, Visser WE, Meima ME
Veröffentlicht in: Thyroid, Issue 33, 2021, ISSN 1050-7256
Herausgeber: Mary Ann Liebert Inc.
DOI: 10.1089/thy.2022.0406

Pesticides With Potential Thyroid Hormone-Disrupting Effects: A Review of Recent Data

Autoren: Michelle Leemans, Stephan Couderq, Barbara Demeneix, Jean-Baptiste Fini
Veröffentlicht in: Frontiers in Endocrinology, Issue 10, 2019, ISSN 1664-2392
Herausgeber: Frontiers
DOI: 10.3389/fendo.2019.00743

Comparative analysis of thyroid hormone systems in rodents with subterranean lifestyle.

Autoren: Gerhardt P, Begall S, Frädrich C, Renko K, Hildebrandt TB, Holtze S, Heinrich A, Sahm A, Meci X, Köhrle J, Rijntjes E, Henning Y
Veröffentlicht in: Nature Scientific Reports, Issue 13, 2023, ISSN 2045-2322
Herausgeber: Nature Publishing Group
DOI: 10.1038/s41598-023-30179-w

Deiodinases control local cellular and systemic thyroid hormone availability.

Autoren: Köhrle J, Frädrich C
Veröffentlicht in: Free Radical Biology and Medicine, Issue 193, 2022, ISSN 0891-5849
Herausgeber: Elsevier BV
DOI: 10.1016/j.freeradbiomed.2022.09.024

Novel (sulfated) thyroid hormone transporters in the solute carrier 22 family.

Autoren: Chen Z, Peeters RP, Flach W, de Rooij LJ, Yildiz S, Teumer A, Nauck M, Sterenborg RBTM, Rutten JHW, Medici M, Edward Visser W, Meima ME
Veröffentlicht in: European Thyroid Journal, Issue 12, 2023, ISSN 2235-0640
Herausgeber: S. Karger AG
DOI: 10.1530/etj-23-0023

Selenium, Iodine and Iron-Essential Trace Elements for Thyroid Hormone Synthesis and Metabolism.

Autoren: Köhrle J
Veröffentlicht in: International Journal of Molecular Sciences, Issue 24, 2023, ISSN 1422-0067
Herausgeber: Multidisciplinary Digital Publishing Institute (MDPI)
DOI: 10.3390/ijms24043393

Thyroid Hormone Transporters in a Human Placental Cell Model

Autoren: Chen Z, van der Sman ASE, Groeneweg S, de Rooij LJ, Visser WE, Peeters RP, Meima ME
Veröffentlicht in: Thyroid, Issue 32, 2022, ISSN 1050-7256
Herausgeber: Mary Ann Liebert Inc.
DOI: 10.1089/thy.2021.0503

Developmental exposure to thyroid disruptors: misprogramming of the brain's stem cells in later life?

Autoren: Vancamp P, Remaud S.
Veröffentlicht in: Neural Regen Res, Issue 18, 2023, ISSN 1673-5374
Herausgeber: Neural Regeneration Research
DOI: 10.4103/1673-5374.346053

Association of urinary bisphenols during pregnancy with maternal, cord blood and childhood thyroid function

Autoren: Arash Derakhshan, Elise M Philips, Akhgar Ghassabian, Susana Santos, Alexandros G Asimakopoulos, Kurunthachalam Kannan, Andreas Kortenkamp, Vincent WV Jaddoe, Leonardo Trasande, Robin P Peeters, Tim IM Korevaar
Veröffentlicht in: Environment International, Issue 146, 2021, Page(s) 106160, ISSN 0160-4120
Herausgeber: Pergamon Press Ltd.
DOI: 10.1016/j.envint.2020.106160

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