Livrables
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 JRCProvisional 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 outcomesQualitative AOP network of the thyroid hormone axis for adverse neurodevelopmental outcomes This deliverable will describe the outcome of Task 101
Risk assessment procedureConcept 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 JRCPolicy 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 libraryA 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 studiesAnalysis 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 JRCPilot 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 assessmentsDocument 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 statusIdentification 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 disseminationRelease 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 developmentReport 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 OATP1C1High 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 JRCData 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 handbookReporting 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 modelsReport 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 guidelinesPreliminary 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
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).
Workshop 1 with international advisory panel month 30
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 websitesRelease of the new QSARs in free public websites month 54 The new models will be released in websites
Publications
Auteurs:
Leemans M, Spirhanzlova P, Couderq S, Le Mével S, Grimaldi A, Duvernois-Berthet E, Demeneix B, Fini JB
Publié dans:
International Journal of Molecular Sciences, Numéro 24, 2023, ISSN 1422-0067
Éditeur:
Multidisciplinary Digital Publishing Institute (MDPI)
DOI:
10.3390/ijms24032588
Auteurs:
Vancamp, P., Le Blay, K., Butruille, L., Sébillot, A., Boelen, A., Demeneix, B. A., & Remaud, S
Publié dans:
Stem Cell Reports, Numéro 17, 2022, ISSN 2213-6711
Éditeur:
Cell Press
DOI:
10.1016/j.stemcr.2022.01.002
Auteurs:
Arash Derakhshan, Huan Shu, Robin P. Peeters, Andreas Kortenkamp, Christian H. Lindh, Barbara Demeneix, Carl-Gustaf Bornehag, Tim I.M. Korevaar
Publié dans:
Environment International, Numéro 133, 2019, Page(s) 105123, ISSN 0160-4120
Éditeur:
Pergamon Press Ltd.
DOI:
10.1016/j.envint.2019.105123
Auteurs:
Ramhøj L, Svingen T, Frädrich C, Rijntjes E, Wirth EK, Pedersen K, Köhrle J, Axelstad M
Publié dans:
Toxicology Letters, 2021, ISSN 0378-4274
Éditeur:
Elsevier BV
DOI:
10.1016/j.toxlet.2021.10.010
Auteurs:
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.
Publié dans:
Proceedings of the National Academy of Sciences, Numéro 118, 2020, ISSN 1091-6490
Éditeur:
National Academy of Sciences
DOI:
10.1073/pnas.2020551118
Auteurs:
Derakhshan A, Shu H, Broeren MAC, Kortenkamp A, Lindh CH, Demeneix B, Peeters RP, Bornehag CG, Korevaar TIM
Publié dans:
Environment International, Numéro 178, 2023, ISSN 0160-4120
Éditeur:
Pergamon Press Ltd.
DOI:
10.1016/j.envint.2023.108091
Auteurs:
Stephan Couderq, Michelle Leemans, Jean-Baptiste Fini
Publié dans:
Molecular and Cellular Endocrinology, Numéro 508, 2020, Page(s) 110779, ISSN 0303-7207
Éditeur:
Elsevier BV
DOI:
10.1016/j.mce.2020.110779
Auteurs:
Vancamp, P., Butruille, L., Herranen, A., Boelen, A., Fini, J. B., Demeneix, B. A., & Remaud, S.
Publié dans:
Environment International, Numéro 172, 2023, ISSN 0160-4120
Éditeur:
Pergamon Press Ltd.
DOI:
10.1016/j.envint.2023.107770
Auteurs:
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
Publié dans:
International Journal of Molecular Sciences, Numéro 21/9, 2020, Page(s) 3123, ISSN 1422-0067
Éditeur:
Multidisciplinary Digital Publishing Institute (MDPI)
DOI:
10.3390/ijms21093123
Auteurs:
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.
Publié dans:
Environment International, Numéro 157, 2021, Page(s) 106795, ISSN 0160-4120
Éditeur:
Pergamon Press Ltd.
DOI:
10.1016/j.envint.2021.106795
Auteurs:
Derakhshan A, Kortenkamp A, Shu H, Broeren MAC, Lindh CH, Peeters RP, Bornehag CG, Demeneix B, Korevaar TIM
Publié dans:
Environment International, Numéro 167, 2022, ISSN 0160-4120
Éditeur:
Pergamon Press Ltd.
DOI:
10.1016/j.envint.2022.107420
Auteurs:
Ramhøj L, Frädrich C, Svingen T, Scholze M, Wirth EK, Rijntjes E, Köhrle J, Kortenkamp A, Axelstad M.
Publié dans:
Environmental Pollution, 2021, ISSN 0269-7491
Éditeur:
Pergamon Press Ltd.
DOI:
10.1016/j.envpol.2021.117135
Auteurs:
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
Publié dans:
Thyroid, Numéro 33, 2021, ISSN 1050-7256
Éditeur:
Mary Ann Liebert Inc.
DOI:
10.1089/thy.2022.0406
Auteurs:
Michelle Leemans, Stephan Couderq, Barbara Demeneix, Jean-Baptiste Fini
Publié dans:
Frontiers in Endocrinology, Numéro 10, 2019, ISSN 1664-2392
Éditeur:
Frontiers
DOI:
10.3389/fendo.2019.00743
Auteurs:
Gerhardt P, Begall S, Frädrich C, Renko K, Hildebrandt TB, Holtze S, Heinrich A, Sahm A, Meci X, Köhrle J, Rijntjes E, Henning Y
Publié dans:
Nature Scientific Reports, Numéro 13, 2023, ISSN 2045-2322
Éditeur:
Nature Publishing Group
DOI:
10.1038/s41598-023-30179-w
Auteurs:
Köhrle J, Frädrich C
Publié dans:
Free Radical Biology and Medicine, Numéro 193, 2022, ISSN 0891-5849
Éditeur:
Elsevier BV
DOI:
10.1016/j.freeradbiomed.2022.09.024
Auteurs:
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
Publié dans:
European Thyroid Journal, Numéro 12, 2023, ISSN 2235-0640
Éditeur:
S. Karger AG
DOI:
10.1530/etj-23-0023
Auteurs:
Köhrle J
Publié dans:
International Journal of Molecular Sciences, Numéro 24, 2023, ISSN 1422-0067
Éditeur:
Multidisciplinary Digital Publishing Institute (MDPI)
DOI:
10.3390/ijms24043393
Auteurs:
Chen Z, van der Sman ASE, Groeneweg S, de Rooij LJ, Visser WE, Peeters RP, Meima ME
Publié dans:
Thyroid, Numéro 32, 2022, ISSN 1050-7256
Éditeur:
Mary Ann Liebert Inc.
DOI:
10.1089/thy.2021.0503
Auteurs:
Vancamp P, Remaud S.
Publié dans:
Neural Regen Res, Numéro 18, 2023, ISSN 1673-5374
Éditeur:
Neural Regeneration Research
DOI:
10.4103/1673-5374.346053
Auteurs:
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
Publié dans:
Environment International, Numéro 146, 2021, Page(s) 106160, ISSN 0160-4120
Éditeur:
Pergamon Press Ltd.
DOI:
10.1016/j.envint.2020.106160
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