New approach methods to improve human health risk assessment of thyroid hormone system disruption–a PARC project
| Autor: | Ramhøj, Louise, Axelstad, Marta, Baert, Yoni, Cañas-Portilla, Ana I, Chalmel, Frédéric, Dahmen, Lars, De La Vieja, Antonio, Evrard, Bertrand, Haigis, Ann-Cathrin, Hamers, Timo, Heikamp, Kim, Holbech, Henrik, Iglesias-Hernandez, Patricia, Knapen, Dries, Marchandise, Lorna, Morthorst, Jane E, Nikolov, Nikolai Georgiev, Nissen, Ana C V E, Oelgeschlaeger, Michael, Renko, Kostja, Rogiers, Vera, Schüürmann, Gerrit, Stinckens, Evelyn, Stub, Mette H, Torres-Ruiz, Monica, Van Duursen, Majorie, Vanhaecke, Tamara, Vergauwen, Lucia, Wedebye, Eva Bay, Svingen, Terje |
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| Přispěvatelé: | Danmarks Tekniske Universitet = Technical University of Denmark (DTU), Vrije Universiteit Brussel (VUB), Instituto de Salud Carlos III [Madrid] (ISC), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), German Federal Institute for Risk Assessment [Berlin] (BfR), University of Antwerp (UA), Vrije Universiteit Amsterdam [Amsterdam] (VU), University of Southern Denmark (SDU), Helmholtz Zentrum für Umweltforschung = Helmholtz Centre for Environmental Research (UFZ), This project is part of the Partnership for the Assessment of Risk from Chemicals (PARC), funding by the European Union’s Horizon Europe research and innovation programme under Grant Agreement No 101057014. Additional co-funders are acknowledged, including the Danish Environmental Protection Agency (DK EPA), the German Federal Institute for Risk Assessment (BfR), the University of Antwerp Research Fund (project ID 44602), the Spanish Government (Grant Number: MCIN/AEI/10.13039/501100011033/PID 2021-125948OB-I00/FEDER, UE), and Chair Mireille Aerens for the Development of Alternative Methods, Vrije Universiteit Brussel., European Project: 101057014,Horizon Europe,PARC(2022), Pharmaceutical and Pharmacological Sciences, Experimental in vitro toxicology and dermato-cosmetology, Basic (bio-) Medical Sciences, Biology of the Testis, Biology, Faculty of Medicine and Pharmacy, Vriendenkring VUB |
| Rok vydání: | 2023 |
| Předmět: |
Adverse outcome pathways
Thyroid disruption regulatory toxicology Endocrine disruption Pharmacology. Therapy Non-animal test methods thyroid disruption chemicals endocrine disruption General Medicine adverse outcome pathways SDG 3 - Good Health and Well-being non-animal test methods [SDV.TOX]Life Sciences [q-bio]/Toxicology [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie Chemicals Regulatory toxicology PARC Biology PARC endocrine disruption thyroid disruption non-animal test methods regulatory toxicology adverse outcome pathways chemicals |
| Zdroj: | Frontiers in Toxicology Frontiers in Toxicology, 2023, 5, pp.1189303. ⟨10.3389/ftox.2023.1189303⟩ Frontiers in toxicology Ramhøj, L, Axelstad, M, Baert, Y, Cañas-Portilla, A I, Chalmel, F, Dahmen, L, De La Vieja, A, Evrard, B, Haigis, A-C, Hamers, T, Heikamp, K, Holbech, H, Iglesias-Hernandez, P, Knapen, D, Marchandise, L, Morthorst, J E, Nikolov, N G, Nissen, A C V E, Oelgeschlaeger, M, Renko, K, Rogiers, V, Schüürmann, G, Stinckens, E, Stub, M H, Torres-Ruiz, M, Van Duursen, M, Vanhaecke, T, Vergauwen, L, Wedebye, E B & Svingen, T 2023, ' New approach methods to improve human health risk assessment of thyroid hormone system disruption-a PARC project ', Frontiers in Toxicology, vol. 5, 1189303 . https://doi.org/10.3389/ftox.2023.1189303 |
| ISSN: | 2673-3080 |
| Popis: | Current test strategies to identify thyroid hormone (TH) system disruptors are inadequate for conducting robust chemical risk assessment required for regulation. The tests rely heavily on histopathological changes in rodent thyroid glands or measuring changes in systemic TH levels, but they lack specific new approach methodologies (NAMs) that can adequately detect TH-mediated effects. Such alternative test methods are needed to infer a causal relationship between molecular initiating events and adverse outcomes such as perturbed brain development. Although some NAMs that are relevant for TH system disruption are available–and are currently in the process of regulatory validation–there is still a need to develop more extensive alternative test batteries to cover the range of potential key events along the causal pathway between initial chemical disruption and adverse outcomes in humans. This project, funded under the Partnership for the Assessment of Risk from Chemicals (PARC) initiative, aims to facilitate the development of NAMs that are specific for TH system disruption by characterizing in vivo mechanisms of action that can be targeted by in embryo/in vitro/in silico/in chemico testing strategies. We will develop and improve human-relevant in vitro test systems to capture effects on important areas of the TH system. Furthermore, we will elaborate on important species differences in TH system disruption by incorporating non-mammalian vertebrate test species alongside classical laboratory rat species and human-derived in vitro assays. |
| Databáze: | OpenAIRE |
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