2026-06-14T03:55:05Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/163162025-06-24T17:56:02Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19610

00925njm 22002777a 4500 dc Ramhøj, Louise author Axelstad, Marta author Baert, Yoni author Cañas Portilla, Ana Isabel author Chalmel, Frédéric author Dahmen, Lars author De la Vieja, Antonio author Evrard, Bertrand author Haigis, Ann-Cathrin author Hamers, Timo author Heikamp, Kim author Holbech, Henrik author Iglesias-Hernandez, Patricia author Knapen, Dries author Marchandise, Lorna author Morthorst, Jane E author Nikolov, Nikolai Georgiev author Nissen, Ana C V E author Oelgeschlaeger, Michael author Renko, Kostja author Rogiers, Vera author Schüürmann, Gerrit author Stinckens, Evelyn author Stub, Mette H author Torres-Ruiz, Mónica author Van Duursen, Majorie author Vanhaecke, Tamara author Vergauwen, Lucia author Wedebye, Eva Bay author Svingen, Terje author 2023 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. Front Toxicol. 2023 May 17;5:1189303. 10.3389/ftox.2023.1189303 2673-3080 Frontiers in toxicology 37265663 http://hdl.handle.net/20.500.12105/16316 PARC Adverse outcome pathways Chemicals Endocrine disruption Non-animal test methods Regulatory toxicology Thyroid disruption New approach methods to improve human health risk assessment of thyroid hormone system disruption-a PARC project