DOAJ Open Access 2023

New approach methods to improve human health risk assessment of thyroid hormone system disruption–a PARC project

Louise Ramhøj Marta Axelstad Yoni Baert Ana I. Cañas-Portilla Frédéric Chalmel +26 lainnya

Abstrak

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.

Topik & Kata Kunci

Toxicology. Poisons

Penulis (31)

Louise Ramhøj

Marta Axelstad

Yoni Baert

Ana I. Cañas-Portilla

Frédéric Chalmel

Lars Dahmen

Antonio De La Vieja

Bertrand Evrard

Ann-Cathrin Haigis

Timo Hamers

Kim Heikamp

Henrik Holbech

Patricia Iglesias-Hernandez

Dries Knapen

Lorna Marchandise

Jane E. Morthorst

Nikolai Georgiev Nikolov

Ana C. V. E. Nissen

Michael Oelgeschlaeger

Kostja Renko

Vera Rogiers

Gerrit Schüürmann

Evelyn Stinckens

Mette H. Stub

Monica Torres-Ruiz

Majorie Van Duursen

Tamara Vanhaecke

Lucia Vergauwen

Eva Bay Wedebye

Terje Svingen

Format Sitasi

APA MLA BibTeX

Ramhøj, L., Axelstad, M., Baert, Y., Cañas-Portilla, A.I., Chalmel, F., Dahmen, L. et al. (2023). New approach methods to improve human health risk assessment of thyroid hormone system disruption–a PARC project. https://doi.org/10.3389/ftox.2023.1189303

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Informasi Jurnal

Tahun Terbit: 2023
Sumber Database: DOAJ
DOI: 10.3389/ftox.2023.1189303
Akses: Open Access ✓