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The goliath project: Towards an internationally harmonised approach for testing metabolism disrupting compounds
Authors
Patrik L. Andersson
Patrick Balaguer
+21 more
Claire Beausoleil
Bruce Blumberg
William Bourguet
Christophe Chesné
Susana Cristobal
Dep Population Health Sciences
dIRAS RA-1
Sibylle Ermler
Bernard Fromenty
Julian L. Griffin
Sebastian Hoffmann
IRAS OH Toxicology
Miriam Jacobs
Fabien Jourdan
Jorke H. Kamstra
Juliette Legler
Luigi Margiotta-Casaluci
Vesna Munic Kos
Angel Nadal
Sylvie Remy
Daniel Zalko
Publication date
1 January 2020
Publisher
'MDPI AG'
Doi
Abstract
Copyright © 2020 by the authors. The purpose of this project report is to introduce the European “GOLIATH” project, a new research project which addresses one of the most urgent regulatory needs in the testing of endocrine-disrupting chemicals (EDCs), namely the lack of methods for testing EDCs that disrupt metabolism and metabolic functions. These chemicals collectively referred to as “metabolism disrupting compounds” (MDCs) are natural and anthropogenic chemicals that can promote metabolic changes that can ultimately result in obesity, diabetes, and/or fatty liver in humans. This project report introduces the main approaches of the project and provides a focused review of the evidence of metabolic disruption for selected EDCs. GOLIATH will generate the world’s first integrated approach to testing and assessment (IATA) specifically tailored to MDCs. GOLIATH will focus on the main cellular targets of metabolic disruption—hepatocytes, pancreatic endocrine cells, myocytes and adipocytes—and using an adverse outcome pathway (AOP) framework will provide key information on MDC-related mode of action by incorporating multi-omic analyses and translating results from in silico, in vitro, and in vivo models and assays to adverse metabolic health outcomes in humans at real-life exposures. Given the importance of international acceptance of the developed test methods for regulatory use, GOLIATH will link with ongoing initiatives of the Organisation for Economic Development (OECD) for test method (pre-)validation, IATA, and AOP development
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