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Project Report

The GOLIATH Project: Towards an Internationally Harmonised Approach for Testing Metabolism Disrupting Compounds

Institute for Risk Assessment Sciences, Department of Population Health Sciences, Faculty of Veterinary Medicine, Utrecht University, 3508 TD Utrecht, The Netherlands
INRAE Toxalim (Research Centre in Food Toxicology), Metabolism and Xenobiotics (MeX) Team, Université de Toulouse, INRAE, ENVT, INP-Purpan, UPS, 31027 Toulouse, France
Centre for Radiation, Chemical and Environmental Hazards, Public Health England, Chilton OXON. OX11 0RQ, UK
Institut NUMECAN (Nutrition Metabolisms and Cancer) INSERM UMR_A 1341, UMR_S 1241, Université de Rennes, F-35000 Rennes, France
Institut de Recherche en Cancérologie de Montpellier (IRCM), INSERM U1194, ICM, Université de Montpellier, 34298 Montpellier, France
Center for Structural Biochemistry (CBS), INSERM, CNRS, Université de Montpellier, 34090 Montpellier, France
Department of Physiology and Pharmacology, Karolinska Institutet, 17177 Stockholm, Sweden
IDiBE and CIBERDEM, Universitas Miguel Hernandez, 03202 Elche (Alicante), Spain
ANSES, Direction de l’Evaluation des Risques, Agence Nationale de Sécurité Sanitaire de l’Alimentation, de l’Environnement et du Travail, 14 rue Pierre et Marie Curie, 94701 Maisons-Alfort CEDEX, France
Department of Biomedical and Clinical Sciences (BKV), Cell Biology, Medical Faculty, Linköping University, SE-581 85 Linköping, Sweden
Sustainable Health, Flemish Institute for Technological Research, VITO, 2400 Mol, Belgium
Department of Life Sciences, College of Health and Life Sciences, Brunel University London, Uxbridge UB8 3PH, UK
Section of Biomolecular Medicine, Division of Systems Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College London, South Kensington, London SW7 2AZ, UK
Department of Developmental and Cell Biology, University of California Irvine, 2011 BioSci 3, University of California, Irvine, CA 92697-2300, USA
Biopredic International, Parc d’Activité de la Bretèche Bâtiment A4, 35760 Saint Grégoire, France
Seh Consulting + Services, 33106 Paderborn, Germany
Chemistry Department, Umeå University, SE-90187 Umea, Sweden
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(10), 3480;
Received: 1 April 2020 / Revised: 29 April 2020 / Accepted: 8 May 2020 / Published: 14 May 2020
(This article belongs to the Special Issue Advances in the Research of Endocrine Disrupting Chemicals 2.0)
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. View Full-Text
Keywords: risk assessment; chemicals; endocrine; obesity; diabetes risk assessment; chemicals; endocrine; obesity; diabetes
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MDPI and ACS Style

Legler, J.; Zalko, D.; Jourdan, F.; Jacobs, M.; Fromenty, B.; Balaguer, P.; Bourguet, W.; Munic Kos, V.; Nadal, A.; Beausoleil, C.; Cristobal, S.; Remy, S.; Ermler, S.; Margiotta-Casaluci, L.; Griffin, J.L.; Blumberg, B.; Chesné, C.; Hoffmann, S.; Andersson, P.L.; Kamstra, J.H., on behalf of the GOLIATH Consortium. The GOLIATH Project: Towards an Internationally Harmonised Approach for Testing Metabolism Disrupting Compounds. Int. J. Mol. Sci. 2020, 21, 3480.

AMA Style

Legler J, Zalko D, Jourdan F, Jacobs M, Fromenty B, Balaguer P, Bourguet W, Munic Kos V, Nadal A, Beausoleil C, Cristobal S, Remy S, Ermler S, Margiotta-Casaluci L, Griffin JL, Blumberg B, Chesné C, Hoffmann S, Andersson PL, Kamstra JH on behalf of the GOLIATH Consortium. The GOLIATH Project: Towards an Internationally Harmonised Approach for Testing Metabolism Disrupting Compounds. International Journal of Molecular Sciences. 2020; 21(10):3480.

Chicago/Turabian Style

Legler, Juliette, Daniel Zalko, Fabien Jourdan, Miriam Jacobs, Bernard Fromenty, Patrick Balaguer, William Bourguet, Vesna Munic Kos, Angel Nadal, Claire Beausoleil, Susana Cristobal, Sylvie Remy, Sibylle Ermler, Luigi Margiotta-Casaluci, Julian L. Griffin, Bruce Blumberg, Christophe Chesné, Sebastian Hoffmann, Patrik L. Andersson, and Jorke H. Kamstra on behalf of the GOLIATH Consortium. 2020. "The GOLIATH Project: Towards an Internationally Harmonised Approach for Testing Metabolism Disrupting Compounds" International Journal of Molecular Sciences 21, no. 10: 3480.

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