The GOLIATH Project: Towards an Internationally Harmonised Approach for Testing Metabolism Disrupting Compounds
by
Juliette Legler 1,*, Daniel Zalko 2
, Fabien Jourdan 2, Miriam Jacobs 3, Bernard Fromenty 4, Patrick Balaguer 5, William Bourguet 6, Vesna Munic Kos 7, Angel Nadal 8, Claire Beausoleil 9, Susana Cristobal 10, Sylvie Remy 11, Sibylle Ermler 12, Luigi Margiotta-Casaluci 12, Julian L. Griffin 13, Bruce Blumberg 14, Christophe Chesné 15, Sebastian Hoffmann 16, Patrik L. Andersson 17 and Jorke H. Kamstra 1
on behalf of the GOLIATH Consortium
Juliette Legler 1,*, Daniel Zalko 2, Fabien Jourdan 2, Miriam Jacobs 3, Bernard Fromenty 4, Patrick Balaguer 5, William Bourguet 6, Vesna Munic Kos 7, Angel Nadal 8, Claire Beausoleil 9, Susana Cristobal 10, Sylvie Remy 11, Sibylle Ermler 12, Luigi Margiotta-Casaluci 12, Julian L. Griffin 13, Bruce Blumberg 14, Christophe Chesné 15, Sebastian Hoffmann 16, Patrik L. Andersson 17 and Jorke H. Kamstra 1
on behalf of the GOLIATH Consortium
1
Institute for Risk Assessment Sciences, Department of Population Health Sciences, Faculty of Veterinary Medicine, Utrecht University, 3508 TD Utrecht, The Netherlands
2
INRAE Toxalim (Research Centre in Food Toxicology), Metabolism and Xenobiotics (MeX) Team, Université de Toulouse, INRAE, ENVT, INP-Purpan, UPS, 31027 Toulouse, France
3
Centre for Radiation, Chemical and Environmental Hazards, Public Health England, Chilton OXON. OX11 0RQ, UK
4
Institut NUMECAN (Nutrition Metabolisms and Cancer) INSERM UMR_A 1341, UMR_S 1241, Université de Rennes, F-35000 Rennes, France
5
Institut de Recherche en Cancérologie de Montpellier (IRCM), INSERM U1194, ICM, Université de Montpellier, 34298 Montpellier, France
6
Center for Structural Biochemistry (CBS), INSERM, CNRS, Université de Montpellier, 34090 Montpellier, France
7
Department of Physiology and Pharmacology, Karolinska Institutet, 17177 Stockholm, Sweden
8
IDiBE and CIBERDEM, Universitas Miguel Hernandez, 03202 Elche (Alicante), Spain
9
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
10
Department of Biomedical and Clinical Sciences (BKV), Cell Biology, Medical Faculty, Linköping University, SE-581 85 Linköping, Sweden
11
Sustainable Health, Flemish Institute for Technological Research, VITO, 2400 Mol, Belgium
12
Department of Life Sciences, College of Health and Life Sciences, Brunel University London, Uxbridge UB8 3PH, UK
13
Section of Biomolecular Medicine, Division of Systems Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College London, South Kensington, London SW7 2AZ, UK
14
Department of Developmental and Cell Biology, University of California Irvine, 2011 BioSci 3, University of California, Irvine, CA 92697-2300, USA
15
Biopredic International, Parc d’Activité de la Bretèche Bâtiment A4, 35760 Saint Grégoire, France
16
Seh Consulting + Services, 33106 Paderborn, Germany
17
Chemistry Department, Umeå University, SE-90187 Umea, Sweden
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(10), 3480; https://doi.org/10.3390/ijms21103480
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
▼
Show Figures
Figure 1
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
- Supplementary File 1:
PDF-Document (PDF, 841 KB)
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.
Show more citation formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.
Search more from Scilit
