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.
Bibliographical noteFunding Information:
This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement GOLIATH No. 825489. All partners acknowledge the contribution of their institutes for additional financial support. We would also like to acknowledge the following additional members of the GOLIATH consortium: Utrecht University, The Netherlands: Anran Cai, Marjo den Broeder, Virissa Lenters, Roel Vermeulen; INRAE France: Sandrine Bruel, Nicolas Cabaton, Anne Hillenweck, Louisa Mediouni, Elodie Person, Nathalie Poupin, Clément Frainay, Maxime Delmas; INSERM France: Anne Corlu, Vanessa Delfosse, Clementine Garoche, Marina Grimaldi, Jakub Gruszczyk, Julie Massart, Jean-Luc Pons, Lucia Toporova, Gilles Labesse; Karolinska Institutet, Sweden: Astrud Tuck; Universitas Miguel Hernandez, Spain: Reinaldo Sousa dos Santos; ANSES, France: Christophe Rousselle; VITO, Belgium: Eva Govarts; Greet Schoeters; Brunel University London, UK: Andreas Kortenkamp; University of Cambridge, UK: Susana Palma; University of California, Irvine, USA: Angelica Amorim Amato, Xiaomin Ren; Biopredic International, France: Ruoya Li; Umeå University, Sweden: Maria Sapounidou (UMU).
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