GOLIATH - Generation Of Novel, Integrated and Internationally Harmonised Approaches for Testing Metabolism Disrupting Chemicals
Funder: European Commission Horizon 2020
GOLIATH focusses on one of the most urgent regulatory needs in the field of endocrine disrupting chemicals, namely the lack of methods for testing EDCs that disrupt metabolism – chemicals collectively referred to as ‘metabolism disrupting chemicals’ (MDCs). MDCs are natural and anthropogenic chemicals that have the ability to promote metabolic changes that can ultimately result in obesity, diabetes and/or fatty liver in humans. GOLIATH will generate the world’s first integrated approach to testing and assessment (IATA) specifically tailored to MDCs. With a focus on the main cellular targets of metabolic disruption – hepatocytes, pancreatic endocrine cells, myocytes and adipocytes – GOLIATH will develop new methods and optimise existing methods that span the entire adverse outcome pathway (AOP) spectrum, using in silico predictive modelling and high throughput screening, (pre-)validated ready-to use in vitro assays and optimised in vivo toxicity testing guidelines. GOLIATH will provide key information on the endocrine mode of action by which MDCs disrupt metabolic pathways and induce adverse effects on human health by incorporating multi-omics technologies, and translating results from in vitro and in vivo assays to adverse metabolic health outcomes in humans at real life exposures.
Within the GOLIATH consortium, led by Professor Juliette Legler (University of Utrecht), the Margiotta-Casaluci Lab will specifically lead the AOP development strategy.
For more information, please visit the project website: https://goliath.wp.hum.uu.nl
(2020) The GOLIATH Project: Towards an Internationally Harmonised Approach for Testing Metabolism Disrupting Compounds. 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; Int. J. Mol. Sci. 2020, 21, 3480.