Description du projet
Nouvelles méthodes de test pour les produits chimiques perturbateurs du métabolisme
Les produits chimiques perturbateurs du métabolisme (MDC) sont des produits chimiques naturels et anthropiques qui perturbent le métabolisme et entraînent finalement l’obésité et le diabète. Le projet GOLIATH, financé par l’UE, vise à développer une approche intégrée pour tester et évaluer les MDC. Les chercheurs se concentreront sur les principales cibles cellulaires de la perturbation métabolique et développeront des modèles prédictifs ainsi que des tests de dépistage de la toxicité. Combinés aux données omiques, ces outils permettront de décrypter le mode d’action endocrinien et les effets néfastes des MDC sur la santé humaine. Les méthodes de test de GOLIATH pourraient être exploitées à des fins réglementaires, conduisant à des lignes directrices très attendues.
Objectif
GOLIATH addresses the work programme topic ‘SC1-BHC-27-2018: New testing and screening methods to identify endocrine disrupting chemicals (EDCs)’ by focussing on one of the most urgent regulatory needs, 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. Given the importance of international acceptance of the developed test methods for regulatory use, GOLIATH will link with ongoing initiatives of the OECD for test method (pre-)validation, IATA and AOP development. With a consortium comprised of world-leading experts in endocrinology, molecular biology, toxicology, epidemiology, test method development, validation and chemical regulation, GOLIATH will be pivotal in the development of an internationally harmonised strategy for testing MDCs, and help to reduce the worldwide rise in metabolic disorders that have reached ‘Goliathan’ proportions.
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RIA - Research and Innovation actionCoordinateur
3584 CS Utrecht
Pays-Bas