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Beating Goliath: Generation Of NoveL, Integrated and Internationally Harmonised Approaches for Testing Metabolism Disrupting Compounds

Descrizione del progetto

Metodi di test innovativi per gli interferenti endocrini

Gli interferenti endocrini sono sostanze chimiche naturali e antropogeniche che alterano il metabolismo e, in definitiva, provocano obesità e diabete. Il progetto GOLIATH, finanziato dall’UE, si propone di sviluppare un approccio integrato per testare e valutare gli interferenti endocrini. I ricercatori si concentreranno sui principali obiettivi cellulari dell’alterazione metabolica ed elaboreranno modelli predittivi e saggi di screening della tossicità. Questi strumenti, combinati con i dati omici, contribuiranno a decifrare la modalità di azione endocrina e gli effetti avversi degli interferenti endocrini sulla salute umana. I metodi di test di GOLIATH hanno le potenzialità per essere sfruttati per uso normativo, portando all’elaborazione di linee guida molto attese.

Obiettivo

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.

Campo scientifico (EuroSciVoc)

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Meccanismo di finanziamento

RIA - Research and Innovation action

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Invito a presentare proposte

(si apre in una nuova finestra) H2020-SC1-BHC-2018-2020

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Coordinatore

UNIVERSITEIT UTRECHT
Contributo netto dell'UE
€ 1 268 269,88
Costo totale
€ 1 268 269,88

Partecipanti (16)