Description du projet
Des essais sur les tétrapodes non amniotes pour tester l’impact des produits chimiques sur la santé humaine
De nombreux produits chimiques que nous utilisons aujourd’hui peuvent avoir un impact négatif sur l’environnement et sur la santé humaine, voire perturber notre système endocrinien. Pour améliorer l’identification et la caractérisation des perturbateurs endocriniens (PE), nous devons mettre au point des outils de dépistage innovants. Les scientifiques du projet ERGO, financé par l’UE, proposent une approche intégrée visant à extrapoler les effets des PE à travers différentes classes de vertébrés. Cela signifie que si un produit chimique a des effets néfastes sur les poissons, il peut également s’avérer dangereux pour l’homme. L’approche ERGO envisage des procédures d’évaluation des dangers et des risques plus rapides, plus sûres et plus simples.
Objectif
ERGO presents a new approach that will support a paradigm shift in the regulatory use of standardized test guidelines (TGs) by breaking the existing wall between mammalian and non-mammalian vertebrate testing and assessment of endocrine disrupting chemicals (EDCs). The highly conserved thyroid system will be used as the “proof of concept”, but also other conserved endocrine axes/systems such as the Retinoid X Receptor (RXR) and the Hypothalamus Pituitary Gonadal (HPG) axis can be adapted to the cross-vertebrate class approach. ERGO will investigate a battery of draft in vitro assays and evaluate thyroid-responsive biomarkers and endpoints (B/E) suitable for extrapolation of effects from fish and amphibian tests to humans and other mammals (and vice versa) and finally validate successful B/E for inclusion in existing in vivo or new in vitro OECD TGs. A cross-class adverse outcome pathway (AOP) network will provide the scientifically plausible and evidence-based foundation for the selection of B/E in lower vertebrate assays predictive of human health outcomes. In silico modeling and biotransformation data will support cross-vertebrate class effect extrapolation. Major outcomes of ERGO will be: 1) New thyroid-related B/E for inclusion in OECD TGs for improved identification of TDC. 2) An Integrated Approach to Testing and Assessment (IATA) of chemicals for TD based on a multi-class vertebrate AOP network connecting endocrine mechanisms in one vertebrate class to adverse outcomes in another class for safer regulation of EDCs. 3) A tool for TG end users, such as regulators and industry, to extrapolate thyroid effects between vertebrate classes. Implementation of the ERGO IATA strategy in regulations of EDC will make hazard and risk assessment faster, cheaper, simpler and safer and support industry in the development of EDC-free products beneficial for environmental and human safety.
Champ scientifique
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RIA - Research and Innovation actionCoordinateur
5230 Odense M
Danemark