Project description
Lower vertebrate assays for testing the effect of chemicals on human health
Many of the chemicals we use today may have a negative impact on the environment and on human health, possibly disrupting our endocrine system. To improve the identification and characterisation of endocrine disrupting chemicals (EDCs), we need to develop innovative screening tools. Scientists of the EU-funded ERGO project are putting forward an integrated approach that aims to extrapolate the effects of EDCs across different vertebrate classes. This means that if a chemical has adverse effects on fish, it may be dangerous for humans too. The ERGO approach envisions faster, safer and simpler hazard and risk assessment procedures.
Objective
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.
Fields of science
Not validated
Not validated
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Funding Scheme
RIA - Research and Innovation actionCoordinator
5230 Odense M
Denmark