The ERGO project specifically accommodates the main scopes of the call (SC1-BHC27-2018), where the urgent regulatory need for improved in vivo and in vitro assays to appropriately identify effects related to less studied endocrine-mediated pathways and international harmonization of testing strategies for EDs are requested. ERGO will optimize the use of existing and new ED data in testing strategies by investigating and identifying the correlation between results of various ED testing tiers and vertebrate classes. This novel approach will improve ED identification as well as hazard identification and ultimately risk assessment. The ERGO project has an adverse outcome pathway (AOP) based approach, where multiple modes of thyroid disruption from in silico to adverse in vivo effects in multiple vertebrate classes will be developed. This is fully in line with the scope of the call where AOP-based research and thyroid disruption are highlighted, and it will support the identification of EDs because information about both the adverse effects and the endocrine MoA and causality between the two is required according to the new EU criteria. Validation is also highlighted as essential to speed up regulatory acceptance of tests. In ERGO, international harmonization of ED testing will be ensured because the partners (academia, the industry and regulators) will collaborate with external organizations such as ECHA, OECD, and US EPA and the development and validation of ED-related endpoints and tests will be based on existing or new OECD test guidelines, or guidelines which are in the process of being submitted to the OECD TG Work Program. This international collaboration will facilitate international acceptance of this new multi-class testing approach concerning vertebrates.
Chemicals causing adverse effects in animals and humans by disrupting the endocrine (hormone) system are defined as endocrine disruptors (EDs). Recently, international workshops arranged by EU have identified gaps in the testing of suspected EDs. Regulators therefore request better tests for assessment of the hazards and risks of EDs to protect human health and the environment. Another challenge identified by EU and OECD is that regulatory procedures for identification and assessment of EDs are separated for human health and the environment in both EU and international legislations. Consequently, useful data obtained from nonmammalian vertebrate tests (fish and amphibians) are disregarded from human health assessments and vice-versa even though the endocrine system is highly conserved among vertebrate classes. The workshops pointed out thyroid disruption as a focus area because the existing vertebrate in vivo tests are not protective enough, and validated in vitro tests for thyroid disruption are not yet available. The ERGO project will break the wall between mammalian and non-mammalian vertebrate regulatory testing by identifying, developing and aligning thyroid disrupting biomarkers and endpoints for linkage of effects between different vertebrate classes. A meta-analysis approach will identify relevant biomarkers and endpoints. Establishment of linkage between vertebrate classes will be possible by development of a multi-class network-based adverse outcome pathway (AOP) approach. AOP is a sequential chain of causally linked events at multiple levels of biological organization that lead to an adverse effect. The AOPs will point out biomarkers and endpoints useful for prediction of effects between vertebrate classes. ERGO will re-think ED testing strategies from in silico methods to in vivo testing and develop, optimize and validate OECD guidelines with novel thyroid disrupting endpoints and consequently reduce the requirement of vertebrate animal testing
|Effective start/end date||26/02/2018 → 18/04/2018|