Report on the comparative outcome of using new mechanism-based testing and consequences for animal testing and uncertainties in risk assessment

KI will make a proposal of the relevant elements to integrate in a tiered assessment strategy (milestone 8.3). The web-based EuroMix tool developed in WP6 will be used for test runs of case studies (identified in WP2-WP4) to test the proposed criteria. The extensive toxicological testing from a wide range of techniques and experimental models, including e.g. in-silico, in-vitro, in-vivo, and PB-PK/D experiments, conducted by EuroMix will provide an excellent basis to evaluate the outcome of proposed approach as compared with current methods/models for risk assessment, and the pro’s and con’s of different approaches will be discussed. The results will be described in deliverable 8.5 (M45) and will be used in WP9 and WP10. KI, in cooperation with INRIS, RIVM, UMIL, DLO-B and DEFRA will elaborate on the consequences for animal testing once the mechanism-based test strategy has been developed. The use of PB-PK modelling, IVIVE and system toxicology should reduce the uncertainties in current risk assessment approaches, and the new uncertainty components of the EuroMix tool (Task 6.5) will be used to evaluate this. KI will write a discussion document for exchanging views with stakeholders, including 3R-focused organisations. Input is required from several work packages (see task 3.4 and 4.4) and The results will be used in WP9 and WP10 for guidance, training and implementation (deliverable D8.5; M45)