Modern methodologies and tools for human hazard assessment of chemicals

This scientific report provides a review of modern methodologies and tools to depict toxicokinetic and toxicodynamic processes and their application for the human hazard assessment of chemicals. The application of these methods is illustrated with examples drawn from the literature and international efforts in the field. First, the concepts of mode of action/adverse outcome pathway are discussed together with their associated terminology and recent international developments dealing with human hazard assessment of chemicals. Then modern methodologies and tools are presented including in vitro systems, physiologically-based models, in silico tools and OMICs technologies at the level of DNA/RNA (transcriptomics), proteins (proteomics) and the whole metabolome (metabolomics). Future perspectives for the potential applications of these modern methodologies and tools in the context of prioritisation of chemicals, integrated test strategies and the future of risk assessment are discussed. The report concludes with recommendations for future work and research formulated from consultations of EFSA staff, expert Panels and other international organisations.