The integration of adverse outcome pathways and aggregate exposure pathways for food safety testing: pesticides as a case study

Chemical risk assessment is moving towards non-animal approaches that rely on the mechanistic understanding of toxicity. In this respect, the adverse outcome pathway (AOP) framework is a promising tool to capture chemical-agnostic mechanistic understanding of toxicological processes. AOPs link a molecular initiating event to a specific adverse outcome via a series of key events and key event relationships. Sharing common key features to the AOP framework, the aggregate exposure pathway (AEP) framework is a complementing tool to systematically collect chemical-specific exposure information from the source to the site of action via key exposure states and key transitional relationships. Integrating exposure and toxicological knowledge into combined AEP-AOP constructs can facilitate prediction of chemical-induced toxicity and enable risk-based decision making. The current chapter focuses on the structure, development, assessment, and applications of the AOP and AEP frameworks, illustrated by a case-study on the hepatotoxicity of the metabolites and environmental residues of pesticides.