WP 3 - Adverse Outcome Pathways
The Adverse Outcome Pathways (AOP) are our means to integrate the knowledge on perturbations by identifying the processes and key events that link chemical exposure to phenotypic effects, and to understand the sequential order of perturbations. We develop physiology-based toxicokinetic (PBTK) models for the zebrafish model system and put particular emphasis on understanding the role of active transport processes. Key molecular initiating events will be captured building on our work with chemoassays, bioanalytical tools and QSAR-type approaches.
The AOP identification are based on exposome and associated omics information from WP 1 and its anchoring with the WP 2 results on exposome-disease associations or exposome-toxicity relationships, targeted experimentation on functional genomics, and organ functional responses. Both the AOP construction and its discrimination from adaptive stress responses rely heavily on bioinformatics. We apply a tiered strategy for constructing bioassay panels in order to prioritise chemicals for risk assessment purposes.