The AOP Concept: How Novel Technologies Can Support Development of Adverse Outcome Pathways
Although the introduction of the adverse outcome pathway (AOP) concept has already triggered a strong increase in the awareness that toxicological activity also needs to be studied at the molecular and cell biological level, the practical implementation of the AOP concept faces a multitude of challenges. The AOP concept first requires the dissection of the observed adverse outcome (AO) into individual events and their subsequent composition into simplified linear AOPs. However, for most adverse effects there is hardly sufficient information about the underlying molecular mechanisms available. To describe relevant events that lead to AOs, the use of high-throughput, high-content, and omics approaches seems to be particularly suitable, if they can be integrated in a standardized and systematic way. Subsequently, the complex molecular and cellular interactions of a linear AOP have to be combined in AOP networks to describe toxicological responses in an intact organism. Finally, essential key events (KE) within the whole network have to be identified and robust in silico, in chemico, or in vitro assays reflecting the molecular or cellular principles underlying these central KE have to be developed and integrated into reliable and predictive testing strategies. Here we discuss some of the challenges ahead that need to be addressed to allow the AOP concept to live up to its promises.