Adverse Outcome Pathways: An update on progress and some near-term applications
Kristie Sullivan (1) and Mathieu Vinken (2)
1 Physicians Committee for Responsible Medicine, Washington, DC
2 Department of In Vitro Toxicology and Dermato-Cosmetology, Vrije Universiteit Brussel, Belgium.
Adverse outcome pathways are currently gaining momentum, especially in view of their many potential applications as pragmatic tools in the fields of human toxicology, ecotoxicology and risk assessment. Among the many applications of adverse outcome pathways are the establishment of (quantitative) structure-activity relationships, the development of novel in vitro toxicity screening tests, and the elaboration of integrated approaches to testing and assessment. The specific application of an adverse outcome pathway is dictated by its degree of maturity. In this respect, the vast majority of currently available adverse outcome pathways are qualitative in nature and/or focus on only one molecular initiating event and a linear series of adverse key events. This may be sufficient for some purposes, yet most applications in toxicology and risk assessment require a more advanced level of adverse outcome pathway development. In this webinar, the cases of skin and respiratory sensitization will be discussed to demonstrate how an AOP can lead to the regulatory applicability of integrated approaches to testing and assessment (IATA). Discussion of the evolution of the OECD AOP and Test Guidelines Programmes in this context will be provided. Furthermore, focus will be put on cholestatic liver toxicity, for which an adverse outcome pathway network is currently being developed that may serve as the basis of an innovative in vitro testing platform