AOP Wiki: A New Tool for Developing and Documenting Adverse Outcome Pathways
Gerald Ankley, United States Environmental Protection Agency
An Adverse Outcome Pathway (AOP) is a conceptual framework that portrays existing knowledge about the linkage between two anchoring points: the molecular initiating event (MIE), and an adverse outcome (AO) that occurs at a level of biological organization relevant to risk assessment (Ankley et al., Environmental Toxicology & Chemistry 29: 730-741). At the heart of an AOP is a description of the causal chain of key events that lead from the MIE to the AO, supported by scientific evidence. The AOP framework is important for expanding the use of mechanistic toxicological data in chemical risk assessment and can guide, for example, the design and development of integrated assessment and testing strategies, weight-of-evidence approaches and computational models.
There are a number of ongoing efforts focused on the development, cataloging and application of AOPs to support both human health and ecological risk assessments. For example, the Organisation for Economic Cooperation and Development (OECD) recently initiated an AOP Development Programme. A key component of this effort involves contributions from an international group of scientists (several of whom are associated with SETAC) from OECD member countries participating in the OECD Extended Advisory Group on Molecular Screening and Toxicogenomics (EAG MST). Activities of the OECD EAG MST have included issuance of guidance on the development and documentation of AOPs, and the initial assembly and review of a candidate set of AOPs. To support this overall effort, an interactive, user-friendly tool is required to capture and communicate AOP information.
An initial version of an IT system to support OECD AOP activities recently was completed through collaborative efforts and contributions of the European Commission's Joint Research Centre (EU JRC), the Office of Research and Development (ORD) of the US Environmental Protection Agency (USEPA), the US Army Corps of Engineers and other parties. The system leads AOP developers through the steps necessary to capture the scientific information needed to document and evaluate an AOP following the recently published OECD guidance, and provides an ideal collaboration space for international AOP-development project teams. The system is quite similar to Wikipedia. A system of user-friendly tables, drop-down boxes and built-in functionality for automatic cross-referencing between related pages makes the system very easy to use. Thanks to the new IT system, AOP developers will be able to create an AOP Wiki page and then link it to related information about MIEs, key events, AOs and chemical initiators. The entry of ontology-based information is simplified by controlled-vocabulary drop-down lists from which to select methods, actions, biological objects, life stages, species, etc. that are related to the AOP being developed. Information regarding key events and AOs shared among multiple AOPs is stored on a single page to eliminate redundant entries and make the collective knowledge about those entities available in all AOPs containing them. This format also facilitates the identification of potential intersections and cross-talk among AOPs.
The system currently is undergoing beta testing. The initial user group is composed of current contributors to the OECD's AOP Development Programme, including members of the EAG MST and the World Health Organization International Programme on Chemical Safety Mode of Action steering group. The beta-testing phase will last until the end of 2013, at which time the AOP Wiki will be modified as needed and made available to the broader scientific and regulatory community.
There will be a special session at the SETAC North America 34th Annual Meeting in Nashville, Tenn. devoted to recent international developments concerning formalization of AOPs for regulatory use, including description of the AOP Wiki. The session, entitled “Integrating Human and Ecological Toxicology Chemical Hazard Assessment via Adverse Outcome Pathways,” will be held on Monday, 18 November. In addition, there are plans to have a demonstration version of the AOP Wiki available at the ORD, USEPA informational exhibit booth at the Nashville meeting.
For more information on the status of the AOP Wiki, please contact Stephen Edwards (USEPA) or Clemens Wittwehr (EU JRC).
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