What is an Adverse Outcome Pathway (AOP)
In 2012, the OECD launched a new programme on the development of Adverse Outcome Pathways. An Adverse Outcome Pathway (AOP) is an analytical construct that describes a sequential chain of causally linked events at different levels of biological organisation that lead to an adverse health or ecotoxicological effect (see figure). AOPs are the central element of a toxicological knowledge framework being built to support chemical risk assessment based on mechanistic reasoning.
Figure: schematic representation of the Adverse Outcome Pathway (AOP) illustrated with reference to a number of pathways.
The AOP development programme addresses the needs of:
- the OECD Test Guidelines Programme for the identification of new in vitro test methods that are candidates to become OECD Test Guidelines;
- The OECD QSAR Project for the identification of new methods/profilers for grouping chemicals, and;
- the OECD Hazard Assessment activities for the development of Integrated Approaches to Testing and Assessment (IATA), also known as Integrated Testing Strategies, for defined hazard endpoints.
The OECD co-ordinates its activities with the WHO/IPCS work on Mode of Action, as the AOP concept and the Mode of Action are closely related.
How to make a project proposal
Project proposals for developing an AOP can be sent to the OECD Secretariat using the submission of proposals form (word file). Government representatives, academic experts, industry experts, non-governmental organisations, scientific societies, etc. can submit project proposals. The National Coordinators of the Test Guidelines Programme are also available for queries, and should be informed about proposals submitted.
Project proposals are reviewed twice a year and included in the workplan if justified. A list of projects already in the workplan is available here.
Process for the development of AOP at OECD
This flow diagram (PDF) shows how AOPs are developed, reviewed, agreed and published at the OECD. The publication of an AOP descriptive document in the Series on Testing and Assessment does not preclude the publication by authors of the AOP of scientific articles in the peer-reviewed literature; in fact, the working group supports broad distribution of the resulting products.
Most of the AOP development and review is intended to take place via a web-based IT management tool (“AOP Knowledge Base”) which was publically launched in September 2014.
Once developed and reviewed by the Advisory Group on Molecular Screening and Toxicogenomics, and other relevant expert groups under the Test Guidelines Programme, the AOP is endorsed by the Working Group of the National Coordinators of the Test Guidelines Programme and the Task Force on Hazard Assessment, and declassified by the Joint Meeting overseeing the OECD work on chemical safety.
AOP Knowledge Base
The AOP Knowledge Base (AOP KB) is a web-based platform which aims to bring together all knowledge on how chemicals can induce adverse effects, therefore providing a focal point for AOP development and dissemination. The project is jointly led by the OECD, the U.S. Environmental Protection Agency and the European Commission's Joint Research Center.
- The first AOP KB module is the AOP Wiki: an interactive and virtual encyclopaedia for AOP development. It is structured in accordance with the original OECD "Guidance document and a template for developing and assessing adverse outcome pathways" (Series No. 184, Series on Testing and Assessment) and the more recent Handbook for AOP developers. The Wiki provides developers the necessary steps to capture the scientific information in a user-friendly manner.
- In the future, it is forseen that other modules of the AOP KB, e.g. Effectopedia, become available. Effectopedia is a knowledge aggregation and modeling platform designed for collaborative development and utilisation of AOPs. Originally built as a standalone project, Effectopedia is currently integrated as part of AOP KB. Effectopedia has a visually expressed modular structure providing easy-to-interpret summary information, supporting experimental evidence, as well as detailed descriptions of the underlying data and assumptions. This design places it at the forefront of AOP research, helping industry, governments and regulatory agencies to make toxicological predictions while simultaneously keeping the information open and accessible for nonprofit organisations and the general public. The first quantitive AOP examples are currently being developed in Effectopedia and are expected to become publically available in the summer of 2015.