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THE ADVERSE OUTCOME PATHWAY (AOP) FRAMEWORK: A FRAMEWORK FOR ORGANIZING BIOLOGICAL KNOWLEDGE LEADING TO HEALTH RISKS.
Herr, D. THE ADVERSE OUTCOME PATHWAY (AOP) FRAMEWORK: A FRAMEWORK FOR ORGANIZING BIOLOGICAL KNOWLEDGE LEADING TO HEALTH RISKS. NASA’s 28th Annual Space Radiation Investigator’s Workshop, Galveston, TX, January 23 - 27, 2017.
Talk presented at NASA’s 28th Annual Space Radiation Investigator’s Workshop, Galveston, TX
An Adverse Outcome Pathway (AOP) represents the organization of current and newly acquired knowledge of biological pathways. These pathways contain a series of nodes (Key Events, KEs) that when sufficiently altered influence the next node on the pathway, beginning from an Molecular Initiating Event (MIE), through intermediate KEs, ending in an Adverse Outcome (AO) which may be used as a basis for decision making. A KE is a measurable biological change, and is linked with other KEs via Key Event Relationships (KERs). A given KE may be involved in several AOPs, leading to a plausible network of biological changes that are involved in an organism’s response to an external stressor. When describing an AOP, five guiding principles have been proposed : 1) an AOP is not specific to a single external stressor, 2) AOPs are modular, with KEs and KERs that can be used in several AOPs, 3) a single AOP is the unit of development, 4) most biological responses will be the result of networks of AOPs, and 5) AOPs will be modified as more biological knowledge becomes available. The collaborative development of AOPs is recommended to be performed using the AOP-Wiki (https://aopwiki.org), which is an effort between the European Commission – DG Joint Research Centre (JRC) and U.S. Environmental Protection Agency (EPA). The Wiki is one part of a larger OECD-sponsored AOP Knowledgebase effort, which is a repository for all AOPs developed as part of the Organization for Economic Cooperation and Development (OECD) AOP Development Effort. The evaluation of an AOP is based on a weight-of-evidence format using criteria such as: 1) biological plausibility (the KEs and KERs are consistent with current biological knowledge), 2) KEs are essential (disruption of the KE is required for the AO via this mechanism), 3) concordance of observations (dose-response and temporal relationships; earlier KEs are altered at lower doses and earlier time points that later KEs), 4) consistency (same pattern of effects is observed in multiple species), 5) analogy (same pattern of effects observed by multiple stressors affecting the same KE). Although construction of formal AOPs is a relatively new endeavor, the computerized linking of KEs holds promise for describing complex biological phenomena as knowledge is added to AOP pathways. This is an abstract of a proposed presentation and does not necessarily reflect EPA policy.
Record Details:Record Type: DOCUMENT (PRESENTATION/SLIDE)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY
TOXICOLOGY ASSESSMENT DIVISION