title: Adverse outcome pathways: From research to regulation scientific workshop report.
abstract: An adverse outcome pathway (AOP) helps to organize existing knowledge on chemical mode of action, starting with a molecular initiating event such as receptor binding, continuing through key events, and ending with an adverse outcome such as reproductive impairment. AOPs can help identify knowledge gaps where more research is needed to understand the underlying mechanisms, aid in chemical hazard characterization, and guide the development of new testing approaches that use fewer or no animals. A September 2014 workshop in Bethesda, Maryland considered how the AOP concept could improve regulatory assessments of chemical toxicity. Scientists from 21 countries, representing industry, academia, regulatory agencies, and special interest groups, attended the workshop, titled Adverse Outcome Pathways: From Research to Regulation. Workshop plenary presentations were followed by breakout sessions that considered regulatory acceptance of AOPs and AOP-based tools, criteria for building confidence in an AOP for regulatory use, and requirements to build quantitative AOPs and AOP networks. Discussions during the closing session emphasized a need to increase transparent and inclusive collaboration, especially with disciplines outside of toxicology. Additionally, to increase impact, working groups should be established to systematically prioritize and develop AOPs. Multiple collaborative projects and follow-up activities resulted from the workshop.
authors.affiliation: National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA. Electronic address: Nicole.kleinstreuer@nih.gov.
authors.forename: Nicole C
authors.initials: NC
authors.lastname: Kleinstreuer
authors.affiliation: Physicians Committee for Responsible Medicine, Washington, DC, USA.
authors.forename: Kristie
authors.initials: K
authors.lastname: Sullivan
authors.affiliation: Integrated Laboratory Systems, Inc., Research Triangle Park, NC, USA.
authors.forename: David
authors.initials: D
authors.lastname: Allen
authors.affiliation: National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Edwards
authors.affiliation: National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR, USA.
authors.forename: Donna L
authors.initials: DL
authors.lastname: Mendrick
authors.affiliation: ILSI Health and Environmental Sciences Institute, Washington, DC, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Embry
authors.affiliation: U.S. Consumer Product Safety Commission, Rockville, MD, USA.
authors.forename: Joanna
authors.initials: J
authors.lastname: Matheson
authors.affiliation: The Dow Chemical Company, Midland, MI, USA.
authors.forename: J Craig
authors.initials: JC
authors.lastname: Rowlands
authors.affiliation: Joint Research Centre, European Commission, Ispra, Italy.
authors.forename: Sharon
authors.initials: S
authors.lastname: Munn
authors.affiliation: National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Maull
authors.affiliation: National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.
authors.forename: Warren
authors.initials: W
authors.lastname: Casey
mesh_terms: D000826:Animal Testing Alternatives; D000818:Animals; D003198:Computer Simulation; D064420:Drug-Related Side Effects and Adverse Reactions / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D008954:Models, Biological; D008958:Models, Molecular; D011786:Quality Control; D015203:Reproducibility of Results; D018570:Risk Assessment; D015398:Signal Transduction / Q000187:drug effects*; D013329:Structure-Activity Relationship; D018675:Toxicity Tests / Q000592:standards
keywords: AOP; Acceptance; Application; Computational; Criteria; Pathway; Quantitative; Regulatory; Toxicology; Workshop