title: Adverse Outcome Pathways-Organizing Toxicological Information to Improve Decision Making.
abstract: The number of chemicals for which environmental regulatory decisions are required far exceeds the current capacity for toxicity testing. High-throughput screening commonly used for drug discovery has the potential to increase this capacity. The adverse outcome pathway (AOP) concept has emerged as a framework for connecting high-throughput toxicity testing (HTT) and other results to potential impacts on human and wildlife populations. As a result of international efforts, the AOP development process is now well-defined and efforts are underway to broaden the participation through outreach and training. One key principle is that AOPs represent the chemical-agnostic portions of pathways to increase the generalizability of their application from early key events to overt toxicity. The closely related mode of action framework extends the AOP as needed when evaluating the potential risk of a specific chemical. This in turn enables integrated approaches to testing and assessment (IATA), which incorporate results of assays at various levels of biologic organization such as in silico; HTT; chemical-specific aspects including absorption, distribution, metabolism, and excretion (ADME); and an AOP describing the biologic basis of toxicity. Thus, it is envisaged that provision of limited information regarding both the AOP for critical effects and the ADME for any chemical associated with any adverse outcome would allow for the development of IATA and permit more detailed AOP and ADME research, where higher precision is needed based on the decision context.
authors.affiliation: Integrated Systems Toxicology Division, National Health and Environmental Effects Research Laboratory (S.W.E., C.A.M.), and Human Exposure & Atmospheric Sciences Division, National Exposure Research Laboratory (Y.-M.T.), Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina; Mid-Continent Ecology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Duluth, Minnesota (D.L.V.); and McLaughlin Centre for Risk Science, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada (M.E.M.) Edwards.stephen@epa.gov.
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Edwards
authors.affiliation: Integrated Systems Toxicology Division, National Health and Environmental Effects Research Laboratory (S.W.E., C.A.M.), and Human Exposure & Atmospheric Sciences Division, National Exposure Research Laboratory (Y.-M.T.), Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina; Mid-Continent Ecology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Duluth, Minnesota (D.L.V.); and McLaughlin Centre for Risk Science, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada (M.E.M.).
authors.forename: Yu-Mei
authors.initials: YM
authors.lastname: Tan
authors.affiliation: Integrated Systems Toxicology Division, National Health and Environmental Effects Research Laboratory (S.W.E., C.A.M.), and Human Exposure & Atmospheric Sciences Division, National Exposure Research Laboratory (Y.-M.T.), Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina; Mid-Continent Ecology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Duluth, Minnesota (D.L.V.); and McLaughlin Centre for Risk Science, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada (M.E.M.).
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Villeneuve
authors.affiliation: Integrated Systems Toxicology Division, National Health and Environmental Effects Research Laboratory (S.W.E., C.A.M.), and Human Exposure & Atmospheric Sciences Division, National Exposure Research Laboratory (Y.-M.T.), Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina; Mid-Continent Ecology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Duluth, Minnesota (D.L.V.); and McLaughlin Centre for Risk Science, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada (M.E.M.).
authors.forename: M E
authors.initials: ME
authors.lastname: Meek
authors.affiliation: Integrated Systems Toxicology Division, National Health and Environmental Effects Research Laboratory (S.W.E., C.A.M.), and Human Exposure & Atmospheric Sciences Division, National Exposure Research Laboratory (Y.-M.T.), Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina; Mid-Continent Ecology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Duluth, Minnesota (D.L.V.); and McLaughlin Centre for Risk Science, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada (M.E.M.).
authors.forename: Charlene A
authors.initials: CA
authors.lastname: McQueen
mesh_terms: D000818:Animals; D003198:Computer Simulation; D064420:Drug-Related Side Effects and Adverse Reactions; D057166:High-Throughput Screening Assays; D006801:Humans; D019451:Information Management / Q000379:methods*; D004364:Pharmaceutical Preparations / Q000378:metabolism; D010599:Pharmacokinetics; D014018:Tissue Distribution; D014116:Toxicology / Q000458:organization & administration*
chemical_list: D004364:Pharmaceutical Preparations