title: Applying Adverse Outcome Pathways (AOPs) to support Integrated Approaches to Testing and Assessment (IATA).
abstract: Chemical regulation is challenged by the large number of chemicals requiring assessment for potential human health and environmental impacts. Current approaches are too resource intensive in terms of time, money and animal use to evaluate all chemicals under development or already on the market. The need for timely and robust decision making demands that regulatory toxicity testing becomes more cost-effective and efficient. One way to realize this goal is by being more strategic in directing testing resources; focusing on chemicals of highest concern, limiting testing to the most probable hazards, or targeting the most vulnerable species. Hypothesis driven Integrated Approaches to Testing and Assessment (IATA) have been proposed as practical solutions to such strategic testing. In parallel, the development of the Adverse Outcome Pathway (AOP) framework, which provides information on the causal links between a molecular initiating event (MIE), intermediate key events (KEs) and an adverse outcome (AO) of regulatory concern, offers the biological context to facilitate development of IATA for regulatory decision making. This manuscript summarizes discussions at the Workshop entitled "Advancing AOPs for Integrated Toxicology and Regulatory Applications" with particular focus on the role AOPs play in informing the development of IATA for different regulatory purposes.
authors.affiliation: Norwegian Institute for Water Research (NIVA), Gaustadalléen 21, N-0349 Oslo, Norway. Electronic address: knut.erik.tollefsen@niva.no.
authors.forename: Knut Erik
authors.initials: KE
authors.lastname: Tollefsen
authors.affiliation: UFZ - Helmholtz Centre for Environmental Research, Department of Bioanalytical Ecotoxicology, Permoserstr. 15, 04318 Leipzig, Germany. Electronic address: stefan.scholz@ufz.de.
authors.forename: Stefan
authors.initials: S
authors.lastname: Scholz
authors.affiliation: Liverpool John Moores University, School of Pharmacy and Biomolecular Sciences, Byrom Street, Liverpool L3 3AF, UK. Electronic address: M.T.Cronin@ljmu.ac.uk.
authors.forename: Mark T
authors.initials: MT
authors.lastname: Cronin
authors.affiliation: U.S. Environmental Protection Agency, Office of Research and Development (ORD), Research Triangle Park (RTP), NC 2771, USA. Electronic address: Edwards.Stephen@epa.gov.
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Edwards
authors.affiliation: Environment Health and Safety Division, Environment Directorate, Organisation for Economic Co-operation and Development (OECD), 2 rue André Pascal, 75775 Paris Cedex 16, France. Electronic address: Joop.DEKNECHT@oecd.org.
authors.forename: Joop
authors.initials: J
authors.lastname: de Knecht
authors.affiliation: U.S. Environmental Protection Agency, Office of Research and Development (ORD), Research Triangle Park (RTP), NC 2771, USA. Electronic address: Crofton.Kevin@epa.gov.
authors.forename: Kevin
authors.initials: K
authors.lastname: Crofton
authors.affiliation: Institute for Genomics, Biocomputing & Biotechnology, Mississippi State University, Starkville, MS, USA. Electronic address: natalia@icnanotox.org.
authors.forename: Natalia
authors.initials: N
authors.lastname: Garcia-Reyero
authors.affiliation: Johns Hopkins University, Bloomberg School of Public Health, Center for Alternatives to Animal Testing (CAAT), 615 N Wolfe St, Baltimore, MD 21205, USA. Electronic address: thartung@jhsph.edu.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hartung
authors.affiliation: European Commission-Joint Research Centre, Institute for Health & Consumer Protection, Systems Toxicology Unit, Via E. Fermi, Ispra, Varese, Italy. Electronic address: Andrew.WORTH@ec.europa.eu.
authors.forename: Andrew
authors.initials: A
authors.lastname: Worth
authors.affiliation: DuPont Haskell Global Centers for Health and Environmental Sciences, Stine-Haskell 320/212, 1090 Elkton Road, Newark, DE 19711, USA. Electronic address: patlewig@hotmail.com.
authors.forename: Grace
authors.initials: G
authors.lastname: Patlewicz
mesh_terms: D000826:Animal Testing Alternatives; D000818:Animals; D003198:Computer Simulation; D003657:Decision Making; D033161:Government Regulation; D057166:High-Throughput Screening Assays; D006801:Humans; D018570:Risk Assessment / Q000379:methods*; D018675:Toxicity Tests
keywords: (Q)SAR; Adverse Outcome Pathway (AOP); Cross species extrapolation; High content screening (HCS); High throughput screening (HTS); Integrated Approaches to Testing and Assessment (IATA); Read-across