title: Adverse Outcome Pathways can drive non-animal approaches for safety assessment.
abstract: Adverse Outcome Pathways (AOPs) provide an opportunity to develop new and more accurate safety assessment processes for drugs and other chemicals, and may ultimately play an important role in regulatory decision making. Not only can the development and application of AOPs pave the way for the development of improved evidence-based approaches for hazard and risk assessment, there is also the promise of a significant impact on animal welfare, with a reduced reliance on animal-based methods. The establishment of a useable and coherent knowledge framework under which AOPs will be developed and applied has been a first critical step towards realizing this opportunity. This article explores how the development of AOPs under this framework, and their application in practice, could benefit the science and practice of safety assessment, while in parallel stimulating a move away from traditional methods towards an increased acceptance of non-animal approaches. We discuss here the key areas where current, and future initiatives should be focused to enable the translation of AOPs into routine chemical safety assessment, and lasting 3Rs benefits.
authors.affiliation: NC3Rs, Gibbs Building, 215 Euston Road, London, NW1 2BE, UK.
authors.forename: Natalie
authors.initials: N
authors.lastname: Burden
authors.affiliation: NC3Rs, Gibbs Building, 215 Euston Road, London, NW1 2BE, UK.
authors.forename: Fiona
authors.initials: F
authors.lastname: Sewell
authors.affiliation: Hamner Institutes for Health Sciences, Research Triangle Park, North Carolina, 27709, USA.
authors.forename: Melvin E
authors.initials: ME
authors.lastname: Andersen
authors.affiliation: Imperial College London, Hammersmith Campus, Du Cane Road, London, W12 0NN, UK.
authors.forename: Alan
authors.initials: A
authors.lastname: Boobis
authors.affiliation: University of Birmingham, School of Biosciences, Edgbaston, Birmingham, B15 2TT, UK.
authors.forename: J Kevin
authors.initials: JK
authors.lastname: Chipman
authors.affiliation: Liverpool John Moores University, School of Pharmacy and Biomolecular Sciences, Byrom Street, Liverpool, L3 3AF, UK.
authors.forename: Mark T D
authors.initials: MT
authors.lastname: Cronin
authors.affiliation: Plymouth University, School of Life Sciences, Drake Circus, Plymouth, PL4 8AA, UK.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Hutchinson
authors.affiliation: University of Manchester, Oxford Road, Manchester, M13 9PT, UK.
authors.forename: Ian
authors.initials: I
authors.lastname: Kimber
authors.affiliation: European Commission Joint Research Centre, EU Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM), 20127, Ispra (VA), Italy.
authors.forename: Maurice
authors.initials: M
authors.lastname: Whelan
mesh_terms: D000826:Animal Testing Alternatives / Q000379:methods* / Q000592:standards / Q000639:trends; D003198:Computer Simulation; D003657:Decision Making; D008954:Models, Biological; D018570:Risk Assessment / Q000379:methods* / Q000592:standards; D018675:Toxicity Tests / Q000379:methods* / Q000592:standards / Q000639:trends
keywords: 3Rs; AOP; chemical; mechanism of action; mode of action; pathway; risk; safety assessment; toxicity