title: Putative adverse outcome pathways relevant to neurotoxicity.
abstract: The Adverse Outcome Pathway (AOP) framework provides a template that facilitates understanding of complex biological systems and the pathways of toxicity that result in adverse outcomes (AOs). The AOP starts with an molecular initiating event (MIE) in which a chemical interacts with a biological target(s), followed by a sequential series of KEs, which are cellular, anatomical, and/or functional changes in biological processes, that ultimately result in an AO manifest in individual organisms and populations. It has been developed as a tool for a knowledge-based safety assessment that relies on understanding mechanisms of toxicity, rather than simply observing its adverse outcome. A large number of cellular and molecular processes are known to be crucial to proper development and function of the central (CNS) and peripheral nervous systems (PNS). However, there are relatively few examples of well-documented pathways that include causally linked MIEs and KEs that result in adverse outcomes in the CNS or PNS. As a first step in applying the AOP framework to adverse health outcomes associated with exposure to exogenous neurotoxic substances, the EU Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM) organized a workshop (March 2013, Ispra, Italy) to identify potential AOPs relevant to neurotoxic and developmental neurotoxic outcomes. Although the AOPs outlined during the workshop are not fully described, they could serve as a basis for further, more detailed AOP development and evaluation that could be useful to support human health risk assessment in a variety of ways.
authors.affiliation: European Commission Joint Research Centre, Institute for Health and Consumer Protection , Ispra , Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Bal-Price
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Crofton
authors.forename: Magdalini
authors.initials: M
authors.lastname: Sachana
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Shafer
authors.forename: Mamta
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authors.lastname: Behl
authors.forename: Anna
authors.initials: A
authors.lastname: Forsby
authors.forename: Alan
authors.initials: A
authors.lastname: Hargreaves
authors.forename: Brigitte
authors.initials: B
authors.lastname: Landesmann
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Lein
authors.forename: Jochem
authors.initials: J
authors.lastname: Louisse
authors.forename: Florianne
authors.initials: F
authors.lastname: Monnet-Tschudi
authors.forename: Alicia
authors.initials: A
authors.lastname: Paini
authors.forename: Alexandra
authors.initials: A
authors.lastname: Rolaki
authors.forename: André
authors.initials: A
authors.lastname: Schrattenholz
authors.forename: Cristina
authors.initials: C
authors.lastname: Suñol
authors.forename: Christoph
authors.initials: C
authors.lastname: van Thriel
authors.forename: Maurice
authors.initials: M
authors.lastname: Whelan
authors.forename: Ellen
authors.initials: E
authors.lastname: Fritsche
mesh_terms: D000818:Animals; D004781:Environmental Exposure / Q000009:adverse effects*; D006801:Humans; D020258:Neurotoxicity Syndromes / Q000209:etiology* / Q000503:physiopathology; D018570:Risk Assessment / Q000379:methods*
keywords: adverse outcome pathway; in vitro testing; key events; molecular initiating event; pathways of neurotoxicity; predictive toxicology