Putative adverse outcome pathways relevant to neurotoxicity

Anna Bal-Price, Kevin M. Crofton, Magdalini Sachana, Timothy J. Shafer, Mamta Behl, Anna Forsby, Alan Hargreaves, Brigitte Landesmann, Pamela J Lein, Jochem Louisse, Florianne Monnet-Tschudi, Alicia Paini, Alexandra Rolaki, André Schrattenholz, Cristina Suñol, Christoph Van Thriel, Maurice Whelan, Ellen Fritsche

Research output: Contribution to journalArticle

59 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)83-91
Number of pages9
JournalCritical Reviews in Toxicology
Volume45
Issue number1
DOIs
StatePublished - Jan 1 2015

Keywords

  • Adverse outcome pathway
  • In vitro testing
  • Key events
  • Molecular initiating event
  • Pathways of neurotoxicity
  • Predictive toxicology

ASJC Scopus subject areas

  • Toxicology

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  • Cite this

    Bal-Price, A., Crofton, K. M., Sachana, M., Shafer, T. J., Behl, M., Forsby, A., Hargreaves, A., Landesmann, B., Lein, P. J., Louisse, J., Monnet-Tschudi, F., Paini, A., Rolaki, A., Schrattenholz, A., Suñol, C., Van Thriel, C., Whelan, M., & Fritsche, E. (2015). Putative adverse outcome pathways relevant to neurotoxicity. Critical Reviews in Toxicology, 45(1), 83-91. https://doi.org/10.3109/10408444.2014.981331