TY - JOUR
T1 - Putative adverse outcome pathways relevant to neurotoxicity
AU - Bal-Price, Anna
AU - Crofton, Kevin M.
AU - Sachana, Magdalini
AU - Shafer, Timothy J.
AU - Behl, Mamta
AU - Forsby, Anna
AU - Hargreaves, Alan
AU - Landesmann, Brigitte
AU - Lein, Pamela J
AU - Louisse, Jochem
AU - Monnet-Tschudi, Florianne
AU - Paini, Alicia
AU - Rolaki, Alexandra
AU - Schrattenholz, André
AU - Suñol, Cristina
AU - Van Thriel, Christoph
AU - Whelan, Maurice
AU - Fritsche, Ellen
PY - 2015/1/1
Y1 - 2015/1/1
N2 - 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.
AB - 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.
KW - Adverse outcome pathway
KW - In vitro testing
KW - Key events
KW - Molecular initiating event
KW - Pathways of neurotoxicity
KW - Predictive toxicology
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U2 - 10.3109/10408444.2014.981331
DO - 10.3109/10408444.2014.981331
M3 - Article
C2 - 25605028
AN - SCOPUS:84921474981
VL - 45
SP - 83
EP - 91
JO - Critical Reviews in Toxicology
JF - Critical Reviews in Toxicology
SN - 1040-8444
IS - 1
ER -