OECD Series on Adverse Outcome Pathways
An Adverse Outcome Pathway (AOP) describes a logical sequence of causally linked events at different levels of biological organisation, which follows exposure to a stressor and leads to an adverse health effect in humans or wildlife. AOPs are the central element of a toxicological knowledge framework, promoted by member countries through OECD, built to support chemical risk assessment based on mechanistic reasoning. These AOPs are available in the AOP-Wiki, an interactive and virtual encyclopaedia for AOP development. Following their development and review, the endorsed AOPs are published in the OECD Series on Adverse Outcome Pathways. As scientific knowledge progresses, the publication of an AOP in this series does not preclude regular updates or new contributions to a given AOP. While the AOP-Wiki is a dynamic tool, only impactful changes to the AOP will be reflected in subsequent updates of the published AOP.
- ISSN: 2415170X (online)
- https://doi.org/10.1787/2415170X
Binding of electrophilic chemicals to SH(thiol)-group of proteins and /or to seleno-proteins involved in protection against oxidative stress during brain development leading to impairment of learning and memory
This Adverse Outcome Pathway (AOP) describes the linkage between binding to proteins involved in protection against oxidative stress and impairment in learning and memory. Production, binding and degradation of Reactive Oxygen Radicals are tightly regulated in the body, and an imbalance between production and protection may cause oxidative stress, which is common to many toxicity pathways. Oxidative stress may lead to an imbalance in glutamate neurotransmission, which is involved in learning and memory. Oxidative stress may also cause cellular injury and death. During brain development and in particular during the establishment of neuronal connections and networks, such perturbations may lead to functional impairment in learning and memory. The weight-of-evidence supporting the relationship between the key events described in this AOP is based mainly on developmental effects observed after an exposure to mercury, a heavy metal known for its strong affinity to many proteins having anti-oxidant properties. This AOP is referred to as AOP 17 in the Collaborative Adverse Outcome Pathway Wiki (AOP-Wiki).
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