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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 chemical 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 the OECD Series on Adverse Outcome Pathways. As scientific knowledge progresses, the publication of an AOP in this series does not preclude the regular update or new contributions to a given AOP in the AOP Wiki. While the AOP Wiki is a dynamic tool, only impactful changes to the AOP will be reflected in subsequent updates of the published AOP. The number 1 in the OECD Series on Adverse Outcome Pathways is the Users’ Handbook, which is a supplement to the Guidance Document for developing and assessing AOPs. This handbook contains an updated template for AOP development and provides focused and practical instructions for both AOP developers and reviewers.

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Adverse Outcome Pathway on aryl hydrocarbon receptor activation leading to early life stage mortality, via increased COX-2

This AOP details the linkage between activation of the aryl hydrocarbon receptor (AhR) and early life stage mortality in oviparous vertebrates. It can be initiated mostly by dioxin-like compounds, which are able to bind to the AhR causing heterodimerisation with the aryl hydrocarbon nuclear translocator (ARNT) and interaction with dioxin-responsive elements on the DNA causing an up-regulation in dioxin responsive genes. One dioxin-responsive gene is cyclooxygenase 2 (COX-2), which has roles in development of the cardiovascular system. Up-regulation in expression of COX-2 causes alteration in cardiovascular development and function resulting in reduced heart pumping efficiency, reduced blood flow, and eventual cardiac collapse and death. Comparable apical manifestations of activation of the AhR have been recorded across freshwater and marine teleost and non-teleost fishes, as well as birds. Despite conservation in the AOP across taxa, great differences in sensitivity to perturbation exist both among and within taxonomic groups.

English

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