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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 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.

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Disruption of VEGFR signaling leading to developmental defects

The cardiovascular system is the first functional organ system to develop in the vertebrate embryo, reflecting its critical role during normal development and pregnancy. This Adverse Outcome Pathway focuses on the regulation and disruption of vasculogenesis-angiogenesis during embryonic development via disruption of the Vascular Endothelial Growth Factor (VEGF) signaling pathway. This pathway is a critical regulatory system for assembly of embryonic blood vessels. Genetic studies have shown that perturbing the VEGF signaling system can invoke varying degrees of adverse consequences, ranging from congenital angiodysplasia to fetal malformations and embryolethality. This AOP is referred to as AOP 43 in the Collaborative Adverse Outcome Pathway Wiki (AOP-Wiki).

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