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.


Adverse Outcome Pathway on inhibition of Thyroperoxidase and subsequent adverse neurodevelopmental outcomes in mammals

This AOP describes one adverse outcome that may result from the inhibition of thyroperoxidase (TPO) during mammalian development. Chemical inhibition of TPO results in decreased thyroid hormone (TH) synthesis, and subsequent reduction in circulating concentrations of THs. THs are essential for normal human brain development, both prenatally and postnatally, modulating genes critical for a normal neuroanatomical development, with subsequent effects on neurophysiology, and finally neurological function. Therefore, chemicals that interfere with TH synthesis have the potential to cause TH insufficiency that may result in adverse neurodevelopmental effects in offspring. Herein, we discuss the implications of developmental TPO inhibition for hippocampal anatomy, function, and ultimately neural function. The hippocampus is known to be critically involved in cognitive, emotional, and memory function. The adverse consequences of TH insufficiency depend both on severity and developmental timing, indicating that exposure to TPO inhibitors may produce different effects at different developmental windows of exposure.


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