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Mary Gilbert, National Health and Environmental Effects Research Laboratory, US EPA, RTP, NC USA <email@example.com>
Anna Price, European Commission Joint Research Centre, Institute for Health and Consumer Protection, Ispra, Italy <firstname.lastname@example.org>
Kevin Crofton, National Center for Computational Toxicology, US EPA, RTP, NC USA <email@example.com>
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This AOP page was last modified on 12/11/2016.
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This AOP describes one adverse outcome that results from the inhibition of the sodium iodine symporter (NIS) during mammalian development. Inhibition of NIS, the molecular-initiating event (MIE), results in decreased iodine uptake, decreased thyroidal iodine content, subsequent decreased synthesis of thyroid hormones (THs), and reduction in circulating levels of THs. THs are essential for normal human brain development, both prenatally and postnatally. Therefore, chemicals that interfere with TH synthesis have the potential to cause TH insufficiency that may result in adverse neurodevelopmental effects in offspring. This AOP includes changes in brain TH concentrations and subsequent impacts on hippocampal development that lead to declines in cognitive spatial behavior. The weight of evidence for this AOP is strong. And, while there are currently computational quantitative models that can predict serum TH levels from NIS inhibition, there is currently a lack of quantitative understanding of the degree of serum TH disruption that leads to the adverse outcome.
Summary of the AOP
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Molecular Initiating Event
|Molecular Initiating Event||Support for Essentiality|
|Na+/I- symporter (NIS), Inhibition||Strong|
|Cognitive Function, Decreased|
Relationships Among Key Events and the Adverse Outcome
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Life Stage Applicability
|Homo sapiens||Homo sapiens||Strong||NCBI|
Overall Assessment of the AOP
Domain of Applicability
Life Stage Applicability,
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Essentiality of the Key Events
Molecular Initiating Event Summary,
Key Event Summary
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Weight of Evidence Summary
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