From AOP-Wiki
Jump to: navigation, search


This is a legacy representation of this AOP. Please see the current version here:

AOP Title

Axonal sodium channel modulation leading to acute mortality
Short name: sodium channel modulation


Kellie Fay


OECD Project 1.29: A catalog of putative AOPs that will enhance the utility of US EPA Toxcast high throughput screening data for hazard identification Please follow the link to snapshots page to view and create Snapshots of this AOP.

Under development: Do not distribute or cite.

This AOP page was last modified on 12/11/2016.

Click here to show/hide revision dates for related pages

Page Revision Date/Time


The voltage-gated sodium channels present on neuronal axons are the primary molecular target of pyrethroid insecticides. These chemicals selectively bind open sodium channels, allowing continuous entry of sodium ions into the cell. This hyperdepolarization of the nerve membrane results in a prolonged tail current, uncontrolled firing and neurotransmitter release. Ultimately, ataxia, paralysis and death result.

Background (optional)

Summary of the AOP

Please follow link to widget page to edit this section.

If you manually enter text in this section, it will get automatically altered or deleted in subsequent edits using the widgets.

Molecular Initiating Event

Molecular Initiating Event Support for Essentiality
sodium channel, modulation

Key Events

Event Support for Essentiality
Depolarization of neuronal membrane, prolonged
Neuronotransmitter release, Overactivation
muscle contraction, Overactivation
Ataxia, paralysis, or hyperactivity, Increased

Adverse Outcome

Adverse Outcome
Mortality, Increased

Relationships Among Key Events and the Adverse Outcome

Event Description Triggers Weight of Evidence Quantitative Understanding
sodium channel, modulation Directly Leads to Depolarization of neuronal membrane, prolonged
Depolarization of neuronal membrane, prolonged Directly Leads to Neuronotransmitter release, Overactivation
Neuronotransmitter release, Overactivation Indirectly Leads to muscle contraction, Overactivation
muscle contraction, Overactivation Directly Leads to Ataxia, paralysis, or hyperactivity, Increased
Ataxia, paralysis, or hyperactivity, Increased Directly Leads to Mortality, Increased

Network View

   Cytoscape Web will replace the contents of this div with your graph.

Click nodes or edges.

Life Stage Applicability

Life Stage Evidence Links
During development and at adulthood

Taxonomic Applicability

Name Scientific Name Evidence Links

Sex Applicability

Sex Evidence Links

Graphical Representation

Click to upload graphical representation

Overall Assessment of the AOP

Domain of Applicability

Life Stage Applicability, Taxonomic Applicability, Sex Applicability
Elaborate on the domains of applicability listed in the summary section above. Specifically, provide the literature supporting, or excluding, certain domains.

Essentiality of the Key Events

Molecular Initiating Event Summary, Key Event Summary
Provide an overall assessment of the essentiality for the key events in the AOP. Support calls for individual key events can be included in the molecular initiating event, key event, and adverse outcome tables above.

Weight of Evidence Summary

Summary Table
Provide an overall summary of the weight of evidence based on the evaluations of the individual linkages from the Key Event Relationship pages.

Quantitative Considerations

Summary Table
Provide an overall discussion of the quantitative information available for this AOP. Support calls for the individual relationships can be included in the Key Event Relationship table above.

Considerations for Potential Applications of the AOP (optional)