Aop:96

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Status

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

https://aopwiki.org/aops/96


AOP Title

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

Authors

Kellie Fay

Status

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.

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Abstract

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

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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

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Life Stage Applicability

Life Stage Evidence Links
During development and at adulthood

Taxonomic Applicability

Name Scientific Name Evidence Links
insects
fish

Sex Applicability

Sex Evidence Links

Graphical Representation

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Overall Assessment of the AOP

Domain of Applicability

Life Stage Applicability, Taxonomic Applicability, Sex 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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Quantitative Considerations

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Considerations for Potential Applications of the AOP (optional)

References