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AOP: 96
Title
Axonal sodium channel modulation leading to acute mortality
Short name
Graphical Representation
Point of Contact
Contributors
- Kellie Fay
Coaches
OECD Information Table
OECD Project # | OECD Status | Reviewer's Reports | Journal-format Article | OECD iLibrary Published Version |
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1.29 |
This AOP was last modified on April 29, 2023 16:02
Revision dates for related pages
Page | Revision Date/Time |
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modulation, sodium channel | September 16, 2017 10:15 |
prolonged, Depolarization of neuronal membrane | September 16, 2017 10:15 |
Overactivation, Neuronotransmitter release | September 16, 2017 10:15 |
Overactivation, muscle contraction | September 16, 2017 10:15 |
Increased, Ataxia, paralysis, or hyperactivity | September 16, 2017 10:15 |
Increased Mortality | July 08, 2022 07:32 |
modulation, sodium channel leads to prolonged, Depolarization of neuronal membrane | December 03, 2016 16:37 |
prolonged, Depolarization of neuronal membrane leads to Overactivation, Neuronotransmitter release | December 03, 2016 16:37 |
Overactivation, Neuronotransmitter release leads to Overactivation, muscle contraction | December 03, 2016 16:37 |
Overactivation, muscle contraction leads to Increased, Ataxia, paralysis, or hyperactivity | December 03, 2016 16:37 |
Increased, Ataxia, paralysis, or hyperactivity leads to Increased Mortality | December 03, 2016 16:37 |
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.
AOP Development Strategy
Context
Strategy
Summary of the AOP
Events:
Molecular Initiating Events (MIE)
Key Events (KE)
Adverse Outcomes (AO)
Type | Event ID | Title | Short name |
---|
MIE | 598 | modulation, sodium channel | modulation, sodium channel |
KE | 599 | prolonged, Depolarization of neuronal membrane | prolonged, Depolarization of neuronal membrane |
KE | 600 | Overactivation, Neuronotransmitter release | Overactivation, Neuronotransmitter release |
KE | 601 | Overactivation, muscle contraction | Overactivation, muscle contraction |
KE | 602 | Increased, Ataxia, paralysis, or hyperactivity | Increased, Ataxia, paralysis, or hyperactivity |
AO | 351 | Increased Mortality | Increased Mortality |
Relationships Between Two Key Events (Including MIEs and AOs)
Title | Adjacency | Evidence | Quantitative Understanding |
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Network View
Prototypical Stressors
Life Stage Applicability
Life stage | Evidence |
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During development and at adulthood |