Aop:36

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Status

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

https://aopwiki.org/aops/36


AOP Title

Peroxisomal Fatty Acid Beta-Oxidation Inhibition Leading to Steatosis
Short name: Peroxisomal Fatty Acid Beta-Oxidation Inhibition Leading to Steatosis

Authors

Michelle Angrish, Brian Chorley, U.S. EPA

Status

Please follow the link to snapshots page to view and create Snapshots of this AOP.

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

Under development: Do not distribute or cite.

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

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Abstract

Summary of the AOP

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Molecular Initiating Event

Molecular Initiating Event Support for Essentiality
PPAR-alpha activation, Decreased
PPAR-beta activation, Decreased
PPAR-gamma activation, Decreased

Key Events

Event Support for Essentiality
Fatty acid, Accumulation
HSD17B10 expression, Decreased
Mitochondrial fatty acid beta-oxidation, Decreased
3-hydroxyacyl-CoA dehydrogenase type-2 activity, Decreased

Adverse Outcome

Adverse Outcome
Liver Steatosis, Undefined

Relationships Among Key Events and the Adverse Outcome

Event Description Triggers Weight of Evidence Quantitative Understanding
Fatty acid, Accumulation Directly Leads to Liver Steatosis, Undefined Strong
PPAR-alpha activation, Decreased Directly Leads to HSD17B10 expression, Decreased Moderate
Mitochondrial fatty acid beta-oxidation, Decreased Directly Leads to Fatty acid, Accumulation Strong
3-hydroxyacyl-CoA dehydrogenase type-2 activity, Decreased Directly Leads to Mitochondrial fatty acid beta-oxidation, Decreased Strong
HSD17B10 expression, Decreased Directly Leads to 3-hydroxyacyl-CoA dehydrogenase type-2 activity, Decreased Strong
PPAR-beta activation, Decreased Directly Leads to HSD17B10 expression, Decreased Moderate
PPAR-gamma activation, Decreased Directly Leads to HSD17B10 expression, Decreased Moderate

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Life Stage Applicability

Life Stage Evidence Links

Taxonomic Applicability

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Sex Applicability

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Graphical Representation

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Overall Assessment of the AOP

Consider the following criteria (may include references to KE Relationship pages): 1. concordance of dose-response relationships; 2. temporal concordance among the key events and adverse effect; 3. strength, consistency, and specificity of association of adverse effect and initiating event; 4. biological plausibility, coherence, and consistency of the experimental evidence; 5. alternative mechanisms that logically present themselves and the extent to which they may distract from the postulated AOP. It should be noted that alternative mechanisms of action, if supported, require a separate AOP; 6. uncertainties, inconsistencies and data gaps.

Weight of Evidence Summary

Summary Table
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Essentiality of the Key Events

Molecular Initiating Event Summary, Key Event Summary
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Quantitative Considerations

Summary Table
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Applicability of the AOP

Life Stage Applicability, Taxonomic Applicability, Sex Applicability
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Considerations for Potential Applications of the AOP (optional)

References