API XML

Aop: 36

AOP Title

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Peroxisomal Fatty Acid Beta-Oxidation Inhibition Leading to Steatosis

Short name:

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Peroxisomal Fatty Acid Beta-Oxidation Inhibition Leading to Steatosis

Graphical Representation

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Click to download graphical representation template

Authors

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Michelle Angrish, Brian Chorley, U.S. EPA

Point of Contact

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Michelle Angrish   (email point of contact)

Contributors

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  • Brian Chorley
  • Michelle Angrish
  • Lyle Burgoon

Status

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Author status OECD status OECD project SAAOP status
Under development: Not open for comment. Do not cite 1.29 Under Development


This AOP was last modified on January 27, 2018 15:34

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Revision dates for related pages

Page Revision Date/Time
Decreased, PPAR-alpha activation September 16, 2017 10:14
Decreased, PPAR-beta activation September 16, 2017 10:14
Decreased, PPAR-gamma activation September 16, 2017 10:14
Accumulation, Fatty acid September 16, 2017 10:14
Decreased, HSD17B10 expression September 16, 2017 10:14
Decreased, Mitochondrial fatty acid beta-oxidation September 16, 2017 10:14
Decreased, 3-hydroxyacyl-CoA dehydrogenase type-2 activity September 16, 2017 10:14
Increased, Liver Steatosis November 27, 2017 12:48
Decreased, PPAR-alpha activation leads to Decreased, HSD17B10 expression December 03, 2016 16:37
Decreased, Mitochondrial fatty acid beta-oxidation leads to Accumulation, Fatty acid December 03, 2016 16:37
Decreased, 3-hydroxyacyl-CoA dehydrogenase type-2 activity leads to Decreased, Mitochondrial fatty acid beta-oxidation December 03, 2016 16:37
Decreased, HSD17B10 expression leads to Decreased, 3-hydroxyacyl-CoA dehydrogenase type-2 activity December 03, 2016 16:37
Decreased, PPAR-beta activation leads to Decreased, HSD17B10 expression December 03, 2016 16:37
Decreased, PPAR-gamma activation leads to Decreased, HSD17B10 expression December 03, 2016 16:37
Accumulation, Fatty acid leads to Increased, Liver Steatosis December 03, 2016 16:37

Abstract

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Background (optional)

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Summary of the AOP

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Events: Molecular Initiating Events (MIE)

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Key Events (KE)

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Adverse Outcomes (AO)

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Sequence Type Event ID Title Short name
1 MIE 231 Decreased, PPAR-alpha activation Decreased, PPAR-alpha activation
2 MIE 232 Decreased, PPAR-beta activation Decreased, PPAR-beta activation
3 MIE 233 Decreased, PPAR-gamma activation Decreased, PPAR-gamma activation
4 KE 327 Accumulation, Fatty acid Accumulation, Fatty acid
5 KE 140 Decreased, HSD17B10 expression Decreased, HSD17B10 expression
6 KE 179 Decreased, Mitochondrial fatty acid beta-oxidation Decreased, Mitochondrial fatty acid beta-oxidation
7 KE 8 Decreased, 3-hydroxyacyl-CoA dehydrogenase type-2 activity Decreased, 3-hydroxyacyl-CoA dehydrogenase type-2 activity
8 AO 459 Increased, Liver Steatosis Increased, Liver Steatosis

Relationships Between Two Key Events
(Including MIEs and AOs)

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Title Adjacency Evidence Quantitative Understanding
Decreased, PPAR-alpha activation leads to Decreased, HSD17B10 expression adjacent Moderate
Decreased, Mitochondrial fatty acid beta-oxidation leads to Accumulation, Fatty acid adjacent High
Decreased, 3-hydroxyacyl-CoA dehydrogenase type-2 activity leads to Decreased, Mitochondrial fatty acid beta-oxidation adjacent High
Decreased, HSD17B10 expression leads to Decreased, 3-hydroxyacyl-CoA dehydrogenase type-2 activity adjacent High
Decreased, PPAR-beta activation leads to Decreased, HSD17B10 expression adjacent Moderate
Decreased, PPAR-gamma activation leads to Decreased, HSD17B10 expression adjacent Moderate
Accumulation, Fatty acid leads to Increased, Liver Steatosis adjacent High

Network View

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Stressors

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Life Stage Applicability

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Taxonomic Applicability

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Sex Applicability

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Overall Assessment of the AOP

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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.

Domain of Applicability

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Essentiality of the Key Events

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Evidence Assessment

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Quantitative Understanding

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Considerations for Potential Applications of the AOP (optional)

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References

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