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AOP: 108
Title
Inhibition of pyruvate dehydrogenase kinase leading to hepatocellular adenomas and carcinomas (in mouse and rat)
Short name
Graphical Representation
Point of Contact
Contributors
- Charles Wood
Coaches
OECD Information Table
OECD Project # | OECD Status | Reviewer's Reports | Journal-format Article | OECD iLibrary Published Version |
---|---|---|---|---|
1.29 |
This AOP was last modified on April 29, 2023 16:02
Revision dates for related pages
Page | Revision Date/Time |
---|---|
Increase, hepatocellular adenomas and carcinomas | December 26, 2020 10:09 |
Increase, Cytotoxicity | September 16, 2017 10:16 |
Peptide Oxidation | November 13, 2017 10:22 |
Increased, Induction of pyruvate dehydrogenase (PDH) | December 03, 2016 16:37 |
Inhibition, Pyruvate dehydrogenase kinase (PDK) enzyme | December 03, 2016 16:37 |
Increase, Oxidative metabolism | December 03, 2016 16:37 |
Inhibition, Pyruvate dehydrogenase kinase (PDK) enzyme leads to Increased, Induction of pyruvate dehydrogenase (PDH) | December 03, 2016 16:37 |
Increased, Induction of pyruvate dehydrogenase (PDH) leads to Increase, Oxidative metabolism | December 03, 2016 16:38 |
Increase, Oxidative metabolism leads to Peptide Oxidation | December 03, 2016 16:38 |
Peptide Oxidation leads to Increase, Cytotoxicity | December 03, 2016 16:38 |
Increase, Cytotoxicity leads to Increase, hepatocellular adenomas and carcinomas | December 03, 2016 16:38 |
Abstract
This putative adverse outcome pathway (AOP) outlines potential key events leading to a tumor outcome in standard carcinogenicity models. This information is based largely on modes of action described previously in cited literature sources and is intended as a resource template for AOP development and data organization. Presentation in this Wiki does not indicate EPA acceptance of a particular pathway for a given reference agent, only that the information has been proposed in some manner. In addition, this putative AOP relates to the model species indicated and does not directly address issues of human relevance.
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 | 724 | Inhibition, Pyruvate dehydrogenase kinase (PDK) enzyme | Inhibition, Pyruvate dehydrogenase kinase (PDK) enzyme |
KE | 768 | Increase, Cytotoxicity | Increase, Cytotoxicity |
KE | 209 | Peptide Oxidation | Peptide Oxidation |
KE | 726 | Increased, Induction of pyruvate dehydrogenase (PDH) | Increased, Induction of pyruvate dehydrogenase (PDH) |
KE | 769 | Increase, Oxidative metabolism | Increase, Oxidative metabolism |
AO | 719 | Increase, hepatocellular adenomas and carcinomas | Increase, hepatocellular adenomas and carcinomas |
Relationships Between Two Key Events (Including MIEs and AOs)
Title | Adjacency | Evidence | Quantitative Understanding |
---|
Network View
Prototypical Stressors
Life Stage Applicability
Taxonomic Applicability
Sex Applicability
Sex | Evidence |
---|---|
Male |
Overall Assessment of the AOP
Domain of Applicability
Essentiality of the Key Events
Evidence Assessment
Known Modulating Factors
Quantitative Understanding
Considerations for Potential Applications of the AOP (optional)
References
U.S. Environmental Protection Agency (Aug 2003). Toxicological Review of Dichloroacetic Acid: In Support of Summary Information on the Integrated Risk Information System (IRIS) (Vol. EPA 635/R-03/007). Washington, DC