Aop:108
Status
This is a legacy representation of this AOP. Please see the current version here:
AOP Title
Authors
Cancer AOP Workgroup. National Health and Environmental Effects Research Laboratory, Office of Research and Development, Integrated Systems Toxicology Division, US Environmental Protection Agency, Research Triangle Park, NC. Corresponding author for wiki entry (wood.charles@epa.gov)
Status
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Under development: Do not distribute or cite.
This AOP page was last modified on 12/11/2016.
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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.
Background (optional)
Summary of the AOP
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Molecular Initiating Event
Molecular Initiating Event | Support for Essentiality |
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Pyruvate dehydrogenase kinase (PDK) enzyme, Inhibition | Strong |
Key Events
Event | Support for Essentiality |
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Oxidative Stress, Increase | |
Cytotoxicity, Increase | |
Induction of pyruvate dehydrogenase (PDH), Increased | Strong |
Oxidative metabolism, Increase | Moderate |
Adverse Outcome
Adverse Outcome |
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Adenomas/carcinomas (hepatocellular), Increase |
Relationships Among Key Events and the Adverse Outcome
Network View
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Life Stage Applicability
Life Stage | Evidence | Links |
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Taxonomic Applicability
Name | Scientific Name | Evidence | Links |
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Mus musculus | Mus musculus | NCBI | |
Rattus norvegicus | Rattus norvegicus | NCBI |
Sex Applicability
Sex | Evidence | Links |
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Male |
Graphical Representation
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Overall Assessment of the AOP
Domain of Applicability
Life Stage Applicability,
Taxonomic Applicability,
Sex Applicability
Elaborate on the domains of applicability listed in the summary section above. Specifically, provide the literature supporting, or excluding, certain domains.
Essentiality of the Key Events
Molecular Initiating Event Summary,
Key Event Summary
Provide an overall assessment of the essentiality for the key events in the AOP. Support calls for individual key events can be included in the molecular initiating event, key event, and adverse outcome tables above.
Weight of Evidence Summary
Summary Table
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Quantitative Considerations
Summary Table
Provide an overall discussion of the quantitative information available for this AOP. Support calls for the individual relationships can be included in the Key Event Relationship table above.
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