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

AOP Title

PPARalpha activation leading to pancreatic acinar tumors in the rat and mouse
Short name: PPARα activation and pancreatic acinar tumors


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 (


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Under development: Do not distribute or cite.

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

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

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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

Key Events

Event Support for Essentiality
PPAR-alpha activation, Increased Strong
bile flow, Decreased Strong
cholestasis, Increased Strong
lipid metabolism, Alteration Weak
elevation of serun CCK, prolonged Strong
Cellular proliferation / hyperplasia of acinar cells, Increased Strong

Adverse Outcome

Adverse Outcome
Pancreatic acinar tumors, Increased

Relationships Among Key Events and the Adverse Outcome

Event Description Triggers Weight of Evidence Quantitative Understanding
PPAR-alpha activation, Increased Indirectly Leads to bile flow, Decreased Moderate
PPAR-alpha activation, Increased Indirectly Leads to cholestasis, Increased Moderate
PPAR-alpha activation, Increased Indirectly Leads to lipid metabolism, Alteration Weak
elevation of serun CCK, prolonged Directly Leads to Cellular proliferation / hyperplasia of acinar cells, Increased Strong
Cellular proliferation / hyperplasia of acinar cells, Increased Indirectly Leads to Pancreatic acinar tumors, Increased Strong
cholestasis, Increased Indirectly Leads to elevation of serun CCK, prolonged
bile flow, Decreased Directly Leads to cholestasis, Increased

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Life Stage Applicability

Life Stage Evidence Links

Taxonomic Applicability

Name Scientific Name Evidence Links
mouse Mus musculus Moderate NCBI
rat Rattus norvegicus Strong NCBI

Sex Applicability

Sex Evidence Links

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)


1. Biegel, L. B., Hurtt, M. E., Frame, S. R., O'Connor, J. C., and Cook, J. C. (2001). Mechanisms of Extrahepatic Tumor Induction by Peroxisome Proliferators in Male CD Rats. Toxicological Sciences 60(1), 44-55, 10.1093/toxsci/60.1.44.

2. Klaunig, J. E., Babich, M. A., Baetcke, K. P., Cook, J. C., Corton, J. C., David, R. M., DeLuca, J. G., Lai, D. Y., McKee, R. H., Peters, J. M., Roberts, R. A., and Fenner-Crisp, P. A. (2003). PPARalpha agonist-induced rodent tumors: modes of action and human relevance. Critical reviews in toxicology 33(6), 655-780, 10.1080/713608372.