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AOP: 166
Title
PPARalpha activation leading to pancreatic acinar tumors in the rat and mouse
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 |
---|---|
Increased, PPAR-alpha activation | September 16, 2017 10:17 |
Decreased, bile flow | September 16, 2017 10:17 |
Increased, cholestasis | September 16, 2017 10:17 |
Alteration, lipid metabolism | October 30, 2023 09:11 |
prolonged, elevation of serun CCK | September 16, 2017 10:17 |
Increased, Cellular proliferation / hyperplasia of acinar cells | September 16, 2017 10:17 |
Increased, Pancreatic acinar tumors | September 16, 2017 10:17 |
Increased, PPAR-alpha activation leads to Decreased, bile flow | December 03, 2016 16:38 |
Increased, PPAR-alpha activation leads to Increased, cholestasis | December 03, 2016 16:38 |
Increased, PPAR-alpha activation leads to Alteration, lipid metabolism | December 03, 2016 16:38 |
prolonged, elevation of serun CCK leads to Increased, Cellular proliferation / hyperplasia of acinar cells | December 03, 2016 16:38 |
Increased, Cellular proliferation / hyperplasia of acinar cells leads to Increased, Pancreatic acinar tumors | December 03, 2016 16:38 |
Increased, cholestasis leads to prolonged, elevation of serun CCK | December 03, 2016 16:38 |
Decreased, bile flow leads to Increased, cholestasis | December 03, 2016 16:38 |
PERFLUOROOCTANOIC ACID | November 29, 2016 18:42 |
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 |
---|
KE | 1057 | Increased, PPAR-alpha activation | Increased, PPAR-alpha activation |
KE | 1058 | Decreased, bile flow | Decreased, bile flow |
KE | 1059 | Increased, cholestasis | Increased, cholestasis |
KE | 1060 | Alteration, lipid metabolism | Alteration, lipid metabolism |
KE | 1061 | prolonged, elevation of serun CCK | prolonged, elevation of serun CCK |
KE | 1062 | Increased, Cellular proliferation / hyperplasia of acinar cells | Increased, Cellular proliferation / hyperplasia of acinar cells |
AO | 1063 | Increased, Pancreatic acinar tumors | Increased, Pancreatic acinar tumors |
Relationships Between Two Key Events (Including MIEs and AOs)
Title | Adjacency | Evidence | Quantitative Understanding |
---|
prolonged, elevation of serun CCK leads to Increased, Cellular proliferation / hyperplasia of acinar cells | adjacent | High | |
Decreased, bile flow leads to Increased, cholestasis | adjacent |
Increased, PPAR-alpha activation leads to Decreased, bile flow | non-adjacent | Moderate | |
Increased, PPAR-alpha activation leads to Increased, cholestasis | non-adjacent | Moderate | |
Increased, PPAR-alpha activation leads to Alteration, lipid metabolism | non-adjacent | Low | |
Increased, Cellular proliferation / hyperplasia of acinar cells leads to Increased, Pancreatic acinar tumors | non-adjacent | High | |
Increased, cholestasis leads to prolonged, elevation of serun CCK | non-adjacent |
Network View
Prototypical Stressors
Life Stage Applicability
Taxonomic Applicability
Sex Applicability
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
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.