API XML

Aop: 166

AOP Title

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PPARalpha activation leading to pancreatic acinar tumors in the rat and mouse

Short name:

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PPARα activation and pancreatic acinar tumors

Graphical Representation

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Click to download graphical representation template

Authors

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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)

Point of Contact

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Charles Wood   (email point of contact)

Contributors

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  • Charles Wood

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 Do not cite 1.29 Under Development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
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 September 16, 2017 10:17
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

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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)

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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 KE 1057 Increased, PPAR-alpha activation Increased, PPAR-alpha activation
2 KE 1058 Decreased, bile flow Decreased, bile flow
3 KE 1059 Increased, cholestasis Increased, cholestasis
4 KE 1060 Alteration, lipid metabolism Alteration, lipid metabolism
5 KE 1061 prolonged, elevation of serun CCK prolonged, elevation of serun CCK
6 KE 1062 Increased, Cellular proliferation / hyperplasia of acinar cells Increased, Cellular proliferation / hyperplasia of acinar cells
7 AO 1063 Increased, Pancreatic acinar tumors Increased, Pancreatic acinar tumors

Relationships Between Two Key Events
(Including MIEs and AOs)

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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

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Stressors

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Name Evidence Term
PERFLUOROOCTANOIC ACID

Life Stage Applicability

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Taxonomic Applicability

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Term Scientific Term Evidence Link
mouse Mus musculus Moderate NCBI
rat Rattus norvegicus High NCBI

Sex Applicability

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Overall Assessment of the AOP

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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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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.