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Aop: 121

AOP Title

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Urinary bladder calculi leading to urothelial papillomas and carcinomas (in mouse and rat)

Short name:

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Urinary calculi- urothelial papilloma/carcinoma

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 Do not cite 1.29 Under Development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
Increase, Urinary bladder calculi October 26, 2017 09:27
Increase, Cytotoxicity (urothelial cells) September 16, 2017 10:16
Increase, Regenerative cell proliferation (urothelial cells) September 16, 2017 10:16
Increase, Hyperplasia (urothelial) September 16, 2017 10:16
Increase, Adenomas/carcinomas (urothelial) September 16, 2017 10:16
Increase, Urinary bladder calculi leads to Increase, Cytotoxicity (urothelial cells) December 03, 2016 16:38
Increase, Cytotoxicity (urothelial cells) leads to Increase, Regenerative cell proliferation (urothelial cells) December 03, 2016 16:38
Increase, Regenerative cell proliferation (urothelial cells) leads to Increase, Hyperplasia (urothelial) December 03, 2016 16:38
Increase, Hyperplasia (urothelial) leads to Increase, Adenomas/carcinomas (urothelial) December 03, 2016 16:38

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 MIE 793 Increase, Urinary bladder calculi Increase, Urinary bladder calculi
2 KE 794 Increase, Cytotoxicity (urothelial cells) Increase, Cytotoxicity (urothelial cells)
3 KE 795 Increase, Regenerative cell proliferation (urothelial cells) Increase, Regenerative cell proliferation (urothelial cells)
4 KE 796 Increase, Hyperplasia (urothelial) Increase, Hyperplasia (urothelial)
5 AO 797 Increase, Adenomas/carcinomas (urothelial) Increase, Adenomas/carcinomas (urothelial)

Relationships Between Two Key Events
(Including MIEs and AOs)

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Title Adjacency Evidence Quantitative Understanding
Increase, Urinary bladder calculi leads to Increase, Cytotoxicity (urothelial cells) adjacent
Increase, Cytotoxicity (urothelial cells) leads to Increase, Regenerative cell proliferation (urothelial cells) adjacent
Increase, Regenerative cell proliferation (urothelial cells) leads to Increase, Hyperplasia (urothelial) adjacent
Increase, Hyperplasia (urothelial) leads to Increase, Adenomas/carcinomas (urothelial) adjacent

Network View

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Stressors

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Life Stage Applicability

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Taxonomic Applicability

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Term Scientific Term Evidence Link
Mus musculus Mus musculus NCBI
Rattus norvegicus Rattus norvegicus NCBI

Sex Applicability

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Sex Evidence
Male
Female

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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Garland, E. M., & Cohen, S. M. (1995). Saccharin-induced bladder cancer in rats. Prog Clin Biol Res, 391, 237-243.

International Agency for Research on Cancer (IARC), W. H. O. (1999). Saccharin and its Salts, IARC Monographs on the Evaluation of Carcinogenic Risks to Humans (Vol. 73-24). France.