API XML

Aop: 118

AOP Title

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Chronic cytotoxicity leading to hepatocellular adenomas and carcinomas (in mouse and rat)

Short name:

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Chronic cytotoxicity- HCC

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 Do not cite 1.29 Under Development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, Cytotoxicity (hepatocytes) September 16, 2017 10:16
Increase, Regenerative cell proliferation (hepatocytes) September 16, 2017 10:16
Increase, Preneoplastic foci (hepatocytes) September 16, 2017 10:16
Increase, Adenomas/carcinomas (hepatocellular) September 16, 2017 10:16
Increase, Cytotoxicity (hepatocytes) leads to Increase, Regenerative cell proliferation (hepatocytes) December 03, 2016 16:38
Increase, Regenerative cell proliferation (hepatocytes) leads to Increase, Preneoplastic foci (hepatocytes) December 03, 2016 16:38
Increase, Preneoplastic foci (hepatocytes) leads to Increase, Adenomas/carcinomas (hepatocellular) February 15, 2017 10:20

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 786 Increase, Cytotoxicity (hepatocytes) Increase, Cytotoxicity (hepatocytes)
2 KE 787 Increase, Regenerative cell proliferation (hepatocytes) Increase, Regenerative cell proliferation (hepatocytes)
3 KE 774 Increase, Preneoplastic foci (hepatocytes) Increase, Preneoplastic foci (hepatocytes)
4 AO 719 Increase, Adenomas/carcinomas (hepatocellular) Increase, Adenomas/carcinomas (hepatocellular)

Relationships Between Two Key Events
(Including MIEs and AOs)

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Title Adjacency Evidence Quantitative Understanding
Increase, Cytotoxicity (hepatocytes) leads to Increase, Regenerative cell proliferation (hepatocytes) adjacent
Increase, Regenerative cell proliferation (hepatocytes) leads to Increase, Preneoplastic foci (hepatocytes) adjacent
Increase, Preneoplastic foci (hepatocytes) leads to Increase, Adenomas/carcinomas (hepatocellular) 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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Holsapple, M. P., Pitot, H. C., Cohen, S. M., Boobis, A. R., Klaunig, J. E., Pastoor, T., . . . Dragan, Y. P. (2006). Mode of action in relevance of rodent liver tumors to human cancer risk. Toxicol Sci, 89(1), 51-56. doi: 10.1093/toxsci/kfj001

Pastoor, T., Rose, P., Lloyd, S., Peffer, R., & Green, T. (2005). Case Study: Weight of Evidence Evaluation of the Human Health Relevance of Thiamethoxam-Related Mouse Liver Tumors. Toxicological Sciences, 86(1), 56-60. doi: 10.1093/toxsci/kfi126