Aop:109

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Status

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

https://aopwiki.org/aops/109


AOP Title

Cytotoxicity leading to bronchioloalveolar adenomas and carcinomas (in mouse)
Short name: Cytotoxicity- bronchiolar adenoma/carcinoma

Authors

Cancer AOP group. 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)

Status

Please follow the link to snapshots page to view and create Snapshots of this AOP.

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

Under development: Do not distribute or cite.

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

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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.

Background (optional)

Summary of the AOP

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Molecular Initiating Event

Molecular Initiating Event Support for Essentiality
Cytotoxicity (club cells), Increase

Key Events

Event Support for Essentiality
Necrosis (terminal bronchiolar cells), Increase
Regenerative cell proliferation (terminal bronchiolar epithelial cells), Increase
Hyperplasia (terminal bronchiolar cells), Increase

Adverse Outcome

Adverse Outcome
Adenomas/carcinomas (bronchioloalveolar), Increase

Relationships Among Key Events and the Adverse Outcome

Event Description Triggers Weight of Evidence Quantitative Understanding
Cytotoxicity (club cells), Increase Directly Leads to Necrosis (terminal bronchiolar cells), Increase
Necrosis (terminal bronchiolar cells), Increase Directly Leads to Regenerative cell proliferation (terminal bronchiolar epithelial cells), Increase
Regenerative cell proliferation (terminal bronchiolar epithelial cells), Increase Directly Leads to Hyperplasia (terminal bronchiolar cells), Increase
Hyperplasia (terminal bronchiolar cells), Increase Directly Leads to Adenomas/carcinomas (bronchioloalveolar), Increase

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Life Stage Applicability

Life Stage Evidence Links

Taxonomic Applicability

Name Scientific Name Evidence Links
Mus musculus Mus musculus NCBI

Sex Applicability

Sex Evidence Links
Male
Female

Graphical Representation

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Overall Assessment of the AOP

Domain of Applicability

Life Stage Applicability, Taxonomic Applicability, Sex Applicability
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Essentiality of the Key Events

Molecular Initiating Event Summary, Key Event Summary
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Weight of Evidence Summary

Summary Table
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Quantitative Considerations

Summary Table
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Considerations for Potential Applications of the AOP (optional)

References