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

AOP Title

Enhanced hepatic clearance of thyroid hormones leading to thyroid follicular cell adenomas and carcinomas in the rat and mouse
Short name: thyroid follicular cell adenomas and carcinomas


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 (


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Under development: Do not distribute or cite.

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

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

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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)

Summary of the AOP

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Molecular Initiating Event

Molecular Initiating Event Support for Essentiality

Key Events

Event Support for Essentiality
induction of UDPGT's in liver, Increased Moderate
T4/T3 catabolism, Increased Strong
serum T4/T3, Decreased Strong
Thyroid-stimulating hormone (TSH), Increased Strong
Hypertrophy and proliferation (follicular cell), Increased Strong
Hyperplasia (follicular cells), Increased Strong

Adverse Outcome

Adverse Outcome
Adenomas/carcinomas (follicular cell), Increased Apoptosis

Relationships Among Key Events and the Adverse Outcome

Event Description Triggers Weight of Evidence Quantitative Understanding
induction of UDPGT's in liver, Increased Indirectly Leads to T4/T3 catabolism, Increased Strong
T4/T3 catabolism, Increased Directly Leads to serum T4/T3, Decreased Strong
serum T4/T3, Decreased Directly Leads to Thyroid-stimulating hormone (TSH), Increased Strong
Thyroid-stimulating hormone (TSH), Increased Directly Leads to Hypertrophy and proliferation (follicular cell), Increased Strong
Hypertrophy and proliferation (follicular cell), Increased Directly Leads to Hyperplasia (follicular cells), Increased Strong
Hyperplasia (follicular cells), Increased Indirectly Leads to Adenomas/carcinomas (follicular cell), Increased Apoptosis Strong

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Life Stage Applicability

Life Stage Evidence Links

Taxonomic Applicability

Name Scientific Name Evidence Links
Rattus sp. Rattus sp. Strong NCBI
mouse Mus musculus Moderate NCBI

Sex Applicability

Sex Evidence Links

Graphical Representation

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Overall Assessment of the AOP

Domain of Applicability

Life Stage Applicability, Taxonomic Applicability, Sex Applicability
Elaborate on the domains of applicability listed in the summary section above. Specifically, provide the literature supporting, or excluding, certain domains.

Essentiality of the Key Events

Molecular Initiating Event Summary, Key Event Summary
Provide an overall assessment of the essentiality for the key events in the AOP. Support calls for individual key events can be included in the molecular initiating event, key event, and adverse outcome tables above.

Weight of Evidence Summary

Summary Table
Provide an overall summary of the weight of evidence based on the evaluations of the individual linkages from the Key Event Relationship pages.

Quantitative Considerations

Summary Table
Provide an overall discussion of the quantitative information available for this AOP. Support calls for the individual relationships can be included in the Key Event Relationship table above.

Considerations for Potential Applications of the AOP (optional)


1. Dellarco, V. L., McGregor, D., Berry, S. C., Cohen, S. M., and Boobis, A. R. (2006). Thiazopyr and thyroid disruption: case study within the context of the 2006 IPCS Human Relevance Framework for analysis of a cancer mode of action. Critical reviews in toxicology 36(10), 793-801, 10.1080/10408440600975242.

2. Finch, J. M., Osimitz, T. G., Gabriel, K. L., Martin, T., Henderson, W. J., Capen, C. C., Butler, W. H., and Lake, B. G. (2006). A mode of action for induction of thyroid gland tumors by Pyrethrins in the rat. Toxicology and applied pharmacology 214(3), 253-62, 10.1016/j.taap.2006.01.009.

3. Hurley, P. M. (1998). Mode of carcinogenic action of pesticides inducing thyroid follicular cell tumors in rodents. Environmental health perspectives 106(8), 437-45.