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

AOP Title

Inhibition of thyroid peroxidase leading to follicular cell adenomas and carcinomas (in rat and mouse)
Short name: Thyroid peroxidase- follicular adenoma/carcinoma


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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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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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
Thyroperoxidase, Inhibition

Key Events

Event Support for Essentiality
Incorporation of active iodide into iodotyrosines, Decrease
Serum thyroid hormone (T4/T3), Decrease
Hypertrophy and proliferation (follicular cell), Increase
Thyroid-stimulating hormone (TSH), Increase
Hyperplasia (follicular cells), Increase

Adverse Outcome

Adverse Outcome
Adenomas/carcinomas (follicular cell), Increase

Relationships Among Key Events and the Adverse Outcome

Event Description Triggers Weight of Evidence Quantitative Understanding
Thyroperoxidase, Inhibition Directly Leads to Incorporation of active iodide into iodotyrosines, Decrease
Incorporation of active iodide into iodotyrosines, Decrease Directly Leads to Serum thyroid hormone (T4/T3), Decrease
Serum thyroid hormone (T4/T3), Decrease Directly Leads to Thyroid-stimulating hormone (TSH), Increase
Thyroid-stimulating hormone (TSH), Increase Directly Leads to Hypertrophy and proliferation (follicular cell), Increase
Hypertrophy and proliferation (follicular cell), Increase Directly Leads to Hyperplasia (follicular cells), Increase
Hyperplasia (follicular cells), Increase Directly Leads to Adenomas/carcinomas (follicular cell), Increase

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Life Stage Applicability

Life Stage Evidence Links

Taxonomic Applicability

Name Scientific Name Evidence Links
Rattus norvegicus Rattus norvegicus NCBI
Mus musculus Mus musculus 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
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Quantitative Considerations

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


Dellarco, V. L., McGregor, D., Berry, S. C., Cohen, S. M., & 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. Crit Rev Toxicol, 36(10), 793-801. doi: 10.1080/10408440600975242

Hurley, P. M. (1998). Mode of carcinogenic action of pesticides inducing thyroid follicular cell tumors in rodents. Environ Health Perspect, 106(8), 437-445.

U.S. Environmental Protection Agency, R. A. F. (Mar. 1998). Assessment of Thyroid Follicular Cell Tumors. Washington, DC.