API XML

Aop: 119

AOP Title

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Inhibition of thyroid peroxidase leading to follicular cell adenomas and carcinomas (in rat and mouse)

Short name:

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Thyroid peroxidase- follicular adenoma/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 Do not cite 1.29 Under Development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
Thyroperoxidase, Inhibition May 31, 2018 19:38
Decrease, Incorporation of active iodide into iodotyrosines September 16, 2017 10:16
Increase, Hypertrophy and proliferation (follicular cell) September 16, 2017 10:16
Increase, Hyperplasia (follicular cells) September 16, 2017 10:16
Increase, Thyroid-stimulating hormone (TSH) September 16, 2017 10:16
Increase, Adenomas/carcinomas (follicular cell) September 16, 2017 10:16
Decrease, Serum thyroid hormone (T4/T3) September 16, 2017 10:16
Thyroperoxidase, Inhibition leads to Decrease, Incorporation of active iodide into iodotyrosines December 03, 2016 16:38
Decrease, Incorporation of active iodide into iodotyrosines leads to Decrease, Serum thyroid hormone (T4/T3) December 03, 2016 16:38
Decrease, Serum thyroid hormone (T4/T3) leads to Increase, Thyroid-stimulating hormone (TSH) December 03, 2016 16:38
Increase, Thyroid-stimulating hormone (TSH) leads to Increase, Hypertrophy and proliferation (follicular cell) December 03, 2016 16:38
Increase, Hypertrophy and proliferation (follicular cell) leads to Increase, Hyperplasia (follicular cells) December 03, 2016 16:38
Increase, Hyperplasia (follicular cells) leads to Increase, Adenomas/carcinomas (follicular cell) 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 279 Thyroperoxidase, Inhibition Thyroperoxidase, Inhibition
2 KE 788 Decrease, Incorporation of active iodide into iodotyrosines Decrease, Incorporation of active iodide into iodotyrosines
3 KE 739 Increase, Hypertrophy and proliferation (follicular cell) Increase, Hypertrophy and proliferation (follicular cell)
4 KE 740 Increase, Hyperplasia (follicular cells) Increase, Hyperplasia (follicular cells)
5 KE 753 Increase, Thyroid-stimulating hormone (TSH) Increase, Thyroid-stimulating hormone (TSH)
6 KE 771 Decrease, Serum thyroid hormone (T4/T3) Decrease, Serum thyroid hormone (T4/T3)
7 AO 741 Increase, Adenomas/carcinomas (follicular cell) Increase, Adenomas/carcinomas (follicular cell)

Relationships Between Two Key Events
(Including MIEs and AOs)

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Title Adjacency Evidence Quantitative Understanding
Thyroperoxidase, Inhibition leads to Decrease, Incorporation of active iodide into iodotyrosines adjacent
Decrease, Incorporation of active iodide into iodotyrosines leads to Decrease, Serum thyroid hormone (T4/T3) adjacent
Decrease, Serum thyroid hormone (T4/T3) leads to Increase, Thyroid-stimulating hormone (TSH) adjacent
Increase, Thyroid-stimulating hormone (TSH) leads to Increase, Hypertrophy and proliferation (follicular cell) adjacent
Increase, Hypertrophy and proliferation (follicular cell) leads to Increase, Hyperplasia (follicular cells) adjacent
Increase, Hyperplasia (follicular cells) leads to Increase, Adenomas/carcinomas (follicular cell) 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
Rattus norvegicus Rattus norvegicus NCBI
Mus musculus Mus musculus 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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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.