API

Aop: 170

AOP Title

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Anti-dopaminergic activity leading to mammary adenomas and carcinomas in the SD rat

Short name:

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Anti-dopaminergic activity and mammary tumors

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

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 Do not cite Under Development 1.29 Included in OECD Work Plan


This AOP was last modified on December 03, 2016 16:37

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Revision dates for related pages

Page Revision Date/Time
Decreased, Dopaminergic activity December 03, 2016 16:37
Increased, prolactin secretion December 03, 2016 16:37
Increased, hyperplasia (mammary gland) September 16, 2017 10:17
Increased, latency period December 03, 2016 16:37
Increased, Adenomas/carcinomas (mammary) September 16, 2017 10:17
Decreased, Dopaminergic activity leads to Increased, prolactin secretion December 03, 2016 16:38
Increased, prolactin secretion leads to Increased, hyperplasia (mammary gland) December 03, 2016 16:38
Increased, hyperplasia (mammary gland) leads to Increased, latency period December 03, 2016 16:38
Increased, hyperplasia (mammary gland) leads to Increased, Adenomas/carcinomas (mammary) December 03, 2016 16:38
Increased, latency period leads to Increased, Adenomas/carcinomas (mammary) December 03, 2016 16:38
Haloperidol November 29, 2016 18:42
Reserpine November 29, 2016 18:42

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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Stressors

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Name Evidence Term
Haloperidol
Reserpine

Molecular Initiating Event

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Key Events

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Title Short name
Decreased, Dopaminergic activity Decreased, Dopaminergic activity
Increased, prolactin secretion Increased, prolactin secretion
Increased, hyperplasia (mammary gland) Increased, hyperplasia (mammary gland)
Increased, latency period Increased, latency period

Adverse Outcome

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Title Short name
Increased, Adenomas/carcinomas (mammary) Increased, Adenomas/carcinomas (mammary)

Relationships Between Two Key Events (Including MIEs and AOs)

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Network View

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Life Stage Applicability

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Taxonomic Applicability

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Term Scientific Term Evidence Link
SD rat Rattus norvegicus Strong NCBI

Sex Applicability

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Sex Evidence
Female Strong

Graphical Representation

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Click to download graphical representation template

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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Weight of Evidence Summary

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Quantitative Considerations

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Considerations for Potential Applications of the AOP (optional)

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References

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1. O'Connor, J. C., Davis, L. G., Frame, S. R., and Cook, J. C. (2000). Detection of dopaminergic modulators in a tier I screening battery for identifying endocrine-active compounds (EACs). Reproductive toxicology 14(3), 193-205.

2. Rudmann, D., Cardiff, R., Chouinard, L., Goodman, D., Kuttler, K., Marxfeld, H., Molinolo, A., Treumann, S., Yoshizawa, K., Inhand Mammary, Z. s. P., and Clitoral Gland Organ Working, G. (2012). Proliferative and nonproliferative lesions of the rat and mouse mammary, Zymbal's, preputial, and clitoral glands. Toxicologic pathology 40(6 Suppl), 7S-39S, 10.1177/0192623312454242.