API

Aop: 168

AOP Title

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GnRH pulse disruption leading to mammary adenomas and carcinomas in the SD rat.

Short name:

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GnRH pulse disruption 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 Do not cite Under Development 1.29 Included in OECD Work Plan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, GnRH pulsatility/release in hypothalamus September 16, 2017 10:17
Decreased, LH Surge from anterior pituitary December 03, 2016 16:37
interruption, Ovulation December 03, 2016 16:37
prolonged, estrus December 03, 2016 16:37
Increased, circulating estrogen levels December 03, 2016 16:37
Increased, prolactin exposure December 03, 2016 16:37
Hyperplasia, Mammary gland September 16, 2017 10:17
Increased, Adenomas/carcinomas (mammary) September 16, 2017 10:17
Increased, latency period December 03, 2016 16:37
Decreased, GnRH pulsatility/release in hypothalamus leads to Decreased, LH Surge from anterior pituitary December 03, 2016 16:38
Decreased, LH Surge from anterior pituitary leads to interruption, Ovulation December 03, 2016 16:38
Decreased, LH Surge from anterior pituitary leads to prolonged, estrus December 03, 2016 16:38
prolonged, estrus leads to Increased, circulating estrogen levels December 03, 2016 16:38
prolonged, estrus leads to Increased, prolactin exposure December 03, 2016 16:38
Increased, circulating estrogen levels leads to Hyperplasia, Mammary gland December 03, 2016 16:38
Increased, prolactin exposure leads to Hyperplasia, Mammary gland December 03, 2016 16:38
Hyperplasia, Mammary gland leads to Increased, latency period December 03, 2016 16:38
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
atrazine 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
atrazine

Molecular Initiating Event

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Key Events

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Title Short name
Decreased, GnRH pulsatility/release in hypothalamus Decreased, GnRH pulsatility/release in hypothalamus
Decreased, LH Surge from anterior pituitary Decreased, LH Surge from anterior pituitary
interruption, Ovulation interruption, Ovulation
prolonged, estrus prolonged, estrus
Increased, circulating estrogen levels Increased, circulating estrogen levels
Increased, prolactin exposure Increased, prolactin exposure
Hyperplasia, Mammary gland 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. Meek, B., Renwick, A., Sonich-Mullin, C., and International Programme on Chemical, S. (2003a). Practical application of kinetic data in risk assessment--an IPCS initiative. Toxicology letters 138(1-2), 151-60.

2. Meek, M. E., Bucher, J. R., Cohen, S. M., Dellarco, V., Hill, R. N., Lehman-McKeeman, L. D., Longfellow, D. G., Pastoor, T., Seed, J., and Patton, D. E. (2003b). A framework for human relevance analysis of information on carcinogenic modes of action. Critical reviews in toxicology 33(6), 591-653, 10.1080/713608373.

3. 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.

4. Simpkins, J. W., Swenberg, J. A., Weiss, N., Brusick, D., Eldridge, J. C., Stevens, J. T., Handa, R. J., Hovey, R. C., Plant, T. M., Pastoor, T. P., and Breckenridge, C. B. (2011). Atrazine and breast cancer: a framework assessment of the toxicological and epidemiological evidence. Toxicological sciences : an official journal of the Society of Toxicology 123(2), 441-59, 10.1093/toxsci/kfr176.