API XML

Aop: 171

AOP Title

?


Chronic cytotoxicity of the serous membrane leading to pleural/peritoneal mesotheliomas in the rat.

Short name:

?

Chronic cytotoxicity of the serous membrane and mesotheliomas.

Graphical Representation

?

Click to download graphical representation template

Authors

?


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

?


Charles Wood   (email point of contact)

Contributors

?


  • Charles Wood

Status

?

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 Do not cite 1.29 Under Development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

?

Revision dates for related pages

Page Revision Date/Time
persistent, cytotoxicity (pleura or peritoneum) September 16, 2017 10:17
Increased, inflammation December 03, 2016 16:37
Increased, Oxidative Stress September 16, 2017 10:16
Increased, secretion of local growth factors September 16, 2017 10:17
Increased, Cell Proliferation (mesothelium) September 16, 2017 10:17
Increased, mesotheliomas December 03, 2016 16:37
persistent, cytotoxicity (pleura or peritoneum) leads to Increased, inflammation December 03, 2016 16:38
persistent, cytotoxicity (pleura or peritoneum) leads to Increased, Oxidative Stress December 03, 2016 16:38
Increased, inflammation leads to Increased, secretion of local growth factors December 03, 2016 16:38
Increased, Oxidative Stress leads to Increased, secretion of local growth factors December 03, 2016 16:38
Increased, secretion of local growth factors leads to Increased, Cell Proliferation (mesothelium) December 03, 2016 16:38
Increased, Cell Proliferation (mesothelium) leads to Increased, mesotheliomas December 03, 2016 16:38

Abstract

?


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

?


Events: Molecular Initiating Events (MIE)

?

Key Events (KE)

?

Adverse Outcomes (AO)

?

Sequence Type Event ID Title Short name
1 KE 1086 persistent, cytotoxicity (pleura or peritoneum) persistent, cytotoxicity (pleura or peritoneum)
2 KE 1087 Increased, inflammation Increased, inflammation
3 KE 1088 Increased, Oxidative Stress Increased, Oxidative Stress
4 KE 1032 Increased, secretion of local growth factors Increased, secretion of local growth factors
5 KE 1089 Increased, Cell Proliferation (mesothelium) Increased, Cell Proliferation (mesothelium)
6 AO 1090 Increased, mesotheliomas Increased, mesotheliomas

Relationships Between Two Key Events
(Including MIEs and AOs)

?

Title Adjacency Evidence Quantitative Understanding
persistent, cytotoxicity (pleura or peritoneum) leads to Increased, inflammation adjacent High
persistent, cytotoxicity (pleura or peritoneum) leads to Increased, Oxidative Stress adjacent High
Increased, secretion of local growth factors leads to Increased, Cell Proliferation (mesothelium) adjacent High
Increased, inflammation leads to Increased, secretion of local growth factors non-adjacent Moderate
Increased, Oxidative Stress leads to Increased, secretion of local growth factors non-adjacent Moderate
Increased, Cell Proliferation (mesothelium) leads to Increased, mesotheliomas non-adjacent High

Network View

?

 

Stressors

?

Life Stage Applicability

?

Taxonomic Applicability

?

Term Scientific Term Evidence Link
rat Rattus norvegicus High NCBI

Sex Applicability

?

Overall Assessment of the AOP

?



Domain of Applicability

?


Essentiality of the Key Events

?


Evidence Assessment

?


Quantitative Understanding

?


Considerations for Potential Applications of the AOP (optional)

?



References

?


1. Bateson, T. F., Benson, R., Christensen, K. Y., Cooper, G., DeVoney, D., Gwinn, M., R., and Kopylev, L. (2014). Toxicological Review of Libby Amphibole Asbestos. In (IRIS, Ed.) Eds.) doi, pp. 685. US Environmental Protection Agency, Washington, DC.

2. Rittinghausen, S., Hackbarth, A., Creutzenberg, O., Ernst, H., Heinrich, U., Leonhardt, A., and Schaudien, D. (2014). The carcinogenic effect of various multi-walled carbon nanotubes (MWCNTs) after intraperitoneal injection in rats. Particle and fibre toxicology 11, 59, 10.1186/s12989-014-0059-z.

3. Suzui, M., Futakuchi, M., Fukamachi, K., Numano, T., Abdelgied, M., Takahashi, S., Ohnishi, M., Omori, T., Tsuruoka, S., Hirose, A., Kanno, J., Sakamoto, Y., Alexander, D. B., Alexander, W. T., Jiegou, X., and Tsuda, H. (2016). Multiwalled carbon nanotubes intratracheally instilled into the rat lung induce development of pleural malignant mesothelioma and lung tumors. Cancer science doi: 10.1111/cas.12954, 10.1111/cas.12954.