This AOP is licensed under a Creative Commons Attribution 4.0 International License.
Chronic cytotoxicity of the serous membrane leading to pleural/peritoneal mesotheliomas in the rat.
Point of Contact
- Charles Wood
- Evgeniia Kazymova
|Author status||OECD status||OECD project||SAAOP status|
|Under Development: Contributions and Comments Welcome||1.29||Under Development|
This AOP was last modified on July 16, 2022 18:37
|persistent, cytotoxicity (pleura or peritoneum)||September 16, 2017 10:17|
|Increased, inflammation||December 03, 2016 16:37|
|Increased, Oxidative Stress||February 03, 2022 14:20|
|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|
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.
AOP Development Strategy
Summary of the AOP
Molecular Initiating Events (MIE)
Key Events (KE)
Adverse Outcomes (AO)
|Type||Event ID||Title||Short name|
|KE||1086||persistent, cytotoxicity (pleura or peritoneum)||persistent, cytotoxicity (pleura or peritoneum)|
|KE||1087||Increased, inflammation||Increased, inflammation|
|KE||1088||Increased, Oxidative Stress||Increased, Oxidative Stress|
|KE||1032||Increased, secretion of local growth factors||Increased, secretion of local growth factors|
|KE||1089||Increased, Cell Proliferation (mesothelium)||Increased, Cell Proliferation (mesothelium)|
|AO||1090||Increased, mesotheliomas||Increased, mesotheliomas|
Relationships Between Two Key Events (Including MIEs and AOs)
|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|
Life Stage Applicability
Overall Assessment of the AOP
Domain of Applicability
Essentiality of the Key Events
Known Modulating Factors
Considerations for Potential Applications of the AOP (optional)
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.