Aop: 171
AOP Title
Short name:
Chronic cytotoxicity of the serous membrane and mesotheliomas.Graphical Representation
Click to download graphical representation templateAuthors
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 Do not cite | 1.29 | Under Development |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 |
|---|
| 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.