Stressor: 338

Title

To create a new stressor, from the Listing Stressors page at https://aopwiki.org/stressors click ‘New stressor.’ This will bring you to a page entitled “New Stressor” where a stressor title can be entered. Click ‘Create stressor’ to create a new Stressor page listing the stressor title at the top. More help

Carbon nanotubes, Multi-walled carbon nanotubes, single-walled carbon nanotubes, carbon nanofibres

Stressor Overview

The stressor field is a structured data field that can be used to annotate an AOP with standardised terms identifying stressors known to trigger the MIE/AOP. Most often these are chemical names selected from established chemical ontologies. However, depending on the information available, this could also refer to chemical categories (i.e., groups of chemicals with defined structural features known to trigger the MIE). It can also include non-chemical stressors such as genetic or environmental factors. More help

AOPs Including This Stressor

This table is automatically generated and lists the AOPs associated with this Stressor. More help

AOP Name	Evidence
Substance interaction with the lung resident cell membrane components leading to lung fibrosis	High

Events Including This Stressor

This table is automatically generated and lists the Key Events associated with this Stressor. More help

Event Name
Pulmonary fibrosis

Chemical Table

The Chemical Table lists chemicals associated with a stressor. This table contains information about the User’s term for a chemical, the DTXID, Preferred name, CAS number, JChem InChIKey, and Indigo InChIKey.To add a chemical associated with a particular stressor, next to the Chemical Table click ‘Add chemical.’ This will redirect you to a page entitled “New Stressor Chemical.’ The dialog box can be used to search for chemical by name, CAS number, JChem InChIKey, and Indigo InChIKey. Searching by these fields will bring forward a drop down list of existing stressor chemicals formatted as Preferred name, “CAS- preferred name,” “JChem InChIKey – preferred name,” or “Indigo InChIKey- preferred name,” depending on by which field you perform the search. It may take several moments for the drop down list to display. Select an entity from the drop down list and click ‘Add chemical.’ This will return you to the Stressor Page, where the new record should be in the ‘Chemical Table’ on the page.To remove a chemical associated with a particular stressor, in the Chemical Table next to the chemical you wish to delete, click ‘Remove’ and then click 'OK.' The chemical should no longer be visible in the Chemical table. More help

AOP Evidence

This table is automatically generated and includes the AOPs with this associated stressor as well as the evidence term and evidence text from this AOP Stressor. More help

Substance interaction with the lung resident cell membrane components leading to lung fibrosis

CNTs are high aspect ratio materials and cause lung fibrosis in experimental animals (Muller et al., 2005; Porter DW et al., 2010). In an intelligence bulletin published by NIOSH on ‘Occupational exposure to carbon nanotubes and nanofibers’, NIOSH reviewed 54 individual animal studies investigating the pulmonary toxicity induced by CNTs and reported that half of those studies consistently showed lung fibrosis (NIOSH bulletin, 2013). Multiwalled carbon nanotubes induce lung fibrosis in mice (Nikota et al., 2017; Rahman et al., 2017). However, the evidence is inconsistent and the occurrence of fibrotic pathology is influenced by the specific physical-chemical properties of CNTs (length, rigidity), their dispersion in exposure vehicle, and the mode of exposure.

Muller, J., Huaux, F., Moreau, N., Misson, P., Heilier, J., Delos, M., Arras, M., Fonseca, A., Nagy, J. and Lison, D. (2005). Respiratory toxicity of multi-wall carbon nanotubes. Toxicology and Applied Pharmacology, 207(3), pp.221-231.
NIOSH (2013). Occupational exposure to carbon nanotubes and nanofibers: current intelligence bulletin 65.
Porter, D., Hubbs, A., Mercer, R., Wu, N., Wolfarth, M., Sriram, K., Leonard, S., Battelli, L., Schwegler-Berry, D. and Friend, S. (2010). Mouse pulmonary dose- and time course-responses induced by exposure to multi-walled carbon nanotubes. Toxicology, 269(2-3), pp.136-147.
Nikota, J., Banville, A., Goodwin, L., Wu, D., Williams, A., Yauk, C., Wallin, H., Vogel, U. and Halappanavar, S. (2017). Stat-6 signaling pathway and not Interleukin-1 mediates multi-walled carbon nanotube-induced lung fibrosis in mice: insights from an adverse outcome pathway framework. Particle and Fibre Toxicology, 14(1).
Rahman L, Jacobsen NR, Aziz SA, Wu D, Williams A, Yauk CL, White P, Wallin H, Vogel U, Halappanavar S. Multi-walled carbon nanotube-induced genotoxic, inflammatory and pro-fibrotic responses in mice: Investigating the mechanisms of pulmonary carcinogenesis. Mutat Res. 2017 Nov;823:28-44.

Event Evidence

This table is automatically generated and includes the Events with this associated stressor as well as the evidence text from this Event Stressor. More help

Pulmonary fibrosis

Carbon nanotubes (CNTs) are allotropes of carbon, are made of rolled up sheet of graphene (single-walled carbon nanotubes) and are tubular in shape. A multi-walled carbon nanotube (MWCNT) is a multi-layered concentric cylinder of graphene sheets stacked one inside the other (N. Saifuddin et al., 2013). CNTs exhibit a combination of unique mechanical, thermal, and electronic properties and are highly desired commercially. They are light weight but their tensile strength is 50 times higher than that of steel, and they are stable chemically as well as in the environment. Consequently, they are produced in massive amounts and are increasingly incorporated in several industrial products.

CNTs are high aspect ratio materials and are shown to cause lung fibrosis in animals (Muller J et al., 2005; Porter DW et al., 2010; Dong and Ma 2016; Vietti, et al., 2016). In an intelligence bulletin published by NIOSH on ‘Occupational exposure to carbon nanotubes and nanofibers’, NIOSH reviewed 54 individual animal studies investigating the pulmonary toxicity induced by CNTs and reported that half of those studies consistently showed lung fibrosis (NIOSH bulletin, 2013). However, the evidence is inconsistent and the occurrence of fibrotic pathology is influenced by the specific physical-chemical properties of CNTs (i.e. length, rigidity), their dispersion in exposure vehicle, and the mode of exposure (Duke and Bonner 2018).

1. Dong, J., & Ma, Q. (2016). Myofibroblasts and lung fibrosis induced by carbon nanotube exposure. Particle and fibre toxicology, 13(1), 60.

2. Duke, K. S., & Bonner, J. C. (2018). Mechanisms of carbon nanotube-induced pulmonary fibrosis: a physicochemical characteristic perspective. Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology, 10(3), e1498.

3. Muller, J., Huaux, F., Moreau, N., Misson, P., Heilier, J. F., Delos, M., Arras, M., Fonseca, A., Nagy, J. B., & Lison, D. (2005). Respiratory toxicity of multi-wall carbon nanotubes. Toxicology and applied pharmacology, 207(3), 221–231.

4. NIOSH: Occupational exposure to carbon nanotubes and nanofibers: current intelligence bulletin 65. 2013.

5. Porter, D. W., Hubbs, A. F., Mercer, R. R., Wu, N., Wolfarth, M. G., Sriram, K., Leonard, S., Battelli, L., Schwegler-Berry, D., Friend, S., Andrew, M., Chen, B. T., Tsuruoka, S., Endo, M., & Castranova, V. (2010). Mouse pulmonary dose- and time course-responses induced by exposure to multi-walled carbon nanotubes. Toxicology, 269(2-3), 136–147.

6. N. Saifuddin, A. Z. Raziah, and A. R. Junizah. Carbon Nanotubes: A Review on Structure and Their Interaction with Proteins. Journal of Chemistry, vol. 2013, Article ID 676815, 18 pages, 2013.

7. Vietti, G., Lison, D., & van den Brule, S. (2016). Mechanisms of lung fibrosis induced by carbon nanotubes: towards an Adverse Outcome Pathway (AOP). Particle and fibre toxicology, 13, 11.

Stressor Info

Text sections under this subheading include the Chemical/Category Description and Characterization of Exposure. More help

Chemical/Category Description

To edit the Chemical/Category Description” section, on a KER page, in the upper right hand menu, click ‘Edit.’ This brings you to a page entitled, “Editing Stressor.” Scroll down to the “Chemical/Category Description” section, where a text entry box allows you to submit text. Click ‘Update’ to save your changes and return to the Stressor page. The new text should appear under the “Chemical/Category Description” section on the page. More help

Julie Mullera, Franc¸ois Huauxa, Nicolas Moreaub, Pierre Missona, Jean-Franc¸ois Heiliera,

Monique Delosc, Mohammed Arrasa, Antonio Fonsecab, Janos B. Nagyb, Dominique Lison

Julie Mullera, Franc¸ois Huauxa, Nicolas Moreaub, Pierre Missona, Jean-Franc¸ois Heiliera,

Monique Delosc, Mohammed Arrasa, Antonio Fonsecab, Janos B. Nagyb, Dominique Lison

Characterization of Exposure

To edit the “Characterization of Exposure” section, on a Stressor page, in the upper right hand menu, click ‘Edit.’ This brings you to a page entitled, “Editing Stressor.” Scroll down to the “Characterization of Exposure” section, where a text entry box allows you to submit text. Click ‘Update’ to save your changes and return to the Stressor page. The new text should appear under the “Characterization of Exposure” section on the page. More help

References

List of the literature that was cited for this Stressor description. Ideally, the list of references, should conform, to the extent possible, with the OECD Style Guide (https://www.oecd.org/about/publishing/OECD-Style-Guide-Third-Edition.pdf) (OECD, 2015).To edit the “References” section, on a Stressor page, in the upper right hand menu, click ‘Edit.’ This brings you to a page entitled, “Editing Stressor.” Scroll down to the “References” section, where a text entry box allows you to submit text. Click ‘Update’ to save your changes and return to the Stressor page. The new text should appear under the “References” section on the page. More help