Pulmonary toxicity of carbon nanotubes and asbestos - similarities and differences

Our plain-English summary of Pulmonary toxicity of carbon nanotubes and asbestos - similarities and differences, by K. Donaldson, C.A. Poland, F.A. Murphy, et al (Advanced Drug Delivery Reviews, 2013).

The study

• Authors: K. Donaldson, C.A. Poland, F.A. Murphy, M. MacFarlane, T. Chernova, A. Schinwald
• Journal: Advanced Drug Delivery Reviews
• Published: 2013;65(15):2078-86
• Type of article: Review
• Cited by: 196 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Carbon nanotubes are a valuable industrial product but there is potential for human pulmonary exposure during production and their fibrous shape raises the possibility that they may have effects like asbestos, which caused a worldwide pandemic of disease in the20th century that continues into present. CNT may exist as fibres or as more compact particles and the asbestos-type hazard only pertains to the fibrous forms of CNT. Exposure to asbestos causes asbestosis, bronchogenic carcinoma, mesothelioma, pleural fibrosis and pleural plaques indicating that both the lungs and the pleura are targets. The fibre pathogenicity paradigm was developed in the 1970s-80s and has a robust structure/toxicity relationship that enables the prediction of the pathogenicity of fibres depending on their length, thickness and biopersistence. Fibres that are sufficiently long and biopersistent and that deposit in the lungs can cause oxidative stress and inflammation. They may also translocate to the pleura where they can be retained depending on their length, and where they cause inflammation and oxidative stress in the pleural tissues. These pathobiological processes culminate in pathologic change - fibroplasia and neoplasia in the lungs and the pleura. There may also be direct genotoxic effects of fibres on epithelial cells and mesothelium, contributing to neoplasia. CNT show some of the properties of asbestos and other types of fibre in producing these types of effects and more research is needed. In terms of the molecular pathways involved in the interaction of long biopersistent fibres with target tissue the events leading to mesothelioma have been a particular area of interest. A variety of kinase pathways important in proliferation are activated by asbestos leading to pre-malignant states and investigations are under way to determine whether fibrous CNT also affects these molecular pathways. Current research suggests that fibrous CNT can elicit effects similar to asbestos but more research is needed to determine whether they, or other nanofibres, can cause fibrosis and cancer in the long term.

© 2013.

In plain English

This article was a review, not a new study. The authors compared asbestos with carbon nanotubes (CNT), drawing on published experimental work. They used the 'fibre pathogenicity paradigm', which holds that thinness, length and biopersistence (resistance to breakdown in the body) decide whether a fibre causes disease. Lung disease linked to CNT had not been identified in human populations. No animal study had reported lung tumours from CNT, mainly because most studies were short-term. In reviewed mouse studies, long CNT placed in the pleural or peritoneal cavity caused inflammation and fibrosis similar to long asbestos. Short asbestos and short or tangled CNT caused no significant inflammation or fibrosis in these experiments. A study of silver and nickel nanowires injected directly into the pleural space found that nanowires 4 micrometres long did not cause acute pleural inflammation, while those 5 micrometres or longer did. The authors concluded that CNT can be pathogenic if thin, long and biopersistent, and that non-fibrous CNT would not be expected to cause fibre-specific pleural disease. They cautioned that peritoneal injection delivers non-physiological, high doses.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Review article (narrative review of published experimental studies)
• Who was studied: No human population was studied. The article reviewed published animal (rodent) and cell (in vitro) studies of fibrous carbon nanotubes and asbestos.
• Exposure: Fibrous carbon nanotubes (single-walled and multi-walled) compared with asbestos, mainly long and short amosite and crocidolite, with chrysotile mentioned in durability tests. The framework was fibre length, thinness and biopersistence.
• Main results:
  • The authors reported that lung disease associated with CNT exposure had not yet been identified in human populations.
  • No animal study had yet reported lung tumours in CNT-exposed animals. The authors attributed this primarily to the short-term nature of most studies.
  • In reviewed mouse studies, long CNT placed in the pleural cavity, or in the peritoneal cavity as a model mesothelium, produced inflammation and fibrosis similar to that produced by long asbestos. Short asbestos fibres and short or tangled CNT did not cause significant inflammation or fibrosis in the two cavities.
  • A reviewed study of silver and nickel nanowires injected directly into the pleural space found a length cut-off for acute pleural inflammation: 4 micrometres was non-inflammogenic and 5 micrometres or longer was inflammogenic.
  • In a reviewed 24-month rat study, carbon nanotubes injected into the peritoneal cavity at 2 or 20 mg produced no significant mesothelioma yield. The authors noted that these nanotubes were very short, 0.7 micrometres in length.
  • In a reviewed durability test in simulated phagolysosomal fluid, 3 of 4 CNT samples showed no or minimal loss of mass. One multi-walled CNT sample lost 30% of its original mass within the first three weeks. Chrysotile asbestos and bio-soluble glass fibres lost appreciable mass, while amosite asbestos did not.
• The authors' conclusion: The authors concluded that, under the fibre pathogenicity paradigm, carbon nanotubes can be pathogenic by being thin, long and biopersistent. Non-fibrous CNT would not be expected to produce fibre-specific pathology in the pleura. They also said targeted definitive studies were needed.
• Limitations the authors state:
  • Most CNT animal studies were short-term, so lung tumours could not yet have been observed.
  • It was not known whether early inflammatory and fibrotic responses to CNT in the peritoneal cavity predict mesothelioma.
  • Intraperitoneal injection is non-physiological and delivers a high dose and dose-rate compared with what normally reaches the pleura.
  • In the pleural CNT study, the threshold length for pleural inflammation could not be determined, because the CNT were not available in strict length classes.

Topics

Medical terms in this study, explained in our Lexicon: Bronchogenic Carcinoma, Mesothelioma, Fibrosis, Pleural Plaques, Pleura, biopersistence, Oxidative Stress, Inflammation.

Related studies

• Differences and similarities between carbon nanotubes and asbestos fibers during mesothelial carcinogenesis: shedding light on fiber entry mechanism — H. Nagai, S. Toyokuni (2012)
• Mechanisms of pulmonary toxicity and medical applications of carbon nanotubes: Two faces of Janus? — A.A. Shvedova, E.R. Kisin, et al. (2009)
• Structural defects play a major role in the acute lung toxicity of multiwall carbon nanotubes: physicochemical aspects — I. Fenoglio, G. Greco, et al. (2008)
• Length-dependent pleural inflammation and parietal pleural responses after deposition of carbon nanotubes in the pulmonary airspaces of mice — F.A. Murphy, C.A. Poland, et al. (2013)
• A critical review of the biological mechanisms underlying the in vivo and in vitro toxicity of carbon nanotubes: The contribution of physico-chemical characteristics — H.J. Johnston, G.R. Hutchison, et al. (2010)
• Comparative proteomics and pulmonary toxicity of instilled single-walled carbon nanotubes, crocidolite asbestos, and ultrafine carbon black in mice — J.G. Teeguarden, B.J. Webb-Robertson, et al. (2011)

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