A critical review of the biological mechanisms underlying the in vivo and in vitro toxicity of carbon nanotubes: The contribution of physico-chemical characteristics

Our plain-English summary of A critical review of the biological mechanisms underlying the in vivo and in vitro toxicity of carbon nanotubes: The contribution of physico-chemical characteristics, by H.J. Johnston, G.R. Hutchison, F.M. Christensen, et al (Nanotoxicology, 2010).

The study

• Authors: H.J. Johnston, G.R. Hutchison, F.M. Christensen, S. Peters, S. Hankin, K. Aschberger, V. Stone
• Journal: Nanotoxicology
• Published: 2010;4(2):207-46
• Type of article: Review
• Cited by: 238 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

This critical review of the available human health safety data, relating to carbon nanotubes (CNTs), was conducted in order to assess the risks associated with CNT exposure. Determining the toxicity related to CNT exploitation is of great relevance and importance due to the increased potential for human exposure to CNTs within occupational, environmental and consumer settings. When this information is combined with knowledge on the likely exposure levels of humans to CNTs, it will enable risk assessments to be conducted to assess the risks posed to human health. CNTs are a diverse group of materials and vary with regards to their wall number (single and multi-walled CNTs are evident), length, composition, and surface chemistry. The attributes of CNTs that were identified as being most likely to drive the observed toxicity have been considered, and include CNT length, metal content, tendency to aggregate/agglomerate and surface chemistry. Of particular importance, is the contribution of the fibre paradigm to CNT toxicity, whereby the length of CNTs appears to be critical to their toxic potential. Mechanistic processes that are critical to CNT toxicity will also be discussed, with the findings insinuating that CNTs can exert an oxidative response that stimulates inflammatory, genotoxic and cytotoxic consequences. Consequently, it may transpire that a common mechanism is responsible for driving CNT toxicity, despite the fact that CNTs are a diverse population of materials. The similarity of the structure of CNTs to that of asbestos has prompted concern surrounding the exposure of humans, and so the applicability of the fibre paradigm to CNTs will be evaluated. It is also necessary to determine the systemic availability of CNTs following exposure, to determine where potential targets of toxicity are, and to thereby direct in vitro investigations within the most appropriate target cells. CNTs are therefore a group of materials whose useful exploitable properties prompts their increased production and utilization within diverse applications, so that ensuring their safety is of vital importance.

In plain English

This article was a critical review, not a new experiment. The authors reviewed published laboratory studies on the toxicity of carbon nanotubes, both single-walled and multi-walled, in mice, rats and cell cultures. Because nanotubes are fibre-shaped, the authors asked whether the 'fibre paradigm' known from asbestos applies to them. They reported that many studies found an acute inflammatory response, oxidative stress, granulomas and fibrosis. In one pilot study they reviewed, long, straight multi-walled nanotubes injected into the abdominal cavity of mice caused inflammation and granulomas resembling the response to long-fibre amosite. Short or tangled nanotubes and short asbestos fibres did not. Two animal studies reported mesotheliomas after multi-walled nanotube injection, while a third, using short nanotubes, found none. The authors criticized the very high doses used in some of these studies. They noted that no peer-reviewed study had shown nanotubes moving from the lungs to the pleura, that genotoxicity was uncertain, and that nanotubes can interfere with test methods. The authors concluded that nanotubes can represent a hazard that may be controlled by changing their physical and chemical characteristics.

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: critical review of published in vivo (animal) and in vitro (cell) toxicity studies of carbon nanotubes, carried out within the EU-funded ENRHES project
• Who was studied: published studies using mice, rats, cell lines and primary cells; no human studies of disease were reviewed
• Exposure: single-walled and multi-walled carbon nanotubes differing in length, metal content, aggregation and surface chemistry; some reviewed studies used asbestos (long and short fibre amosite, crocidolite) as comparison
• Main results:
  • Across the studies reviewed, carbon nanotubes caused acute neutrophil-driven inflammation, oxidative stress, granuloma formation and fibrosis
  • In a pilot study in mice (Poland et al. 2008), long straight multi-walled nanotubes injected into the abdominal cavity caused inflammation and granulomas paralleling long-fibre amosite; short or entangled nanotubes and short asbestos fibres did not
  • In a rat study (Sakamoto et al. 2009), only 1 of 7 rats given multi-walled nanotubes survived the full study, and mesotheliomas were seen in the nanotube group but not in the crocidolite asbestos group
  • In a 2008 mouse mesothelioma study (Takagi et al., using p53 mice), the authors judged the relevance debatable because the dose of multi-walled nanotubes was excessively high
  • No peer-reviewed study had shown nanotubes moving to the pleural cavity after inhalation and causing mesothelial disease
  • Metal (particularly iron) contamination contributed to toxicity but was not solely responsible
  • The genotoxic potential of carbon nanotubes was uncertain
• The authors' conclusion: The authors concluded that the data suggest carbon nanotubes can represent a hazard, but that the hazard can be manipulated and potentially controlled by varying physico-chemical characteristics
• Limitations the authors state:
  • The studies were disparate, so no clear consensus on toxicity could be reached
  • Many toxic effects may result from the high doses used in some studies
  • Lack of human exposure information makes the toxicity data hard to interpret
  • Nanotube length was often not reported
  • Nanotubes can interfere with the toxicity assays used
  • Mesothelial tumours in humans would be needed to confirm the relevance of the animal findings

Related studies

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• Extensive temporal transcriptome and microRNA analyses identify molecular mechanisms underlying mitochondrial dysfunction induced by multi-walled carbon nanotubes in human lung cells — P. Nymark, P. Wijshoff, et al. (2015)
• Review of carbon nanotubes toxicity and exposure--appraisal of human health risk assessment based on open literature — K. Aschberger, H.J. Johnston, et al. (2010)
• Mechanisms of pulmonary toxicity and medical applications of carbon nanotubes: Two faces of Janus? — A.A. Shvedova, E.R. Kisin, et al. (2009)
• In vitro and in vivo genotoxic effects of straight versus tangled multi-walled carbon nanotubes — J. Catalán, K.M. Siivola, et al. (2016)

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