Carbon nanotubes introduced into the abdominal cavity of mice show asbestos-like pathogenicity in a pilot study

Our plain-English summary of Carbon nanotubes introduced into the abdominal cavity of mice show asbestos-like pathogenicity in a pilot study, by C.A. Poland, R. Duffin, I. Kinloch, et al (Nature Nanotechnology, 2008).

The study

• Authors: C.A. Poland, R. Duffin, I. Kinloch, A. Maynard, W.A. Wallace, A. Seaton, V. Stone, S. Brown, W. Macnee, K. Donaldson
• Journal: Nature Nanotechnology
• Published: 2008;3(7):423-8
• Cited by: 1,392 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Carbon nanotubes have distinctive characteristics, but their needle-like fibre shape has been compared to asbestos, raising concerns that widespread use of carbon nanotubes may lead to mesothelioma, cancer of the lining of the lungs caused by exposure to asbestos. Here we show that exposing the mesothelial lining of the body cavity of mice, as a surrogate for the mesothelial lining of the chest cavity, to long multiwalled carbon nanotubes results in asbestos-like, length-dependent, pathogenic behaviour. This includes inflammation and the formation of lesions known as granulomas. This is of considerable importance, because research and business communities continue to invest heavily in carbon nanotubes for a wide range of products under the assumption that they are no more hazardous than graphite. Our results suggest the need for further research and great caution before introducing such products into the market if long-term harm is to be avoided.

In plain English

This was a short-term pilot experiment in female mice. It tested whether multiwalled carbon nanotubes behave like asbestos when placed directly on the lining of the abdominal cavity, which the authors used as a stand-in for the lining of the chest. Mice were injected in the abdomen with one of seven materials or with the injection liquid alone. The materials were two nanotube samples with many long, straight fibres, two made of short or tangled clumps, long-fibre amosite asbestos, short-fibre amosite asbestos, and a non-fibrous carbon black. Each group held three to eight mice. After 24 hours, only long-fibre amosite and the two long-nanotube samples caused significant inflammation. After 7 days, these samples produced giant cells and granulomas (scar-like lesions) on the abdominal side of the diaphragm. Short amosite, carbon black and the tangled nanotubes caused no significant effects. The authors reported that metal contaminants and bacterial endotoxin did not explain the differences. They concluded that asbestos-like behaviour of nanotubes depended on fibre length. They stated that the study did not test whether inhaled nanotubes reach the lining in sufficient numbers, or whether the mice would develop mesothelioma.

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: Short-term animal experiment (described in the title as a pilot study): single injection into the abdominal (peritoneal) cavity of mice, with abdominal washing (lavage) at 24 hours and examination of the diaphragm at 7 days
• Who was studied: Female C57Bl/6 mice aged 8 weeks. Groups of 3 to 8 mice per material, depending on the measurement. The total number of mice and the study dates are not stated.
• Exposure: Four multiwalled carbon nanotube samples were tested. NTlong1 (Mitsui & Co.) and NTlong2 (University of Manchester) contained long fibres: 11.54% and 76.85% of fibres longer than 20 micrometres, respectively. NTtang1 and NTtang2 (NanoLab) were short or tangled. The comparison materials were long-fibre South African amosite (positive control), short-fibre amosite made by ball-milling the long sample (negative control), nanoparticulate carbon black (Printex 90), and a vehicle control (0.5% albumin in saline). Each mouse received one injection; the dose is printed in this copy as 50 mg per mouse (see text problems).
• Main results:
  • At 24 hours, only the samples containing long fibres (long-fibre amosite, NTlong1 and NTlong2) caused significant inflammatory-cell (PMN) or protein exudation in the abdominal cavity
  • At 7 days, granulomatous inflammation was seen on the diaphragm of mice exposed to long-fibre amosite, NTlong1 and NTlong2
  • Carbon black, short-fibre amosite, NTtang1 and NTtang2 caused no significant inflammation at 1 day and no significant giant cell formation at 7 days
  • One of three mice treated with NTtang2 showed a small granuloma response that was not statistically significant
  • The mesothelial lining on the chest (pleural) side of the diaphragm was normal in every case
  • Soluble metals and endotoxin did not correlate with the greater responses to the long nanotube samples
  • Water-soluble components extracted from NTlong1 and NTlong2 produced no significant inflammation 24 hours after injection
  • Images from the abdominal washings of mice exposed to long-fibre amosite and long nanotubes showed 'frustrated phagocytosis', meaning immune cells were unable to fully engulf long fibres
• The authors' conclusion: The authors concluded that asbestos-like harmful behaviour of carbon nanotubes followed a relationship based on fibre length, as asbestos and other harmful fibres do. They also stated that the long nanotubes produced inflammation, giant cells and granulomas similar to those caused by long asbestos.
• Limitations the authors state:
  • The groups were small; the authors said a similar study in more animals would give greater confidence in the differences
  • The study did not address whether inhaled nanotubes would reach the mesothelium in sufficient numbers to cause mesothelioma
  • The study did not address whether the mice with inflammatory and granulomatous changes would go on to develop mesothelioma
  • The assays detect only fibre-type effects; the study did not rule out harm from short nanotubes acting as particles
  • The commercial samples differed in source, preparation and purification; the two short tangled samples had been acid-treated
  • It remains unknown whether workplace or environmental exposure would be high enough to reach a threshold dose at the mesothelium
  • The authors had no quantitative data on frustrated phagocytosis

Topics

The National Library of Medicine indexes this study under subjects our site covers: Asbestosis.

Medical terms in this study, explained in our Lexicon: Mesothelioma, Inflammation, Granuloma.

Related studies

• Asbestos-like pathogenicity of long carbon nanotubes alleviated by chemical functionalization — H. Ali-Boucetta, A. Nunes, et al. (2013)
• Length-dependent retention of carbon nanotubes in the pleural space of mice initiates sustained inflammation and progressive fibrosis on the parietal pleura — F.A. Murphy, C.A. Poland, et al. (2011)
• Threshold Rigidity Values for the Asbestos-like Pathogenicity of High-Aspect-Ratio Carbon Nanotubes in a Mouse Pleural Inflammation Model — D.K. Lee, S. Jeon, et al. (2018)
• Multi-walled carbon nanotubes translocate into the pleural cavity and induce visceral mesothelial proliferation in rats — J. Xu, M. Futakuchi, et al. (2012)
• 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)
• Nanotoxicology: the asbestos analogy revisited — A.B. Kane, R.H. Hurt (2008)

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