Asbestos-like toxicity of some carbon nanotubes

It has become commonplace amongst critics of nanotechnology to compare carbon nanotubes to asbestos, on the basis that they are both biopersistent, inorganic fibres with a high aspect ratio. Asbestos is linked to a number of diseases, most notably the incurable cancer mesothelioma, of which there are currently 2000 new cases a year in the UK. A paper published in Nature Nanotechnology today, from Ken Donaldson’s group at the University of Edinburgh, provides the best evidence to date that some carbon nanotubes – specifically, multi-wall nanotubes longer than 20 µm or so – do lead to the same pathogenic effects in the mesothelium as asbestos fibres.

The basis of toxicity of asbestos and other fibrous materials is now reasonably well understood; their toxicity is based on the physical nature of the materials, rather than their chemical composition. In particular, fibres are expected to be toxic if they are long – longer than about 20 µm – and rigid. The mechanism of this pathogenicity is believed to be related to frustrated phagocytosis. Phagocytes are the cells whose job it is to engulf and destroy intruders – when they detect a foreign body like a fibre, they attempt to engulf it, but are unable to complete this process if the fibre is too long and rigid. Instead they release a burst of toxic products, which have no effect on the fibre but instead cause damage to the surrounding tissues. There is every reason to expect this mechanism to be active for nanotubes which are sufficiently long and rigid.

Donaldson’s group tested the hypothesis that long carbon nanotubes would have a similar effect to asbestos by injecting nanotubes into the peritoneal cavity of mice to expose the mesothelium directly to nanotubes, and then directly monitor the response. This is a proven assay for the initial toxic effects of asbestos that subsequently lead to the cancer mesothelioma.

Four multiwall nanotube samples were studied. Two of these samples had long fibres – one was a commercial sample, from Mitsui, and another was produced in a UK academic laboratory. The other two samples had short, tangled fibres, and were commercial materials from NanoLab Inc, USA. The nanotubes were compared to two controls of long and short fibre amosite asbestos and one of non-fibrous, nanoparticulate carbon black. The two nanotube samples containing a significant fraction of long (>20 µm) nanotubes, together with the long-fibre amosite asbestos, produced a characteristic pathological response of inflammation, the production of foreign body giant cells, and the development of granulomas, a characteristic lesion. The nanotubes with short fibres, like the short fibre asbestos sample and the carbon black, produced little or no pathogenic effect. A number of other controls provide good evidence that it is indeed the physical form of the nanotubes rather than any contaminants that leads to the pathogenic effect.

The key finding, then, is that not all carbon nanotubes are equal when it comes to their toxicity. Long nanotubes produce an asbestos-like response, while short nanotubes, and particulate graphene-like materials don’t produce this response. The experiments don’t directly demonstrate the development of the cancer mesothelioma, but it would be reasonable to suppose this would be the eventual consequence of the pathogenic changes observed.

The experiments do seem to rule out a role for other possible contributing factors (presence of metallic catalyst residues), but they do not address whether other mechanisms of toxicity might be important for short nanotubes.

Most importantly, the experiments do not say anything about issues of dose and exposure. In the experiments, the nanotubes were directly injected into peritoneal cavity; to establish whether environmental or workplace exposure to nanotubes present a danger one needs to know how likely it is that realistic exposures of inhaled nanotubes would lead to enough nanotubes crossing the lungs through to the mesothelium lead to toxic effects. This is the most urgent question now waiting for further research.

It isn’t clear what proportion of the carbon nanotubes now being produced on industrial, or at least pilot plant, scale, would have the characteristics – particularly in their length – that would lead to the risk of these toxic effects. However, those nanotubes that are already in the market-place are mostly in the form of advanced composites, in which the nanotubes are tightly bound in a resin matrix, so it seems unlikely that these will pose an immediate danger. We need, with some urgency, research into what might happen to the nanotubes in such products over their whole lifecycle, including after disposal.

7 Responses to “Asbestos-like toxicity of some carbon nanotubes”

  1. Dear Dr. Jones,
    ICON has produced some backgrounder materials on this subject which may be of interest to your readers. To add to your excellent synopsis of the findings of this paper we have commentaries by the authors of this and a related prior publication, as well as several other stakeholders. We also have a modest graphic that attempts to show the successful vs frustrated phagocytosis that occurs upon exposure to the short, tangled and long straight nanotubes.

  2. Richard Jones says:

    Thanks, Kristen – for other readers, the ICON backgrounder is here.

  3. M Q says:

    If we invest in lab automation with isolated chambers then researchers would have less exposure to harmful materials because there would be no need to put fingers on samples or breath air from them.

    Would you stop your research if I prove to you that your sample materials cause cancer in mice? Yes or No?

  4. Richard Jones says:

    Many branches of experimental research use some potentially very dangerous chemicals, so, no, one doesn’t necessarily stop research because the materials maybe harmful; instead one uses the precautions that are appropriate. In the UK and the rest of the EU this is a legal requirement. Certainly the labs I know about that have been making long nanotubes have been aware of the potential risks for a while, and are already using equipment and working practices that minimise the dangers to researchers.

  5. David Lashmore says:

    The authors of this study did not remove the nickel or cobalt contained in every one of their tubes! Since these metals are known mutagens when injected in mice, it is difficult understand how they arrived at the conclusions that the tubes were responsible for the observed effects and not the metal catalysts.

    Further it is known that tubes contain high molecular weight hydrocarbons adsorbed on their surface. Some of these are also known mutagens (benzene for example).

    This paper seems to be written for the publicity not for the science.

  6. Richard Jones says:

    David, I wonder if you’ve read the paper in full. The assay the authors used was specific for the particular pathologies induced by long fibres, rather than for detecting any non-specific mutagenic effect, and they directly compared long-fibre nanotubes with short fibre nanotubes and with nanoparticulate carbon, finding this pathogenic effect only with the long nanotubes. Do you know the details of the synthesis routes of the nanotubes the authors looked at?

    I don’t think it’s either helpful or wise to try and discredit a paper like this by suggesting that it’s been “written for publicity”.

  7. My first instincts were to suggest longer dimensioned phagocytes as the long-term cure, then to suggest some sort of larger-than-20-micron-CNT buckling mechanism. Both are silly. It shouldn’t be too hard to engineer a 3D filter of some sort, that captures most/all CNTs larger than 20 microns.

    Sucks that being a CNT researcher exposes one to the same hazards as being a housing demolition labourer. But not that much, given the latter paid $7.50/hr in 2004.