Sunday, May 4, 2008

Are Multi-Walled Carbon Nanotubes More Like Asbestos Than We Thought?

April 17, 2008 | Posted by John Balbus in Carbon Nanotubes, Health, Research, Testing

John Balbus, M.D., M.P.H., is Chief Health Scientist.

We and many others have made analogies between nanoparticles and asbestos. The purpose of the analogy has generally been to emphasize the long latency that can occur between exposure to toxic materials and the development and subsequent recognition of disease arising from that exposure. And, of course, the enormous legal and financial burden of failing to adequately consider risks before allowing widespread exposure. But a new study suggests that the analogy may be even stronger than we thought: It may extend to the capacity to cause mesothelioma, the rare form of cancer associated with exposure to asbestos.

In a recent study published in the Journal of Toxicological Sciences, researchers at Japan’s National Institute of Health Sciences injected commercial multi-walled carbon nanotubes (MWCNTs) into the peritoneal cavities of mice that were bred to be especially susceptible to mesothelioma. (The peritoneal cavity is the space between the abdominal organs and abdominal wall that is lined with mesothelial cells, which can give rise to mesotheliomas).

They compared the mice’s response to injected MWCNTs to the response to crocidolite asbestos (the form of asbestos most strongly associated with mesothelioma), and also to fullerenes. They found that the potency of MWCNTs in causing mesotheliomas in these mice was at least as high as the asbestos. In contrast, fullerenes did not cause any mesotheliomas.

The physicochemical characteristics of MWCNTs are similar in many ways to asbestos. Both are rigid, rod-like shapes with a high length to width (aspect) ratio and lengths that can extend to 5 microns or longer. Both are biopersistent and contain iron. Given that all of these characteristics collectively contribute to the carcinogenicity of asbestos, this study suggests these same characteristics may cause MWCNTs to be carcinogenic as well.

This study doesn’t prove that inhaling MWCNTs causes mesothelioma; it would first have to be shown that inhaled MWCNTs can make their way through the lung to contact mesothelial cells, and then persist there long enough to initiate carcinogenesis in less susceptible animals. Asbestos does this, of course, and there’s no obvious reason why MWCNTs should behave differently. More pieces of the puzzle need to be filled to demonstrate the actual degree of risk, but this is clearly a large red flag.

Because MWCNTs, unlike asbestos, are deliberately engineered, it’s possible that characteristics like iron content and fiber length may be controlled to render the tubes less or even non-carcinogenic. But with the wide variations noted for single-walled carbon nanotubes (see our earlier post), manufacturers of MWCNTs would have to demonstrate the ability to manufacture product consistently to specifications, and users of MWCNTs would need to be wary of variations from producer to producer. In the meantime, researchers developing and using MWCNTs, especially for applications that could yield long-term exposures, such as incorporation into hip prostheses, need to proceed with extreme caution and carefully assess the potential for carcinogenicity from their devices.



The Journal of Toxicological Sciences
Vol. 33 (2008) , No. 1 February 105-116
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Induction of mesothelioma in p53+/− mouse by intraperitoneal application of multi-wall carbon nanotube
Atsuya Takagi1), Akihiko Hirose2), Tetsuji Nishimura3), Nobutaka Fukumori4), Akio Ogata4), Norio Ohashi4), Satoshi Kitajima1) and Jun Kanno1)
1) Division of Cellular and Molecular Toxicology, Biological Safety Research Center, National Institute of Health Sciences
2) Division of Risk Assessment, Biological Safety Research Center, National Institute of Health Sciences
3) Division of Environmental Chemistry, National Institute of Health Sciences
4) Department of Environmental Health and Toxicology, Tokyo Metropolitan Institute of Public Health
(Received November 20, 2007)
ABSTRACT- Nanomaterials of carbon origin tend to form various shapes of particles in micrometer dimensions. Among them, multi-wall carbon nanotubes (MWCNT) form fibrous or rod-shaped particles of length around 10 to 20 micrometers with an aspect ratio of more than three. Fibrous particles of this dimension including asbestos and some man-made fibers are reported to be carcinogenic, typically inducing mesothelioma. Here we report that MWCNT induces mesothelioma along with a positive control, crocidolite (blue asbestos), when administered intraperitoneally to p53 heterozygous mice that have been reported to be sensitive to asbestos. Our results point out the possibility that carbon-made fibrous or rod-shaped micrometer particles may share the carcinogenic mechanisms postulated for asbestos. To maintain sound activity of industrialization of nanomaterials, it would be prudent to implement strategies to keep good control of exposure to fibrous or rod-shaped carbon materials both in the workplace and in the future market until the biological/ carcinogenic properties, especially of their long-term biodurability, are fully assessed.

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To cite this article:
Atsuya Takagi, Akihiko Hirose, Tetsuji Nishimura, Nobutaka Fukumori, Akio Ogata, Norio Ohashi, Satoshi Kitajima and Jun Kanno: “Induction of mesothelioma in p53+/− mouse by intraperitoneal application of multi-wall carbon nanotube”: J. Toxicol. Sci., Vol. 33: No. 1, 105-116. (2008) .

JOI JST.JSTAGE/jts/33.105
Copyright (c) 2008 The Japanese Society of Toxicology


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