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Multi-walled Carbon Nanotubes and Mesothelioma
An ICON Backgrounder

Written by Kristen M. Kulinowski, PhD
Last Updated on September 4, 2009

Print pdf                               Commentaries                    Click here to take a short survey 

Japanese Translations 

Two recent studies published in the Journal of Toxicological Sciences and Nature Nanotechnology have demonstrated that some multi-walled carbon nanotubes (MWCNT or MWNT) can induce in mice a response similar to that induced by certain asbestos fibers. At a first glance, MWCNT and asbestos fibers have one major thing in common, their needle-like shape.

Experimental Method
In both studies, suspensions of MWCNT were injected into the abdominal cavities of mice to directly expose the mesothelium and compared against asbestos as a positive control for mesothelioma. A positive control is a substance known to cause the effect under investigation. One group used a panel of four samples of MWCNT: two samples that contain long needle-like nanotubes and two that contain short, tangled nanotubes. Different types of asbestos were used as positive controls in each study (crocidolite or amosite) but both types are known to pose a hazard to human health. As negative controls (substances known or hypothesized not to cause the effect) one group of researchers used a commercial pigment known as Printex 90, which is a carbon-containing material that is nanostructured but not fiber-shaped.  The other group used solution that did not have nanoparticles in it. Because the route of exposure was injection and not inhalation, neither study addresses the question of whether inhalation of MWCNT leads to asbestos-like health effects.

About the Journal of Toxicological Sciences Study
In this work, the authors tested the hypothesis that due to their fibrous shape and embedded iron content MWCNT would have carcinogenic potential similar to asbestos. A concentrated suspension of stiff fibrous MWCNT was injected into the abdominal (peritoneal) cavity of mice that have been specially bred to be susceptible to cancer. Blue asbestos (crocidolite), which is known to cause mesothelioma, and fullerene aggregates, which were hypothesized not to cause mesothelioma, were also studied so the results could be compared. An examination of the animals between 10 days and 25 weeks after exposure revealed that the MWCNT and asbestos both resulted in the formation of cancerous lesions that are consistent with the disease mesothelioma. The mice exposed to the fullerene aggregates did not develop these lesions. The authors suggest that the aspect ratio and biopersistence of MWCNT may be important factors in understanding their effect on the body but caution that the presence of iron cannot be ruled out as a causative agent.

About the Nature Nanotechnology Study
In this work, the authors tested the hypothesis that long straight nanotubes act like long straight asbestos fibers and cause mesothelial injury. Samples consisting of suspensions of long, straight MWCNT, short tangled MWCNT, long-fiber amosite (asbestos), short-fiber amosite (asbestos) and a nonfibrous nanoparticulate carbon black material were each injected into the abdominal (peritoneal) cavity of normal mice. Twenty-four hours later, the cavity was washed out with a salt solution which was analyzed for the presence of proteins and cells consistent with inflammation. Tissue samples measured at 7 days were examined for the formation of scar-like lesions called granulomas that typify the body's response to long fibers. Only the mice exposed to the long straight fiber asbestos and the long straight MWCNT showed the presence of inflammatory proteins, cells and granulomas, leading the authors to conclude that frustrated phagocytosis was an important mechanism of injury . One mouse exposed to short tangled MWCNT had a small but non-significant granuloma. This seven-day study did not last long enough to demonstrate that mice exposed to MWCNT develop the disease mesothelioma, though the symptoms observed look very similar to those induced by the harmful versions of asbestos.

Interpreting the Results
These studies do not address whether humans may be exposed to MWCNT in a way that causes disease. While more research is needed to understand the potential implications of this work for human health, the two studies taken together point to the need for a careful assessment of the potential for MWCNT to cause injury to humans. The many outstanding questions that these papers raise include

  • How dose is measured for MWCNT and what constitutes an appropriate dose in mice to correlate with human risk;
  • The role of metals within the nanotube samples. (The Nature Nanotechnology study found that metals derived from the MWCNT could not explain the different effects of exposure to long straight vs. short tangled MWCNT. The J. Tox. Sci. study did not rule out the iron contaminant within the MWCNT samples as the agent responsible for promoting the formation of the cancerous lesions.)
  • Whether short, tangled MWCNT, which are non-fibrous, have a toxic effect unrelated to effects associated with exposure to fiber-like particles;
  • Whether MWCNT can persist long enough in the body and migrate to the mesothelium to induce the effects seen here in mice;
  • Whether humans can be exposed to MWCNT in quantities sufficient to induce the effect seen here in mice.

Despite these caveats both groups of authors believe that their findings are important for understanding the potential hazards of MWCNT and should inform industrial risk management practices so that exposure to humans is limited.  As they note, without exposure there is no risk, even if the substance is very hazardous.

Read more 

 

 

Click on the image below to open an animation of the experiment (Updated 6/4/2008)

Learn more about the different effects of long straight fibers vs. short tangled fibers
(pdf document)


 


UICC Asbestos Crocidolite standard (US Geological Survey image)

 


  An artist’s depiction of a single-walled carbon nanotube (left) and a multi-walled carbon nanotube (right).

 


A fullerene C60 molecule

 

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Commentaries
ICON asked several experts to comment about the significance of these findings for human
health. Keep reading and visit the ICON blog to join the discussion.


Ken Donaldson

Ken Donaldson, PhD, DSc; University of Edinburgh

"The study is a long way from saying if you inhale long multi-walled carbon nanotubes you will get mesothelioma. This study shows it’s possible, but we have to go quite a distance to show that inhaled nanotubes can find their way to the mesothelium, as asbestos does… An important next step is to go into work places and see what is in the air. We don’t have to worry if workers are not exposed to long nanotubes. But we need exposure measurements. Risk is composed of two parts – hazard and exposure; we showed that long nanotubes could be a considerable hazard to the mesothelium and we now need more exposure studies to be able to predict risk. It’s important to point out that the study exclusively addressed fiber effects of nanotubes; different studies are needed to address whether nanotubes can have adverse effects by virtue of being particles."
Read the whole interview            Japanese Translation 
Perspective in Nano (pdf)


     
Jun Kanno 
(left) 
Akihiko Hirose 
(right)


Jun Kanno, MD, PhD and Akihiko Hirose, PhD
National Institute of Health Sciences,
Japan 

“[We found] that a certain form of multi-walled carbon nanotubes (MWNT) causes mesothelioma when administered to genetically modified mice …This type of data can inform the manufacturers so that they can produce a safer product and, in the long run, create a win-win situation for both the consumers and the producers.”       
Read the whole interview        Japanese Translation 

Response by Dr. Kanno and Dr. Hirose to Comments/Critique by Prof. Ken Donaldson in his interview with ICON (see above): "Thank you for giving us an opportunity to comment on the work of Dr. Ken Donaldson's recent paper, as well as to reply to his critiques of our paper in his interview as posted at the ICON website."
Read the whole commentary



Shuji Tsuruoka


Shuji Tsuruoka , PhD; Mitsui & Co., Ltd.

"The risk [of humans developing mesothelioma from MWNT] is very low… Our materials have become a benchmark for [toxicology] studies and we are working closely with various federal agencies and universities to test them.… We have to think about where the exposure might occur during the actual application of the product. Exposure is a critical issue and must be taken into account.”  
Read the whole interview           Japanese Translation 

 


  
Günter Oberdörster


Günter Oberdörster, DVM, PhD; University of Rochester, Rochester, NY USA

“[These findings] didn’t surprise me too much given the high dose and a certain similarity of individual MWCNT fibers with asbestos, and given that elemental carbon is not soluble and very biopersistent like asbestos.  …This is a “Proof of Principle” study:  MWCNT under these conditions can induce effects.  The question is:   Will it happen in vivo following inhalation exposure? We need to know that before we come to a final judgment.”     
Read the whole interview (corrected May 22, 2008)

 

 
John Balbus


John Balbus, MD, MPH; Environmental Defense Fund

"…asbestos is an iconic hazard that comes with a lot of associations. Getting this kind of toxicology information out into the public domain early and investigating it thoroughly can help the industry to avoid repeating the more notorious aspects of the asbestos story. The studies themselves are neither good nor bad for the nanotechnology industry; what matters is what happens in response to this information."
Read the whole interview
Read Balbus' blog



Peter Gehr


Peter Gehr, PhD; University of Bern

"the results suggest that it would be prudent to implement strategies which include a careful investigation of MWCNT’s biological and carcinogenic properties, in particular also their biopersistence, before introducing products into the market The public shouldn’t panic. There is clearly no reason to do so. But the public should be informed or inform itself about the possibility of risk and hazards. The public could ask for declaration of materials etc. manufactured from MWCNT in order to have the possibility to choose non-MWCNT materials."
Read the whole interview

 


Bill Kojola
 


William (Bill) Kojola; Industrial Hygienist, AFL-CIO Department of Occupational Safety and Health

"When the science is just developing – as it is for nanotechnology and its human health effects - it is a difficult call to know when to take action to protect or at least monitor workers. I think we learned from the impacts of asbestos exposure that if there is a technical uncertainty then precaution is well advised. We need to ensure that we make efforts to protect worker health and make sure all employers do so."
Read the whole interview

 




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This work is supported in part by the Nanoscale Science and Engineering Initiative of the National Science Foundation
under NSF Award Number EEC-0118007.

 
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