Two studies have just recently been published describing some potentially important features of a promising form of nanotechnology. Articles in the Journal of Toxicological Sciences and Nature Nanotechnology have reported results of experiments in which some multi-walled carbon nanotubes seem able to induce in mice a response similar to that induced by certain asbestos fibers.

Many readers of MassTortDefense know that nanotechnology refers to a new field of technology that seeks to manipulate and control products, really matter, on the atomic and molecular scale, typically 100 nanometers or smaller. To give some sense of scale, one nanometer is one billionth, or 10-9 of a meter. A nanometer compared to a meter is the roughly the same ratio as that of a baseball to the size of the Earth. Or another analogy, a nanometer is the length a man’s whiskers grow in the time it takes him to lift his razor to his face to shave.

Two main approaches are used in nanotechnology. In a bottom-up approach, materials and devices are built from molecular components which more or less assemble themselves chemically. In a top-down approach, nano-objects are de-constructed from larger entities. While scientists speculated about nanotechnology in the 1950’s, it is really the modern generation of analytical tools such as the most powerful atomic microscopes which allow the potential deliberate manipulation of nanostructures.

What is so fascinating, and potentially useful, about nanotechnology is that normal sized physical phenomena may be altered as the size of the product decreases. Some features may be enhanced, even dominant at smaller sizes. Moreover, a number of physical, mechanical, electrical, or other properties can change as the size of the particle decreases. As the ratio of surface area to volume changes, the mechanical, thermal and catalytic properties of materials may be altered. Third, novel mechanical properties of nanosystems have also been identified in the lab. For example, opaque substances like copper become transparent; inert materials like platinum become catalysts; some stable substances like aluminum become combustible. Similarly, some solids turn into liquids even at room temperature.

Examples of nanotechnology include new polymers, and computer chips. Nanotechnologies have already found commercial application in suntan lotions, cosmetics, protective coatings, and stain resistant apparel. Significant research is being done on the targeted delivery of drugs to tumors or infections sites using nanotechnology.

Potential Issues
As with any new technology, questions about potential health and environmental risks have been raised. The unique properties of nano-materials make them at once attractive to product makers, but also raise questions about whether conventional thinking about product safety are adequate. For example, the enhanced catalytic activity of certain nano-materials may raise potential questions about their theoretical interaction with biomaterials. Moreover, as seen in the two new studies, the size of the particles raises issues in their own right.

Carbon Nanotubes
In both studies, suspensions of carbon nanotubes were injected into the abdominal cavities of mice, and the results compared against asbestos as a positive control for mesothelioma. Carbon nanotubes are generally made from sheets of graphite no thicker than an atom—about a nanometer, or one billionth of a meter wide—and formed into cylinders, with the diameter varying from a few nanometers up to tens of nanometers. They are excellent conductors of electricity. Carbon nanotubes can also be used to reinforce polymers to create very strong plastics. Carbon nanotubes show promise as building blocks for computer chips that are smaller and faster than those made of silicon. Economists predict that the market for carbon nanotubes will grow to more than $1 billion by 2014.

The Studies
In the JTS study, Atsuya Takagi, et al., “Induction of mesothelioma in p53+/− mouse by intraperitoneal application of multi-wall carbon nanotubes,” J. Toxicol. Sci., Vol. 33: No. 1, 105-116 (2008), researchers tested the hypothesis that due to their fibrous shape and embedded iron content multi-walled carbon nanotubes would have carcinogenic potential similar to asbestos. 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. Examination of the mice from 10 days to 25 weeks after exposure revealed that the MWCNT and asbestos both resulted in the formation of cancerous lesions that the authors saw as consistent with the disease mesothelioma. (The mice exposed to the other control did not develop these lesions.) The authors suggest that these results point out the possibility that carbon-made fibrous or rod-shaped micrometer particles may share the carcinogenic mechanisms postulated for asbestos. The researchers suggest that the aspect (length/width) ratio and biopersistence of MWCNT may be important factors in understanding their effect on the body.

In the NN study, C. Poland, et al., Carbon nanotubes introduced into the abdominal cavity display asbestos-like pathogenic behavior in a pilot study, Nature Nanotechnology, Published online: 20 May 2008 (doi:10.1038/nnano.2008.111), researchers tested the hypothesis that long straight nanotubes act like long straight asbestos fibers and can cause injury like that seen in mesothelioma. They reported 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 behavior. They used various materials for comparison: long, straight MWCNT, short tangled MWCNT, long-fiber amosite asbestos, short-fiber amosite, and a nonfibrous nanoparticulate carbon black material as a control. Tissue samples measured at 7 days were examined for the formation of scar-like lesions called granulomas that often typify the body’s response to long fibers. They observed that the mice exposed to the long straight fiber asbestos and the long straight MWCNT showed the presence of inflammatory proteins, cells and granulomas, but not the other substances.

What to Make of the Results
The two studies suggest a need for a careful ongoing assessment of the potential for MWCNT to cause injury. They do not prove or even strongly suggest that nanotubes can cause cancer. The route of exposure is a crucial aspect of toxicology and here it was injection and not inhalation; neither study addresses the question whether inhalation of MWCNT leads to serious health effects like asbestos. It is not clear that carbon nanotubes will become airborne and be inhaled, or whether, if they do reach the lungs, they can get to the mesothelium to cause the effects seen here in mice. Another recent study showed that when mice inhaled nanotubes their lungs returned to normal within one or two months.

Of course, both studies are animal studies, and one used mice that have been specially bred to be susceptible to cancer. Measuring dose is not necessarily easy with nanomaterials, and it is unclear what constitutes an appropriate dose in mice to correlate with human exposures and risk. It is unclear that any humans are or can be exposed to MWCNT in quantities sufficient to induce the effect seen here in mice. If there is a potential hazard, there will be no disease if workers are not overly exposed to long nanotubes. Risk is composed of two parts – hazard and exposure.

Confounding factors involved include the presence of metals, like iron, in the nanotube samples. The JTS study explicitly could not rule out the iron contaminant within the MWCNT samples as the agent responsible for promoting the formation of the cancerous lesions.

Given the importance of this new field, and this new type of product, counsel involved in toxic tort and product liability  litigation will want to keep a close eye on the developing science.