IARC's Review of Carbon Nanotubes: Substantiating Early Warnings of Harm
November 20, 2014
This fall, the International Agency for Research on Cancer (IARC) convened 21 experts from ten countries to assess the carcinogenicity of carbon nanotubes (CNTs), a class of nanomaterials. What did they find? As published in the October 31, 2014 issue of The Lancet Oncology Online, their conclusion was this: there is sufficient evidence from existing toxicological studies to warrant a classification of “possibly carcinogenic to humans (Group 2B)” for one type of CNTs – multi-walled carbon nanotube-7 (MWCNT-7). These IARC findings reveal complexities facing our growing understanding of the hazards posed by CNTs, and the need to act on early predictions of harm.
Current and anticipated uses of engineered carbon nanotubes are numerous and diverse: sporting equipment, anti-static paints, solar cells, wind turbines, disk drives, batteries, biosensors and water filters, among others. CNTs are also being marketed as replacements for known chemicals of high concern, such as halogenated flame retardants in textiles and polymers and tributyltin in anti-fouling paints.
50,000-plus new substances?
CNTs are not a single, uniform material. Multi-walled CNTs consist of single-walled carbon nanotubes (SWCNTs) stacked inside of one another. It has been suggested that there are up to 50,000 potential combinations of SWCNTs and inevitably many more MWCNTs. CNTs can differ dramatically in size, shape and chemical composition, either by design or as a result of contamination during production. They may be straight, bent or curly, rigid or partly flexible. They can exist as single entities or bundled together in ropes or compact tangles that look and act like particles rather than tubes. In addition, they may be functionalized with a wide variety of chemicals on their surface to enhance desired chemical biochemical, electrical, or physical properties, and may contain a variety of contaminants, often metal catalysts used in manufacturing the nanomaterial. These physical-chemical characteristics govern the inherent hazards of a specific carbon nanotube.
Carcinogenic in rodents
MWCNT-7 can be purchased commercially and has been the test sample used in several rodent carcinogenicity studies. (No epidemiological studies have been conducted to date). The rodent studies demonstrate that this mixture of MWCNTs can cause mesothelioma tumors and can promote the development and growth of malignant lung tumors following exposure to a chemical known to initiate the disease. As described in one of these studies by Takagi and colleagues (see footnote 3b below), MWCNT-7 has a “considerable percentage of particles similar to asbestos in length and diameter.”
MWCNT-7 includes a large fraction of MWCNTs that are long and narrow, and similar to asbestos fibers, these physical characteristics appear to significantly influence their carcinogenicity. For SWCNTs or MWCNTs with different physical-chemical characteristics, IARC did not find “coherent” evidence of carcinogenicity and classified all other SWCNTs and MWCNTs as “not classifiable as to their carcinogenicity (Group 3)”. However, the tens of thousands of possible variations of CNTs have simply not been studied.
IARC’s review substantiates early warnings of harm. Health scientists raised concern about the similarity of CNTs and asbestos soon after their discovery in 1991. Moreover, we have known for decades that “size matters” with regard to the impact of airborne particles on health, and that particles smaller than about 4 µm can settle in the deepest regions of the lung and also cross into the blood stream to impart systemic effects. Being biopersistent, CNTs not only can travel to and settle in the deep regions of the lung; they can also accumulate and continue to impart effects long after exposure ceases.
It is not just cancer that is of concern in regard to carbon nanotubes. In 2013, the National Institute for Occupational Safety and Health issued a report based on a comprehensive review of the science, which concluded that both SWCNTs and MWCNTs can cause pulmonary inflammation and progressive pulmonary fibrosis. Physical-chemical characteristics such as metal content and structural defects enhance these toxic effects.
Predicting inherent hazards
The current evidence regarding health hazards posed by CNTs, including IARC’s recent review, substantiates the opportunity and the importance of using physical-chemical characteristics as predictors of the inherent hazard of engineered nanomaterials. Even if a fraction of the tens of thousands of possible variations of CNTs are commercialized, to expect the Environmental Protection Agency to comprehensively review the risk for every CNT added to the Toxics Substances Control Act Inventory would be so resource-intensive as to be undeniably impractical and manifestly impossible. As acknowledged in a recent report by the World Health Organization, effectively protecting health and environment from the threats posed by CNTs and other nanomaterials requires developing the capacity to predict their effects.4
For CNTs, which are expected to target the lung, high-throughput testing methods have been developed to reveal specific cellular mechanisms indicative of pulmonary effects. High-throughput testing can screen for other potential health impacts as well, since the expression of specific genes or biological markers are indicative of specific toxicity pathways – carcinogenic, immunological or developmental, among others. By using these testing technologies, varied CNT compositions, shapes and sizes can be screened and ranked on specific hazard traits.
High-throughput data holds promise for providing information to help regulators make decisions that protect public health. Yet the greatest benefit of these data may be their use by product designers in the field of green chemistry and green engineering who are working to identify safer and sustainable nanotechnologies, and those using tools such as alternatives assessment to determine whether CNTs are indeed safer substitutes for known toxic chemicals.
Known 20 years ago
Over 20 years ago, health scientists predicted that CNTs like MWCNT-7 were “possibly carcinogenic to humans”, the classification confirmed by IARC this fall. If product designers had acted on those predictions two decades ago, we could have prevented yet another toxic chemical from entering our global marketplace or, at a minimum, ensured that it was introduced in a responsible manner. Further development and commercialization of CNTs must proceed with great caution. Where CNTs can serve as safer or more sustainable replacements for synthetic chemicals of concern, it is critical to have thoughtful yet flexible processes in place that not only consider the “necessariness” of CNTs for a particular chemical function, but also compare a wide range of other chemical and non-chemical alternatives and the potential trade-offs that might occur from their use.
 See: (a) Sakamoto Y, et al. J Toxicol Sci 2009;34:65-76; (b) Takagi A, et al. Cancer Sci 2012;103:1440-1444; (c) Sargent LM, et al. Part Fibre Toxicol 2014;11:3.
 Coles G. Nature. 1993;359:99.
 Murphy F, et al. Am J Pathol 2011;178:2587–2600.
 See: (a) Kagan V, et al. Toxicol Lett 2006;165:88–100; (b) Pumera M and Y Miyahara. Nanoscale 2009;1:260–265; (c) Muller J, et al. Structural defects play a major role in the acute lung toxicity of multi-wall carbon nanotube: toxicological aspects. Chem Res Toxicol 2008;21:1698–1705.
 Nel A, et al. ACS Nano 2013;7:6422–6433.