One of the most promising new nanomaterials, multi-walled carbon nanotubes (MWCNTs) has been limited in its use and application due to its tendency to cause respiratory injury, in a manner similar to asbestos. On October 3, 2014, researchers announced results from a new study which may lead to the availability of safer MWCNTs.

Carbon nanotubes have been a suspected cause of respiratory injury since a 2008 research study raised concerns that carbon nanotubes may behave similarly in the body to asbestos fibers. See, Poland C, Duffin R, Kinloch I, Carbon nanotubes introduced into the Abdominal Cavity of Mice Show Asbestos-like Pathogenicity in a Pilot Study, Nature Nanotechnology, 3, 423-428 (2008). Researchers have determined that after mice inhaled MWCNTs, immune system cells, called macrophages, migrate to the lung tissue and engulf the MWCNTs. A number of substances, called cytokines, are secreted during this process, which may positively or detrimentally affect other cells in the lung tissue. In this study, scientists identified that the mice exposed to MCWNTs produced four different kinds of fibrosis promoting cytokines including interleukin (IL)-1â, IL-6, tumor necrorosis factor (TNF)-á, and osteoponin (OPN). Interleukin is associated with the body’s inflammatory response in both positive and negative ways. However tumor necrosis factor, which plays a role in cell death (apoptosis) within the body, and osteoponin which are associated with human cancers, are harmful to living tissue when present in large quantities.

The researchers had two goals: First to determine whether MWCNTs coated with aluminum oxide would be less likely to promote fibrosis in lung tissue and second to determine whether immune cells would be less reactive to the aluminum-coated particles. To conduct their experiment, researchers exposed laboratory mice and human immunocells to coated and uncoated MWCNTs and examined the exposed tissue at 1 and 28 days. Researchers evaluated the cells under a microscope and also studied the inflammatory cells and immune system proteins in the cells’ environment. The study demonstrated that all mice exposed to the uncoated MWCNTs had developed fibrosis by the end of the 28 days. Mice exposed to the aluminum oxide coated MWCNTs displayed reduced fibrosis and protein response. The researchers’ findings: (1) indicate that a thin coating of aluminum oxide can make MWCNTs safer, and (2) provide further support that raw MWCNTs are harmful to rodent pulmonary tissue, suggesting a human risk as well. In addition, the proteins secreted from human monocytes and macrophages (immune system cells) suggested an increased human risk for lung fibrosis.

The researchers also determined that while the aluminum oxide coating of the MWCNTs did not affect the immune system’s response to the nanoparticles on day 1, the coated MWCNTs did show markedly decreased fibrogenicity at the end of the 28 day cycle in the lung tissue studied. Examination of lung tissue on the first day after inhalation exposure to the coated and uncoated MWCNTs showed similar levels of macrophage activity engulfing the nanoparticles as the immune system worked to break down the foreign substance in the lungs, with nanotubes present in over 40 percent of the macrophages observed under microscope. However on day 28, the coated and uncoated populations showed a third less fibrosis.

One hypothesis identified by the researchers is whether the aluminum oxide coated nanoparticles were more prone to fracturing and therefore more readily digested by the macrophages than the uncoated MWCNTs. Researchers also plan to conduct further research into the role of aluminum oxide, which can cause toxic or therapeutic effects, in the lung tissue. We have observed a similar trend in research by the Harvard School of Public Health, which found that coating nanoparticles with silica oxide reduces tissue fibrosis, despite the fact that silica can cause a range of health impacts in occupational exposure scenarios.

The study was conducted by scientists from North Carolina State University and the National Institute of Environmental Health Sciences (NIEHS). Lead researcher James Bonner told that “this could be an important finding in the larger field of work that aims to predict and prevent future diseases associated with engineered nanomaterials.” “The aluminum oxide coating doesn’t eliminate health risks related to multi-walled CNTs,” Bonner says, “but it does lower them.” Bonner added, “Because multiwalled CNTs are increasingly used in a wide variety of products, it seems likely that humans will be exposed to them at some point. That means it’s important for us to understand these materials and the potential risk they pose to human health.” The study has been made available for open access review by researchers and the public. Atomic Layer Deposition Coating of Carbon Nanotubes with Aluminum Oxide Alters Pro-Fibrogenic Cytokine Expression by Human Mononuclear Phagocytes In Vitro and Reduces Lung Fibrosis in Mice In Vivo by Alexia J. Taylor, Christina D. McClure, Kelly A. Shipkowski, Elizabeth A. Thompson, Salik Hussain, Stavros Garantziotis, Gregory N. Parsons, and James C. Bonner. Published: September 12, 2014 DOI: 10.1371/journal.pone.0106870.

The U.S. government is steadfastly increasing its regulation and oversight of nanomaterials. The U. S. Environmental Protection Agency began regulating the use of certain types of carbon nanotubes as of April 12, 2014. The new regulations, which apply only under specific circumstances, (1) require manufacturers to conduct health studies for some products incorporating multi-walled carbon nanotubes, (2) require the use of personal protective equipment including respiratory protection, and (3) ban surface water releases as a result of manufacturing of carbon nanotubes. According to an October 20, 2014 report in Bloomberg’s Chemical Regulation Reporter, the EPA’s new chemical’s program has reviewed over 160 premanufacture notices (PMNs) for nanoparticles entering commerce and has found that nearly all of the uses of nanotechnology in products are subject to regulation. NIOSH has also issued a standard regarding occupational exposure to carbon nanotubes.

The enormous promise of nanotechnology to improve our world, with safer food, better products and revolutionary medical treatments must be moderated by a careful evaluation of the potential harm that this technology could cause to our environment and our health. This study adds to the knowledge about the potential dangers of MWCNTs but may also lead to a safer way to utilize this important material in the future. From a legal perspective, this study supports the fact that nanomaterials can be made safer and increases the burden on manufacturers to demonstrate that they have made adequate efforts to ensure that they are bringing a safe product to the market.