New Findings on Lung Tumor Formation in Laboratory Mice Exposed to Multi-Walled Carbon Nanotubes

Earlier today, at the annual meeting of the Society of Toxicology, NIOSH researchers reported preliminary findings from a new laboratory study in which mice were exposed by inhalation to multi-walled carbon nanotubes (MWCNT).  The study was designed to investigate whether these tiny particles have potential to initiate or promote cancer.  By “initiate,” we mean the ability of a substance to cause mutations in DNA that can lead to tumors.  By “promote,” we mean the ability of a substance to cause cells that have already sustained such DNA mutations to then become tumors.

It is very important to have new data that describe the potential health hazards that these materials might represent, so that protective measures can be developed to ensure the safe advancement of nanotechnology in the many industries where it is being applied.

In the NIOSH study, a group of laboratory mice were injected with a chemical that is a known cancer initiator, methylcholanthrene.  Another group of mice were injected with a saline solution as a control group.  The mice then were exposed by inhalation either to air or to a concentration of MWCNT.   These protocols enabled the researchers to investigate whether MWNCT alone would initiate cancer in mice, or whether MWCNT would promote cancer where the initiator, methylcholanthrene, had already been applied.

Mice receiving both the initiator chemical plus exposure to MWCNT were significantly more likely to develop tumors (90% incidence) and have more tumors (an average of 3.3 tumors/mouse lung) than mice receiving the initiator chemical alone (50% of mice developing tumors with an average of 1.4 tumors/lung).  Additionally, mice exposed to MWCNT and to MWCNT plus the initiator chemical had larger tumors than the respective control groups.  The number of tumors per animal exposed to MWCNT alone was not significantly elevated compared with the number per animal in the controls.  These results indicate that MWCNT can increase the risk of cancer in mice exposed to a known carcinogen.  The study does not suggest that MWCNTs alone cause cancer in mice.

Several earlier studies in the scientific literature indicated that MWCNT could have the potential to initiate or promote cancer. The new NIOSH study is the first to show that MWCNT is a cancer promoter in a laboratory experiment, and reports the growth of lung tumors in laboratory mice following inhalation exposure to MWCNT rather than injection, instillation, or aspiration.  Inhalation exposure most closely resembles the exposure route of greatest concern in the workplace. In the study, laboratory mice were exposed to one type of MWCNT through inhalation at a concentration of 5 milligrams per cubic meter of air for five hours per day for a period of 15 days.

Risk of occupational cancer depends on the potency of a given substance to cause or promote cancer and the concentration and duration of worker exposure to that substance.  This research is an important step in our understanding of the hazard associated with MWCNT, but before we can determine whether MWCNT pose an occupational cancer risk, we need more information about actual exposure levels and the types and nature of MWCNT being used in the workplace, and how that compares to the material  used in this study.  We also need to identify what work processes, tasks, and physical forms of the MWCNT are associated with exposure.  Workplace studies are underway at NIOSH to learn more about actual worker exposure and to develop guidance on how to contain and control MWCNT processes to eliminate exposures, based on advancing knowledge about exposures. Further, similar research is needed for understanding the potential health effects and potential occupational risk of other types of carbon nanotubes and nanofibers, as well as other nanomaterials.

While NIOSH and others continue research to help answer these questions, controlling exposure is a vital factor in the prudent manufacture and workplace use of nanomaterials, particularly where other risk factors are as yet unknown or little understood.  Until more is known, NIOSH’s existing recommendations for prudent workplace practices offer our guidance on controlling exposures to MWCNT and other nanomaterials, based on our current scientific knowledge. Containment, local exhaust ventilation, filtration, and use of personal protective equipment, including respirators have proven effective in reducing exposure and are recommended as prudent practices.  Details can be found in Approaches to Safe Nanotechnology.

In our draft Current Intelligence Bulletin on single-walled and multi-walled carbon nanotubes, issued for public review and comment in December 2010, we also extensively discussed the available scientific evidence on occupational health implications of carbon nanotubes, and offered potential recommendations for public comment.  We expect to issue a final version of the Current Intelligence Bulletin, incorporating our review of the public comments, soon. The draft CIB is available on the NIOSH web and the final document will be posted on the nanotechnology topic page.

These laboratory studies are part of a strategic program of NIOSH research to better understand the occupational health and safety implications of nanoparticle exposure, and to make authoritative science-based recommendations for controlling exposures so that the technology is developed responsibly as the research advances, and the societal benefits of nanotechnology can be realized.  NIOSH has worked closely with diverse public and private sector partners over the past decade to incorporate occupational health and safety into practical strategies for safe development of this revolutionary technology. More information is available on the NIOSH nanotechnology topic page.

The preliminary results of the laboratory study were presented as a poster at the annual meeting of the Society of Toxicology on Monday, March 11, 2013.  The research will be submitted to a peer-reviewed journal for publication.

Vincent Castranova, PhD; Charles L Geraci, PhD;  Paul Schulte, PhD

Dr. Castranova is chief of the Pathology and Physiology Research Branch (PPRB) in the NIOSH Health Effects Laboratory Division (HELD).

Dr. Geraci is a Supervisory Physical Scientist in the NIOSH Education and Information Division and is the Coordinator of the Nanotechnology Research Center.

Dr. Schulte is the Director of the NIOSH Education and Information Division and Manager of the Nanotechnology Research Center.

Reference:

LM Sargent, DW Porter, D Lowry, L Battelli, K Siegrist, ML Kashon, BT Chen, D Frazer, L Staska, AF Hubbs,  W McKinney, M Andrew, S Tsuruoke, M Endo, V Castranova and SH Reynolds (2013, March).
Multi-walled Carbon Nanotube-induced Lung Tumors. The Toxicologist 130:A457, 2013.  Poster presented at the 2013 annual meeting of the Society of Toxicology.