Persistent Pulmonary Fibrosis, Migration to the Pleura, and Other Preliminary New Findings after Subchronic Exposure to Multi-Walled Carbon NanotubesPosted on by
Multi-walled carbon nanotubes, known as MWCNTs for short, are a type of engineered nanomaterial that shows promise for various applications. These include the potential for creating stronger, more durable building materials; improving cancer therapies; creating more efficient means of energy generation, storage, and transmission; and speeding computer processes. However, as with other types of engineered nanomaterials, the potential occupational health implications of MWNCTs are not well understood at this emergent stage of the technology. A broad group of health and safety practitioners and business observers have agreed that research is vital for determining if MWCNTs pose a health risk for workers engaged in their production and industrial use, and for informing the responsible development of this technology. There is general agreement that this issue must be approached in a proactive manner with good research in order for society to benefit from the many promises this new class of materials has to offer.
One critical avenue of research explores the toxicological aspects of MWCNTs. Some of the critical questions that need to be addressed are these:
- Once these materials enter the body, how do they interact with the body’s biological systems?
- What effects may occur in the genes, cells, or tissues as a result?
- Do those effects pose a health risk, either in themselves, or as early warnings of subsequent effects?
The National Institute for Occupational Safety and Health (NIOSH) has worked closely with its partners to stimulate, design, conduct, and report pioneering research in this area. Today, at the 2009 Annual Meeting of the Society of Toxicology, a team of NIOSH researchers reported new, preliminary scientific findings that add significantly to the data that scientists and policymakers need in ongoing risk assessment. The preliminary findings were presented at the conference to keep NIOSH’s colleagues and partners up to date on this research, and to engage their interaction in the setting of the scientific forum. An abstract of these preliminary findings can be found in The Toxicologist 108:A2193, 2009. Because we know there will be wide interest in these preliminary data as a result of the conference presentation, we wanted to comment on the research here, and to note that the preliminary data have not yet been formally peer-reviewed. More complete data will be included in articles that we are preparing for future publication in the peer-reviewed scientific literature.
The NIOSH investigators reported on a scientifically ambitious study of laboratory mice exposed to multi-walled carbon nanotubes by pharyngeal aspiration causing the lab animal to inhale a small drop of liquid with suspended material that closely resembles inhalation of the same material suspended in the air. The research showed inflammation in the lungs of the mice, and fibrosis in their lungs, which persisted following exposure. Such effects are similar to the interstitial pulmonary fibrosis reported previously by NIOSH researchers using single-walled carbon nanotubes.
Most significantly in terms of generating new knowledge, the study demonstrated the ability of MWCNTs to migrate from the lungs to the pleura (the tissue that surrounds the lungs). The preliminary findings are the first to demonstrate that carbon nanotubes aspirated by laboratory mice can actually migrate from the alveoli in the lungs (the tiny structures in the lung that are critical for gas exchange), through the lungs, to the pleura. The preliminary findings offer significant new evidence of MWCNTs appearing to behave like durable fibers in that they translocate to the pleura.
The preliminary findings are not definitive in answering two questions:
- If inhaled by workers, would MWCNTs or the broader class of carbon nanotubes migrate from the workers’ lungs to the pleura?
- If MWCNTs migrated to the pleura after being inhaled into the lungs, would they cause mesothelioma like another well-studied fiber, asbestos?
However, the preliminary findings provide the first scientific evidence ever that such migration is possible, given similarities between the body systems of the mouse and those of humans. These preliminary findings, when combined with previous studies by other investigators, which reported inflammation and mesothelioma of the abdominal lining after intraperitoneal instillation (injection into the lining of the abdominal cavity) of MWCNTs in mice, provide additional justification for further research.
There are limitations to the study that need to be explored, addressed, and answered by further research before the findings can be used with confidence for human risk assessment. These limitations involve the magnitude of the dose, the means of exposure (pharyngeal aspiration), and the generalizability from the strain of mice used, the C57BL/6J type. These findings point to the need for further studies with different doses, by inhalation, and a different species, such as the rat.
In the interim, as we prepare them for peer-reviewed publication and look ahead to subsequent research needs, these new preliminary findings reinforce the need to adopt a system of prudent risk management practices, including a continued rigorous approach to controlling occupational exposures among workers during the production and use of MWCNTs. As new research continues to address a number of health and safety questions, there will continue to be a degree of uncertainty that requires a prudent and proactive strategy. This strategy of prudence is outlined in NIOSH’s document Approaches to Safe Nanotechnology along with interim recommendations for controlling such exposures pending further research to fill gaps in present knowledge. Additional resources pertaining to NIOSH findings and recommendations on the occupational health and safety implications of nanotechnology can be found on NIOSH’s nanotechnology topic page. NIOSH is gratified that its strategic research program has formed the basis for both national and international recommendations and policies.
Dr. Castranova is chief of the Pathology and Physiology Research Branch (PPRB) in the Health Effects Laboratory Division (HELD). Dr. Hubbs is a veterinary pathologist, Dr. Porter is a pulmonary toxicologist, and Dr. Mercer is a bio-engineer in PPRB/HELD. The authors all have expertise in pulmonary toxicology.