Tag Archives: US National Institute of Occupational Safety and Health

Lung injury, carbon nanotubes, and aluminum oxide

It’s pretty much undisputed that long, multi-walled carbon nanotubes (MWCNTs) are likely to present a serious health hazard given their resemblance to asbestos fibres. It’s a matter of some concern that has resulted in a US National Institute of Occupational Safety and Health (NIOSH) recommendation for workplace exposure to all carbon nanotubes that is stringent. (My April 26, 2013 posting features the recommendation.)

Some recent research from North Carolina State University (NCSU) suggests that there may be a way to make long, multi-walled carbon nanotubes safer. From an Oct. 3, 2014 news item on Nanowerk,

A new study from North Carolina State University and the National Institute of Environmental Health Sciences (NIEHS) finds that coating multiwalled carbon nanotubes (CNTs) with aluminum oxide reduces the risk of lung scarring, or pulmonary fibrosis, in mice.

“This could be an important finding in the larger field of work that aims to predict and prevent future diseases associated with engineered nanomaterials,” says James Bonner, a professor of environmental and molecular toxicology at NC State …

An Oct. 3, 2014 NCSU news release, which originated the news item, describes the research in a little more detail,

Multiwalled CNTs have a wide array of applications, ranging from sporting goods to electronic devices. And while these materials have not been associated with adverse health effects in humans, research has found that multi-walled CNTs can cause pulmonary fibrosis and lung inflammation in animal models.

“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,” Bonner says. “That means it’s important for us to understand these materials and the potential risk they pose to human health. The more we know, the better we’ll be able to engineer safer materials.”

For this study, the researchers used atomic layer deposition to coat multiwalled CNTs with a thin film of aluminum oxide and exposed mice to a single dose of the CNTs, via inhalation.

The researchers found that CNTs coated with aluminum oxide were significantly less likely to cause pulmonary fibrosis in mice. However, the coating of aluminum oxide did not prevent lung inflammation.

“The aluminum oxide coating doesn’t eliminate health risks related to multi-walled CNTs,” Bonner says, “but it does lower them.”

Here’s a link to and a citation for the paper,

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

This is an open access article.

The researchers offered this conclusion (part of the paper’s abstract),

These findings indicate that ALD [atomic layer deposition] thin film coating of MWCNTs with Al2O3 reduces fibrosis in mice and that in vitro phagocyte expression of IL-6, TNF-α, and OPN, but not IL-1β, predict MWCNT-induced fibrosis in the lungs of mice in vivo.

However, what I found most striking was this from the paper’s Discussion (section),

While the Al2O3 coating on MWCNTs appears to be the major factor that alters cytokine production in THP-1 and PBMCs in vitro, nanotube length is still likely an important determinant of the inflammatory and fibroproliferative effects of MWCNTs in the lung in vivo. In general, long asbestos fibers or rigid MWCNTs (i.e., >20 µm) remain in the lung and are much more persistent than shorter fibers or nanotubes [20]. Therefore, the nanotube fragments resulting from breakage of A-MWCNTs coated with 50 or 100 ALD cycles of Al2O3 would likely be cleared from the lungs more rapidly than uncoated long MWCNTs or those coated with only 10 ALD cycles of Al2O3. We observed that the fracturing of A-MWCNTs occurred only after sonication prior to administration to cells in vitro or mice in vivo. However, unsonicated A-MWCNTs could be more likely to fracture over time in tissues as compared to U-MWCNTs [uncoated]. We did not address the issue of A-MWCNT clearance before or after fracturing in the present study, but future work should focus the relative clearance rates from the lungs of mice exposed to A-MWCNTs in comparison to U-MWCNTs. Another potentially important consideration is whether or not ALD coating with Al2O3 alters the formation of a protein corona around MWCNTs. It is possible that differences in cytokine levels in the supernatants from cells treated with U- or A-MWCNTs could be due to differences in protein corona formation around functionalized MWCNTs that could modify the adsorptive capacity of the nanomaterial. Characterization of the protein corona and the adsorptive capacity for cytokines after ALD modification of MWCNTs should be another important focus for future work. [emphases mine]

In other words, researchers think coating long, MWCNTs with a certain type of aluminum might be safer due to its effect on various proteins and because coated MWCNTs are likely to fracture into smaller pieces and we know that short MWCNTs don’t seem to present a problem when inhaled.

Of course, there’s the research from Duke University (my Oct. 3, 2014 post) which suggests CNTs could present a different set of problems over time as they accumulate in the environment.

‘Safe’ nano, a report covering US National Institute of Occupational Health and Safety activities from 2004 to 2011

The Nov. 9, 2012 news item on Nanowerk lists the report title as “Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace“,

In 2007 and 2009, NIOSH [US National Institute of Occupational Safety and Health] published progress reports detailing the accomplishments of the NTRC [Nanotechnology Research Center], including the results of ongoing laboratory and field research and the publication of technical and other guidance documents on the safe handling of engineered nanomaterials (see Progress Toward Safe Nanotechnology in the Workplace, www.cdc.gov/niosh/topics/nanotech/pubs.html).

This 2012 update presents the program accomplishments of the NTRC from its inception in 2004 through 2011. It includes an analysis of the progress made toward accomplishing the goals and objectives of the NIOSH Strategic Plan for Nanotechnology Research and toward addressing the goals and research needs identified in the U.S. National Nanotechnology Initiative (NNI) Environmental, Health, and Safety (EHS) research strategy.

The report  is approximately 400 pp. most of which are devoted to descriptions of various projects, both completed and currently underway. The actual report comes in at roughly 65 pp.  I find the cover art to be particularly interesting given my interest in data visualization,

“Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace” cover: A graphical representation of the reach of a highly cited NIOSH journal article specific to nanomaterials. The scatter plot illustrates the initial publication (red dot) surrounded by the number of times it was directly cited in other papers (primary citations are yellow dots) and then the number of times the primary citation papers were cited by other papers (secondary citations are white dots). This diagram was developed using Cytoscape, an open source platform for complex network analysis and visualization.

For those who don’t fancy reading the report, here’s a list of the accomplishments from the report’s Executive Summary (p. 8-9 PDF version),

Summary of NTRC Program Outputs and Impacts

Among the many program outputs and impacts, the NTRC researchers:

■ Developed some of the earliest guidance on the design and conduct of nano­toxicology studies.

■ Identified pulmonary and cardiovascular hazards of some types of carbon nano­tubes in animals.

■ Determined that the dispersion of ultrafine carbon black nanoparticles in the lungs of rats following intratracheal instillation results in an inflammatory response that is greater than agglomerated ultrafine carbon black.

■ Determined that ultrafine TiO2 or carbon black is more inflammogenic than fine TiO2 or carbon black on a mass-dose basis.

■ Developed a system to generate nanoparticle aerosols for inhalation toxico­logic studies.

■ Conducted over 40 field assessments in nanomaterial manufacturer and user facilities.

■ Produced more than 400 peer-reviewed scientific publications, resulting in over 5,000 primary and 82,000 secondary citations.

■ Provided over 650 invited presentations.

■ Published a framework for conducting workplace emission testing.

■ Developed innovative sampling methods for engineered nanomaterials.

■ Contributed to the development of a bio-mathematical model in rats to describe clearance, retention, and translocation of inhaled nanoparticles throughout the body.

■ Developed recommended exposure limits (RELs) for TiO2 and carbon nano­tubes (CNTs) and carbon nanofibers (CNFs).

■ Developed interim guidance for medical screening and hazard surveillance.

■ Identified what research will be needed to ensure the health of workers han­dling nanomaterials.

■ Established formal partnerships and collaborations with private, governmen­tal and academic centers in the U.S. and globally.

■ Co-chaired the NNI Nanotechnology Environmental and Health Implications (NEHI) Working Group and contributed significantly to the development of the 2011 NEHI environmental health and safety (EHS) strategy.

■ Chaired the Organization for Economic Cooperation and Development (OECD) Working Party on Manufactured Nanomaterials Steering Group 8 on exposure measurement and exposure mitigation for manufactured nanomaterials.

■ Provided widely used guidance on responsible development of nanotechnology.

■ Helped to establish the U.S. and international position that a precautionary approach to controlling exposures to engineered nanoparticles is warranted.

■ Have shown how responsible nanotechnology development and worker safety and health can be achieved.