I’m afraid the “A” word just won’t go away.  It seems that every time people start thinking about the possible health effects of long, thin, fibrous nanomaterials, the question pops up “is this the next asbestos?”  You’d have thought that the issue would have been resolved by now—after all, nanomaterials like carbon nanotubes have been around for some time.  But as the years go by the question persists, and the answer remains elusive.  I’d like to say that this isn’t for want of trying, but sadly there hasn’t been that much interest in funding the right research so far.

This blog was prompted by the recent publication of a report assessing the state of knowledge on fiber-like nanoparticles and their potential health impacts.  The report, commissioned by the Department for Environment, Food and Rural Affairs (DEFRA) in the UK and prepared/published by the Institute for Occupational Medicine (IOM), addresses whether “High Aspect Ratio Nanoparticles” (aka “HARN”) should raise the same health concerns as asbestos fibres.  Here we go again you might say—and indeed the report covers a lot of old ground.  Yet repetitive as the messages might be, the reality is that this is an issue which remains far from being resolved, and could cost some sectors of the nanotechnology industry dearly if clear information and safe working guidelines aren’t forthcoming soon.

To be honest, the report is not an easy read—it was prepared as a report to a government department, and reads as a report to government department.  In other words, it’s not that accessible to anyone outside the immediate target audience.  Nevertheless, it does contain critical information on how this specific class of engineered nanomaterials should be approached if it is to be used safely and successfully.

I’ll get to the report’s key points in a moment.  But first it is worth sketching out an incomplete but interesting nevertheless timeline for carbon nanotube safety questions—picking on carbon nanotubes as, in certain forms, they are the archetypal HARN…

Carbon nanotubes were observed by a number of researchers between the 1950’s and 1980’s, although the relevance of the observations went largely unnoticed (I hate to say it, but Wikipedia covers this pretty well).  It wasn’t until Sumio Ijima published the paper “Helical microtubules of graphitic carbon” in the journal Nature in 1991 that things began to get interesting.

The following year there was a letter published in the same journal raising a cautious note.  The letter was written in response to an article by Paul Calvert on the potential utility of emerging nanofibers—including carbon nanotubes.  In it, Gerald Coles—an occupational hygienist—writes:

“Sir—Attractive though they are, the technical properties of ultra-thin man-made fibres pointed out by Paul Calvert (Nature 357 365; 1992) should not hide the potential—at least for those fibres resistant to biological degradation in vivo—for related occupational risks to workers.

Fortunately, most reinforcing fibres hitherto produced in quantity have, as Calvert pointed out, been of diameter 10 µm or more; the practical risk from occupational or other exposure to their airborne dusts remains doubtful.  But work on fibres other than asbestos has shown the morphology and biological persistence of fibrous materials to be of greater significance in relation both to pnemoconiosis and, more seriously, to mesothelioma, than their chemical constitution.

A need for stringent precautions in preventing occupational exposure to the dusts of these thinner materials might well result in cost increases in manufacture that would outweigh the “dramatic reduction in production costs” hypothesized by Calvert.”

Nothing much happened then until 1998, when Science reporter Bob Service filed a news piece under the headline “Nanotubes: The Next Asbestos?” Service writes

“The dangers of asbestos first came to light in the early 1960s, when studies linked exposure to these silicate fibers with mesothelioma–a rare cancer of the lining of the chest or abdomen that’s commonly fatal. Asbestos fibers were found to be so small that they could be inhaled into the deep lung, where they could stick around for decades. Once there, metals in the silicate fibers could act as catalysts to create reactive oxygen compounds that go on to damage DNA and other vital cellular components.

Whether nanotubes could reproduce this behavior is unknown: Their toxicity has yet to be tested. But already views on their safety differ sharply. “[Nanotubes] may be wonderful materials,” says Art Langer, an asbestos expert at the City University of New York’s Brooklyn College. “But they reproduce properties [in asbestos] that we consider to be biologically relevant. There is a caution light that goes on.” Most notably, says Langer, nanotubes are the right size to be inhaled, their chemical stability means that they are unlikely to be broken down quickly by cells and so could persist in the body, and their needlelike shape could damage tissue.”

Did these concerns lead to action?  Nope.  A few studies began to emerge a few years later observing unusual effects in the lungs associated with single walled carbon nanotubes (see for instance Lam’s review)—but in the main these weren’t materials that physically resembled asbestos.

The next major milestone was in 2006, when a bunch of us published the commentary “Safe Handling of Nanotechnology” in Nature.  Here we stated

“Fibre-shaped nanomaterials possibly represent a unique inhalation hazard, and their pulmonary toxicity should be evaluated as a matter of urgency. Inhalation of a sufficient dose of asbestos fibres can lead to the malignant disease mesothelioma, the causation of which is related to the length, width and chemistry of the fibres, as well as their ability to persist in the lungs.

Although it is not clear whether fibre-shaped nanoscale particles formed from carbon and other materials will behave like asbestos or not, some materials are sufficiently similar to cause concern: any failure to pick up asbestos-like behaviour as early as possible would be potentially devastating to the health of exposed people and to the future of the nanotechnology industry. We propose that the potential health impact of high-aspect-ratio, biopersistent engineered nanotubes, nanowires and nanofibres is systematically investigated within the next 5 years.”

Since then, there have been a couple of studies exploring the potential of fiber-like carbon nanotubes to cause mesothelioma—most notably the Poland et al. study that appeared in Nature Nanotechnology in 2008.  The study indicated (in a nutshell) that carbon nanotubes that look like harmful asbestos fibers, seem to behave like harmful asbestos fibers.

Looking through this rather roughly sketched out timeline, it is clear that questions over similarities between carbon nanotubes and asbestos have been circulating for some years, yet little has been done to discover the extent of this similarity, and actions that need to be taken as a consequence.

So back to the DEFRA report.  In amongst a whole heap of scientific information, there are some key messages that come through:

The Fiber Paradigm. Over the years, experts have developed a profile for fibers that are more likely to be harmful if inhaled.  According to this profile, for something to show asbestos-like toxicity, it needs to satisfy three criteria:

• Diameter: Fibres must be thin enough reach past the upper  airways and into the sensitive region of the lungs where oxygen diffuses into the bloodstream.  (Penetration into the lungs is not affected that much by fiber length.)
• Length: Fibers must be long enough to initiate harm through mechanisms such as frustrated phagocytosis—where the lung’s natural defenses break down because scavenger cells (macrophages) cannot physically engulf the fibers.
• Biopersistence: Fibers must stick around for a long time in the lungs (tens of years) without dissolving or breaking up.

There are other factors that may be important in determining toxicity, but these are the big three.

High Aspect Ratio Nanoparticles and the Fiber Paradigm. The review concluded that there are some HARN that satisfy the profile of the fiber paradigm—certain forms of carbon nanotubes in particular—and that these should be approached with caution.  Quoting from the document:

“This review has identified many similarities between HARN and asbestos with regard to their physico-chemical properties and toxicological effects and has concluded that there is sufficient evidence to suggest that HARN which have the same characteristics (diameter, length and biopersitence) as pathogenic fibres are likely to have similar pathology.”

Identifying potentially harmful asbestos-like substances. The review’s authors put together a handy flow-chart for identifying nanomaterials which might be more likely to cause harm in a similar way to asbestos.  It’s just a suggestion, but I thought it was a useful one:

Research priorities: Finally, the report’s authors highlight areas requiring further research if progress is to be made:

• Hazard Identification: The characterisation of the physico-chemical properties
  of HARN especially the length of the fibres and their biopersistence
• Dose-Response Assessment: Acute and chronics adverse effects of HARN;
  Cellular and molecular mechanisms of HARN toxicity investigated with in vitro
  and in vivo models
• Exposure Assessment: Identification and quantification of the routes (e.g.
  inhalation, dermal); the pattern and the  intensity of exposure
• The Risk Assessment of HARN: Combining exposure and Hazard to
  calculate the health risks from exposure to HARN.

To me, this seems a no-brainer.  Carbon nanotubes in particular are such an important material that we cannot afford not to commercialize them.  But at the same time, it would be morally reprehensible to plow ahead without heeding the warning signs that this material—in some forms at least—needs to be handled with care.  It still amazes me that 17 years after health and safety questions were first raised, we are still framing the questions rather than finding the answers.

Hopefully though this will change and the DEFRA report will be the precursor to some solid research.  It’s certainly needed.