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From 2020 Science:

I’m looking at an electron microscope image of a carbon nanotube - as I cannot show it here, you’ll have to imagine it.  It shows a long, straight, multi-walled carbon nanotube, around 100 nanometers wide and 10 micrometers long.  There is nothing particularly unusual about this.  What is unusual is that the image also shows a section of the lining of a mouse’s lung.  And the nanotube is sticking right through the lining, like a needle through a swatch of felt.

The image was shown at the annual Society of Toxicology meeting in Baltimore last week, and comes from a new study by researchers at the National Institute for Occupational Safety and Health (NIOSH) on the impact of inhaled multi-walled carbon nanotubes on mice.

It’s highly significant because it takes scientists a step closer to understanding whether carbon nanotubes that look like harmful asbestos fibers, could cause asbestos-like disease.

Questions were raised about carbon nanotubes and their superficial similarity to asbestos fibers as far back as 1992.  Yet it wasn’t until last year that research was published suggesting carbon nanotubes that look like harmful asbestos fibers could possibly also cause asbestos-like diseases—specifically the disease of the lungs’ lining mesothelioma.

The Poland study, published in the journal Nature Nanotechnology, indicated that development of the disease mesothelioma was theoretically possible following inhalation exposure.  But it didn’t establish whether exposure could occur to asbestos-like carbon nanotubes in practice or, if they were inhaled, whether the nanotubes could move to and penetrate the sensitive outer layer of the lungs.

Both steps would have to occur for there to be a chance of mesothelioma developing.

The current study from NIOSH seems to close the loop on one of those steps.  Some caution is needed here as the research has yet to be peer reviewed (see Richard Denison’s comments for instance).  Yet the findings are so significant that NIOSH thought it important to keep people abreast of developments before the work is finally reviewed and published.

In the study, a suspension of carbon nanotubes was introduced into the mice lungs using the pharyngeal aspiration technique, and the movement of the nanotubes through the lungs subsequently tracked.  The researchers found that some of the nanotubes migrated from the alveoli in the lungs (the tiny sacs where oxygen passes form the air to the blood) to the pleura—the delicate membrane surrounding the lungs.  As seen in the image described above, there was direct evidence that some of these needle-like fibers physically penetrated through the lung lining, into the region where mesothelioma can develop.

The researchers are at pains to point out that these data are preliminary, and are not conclusive.  The results could have been influenced by the way the nanotubes were delivered to the lungs, the amount of material applied, or the types of animals used.  Nevertheless, they demonstrate that, in principle, some forms of carbon nanotubes have the potential to migrate to the outer layer of the lungs.  And this, combined with the data from Poland et al., raises the stakes considerably regarding potential health impacts.

The data from this study will be peer-reviewed and published shortly, allowing a more critical evaluation.  But given the significance of the preliminary findings, it seems  there is an urgent need for a more extensive strategic research program to establish how harmful different types of carbon nanotubes are, and how they can be handled safely.

Without this, it’s hard to see how manufacturers will be able to make informed choices on good practices that don’t either endanger workers and users, or place an overwhelming burden on production processes.

In the meantime, the best advice seems to be: Take great care to avoid airborne exposures when working with carbon nanotubes that bear a physical resemblance to asbestos.

[Read the original article at http://2020science.org/2009/03/26/new-carbon-nanotube-study-raises-the-health-impact-stakes/]

From 2020science: Ten years ago to the month, one of the first research reports detailing the challenges of ensuring the safe use of engineered nanomaterials was delivered to the UK Health and Safety Executive.  The report wasn’t for general release, and you’ll be hard pressed to find a copy of it in the public domain.  But as a co-author, I have a copy skulking around in my archives.  And given it’s ten year anniversary, I’ve been browsing through it, to find out how much has progressed - or not, as the case may be!

The report focused on ultrafine aerosols, and the Health and Safety Laboratory’s ability to respond to then-current, and future, research needs.  As such it was pretty wide ranging, and focused extensively on exposure to incidental nanoscale aerosols - such as welding fume and engine emissions - in the workplace.  But it did encompass the then-nascent field of nanotechnology and “nanophase material synthesis.”  And some of these early assessments of the field bear revisiting.

For anyone interested in what was being written about the potential health and safety issues raised by engineered nanomaterials ten years ago, I’ve extracted a few sections of the report below - for the full thing, you’ll have to go to the UK Health and Safety Executive.

My apologies that the post is so long - I’m only expecting a dedicated few to plough through it.  But at the least, you might want to skip to the end to see how the research recommendations of 1999 compare to those of today - you might be surprised!

A scoping study into ultrafine aerosol research and HSL's ability to respond to current and future research needs.
IR/A/99/03

Kenny, Maynard et al. 1999

The introduction to the report starts:

Over the past few years a number of epidemiological studies have indicated a tentative link between ambient particulate concentrations, and morbidity and mortality rates (e.g. Dochery et al. 1993, Pope 1996, Schwartz et al. 1993, Schwartz et al. 1991).  In all studies, particles with an aerodynamic diameter less than 10 µm (the PM10 fraction) have been implicated as the key agents.  The lack of an apparent association between particles of specific composition and health effects has indicated the observed effects to be due to some physical aspect of the inhaled particles.  A further link between particle size and health has been indicated by Dochery et al. (1993) who showed a more positive correlation between ill health and particles smaller than 2.5 µm than was seen than with the PM10 fraction.  The possibility of correlations between particle size and number concentration and toxicity has been demonstrated by Oberdörster et al. (1995) by exposing rats to PTFE particles ~20 nm in diameter.  At concentrations of 106 particles cm-3 (corresponding to an equivalent mass concentration of approximately 60 µg m-3) rats exposed for 30 minutes died within 4 hours. At lower concentrations a steep dose response curve was observed between pulmonary inflammatory responses and particle number.  More recent research has begun to indicate a possible material-independent link between inhaled particle surface area and selected toxicological endpoints (e.g. Lison et al. 1997). The possibility of a relationship between fine inhaled particles and ill health is now readily accepted,  although research is still at a very early stage and most published data to date are open to a wide range of interpretations.  Tentative hypotheses concerning possible mechanisms leading to toxicity have been proposed (e.g. Schlesinger 1995, Seyton et al. 1995, Donaldson and McNee 1998), and the impact of inhaling ultrafine particles on both the respiratory and cardiovascular systems have been speculated on.  The US EPA have already acted, partially as a response to earlier epidemiological studies, and introduced the PM2.5 sampling standard for environmental particulates.  Whether the UK is to follow this lead is still under discussion.  However, despite these steps, research so far has raised more questions than answers.  There is debate over the interpretation of the epidemiological studies, and the appropriateness of chosen endpoints in toxicology tests.  Contradictory experimental results are beginning to be published regarding ultrafine particle impact on health (e.g. Pekkanen et al. 1997).  There also appear to be widely conflicting views on what constitutes an ultrafine particle, with implicit cut-off points ranging from 10 µm down to a few nm!

In amongst all the current confusion is the question of whether the alleged health implications of inhaling ultrafine aerosols are of relevance to the workplace.  Much has been made of the apparent health problems amongst vulnerable sectors of the general population following environmental exposures, and the argument is followed through to the conclusion that within a healthy workforce similar problems are unlikely to be seen (backed up by a lack of evidence of severe health problems that are clearly linked to ultrafine aerosols).  However, in part the current uncertainty over the toxicity of ultrafine particles is due to the very limited information available on the nature of so-called ultrafine particles.  Inhaled particles associated with health in epidemiology studies have been very poorly defined, and even the particles used in most well controlled in vitro and in vivo experiments have been poorly characterised.  Without basic information on particle size, morphology, composition and structure, it is clearly not feasible to make value judgements on the nature of inhaled particles, either in the general environment or in the workplace. In the light of the scarcity of information on particle characteristics, the Committee on the Medical Aspects of Air Pollutants has recommended the monitoring of such parameters at a number of environmental locations (COMEAP 1996).  Similar measurements will be essential within the workplace before further speculations on the importance of ultrafine aerosols are made.

In reading this, it is important to remember that the state of the science is ten years on from when this was written—there are now a wealth of publications on the potentially health-relevant behavior of nanometer-scale particles.  Yet the framework of questions set out largely remains as relevant now as it did then.

Perhaps more interestingly, in 1999 the discussion was focused on understanding and managing the health impacts of inhaled particles, NOT whether those particles could be classified as arising from nanotechnology or not.  As a result, the document tends to be more grounded in the science of how fine particles potentially impact on health, rather than how the poorly defined field of “nanotechnology” might lead to health effects.

The report goes on to consider the generation of ultrafine aerosols in the workplace:

In general, very little is known about any aspect of ultrafine aerosols in the workplace.  There are a number of processes such as welding and soldering where intuitively one would expect large numbers of sub-µm particles.  However even in these areas, detailed measurements of particle size do not appear to have been made.  There is a general feeling that in situations where large concentrations of particles are generated, agglomeration will remove ultrafine particles from the aerosol before it is inhaled, thus removing the need to consider ultrafines. However this has not been verified, and evidence exists for significant mass concentrations of ultrafines existing close to generation sources.  Interestingly, researchers are currently speculating that agglomerates with ultrafine primary particles may have the equivalent impact on the lungs as the individual primary particles.  More is known about the products of internal combustion engines, although mainly from the view point of monitoring and reducing environmental emissions.  However very little information on the nature of individual particles in the workplace exists.

Ultrafine aerosols tend to be formed either through nucleation (in particular homogeneous nucleation), gas to particle reactions or through the evaporation of liquid droplets.  The majority of workplace ultrafine particles are likely to arise from the nucleation route, either as combustion products, or within saturated vapours arising from other sources (e.g. welding, smelting, laser ablation).  Evaporation of sub-micron and even micron sized droplets of relatively high purity solvents will result in very small particles.  Where the initial particles are highly charged, there is the possibility of any resulting fine particles exceeding the Rayleigh charge limit and fragmenting into even finer particles.  This is a recognised method of generating ultrafine particles through electrospraying.  To what extent this generation route is present in the workplace is unknown, although it is used for the specific generation of ultrafine particles during nanofabrication.  Gas to particle generation of ultrafine aerosols accounts for the majority of non-combustion particles in the environment, although again the significance of this route within the workplace is unclear.

Following current interest in nanophase technology, and the use of ultrafine particles as precursors in nanophase materials, it is likely that the next few years will see an increase in the industrial generation and use of ultrafine particles.  At present the planned generation of particles tends to be isolated to the production of ultrafine metal oxides such as TiO2, ZnO and fumed silica.  Ultrafine carbon black is also currently generated on a commercial scale. Although the full extent to which ultrafine aerosols are generated as an unwanted by-product within industry is still largely unknown, there are clear cases where the generation rate is high, such as in welding and from internal combustion engines.  Even so, data on the nature of generated aerosols in these areas are sparse.

There follows an assessment of different sources of nanoscale particles in the workplace, from welding to plastic fumes from laser cutting, and a range of other sources.  This is all interesting information, but here I want to focus on the section on ultrafine aerosol precursors in nanophase technology:

Over the last ten years, interest in the unique properties associated with materials having structures on a nanometer scale has been increasing at something approaching an exponential rate.  By restricting ordered atomic arrangements to increasingly small volumes, materials begin to be dominated by the atoms and molecules at the surfaces of these ‘domains’, often leading to properties that are startlingly different from the bulk material.  As the domains become smaller, and hence more dominated by surface atoms and surface energies, so the properties become increasingly unique from either the bulk material or the constituent atoms. So for instance, a relatively inert metal or metal oxide may become a highly effective catalyst when manufactured as ultrafine particles; opaque materials may become transparent when composed of nanoparticles, or vice versa; conductors may become insulators, and insulators conductors; nanophase materials may have many times the strength of the bulk material.  All of these effects and many more have been observed with various materials.  Such material properties that are unique to nanostructured materials that have excited both the scientific and industrial communities in recent years.

Most nanophase materials are fabricated either from the liquid state, or the aerosol state, although some routes combine the two.  The liquid route perhaps gives more control over the process in some cases.  However there is a general feeling at the present that using aerosols is an inexpensive and versatile route to constructing these materials.  Although there are many different production methods being explored, the general approach is to generate, capture and process an aerosol of particles with the dimensions of the final nanostructure.  Typically this requires the generation of particles from 1 to 2 nm in diameter up to around 20 – 30 nm in diameter, depending on the required properties of the final material.  Generation rates in research laboratories tend to be low (of the order of mg/hour), although where industrial production of nanoparticles has commenced, production rates of the order of tonnes per hour are seen.

At present, nanophase materials are an emerging technology, with the emphasis most definitely still on the research lab.  However, there is considerable commercial commitment to the field, and it is certain that as scale-up problems are overcome, the mass production of both nanoparticles and nanophase materials will increase rapidly world-wide.  When this occurs, the unique health problems associated with a unique product that can neither be treated as a bulk material or on a molecular level will have to be fully addressed.  In the meantime, there is a clear need to keep up to date with both developments in the technology, and any health concerns that may be associated with it.

Over the past ten years, commercial-scale production of nanoscale materials has moved on significantly, although perhaps not as much as some would have predicted.  Yet the issues surrounding their safety still reflect (by on large) the issues raised here.

The report summarizes the state of nanotechnology research in 1999—which I’ll skip over—and goes on to consider where the rather quaintly termed nanophase technology was heading:

The indication from the scientific press is that there are as many potential applications for nanophase technology as there are groups working in the field.  However a relatively small number of areas can be identified where commercial production of materials is most likely to be seen in the next 5 - 10 years.  To understand the commercial pressure behind the progress of nanophase technology and its likely integration into industry, you only have to consider the potential market for successful applications.  In the electronics industry in particular, the revenue arising from nanotechnology is likely to be well in excess of hundreds of billions of dollars.  In other areas, such as coatings and catalysts, similar markets exist for successful applications.  The market for ‘intelligent’ drug delivery systems, if successful, is likely to be immense.  Reflecting this, the pharmaceutical industry is currently investing in excess of $14B per annum into advanced delivery systems.

Electronic applications

The reduction in particle size has a profound effect on electronic structure as nanometre dimensions are reached, leading to a number of unique electronic properties seen in individual and groups of nanoparticles.  As an illustration, Si, which is semiconducting in the bulk solid, may be used to form nanometre sized pseudo-crystals with one of two types of atomic structure dominating its faces.  Particles with one structure are fully conducting. Those with the other are good insulators. What does this mean/what are the general implications?

Perhaps the most widely recognised electronic property of nanoparticles is their ability to act as quantum dots.  In arrays of such particles, the overall electronic characteristics are dominated by quantum effects within the particles, leading to novel applications.  For instance, quantum dot devices can be used to create high efficiency LED’s and electroluminescent plastics.  High frequency solid state lasers based on quantum dot technology are expected to form the basis of a major breakthrough in telecommunications, leading to significantly higher communication bandwidths.  High speed and high capacity computer memory will also be possible using quantum dot technology.  Success in fabricating viable quantum dot devices will bring about a major technological step within the electronics industry, leading to a $B production industry, although progress at present is limited by the need to fabricate very precise arrays of well characterised particles.  Current approaches include the use of colloids, nanolithography and aerosols.

Porous nanostructured semiconductors such as silicon have recently been shown to have electroluminescent properties.  If this can be fabricated into integrated circuits, the basis for the next generation of high speed optoelectronic computers will be laid.  Nanoparticles are also being found to lead to improved properties in resistors and capacitors.  Ultrafine conducting particles embedded in an insulating matrix have been shown to give a great range of resistances as well as showing very high temperature stability.  Similarly, the use of nanoparticles in capacitors has been shown to give a high dielectric permitivity and a low dissipation factor, making them ideal for high speed computer memory.

A particularly interesting phenomenon seen in nanophase materials is that of electrochromism; the modification of optical properties by the application of an electric field. Windows or mirrors coated with thin layers of these materials show variable light transmittance or reflection based on the magnitude of an applied electric field.  It has also been found that nanophase materials may be used to form thin transparent films with high conductivity.

A number of other important areas relating to electronics are increasingly relying on the use of nanostructured materials.  Solid state gas sensors show improved sensitivity when using films of sintered nanometre particles; high temperature superconductors have a higher performance when formed of nanostructured materials; thermocouples benefit from nanostructure and the magnetic properties of some nanostructured materials is already exploited to the full in magnetic storage media.

Coatings

Using nanophase materials to coat a wide range of substrates is being explored, and has been exploited in a wide range of applications.  Hard nanophase coatings are important in the construction industry.  The use of coatings with specific optical properties is of interest within the glass and photographic film industries.  Dry coating technology is also benefiting from nanophase materials.  It has been shown that the transport properties of large particles may be radically altered by the addition of a thin coating of fine particles of a suitable material.  For instance, coating starch grains with fumed silica results in a highly flowable powder.  In many cases, this coating need only be of the order of nanometres thick, and the use of nanoparticles in dry coating processes is already under investigation.

Chemical-mechanical polishing using nanoparticle slurries.

Surface polishing is a critical step in the processing of silicon wafers prior to semiconductor chip fabrication.  Surface blemishes are a major source of both wafer and chip rejection in the electronics industry.  By using polishing slurries consisting of nanoparticles, planarisation of wafer surfaces with fewer blemishes is possible.

Drug delivery systems.

A key goal in current drug delivery system research is the development of ‘intelligent’ systems that will deliver doses to specific sites within the body.  One approach being actively considered is the use of coated nanoparticles.  These would be capable of penetrating capillaries and being transported directly to the target site.  The coating would include the drug to be delivered, components to prevent an immune response from the body and components to achieve site-specific or condition-specific delivery.

Nanoparticle catalysts

The modified surface chemistry of nanoparticles is well recognised for its catalytic properties in many materials.  This, together with the associated surface area to mass ratio for such particles, has led to intense interest in nanostructured catalysis within many fields.

After laying out the state of the science regarding the potential risks of inhaling nanoscale particles (which has advanced considerably over the past ten years), the report summarises (on the health impacts):

There has been little work in this field to date, so it is difficult to draw meaningful general conclusions from the published data. One of the reasons for this lack of data appears to be the difficulty in generating particles of standard and known size for use in in vitro studies. Particles used in both in vitro and in vivo studies have also tended to be relatively poorly characterised. Different effects both in vitro and in vivo have been observed with different sources of ultrafine particles, so the responses measured may be a function of the particle constituents rather than the particles per se. The differences observed have been attributed to the ability of particles with a particular composition to have different levels of free radical activity at their surface. Whilst there has been some work investigating synergy between acid aerosols and ultrafine particles (see below), there has been no work investigating the synergy between ultrafine particles and other potential airborne contaminants, e.g. allergens, VOC’s and bacteria. Some of the animal models used to demonstrate toxicological endpoints require exposure regimes which are far in excess of any possible exposure in humans (e.g.  6 hours a day, 5 days a week for 3 months). Therefore, the extrapolation of such health effect data to humans should be treated with some caution.
…
Interest in possible health effects following inhalation of ultrafine particles is high at present, and research is beginning to follow this interest.  Inhalation toxicology has taken over from epidemiology over the past few years, and dominates the field at present.  Dose response relationships in rodents are being seen that indicate particle number or surface area to be more appropriate metrics than mass.  The possibility of ultrafine particles acting as vectors to transport  acids and metals to the alveolar region of the lung is also being explored.  However it is recognised that many of the current approaches being taken are lacking in various aspects, particularly regarding the significance of chosen endpoints and the characterisation of particle exposure, and a number of groups are now beginning to address these issues.  This is an area that is particularly ripe for good research proposals to sympathetic funding bodies. The need to fully characterise the particles used in exposure and inhalation tests, as well as those that people are exposed to in the workplace and environment, is well understood, although the right combination of technical skills to achieve this seems to be lacking in many establishments.  In particular there would appear to be significant scope for transferring analytical electron microscopy skills used in materials science and nanostructure analysis to the analysis of ultrafine aerosol particles.  There is also a recognised need for in-vitro test systems that allow cell cultures to be exposed to the aerosol, rather than a particulate suspension.  A small number of research groups are currently developing test systems allowing direct aerosol deposition.  Funding for fine particle research (PM2.5 sampling, and mass-based aerosol sampling) still dominates, but all aspects of ultrafine particle research are on the increase, and it is likely that the next few years will see significant funding opportunities and research in this area.  Driven by concerns over environmental exposure, together with the need to address exposure limits for nuisance dusts, there is increasing interest in examining the impact of ultrafine particle exposure in the workplace.

The report covers a lot of ground on exposure measurement and control, which I won’t duplicate here (although a lot of the information remains highly pertinent).  Instead, I’ll jump right to the end of the report, where a number of research recommendations are made.  Remembering that these are focused specifically on inhalation exposure in the workplace, they sound surprisingly contemporary, being written 10 years ago:

Full quantification of ultrafine aerosol exposure in the workplace:

• Measurement of number, size, surface area, composition, morphology, structure
• Investigation of the surface properties of workplace particles.
• Investigation of surface enrichment, role of modified surface activity below 10 nm, relevance of internal structure.
• Development of instrumentation and analytical techniques for surface area
• measurement and individual particle characterisation (Analytical Electron Microscopy)

Targeted epidemiology and toxicology studies.

• Epidemiological evidence for ultrafine particle toxicity in the workplace
• Toxicity of well defined particles, and of particles characteristic of those found in the workplace.
• Investigation of mechanisms resulting in toxic responses, in relation to the known physical and chemical attributes of workplace particles.

Instrumentation

• Identification of deficiencies in instrumentation and monitoring requirements, and development of new technologies and methods.

Control

• Reassessment of  the applicability of conventional control systems (including RPE) to reduce exposure to ultrafine particles, and the development of new approaches to exposure control.

Exposure Limits

• Assessment of current exposure limits in the light of available data on ultrafine particle toxicity, and the development of more appropriate approaches to exposure limits.

Ten years on, it is surprising how relevant this document still is.  The major issues facing the safe use of nanomaterials were reasonably clear ten years back.  And many of the research needs raised then remain today.  Progress certainly has been made since then, and an understanding of the types of nanomaterials of greater concern has increased—the 1999 report doesn’t mention carbon nanotubes for instance.  But on the flip side, this is a report that was clearly unencumbered by the politics of nanotechnology that seem to have diffused through things today

Perhaps most surprisingly though, is that governments and others are still talking about the same issues - often as if they have discovered them for the first time - without doing that much about them.  It would be churlish to ask where we might have been now if some of those 1999 recommendations were listened to.  But at least I can ask where we might be in 2019, if only we can break out of this endless cycle of re-inventing the nanotech risk report!

Endnote

Because this was an internal report, I have been careful to extract only parts of it that are of general interest and are not in any sense proprietary.  That said, there is a lot of information in the full report that would be helpful to anyone grappling with addressing and managing potential occupational risks arising from nanoscale particle exposure in the workplace.  It would be great if the UK Health and Safety Executive could release it for public use!

References

COMEAP (1996).  Non-biological particles and health.   HMSO Publications.

Dochery, D. W., Pope, C. A., Xu, X., Spengler, J. D., Ware, J. H., Fay, M. E., Ferris, B. G. and Speizer, F. E. (1993).  An association between air pollution and mortality in six U.S. cities.  N. Engl. J. Med, 329, 24, 1753-1759.

Donaldson, K. and McNee, W. (1998).  The mechanics of lung injury caused by PM10.  In: Air Pollution and Pealth.  Eds:  Hester and Harrison.  Royal Society of Chemistry.  ISBN 0-85404-245-8.  pp21-32.

Lison, D., Lardot, C., Huaux, F., Zanetti, G. and Fubini, B. (1997).  Influence of particle surface area on the toxicity of insoluble manganese dioxide dusts. Arch. Toxicol. 71, 725-729

Oberdörster, G., Gelein, R. M., Ferin, J. and Weiss, B. (1995).  Association of particulate air pollution and acute mortality:  involvement of ultrafine particles?  Inhal. Toxicol., 7, 111-124.

Pekkanen J, Timonen KL, Ruuskanen J, Reponen A, Mirme A (1997) Effects of ultrafine and fine particles in urban air on peak expiratory flow among children with asthmatic symptoms. Environ Res 74: 24-33

Pope, C. A. (1996).  Adverse health effects of air pollutants in a nonsmoking population.  Toxicology, 111, 149-155.

Schlesinger, R. B. (1995).  Toxicological evidence for health effects from inhaled particulate pollution:  does it support the human experience?  Inhal. Toxicol., 7, 99-109.

Schwartz, J., Spix, C., Wichmann, H. E. and Malin, E. (1991).  Air pollution and acute respiratory illnessin five German communities.  Environ. Res., 56, 1-4.

Schwartz, J., Slater, D., Larson, T. V., Pierson, W. E. and Koenig, J. Q. (1993).  Particulate air pollution and hospital emergency room visits for asthma in Seattle.  Am. Rev. Respir. Dis., 147, 826-831.

Seyton, A., MacNee, W., Donaldson, K. and Godden, D. (1995).  Particulate air pollution and acute health effects.  The Lancet, 345, 176-178.

Read more: "Nanotechnology risk research, ten years on" - http://2020science.org/2009/03/02/nanotechnology-risk-research-ten-years-on/#ixzz08iLutTS0

From 2020science.org:

The National Research Council of the National Academies releases its review of the National Nanotechnology Initiative Strategy for Nanotechnology-Related Environmental, Health, and Safety Research.  And it’s not pretty.

Most people acknowledge that innovation is vital to economic and social prosperity.  But what do you do when science and technology innovation are in danger of being stymied by bad habits and misguided thinking?  One solution: apply a little tough love.  Something a new report from the US National Academies does in spades.

By the end of the next US administration, there will be an estimated seven billion people on the planet, all wanting food, shelter, and water, and most of them striving for a first-world quality of life.  With dwindling natural resources and an environment struggling to absorb humanity’s assaults, old technologies are coming to the end of their shelf life.   Energy security, curing cancer, quality of life in old age, plentiful clean water, climate change—none of these challenges will be met without science and technology innovation.

More to the point, without a constant stream of science and technology innovation, the economy will be starved of the knowledge-capital so desperately needed for stability and growth.

Given this backdrop, you would think that the US federal government would be on top of spotting and navigating around potential barriers to innovation.  Yet according to a new report from the National Research Council of the National Academies, the feds seem to have their collective heads in the sand when it comes to ensuring investment in science and technology research delivers sustainable results...

The new report specifically addresses nanotechnology.  And it focuses on federal government plans to address potential risks associated with this emerging technology.  But the cracks in the system it reveals are most likely endemic across all areas of science and technology innovation.  [Continue reading...]

From 2020science.org:

First impressions of the ICON EHS Database Analysis Tool

What do you do this holiday season when the turkey’s lost its appeal, you’ve seen every movie worth watching ten times over, and conversational déjà-vu sets in?  If you are really desperate, you could play “nano-trivia”—and thanks to the fine folks at the International Council On Nanotechnology (ICON) you now have the perfect widget to help craft those cunning questions that will have your nearest and dearest wracking their brains.

Questions like “between 2000 and 2006, what percentage of scientific papers addressing the toxicity of carbon-based nanomaterials considered exposure via mucous membranes (or the skin)?”

OK, so maybe playing “toxic particle trivial pursuits” is the last resort of the desperate, and likely to result in an ever-decreasing circle of close friends.  But for all that, the new ICON Environmental Health and Safety Database Analysis Tool has its merits... Most importantly, it provides a fascinating insight into how new knowledge on nanomaterial safety is progressing—or not, as the case may be.

Backtracking a little, the EHS Database Analysis Tool (lets just call it “the widget”) is an add-on to the ICON nanoEHS Virtual Journal.  I'm a long-time fan of the Virtual Journal, which is probably the foremost repository of information on scientific papers addressing the potential health and environmental impacts of engineered nanomaterials.  Established and maintained by ICON, it links to close-to every paper published that has some relevance to understanding and addressing the possible impacts of nanomaterials, and is an essential resource for anyone doing work in this area.

But those clever people down at Rice University didn’t just stop at cataloging the constant stream of publications coming out of researchers around the world.  They went one step further and added some useful information—such as what material was studied in the published research, how it was studied, which aspects of hazard or risk were addressed, who the publication was aimed at, and so on.

And that opened up the way for “the widget.”

What the widget does is enable sophisticated searches on the database, and then displays the information graphically (as well as giving direct access to the source-paper records).

Imagine for a moment you are interested in the relative numbers of papers that have been published to date on different routes for carbon-based particles to get into the body—ingestion, inhalation, or through the skin or mucous membranes.  Plug the desired information into a reasonably easy to use matrix on the widget’s web page, select a “Simple Distribution Analysis” plot for the years 1961 through to the end of 2008, and press “Generate Report.”

Hey presto, the widget creates a neat little pie chart clearly showing the requested information.  (For the interested, across these three exposure routes and for the years and material in question, 86% of papers address inhalation, 11% dermal/mucous membrane penetration, and 3% ingestion).

This analysis gives you a sense of how research has balanced out over different areas over a number of years.  But what if you want to know how things are changing—whether more is being published now on carbon nanoparticles for instance than was being published five years ago?  You should not be surprised to hear that the widget can handle this also... (More...)

From 2020science.org:

UK Consumer Organization Which? Releases New Report

Who needs an emerging technologies blog when you have The Daily Mail?  For those of you that missed it, Wednesday’s on-line issue of the British tabloid newspaper highlighted

“The beauty creams with nanoparticles that could poison your body”

I’m so glad someone’s tracking this issue, while us folks over on the other side of the pond are dealing with the considerably less-interesting issues surrounding the incoming Obama administration.  The only trouble is, the Mail didn’t quite get it right.  In fact on a scale of 1 – 10, I’m not even sure they even make it to first base...

The article is based on a new report from the UK-based consumer organization Which? The report “Small Wonder? Nanotechnology and Cosmetics” [PDF, 3.9 MB] takes a clear-eyed view of nanotechnology-based cosmetics on the market, and asks what information is available about them, and whether or not users can be sure they are safe.

Unlike The Daily Mail story, this is an exceedingly good report.  If you are at all interested in nanotechnology and cosmetics, read it—it’s only a few pages long, but conveys the issues with clarity and style.  And by building on perspectives from industry, researchers and consumers, it presents a well-balanced overview.

The report is so accessible that it’s hardly worth summarizing it.  But here anyway are the take-home messages—Which?’s 10 point action plan:

• CO-ORDINATION:  The Government should establish a strategic stakeholder group to ensure there is effective input from all sectors of society and that the necessary measures are implemented and progress monitored.
• DEFINITIONS:  International agreement is needed on definitions for nanotechnologies.
• PRODUCTS:  The Government and EU need to understand what products are already on the market, in the pipeline or at the research stage and identifying those likely to raise most concerns based on current understanding.
• RESEARCH:  The Government and EU need to ensure that uncertainties around the environmental and health risks presented by some manufactured nano materials are urgently addressed – and ensure that research to enable this is funded.
• ASSESSMENT:  The Government and EU must provide clarity over how the safety of nano materials should be assessed given the current knowledge gaps.
• PRECAUTION:  The precautionary principle should be applied to products where there are potential risks, but where it is not currently possible to assess their safety, so that consumers are not put at risk.
• TRANSPARENCY:  Government and industry should be open about the uncertainties that some nano materials may raise, the research underpinning safety assessments as well as claims about potential benefits.
• REGULATION:  The EU needs to address the loopholes in regulations so that nano materials are included and there is clear guidance on how the regulations apply.
• INFORMATION:  The Government must ensure consumers, industry and regulators have clear information about where nano materials are being used and that any claims they make are true.
• ENGAGEMENT:  The public should be involved in meaningful discussions, at all levels, about the development of the technology, priority applications and any no-go areas.

This is a reasonable action plan, and a far cry from the scare-mongering pervading The Daily Mail story.

And unlike many of the reports that appeared in the popular press, Which? do an admirable job of fitting the story to the facts—rather than the other way around!

First posted on 2020science.org, 20th October 2008:

 Is the RBC Life Sciences® nanotechnology product Slim Shake approved for use by the US Food and Drug Administration (FDA)?  According to the BBC Radio 4 science program Frontiers—broadcast on Monday evening—there may be some doubt.  But I get ahead of myself.

The US-based company RBC Life Sciences® sells a range of dietary supplements and food products allegedly based on nanotechnology—8 of them are listed in the Project on Emerging Nanotechnologies public inventory of nanotech-enabled consumer products.  As with many of the products in the inventory, it’s hard to tell whether they are truly using nanotechnology, and even harder to tell what steps have been made to assure their safety.  But Monday’s edition of Frontiers shed a little light on this issue...

Monday’s program, called very simply “Nanofoods,” provided a thoughtful and balanced perspective on the development and use of nanotechnology in the UK food industry, and included interviews with representatives from the companies Unilever and Leatherhead Foods International, as well as the UK’s Institute for Food Research, the Central Science Laboratory and the Food Standards Agency.

Presenter Sue Broom started off looking into what nanotech can do for food—from futuristic drinks with dial-up flavours to low-fat mayonnaise that still manages to taste… well, tasty.  But as the program progressed, the discussion gradually turned to the issue of safety.  And when it got there, things began to get interesting.

Asked whether nanotech food additives that can be metabolized—i.e. broken down by the body—present a greater safety risk than their non-nano counterparts, most of the interviewees suggested that they probably did not.  But Sandy Lawrie of the Food Standards Agency did caution that these assumptions really need to be tested in the laboratory.

However, when it came to nanoparticles that aren’t metabolized—nanoparticles that retain their particle-ness after being eaten and as they pass through the gut—there was less confidence that nanoscale ingredients could be assumed to be safe.  Qasim Chaudhry from the UK’s Central Science Laboratory was particularly concerned about the possibility of such particles being transported to normally inaccessible parts of the body, and perhaps causing harm because of their small size and their durability.  These concerns are echoed in a draft report on nano and food published by the European Food Safety Agency (EFSA) last week.

At this point, the RBC Life Sciences® product Slim Shake was introduced—to a backdrop of eerie music (OK, so I guess radio producers are allowed a little dramatic license in setting the sound-stage.).  As explained by Kimberly Lloyd of RBC, the Slim Shake Chocolate contains “cocoa clusters”—individual particles of silica 4 – 6 nm in diameter, that are coated with the molecules responsible for giving chocolate its flavour.  The high surface area of these nanoparticles supposedly gives an over-sized taste-hit when you drink the shake, which masks the taste of other ingredients in the drink (whatever they may be)—the point being that the Slim Shake tastes good without using too many of the ingredients that any self-respecting dieter would prefer to avoid.

The science actually makes sense, and RBC Life Sciences® should be applauded for actually coming out and explaining it.  But there is a possible problem with those nanoscale silica particles—which are described on the program as being discrete particles, not aggregates.  The folks producing Frontiers got in touch with the US Food and Drug Administration to see whether these silica nanoparticles were approved for use in Slim Shake.  This is what they got back from the FDA:

“we are not aware of any tests that have been carried out to specifically demonstrate the safety of nanosized silica for this use.  For those uses that FDA has determined to be safe, the silica is generally a fine powder but no lower limits on size exist other than those encompassed by good manufacturing practice.”

Mmm, so is RBC Life Sciences® using an unapproved food ingredient, or is life more complicated than this?

Amorphous silica has been used for decades as a food additive, and for specific applications it is Generally Regarded As Safe (a designation referred to as GRAS) by the FDA.  But GRAS status depends on how a material is used, as well as what it is made of.  And reading between the lines of the FDA statement, RBC have not established that their particular use of nano-silica as a food additive is GRAS; nor have FDA worked out whether existing determinations of silica safety apply to nanoscale forms of the material.

To be fair, much of the amorphous silica used in foods these days does have a nanostructure (the material Aerosil® is a good example).  But it is typically used as large aggregates of nanoparticles—i.e. the resulting particles in the additive are much larger than the nanoparticles they are made up from.  In contrast, RBC is claiming that their product contains individual nanoparticles—a departure that could alter the transport of the material within the body, and possibly its subsequent behavior.

Is it possible that RBC Life Sciences® think they are selling an FDA-approved product because of confusion over how existing regulations apply to nanomaterials?  I shouldn’t speculate, but I would like to give them the benefit of the doubt.  (It should also be noted that the company would be well within its rights to determine whether their nano-silica was GRAS without input from FDA—you don’t need prior FDA approval to put something like this on the market, but deciding to go it alone is often ill-advised.)

If this is the case, the faster guidance is developed by the FDA on how nanotechnology fits into existing regulations, the better.  Because as Slim Shake seems to demonstrate, nanotech-enabled foods are appearing in the US that seem to be slipping through the regulatory net.

____________________________________

Postscript (added on 21st October)

For an illuminating discussion on the UK Food Standards Agency response to Slim Shake in particular, and nanotechnology-based ingredients in food in general, fast forward to 23 minutes and 35 seconds into the Frontiers program - available on the web here.

From 2020science.org:

After three years of hard work, International Standards Organization (ISO) Technical Committee TC229—set up in 2005 to develop nanotechnology-related standards—has finally begun delivering the goods.  And the first documents off of the blocks tackle head-on the challenges of working safely with engineered nanomaterials.

September saw the publication of the Technical Specification 27687—“Nanotechnologies—Terminology and definitions for nano-objects—Nanoparticle, nanofibre and nanoplate” (ISO/TS 27687).  True to its title, TS 27687 does exactly what it promises... what you get is beautifully crafted definitions of the terms “nanoparticle” , “nanofibre” and “nanoplate”.  But what is clever about this document is that it develops a systematic hierarchy of terms under the umbrella of “nano-objects”.  Clever, because it neatly resolves the question of “when is a nanoparticle not a nanoparticle” that so often paralyzes discussions on handling nanomaterials safely.

According to TS 27687, a nano-object is a material with either one, two or three dimensions in the nanoscale (roughly, but not exclusively, 1 nm – 100 nm).  Under this overarching term come nanoparticles (having all three external dimensions in the nanoscale), nanoplates (with only one external dimensions in the nanoscale) and nanofibres (nano-objects with two similar dimensions in the nanoscale, and a third dimension that is significantly larger).

Nanofibres are further subdivided into three categories: Nanowires (electrically conductive nanofibres), nanotubes (hollow nanofibres) and nanorods (rigid nanofibres).

The result is a neat and logical way of describing nanoscale materials that differentiates between objects that have previously all been lumped together as nanoparticles.

TS 27687 is not directly focused on health and safety—this is a general Technical Specification designed to aid the development and application of nanotechnologies.  Yet I suspect that the primary utility of this document will be to establish a common language for addressing health and safety concerns when handling nanomaterials that could become airborne when handled.  In recognition of this, the introduction to the Technical Specification states:

“It is … essential that regulators and health and environmental protection agencies have available reliable measurement systems and evaluation protocols supported by well-founded and robust standards”

My guess is that TS 27687 will help a great deal in developing such systems and protocols.

But there is clearly more to working safely with engineered nanomaterials than being able to tell a nano-rod from a nano-plate.  The international nanotechnology standards community obviously though the same, because hot on the heels of TS 27687 comes ISO Technical Report 12885, “Nanotechnologies—Health and safety practices in occupational settings relevant to nanotechnologies” (ISO/TR 12885).  Published in early October, TR 12885 presents an in-depth assessment of the issues surrounding and possible solutions to working safely with engineered nanomaterials.  At 79 pages long, it is perhaps the most weighty document addressing nanotechnology to come out of a standards organization to date!

TR 12885 is heavily based on the NIOSH document “Approaches to Safe Nanotechnology: An Information Exchange with NIOSH” (originally published in 2005, and updated in 2006).  While much of the information presented closely reflects that in the NIOSH document, the ISO Technical Report expands significantly on the original document in a number of areas.  For instance, TR 12885 goes into far greater depth on exposure monitoring and exposure control than the NIOSH document.

This new report isn’t perfect. For instance, I was surprised to see no mention of the DuPont/Environmental Defence Nano Risk Framework in the Product Stewardship section.  And it would have been useful to have a fuller discussion on risk management techniques such as control banding and how they might be applied to working with engineered nanomaterials [see end notes for more information].  But as a comprehensive review of the issues relevant to working safely with engineered nanomaterials, it’s not bad.

However, this new guide on health and safety practices for nanotechnologies is entering an already-crowded marketplace.  ASTM International were the first standards kids on the block with E 2535-07 (Standard Guide for Handling Unbound Engineered Nanoscale Particles in Occupational Settings), published in October 2007.  This was followed a few weeks later by BSI guide PD 6699-02:2007 (Nanotechnologies – Part 2: Guide to safe handling and disposal of manufactured nanomaterials), published in December 2007.  And of course, you have the original NIOSH document, that beat all the others in its first incarnation by two years—having hit the streets in October 2005.

So does this new document from ISO add anything to the mix?

Having looked through the new Technical Report, I have to say yes.  But this is a qualified yes: The ISO document is great for laying out the current state of knowledge and offering options and possibilities for working safely with engineered nanomaterials, but it falls short on clear and concise advice.  In contrast, BSI PD 6699-02 offers what I have previously described as a “shop-floor manual for making decisions where the rubber hits the road.”  ASTM E 2535-07 is similarly more direct in its guidance, although more narrowly focused on what are termed “unbound nanoparticles.”

At the end of the day, these three documents complement each other.  ISO TR 12885 is the reference manual, while BSI PD 6699-02 and ASTM E 2535-07 provide on-the-job advice that is unencumbered with over-much background and analysis.  None of them are perfect—the ISO document is perhaps too reticent in providing guidance, and struggles to keep up with the latest developments (perhaps belying it’s origins in a document published originally three years ago), while the BSI and ASTM International guides could be described as too simplistic in places.  Yet together, they form a firm foundation for ensuring safer workplaces when handling engineered nanomaterials.  And as such they are all highly recommended.

But back to the ISO documents.  These are both strong documents to come out of ISO TC229, and will be extremely useful in helping to develop the knowledge, protocols and methodologies necessary for working safely with engineered nanomaterials.

All we need now is a new guide to make sense of the alphabet soup that these standards organization documents seem to emerge from!

________________________________________________________
End Notes

The work programme of ISO TC229 can be accessed here.

It should be noted that you have to pay for the privilege of owning ISO TS 27687, ISO TR 12885 and ASTM E 2535-07.  BSI PD 6699-02 on the other hand, is free.

And on this note, I cannot resist but point out that the core of ISO TS 27687 is twelve defined terms.  I make that just over $4 per term if you purchase the document!  But for $4, you couldn’t get a more beautifully crafted term ☺

Control banding remains an interesting option when it comes to making practical judgements on minimizing exposure to engineered nanomaterials in the absence of good information, which is why I was surprised not to see more discussion of it in the ISO document.  A fuller discussion on the utility of the concept for working with nanomaterials can be found here, and a possible implementation, developed by the Nanotechnology Industries Association, can be accessed here.

And finally, for future reference, this blog entry should be referred to as TTS-AM:23A4FD5PO245FF6/TTFN-2008

A just-released national survey on awareness of and attitudes toward nanotechnology and synthetic biology from the Wilson Center Project on Emerging Nanotechnologies should help kick-start this conversation.  For the first time, this annual telephone poll has included questions on synthetic biology—the use of advanced science and engineering to make or re-design living organisms (such as bacteria) so that they can carry out specific functions.  The results are intriguing, and should help inform the path toward responsible and socially acceptable uses of synthetic biology.  But more on this later…

I have been eagerly awaiting the results of the survey for some time.  Would people’s awareness and attitudes match those found for nanotechnology, or would the extension of nanometer-scale manipulation to the biological world raise new fears and hopes?  And how would the concept of making new life from dead chemicals resonate with the religiously inclined?

Impatient for results, I tried out a quick experiment on my eleven-year-old son.  Presented with a one-line definition of synthetic biology similar to the one above, I asked what his first thoughts were.  The results: “Isn’t that against the Bible?”  Followed immediately by “Isn’t that like Frankenstein’s monster?”

At this point I should establish that the reason for using such a young and naïve subject was to gauge how accessible the definition for synthetic biology was that we were developing.  But his responses intrigued me.  He is not overtly religious (although he does attend church regularly), and he is untainted by the Frankenfood debates surrounding genetically modified foods.  Yet he immediately focused in on two key areas that seem to dog attitudes toward biological manipulation.  Understandably therefore, I was keen to see whether the results of the current telephone poll—conducted across the United States by Peter D. Hart Research Associates Inc.—matched these concerns.

The results of the poll weren’t as clear-cut as my son’s response, but they did highlight some interesting points.

First off, synthetic biology is not on the radar for most people.  67% of the thousand people polled had never heard of the field, while a mere 2% claimed they had heard a lot about it.  Yet when asked whether they thought the benefits would outweigh the risks (or vice versa), 60% of people who had never previously heard of synthetic biology voiced an opinion.  That’s right—they didn’t know what it was, but they sure knew whether they liked it or not!

This has echoes of Dan Kahan’s work at the Cultural Cognition Project at Yale Law School.  Dan has shown previously that when people are initially introduced to nanotechnology, their attitudes are driven by an emotional response—their gut feeling.  Such a gut-response to nanotechnology is seen in the current poll.  But in this case, more people were willing to make an initial judgment on synthetic biology than nanotechnology.

I mention Dan’s work because he found that when people leaned more about nanotechnology, their opinions were heavily influenced by their value systems; moral, political, religious, or otherwise; and not just by the science.  If this holds true for synthetic biology, people with strong religious beliefs might be expected to respond differently to more information on synbio than those less-inclined to a religious perspective—the “Isn’t that against the Bible?” response.

To gauge poll participants’ informed responses to synthetic biology, they were read two short paragraphs—one discussing its potential benefits and the other discussing its potential risks (see the PEN report for the paragraphs).  The order in which these were read was randomly rotated.  Participants were then asked again whether they thought the risks of synbio would be greater, the benefits greater, or whether the two would be about equal.

I was particularly interested in this question of how religious values affected people’s informed response.  Delving into the data, respondents who never attend religious services were ambivalent on the risks and benefits of synthetic biology—there was no statistical difference between the numbers of people who thought benefits would outweigh risks, and vice versa.  But people who attended religious services once or more per week were on balance more likely to feel that potential risks would dominate potential benefits.

Of course, it may be that this trend simply reflects a more risk-averse attitude amongst the religiously active.  But comparing the synthetic biology data with the informed attitudes to nanotechnology counters this suggestion.  In the case of nanotechnology, people who attended religious services once or more per week were ambivalent on whether the risks and benefits of the technology would dominate, while the religiously un-engaged clearly felt on balance that the benefits outweighed the risks.

A similar comparison between attitudes toward synthetic biology and nanotechnology was seen when poll subjects were separated out by gender, education and income.
Men on balance felt the benefits of nanotechnology would outweigh the risks, while women were on the fence.  But when it came to synthetic biology, men were on the fence, and on balance women felt the risks would dominate.

College graduates anticipated the benefits of nanotechnology would dominate the risks on balance, while people educated to high school or less were ambivalent.  For synbio, the graduates were undecided on whether risks or benefits were greater, while on balance those who only reached high school education or less thought the risks would be greater.

People earning more than $75 thousand a year thought the benefits of nanotechnology would be more significant on balance, while those earning less than $30 thousand per year weren’t sure.  In the case of synthetic biology, the participants earning $75 thousand or more weren’t so sure about risks and benefits, while those earning less than $30 thousand were sure on balance that the risks would be greater.

Overall, there were plenty of people within each gender, education, income and religious observance group who bucked the trends—anticipating more benefits when the majority were expecting higher risks, and vice versa.  But the overall picture is one of nanotechnology as an area where people are on balance either ambivalent about risks and benefits or anticipating the benefits to dominate, and synthetic biology as an area where people are either on the fence or anticipating the risks to dominate.

This is critical information to anyone trying to chart a course to successful and sustainable uses of synthetic biology.  Clearly, there’s something about the conjunction of “synthetic” and “biology” that drives an emotive and values-driven response in people that isn’t seen for nanotechnology.  But what to do about this?  If synthetic biology is truly as important as its proponents believe, there’s a lot of work to do ahead in engaging with people to help develop socially acceptable applications.

Fortunately, this “new cool science” is still in its infancy, and the opportunities to engage with “the public” are still there.  But it is growing up fast—The J. Craig Venter Institute is racing ahead towards creating the first artificial bacteria, and “biohackers” are learning how to re-engineer life at an increasingly rapid pace.

Some deep soul-searching between synthetic biologists and the public may not be in the making yet.  But a serious heart to heart will be needed sooner rather than later, if synbio is to reach its full potential without major growing pains.