Last week, the Victoria branch of the Australian Education Union (AEU) passed a resolution recommending that “workplaces use only nanoparticle-free sunscreen” and that sunscreens used by members on children are selected from those “highlighted in the Safe Sunshine Guide produced by Friends of the Earth” as being nano-free.  The AEU also resolved to provide the Friends of the Earth Safe Sunscreen Guide and Recommendations to all workplaces their members are associated with.  Given what is currently known about sunscreens – nano and otherwise, I can’t help wonder whether this is an ill-advised move.

The debate over the safety or otherwise of nanoparticle-containing sunscreens has been going on for over a decade now.  Prompted by early concerns over possible penetration through the skin and into the body of the nanosized titanium dioxide and/or zinc oxide particles used in these products – and potential adverse impacts that might result – there has been a wealth of research into whether these small particles can actually get through the skin when applied in a sunscreen.  And the overall conclusion is that they cannot.  There have been a small number of studies that demonstrate that, under specific conditions, some types of nanoparticle might penetrate through the upper layers of the skin.  But the overwhelming majority of studies have failed to find either plausible evidence for significant penetration, or plausible evidence for adverse health impacts – a body of evidence that led the Environmental Working Group to make an about-face from questioning the use of nanoparticle-containing sunscreens to endorsing them in 2010.

So why is the AEU now advising against their use?  And why are they advocating selecting sunscreens based on a document that does not provide evidence-based advice on efficacy or safety – and may end up leading to decisions that increase the risk of sun-related skin damage in children (more on this below)? (Update 5/25/11 – see notes below)

In part, the answer lies in the uncertainty inherent in proving anything safe.  It’s not too difficult to show that something is unlikely to be harmful, or is probably safe.  But proving something is absolutely safe under all conditions of use is simply not possible – there is always some room for doubt.  This is why decisions on health risks are typically based on plausible risk and weight of evidence – evaluating the most reasonable and defensible interpretation of the data, and not basing decisions on speculation and fantasy.

With the use of nanoparticles in sunscreens, the weight of evidence is that they are safe and effective – and may be safer and more effective than a number of non-nanoparticle alternatives as they work by coating the skin rather than being absorbed into it.  That said, it’s always prudent to check whether anything has been missed with a relatively new technology like this, and so research is ongoing just to make doubly sure that the nanoparticles currently being used stay on top of the skin, and that manufacturers are using the safest possible types of nanoparticles.

But there is another reason I suspect why the ASU have released this advice, and that is due to a study using human volunteers that was published last year.

In this study by Brian Gulson and colleagues, sunscreens were formulated with zinc oxide particles made from a stable isotope of zinc that doesn’t occur in great abundance naturally: Zn-68. Using Zn-68 as a tracer, they were able to tell whether zinc from the applied sunscreen entered the bodies of the volunteers, and ended up in their blood and urine.

The detected presence of Zn-68 in the urine and blood of volunteers was used by Friends of the Earth Australia to renew their recommendations against using nanoparticle-containing sunscreens until more is known about their safety in.  And given the ASU’s reliance on the Friends of the Earth document, it seems to have influenced their decision to recommend not using nanoparticle-containing sunscreens.

But what does the Gulson study actually conclude?  In a nutshell, the researchers showed that:

• Small amounts of zinc from sunscreens containing any form of zinc oxide particles tested found their way into the blood and urine of volunteers.
• The amounts of zinc entering the body over the five day study were miniscule – around one thousandth of the concentration of zinc already in the volunteers’ bloodstream, and around one thousandth of the amount of zinc recommended in a person’s daily diet.
• Women in the test generally showed higher uptakes of zinc than men.
• Zinc levels in blood associated with the sunscreen peaked some days after applications ended, suggesting the zinc or zinc oxide was stored somewhere in or on the body and slowly released.
• For men, zinc uptake from sunscreens was independent of particle size.  For women, zinc uptake was greater from the sunscreens containing smaller particles.

So did the particles go through the skin?  The study only showed that the zinc passed through the skin, and did not provide any evidence of particle penetration.  Two possible explanations for this are that the particles penetrated and entered the bloodstream, or that the applied particles dissolved, and that it was dissolved zinc that was penetrating into the body.

Out of the two possibilities, there is minimal evidence for particle penetration being a plausible mechanism. On the other hand, zinc oxide is sparingly soluble, and under the acid-conditions of the outer layers of the skin the particles would have readily released zinc ions.  The weight of evidence to date therefore strongly supports dissolution of the particles and subsequent dermal penetration of dissolved zinc.  This is supported by the similarity in uptake seen in men of zinc for two different sizes of zinc oxide particles.

In other words, this study provides neither compelling evidence that nanoparticles in sunscreens can pass through the skin, or that they can lead to worrying internal exposure to harmful materials.  It did indicate on the other hand that any sunscreen containing zinc oxide will lead to zinc entering the body via the skin – including sunscreens that rely on large zinc oxide particles.

And this is where it is worth returning to the Friends of the Earth recommendations.

The Friends of the Earth Safe Sunscreen Guide recommends:

Use a nano-free zinc-based SPF 30+ broad spectrum sunscreen in conjunction with protective clothing, a broad-brimmed hat, sunglasses and shade to stay sun safe.

It goes on to list sunscreens that are “nano and chemical free”, “may use nano” and “use nano” (based on information from manufacturers and assumptions from Friends of the Earth).

Passing over the fact that Friends of the Earth are advocating the use of sunscreens that demonstrate the same behavior – zinc penetration through the skin into the body – as the sunscreens they recommend people don’t use, it’s hard to understand how this document provides an authoritative and evidence-based guide for the use of sunscreens on school children – as suggested by AEU.

For a start, this is a document that is specifically concerned with nanoparticle-containing sunscreens, and is not aimed at providing advice on selecting sunscreens as a whole based on their safety and efficacy.  It is advocating a specific course of action, and is not a tool for taking informed action. And in this respect alone it is a questionable document to be distributing to school workers. But it gets worse.

The sunscreens listed in the document are listed solely with respect to their nanoparticle content.  There is no – let me repeat that no – information on how effective these sunscreens are at protecting against UVA and UVB, and what the specific safety issues associated with their use are (update 5/25/11 – see notes below).  What is more, the top tier products – those that appear to be most strongly endendorsed by Friends of the Earth – also claim to be “free of UV-absorbing chemicals”.  In other words, this is a document that appears to be endorsing the use of products that do not necessarily protect against ultraviolet light. (Update 5/25/11 – see notes below).

To be fair to Friends of the Earth – and this is not a critique of their document so much as a questioning of its use as authoritative guidance – they do recommend the use of sunscreens providing substantial UV protection that are (presumably) based on large zinc oxide particles.  But if school workers were to base their choice of what to slather onto kids on the list of products, rather than the one sentence top level recommendation, they could well be applying sunscreens that do not protect against skin damage.

And this is my greatest concern here – by advocating the use of the Friends of the Earth document, AEU could actually be endangering the health of children in the care of their members. (Update 5/25/11 – see notes below)

Of course, there are important issues to grapple with here – including how appropriate sunscreens should be selected for use on children, irrespective of the technology being used.  But surely these selections should be based on the best possible evidence that is focused on what is most appropriate for the children, and not on an action campaign by an advocacy group, no matter how well intentioned.

Update, 5/25/11:  As clarified by Georgia Miller of Friends of the Earth Australia in the comments below, the sunscreens listed in the top tier of the Friends of the Earth document are all – as far as I can tell – marketed as offering SPF 30 + protection.  This is something that I do not think is explicitly clear in the document, and the heading of “nano and chemical-free”, clarified with “products also free of UV-absorbing chemicals” raises an obvious question to the naive reader over whether these products do indeed offer significant protection.  I also continue to have serious reservations over the use of a document designed to steer people away from nanoparticle-containing sunscreens as authoritative advice on sunscreen protection for children, given it’s lack of independent testing and evaluation of all significant factors that might affect choice in a given situation.  Nevertheless, given the protection ratings of the recommended sunscreens, I have on reflection retracted the statements made in regard to the protection offered above.

Back in the mists of time, I was approached with a crazy proposition – would I help co-edit a book on nanotechnologies regulation!  In a moment of weakness I said yes, and a little more than two and a half years later, the book is finally about to hit the shelves.

I actually think the resulting International Handbook on Regulating Nanotechnologies rather a useful, coherent and engaging collection of chapters – my co-editors Di Bowman and Graeme Hodge did a wonderful job encouraging a bunch of top thinkers in the field to write under occasionally whimsical but always relevant titles.

To whet your appetite prior to the book’s release sometime in November, here’s a sneak peak at the contents:

PART I:    Concepts and Foundations

1.    Introduction: the regulatory challenges for nanotechnologies

Graeme A. Hodge, Diana M. Bowman and Andrew D. Maynard

2.    Philosophy of technoscience in the regime of vigilance

Alfred Nordmann

3.    Tracing and disputing the story of nanotechnology

Chris Toumey

4.    The age of regulatory governance and nanotechnologies

Roger Brownsword

PART II:    Frameworks for Regulating Nanotechnologies

5.    Nanotechnology captured

John Miles

6.    The scientific basis for regulating nanotechnologies

David Williams

7.    The current risk assessment paradigm in relation to the regulation of nanotechnologies

Qasim Chaudhry, Hans Bouwmeester and Rolf F. Hertel

8.    Regulating risk: the bigger picture

Karinne Ludlow and Peter Binks

9.    Producing safety or managing risks? How regulatory paradigms affect insurability

Thomas K. Epprecht

PART III:    Case Studies in Regulating Nanotechnologies and Nano-Products

10.    The evolving nanotechnology environmental, health, and safety landscape: A business perspective

Oliver Tassinari, Jurron Bradley and Michael Holman

11.    Regulation of carbon nanotubes and other high aspect ratio nanoparticles: approaching this challenge from the perspective of asbestos

Robert J. Aitken, Sheona Peters, Alan D Jones and Vicki Stone

12.    Approaching the nanoregulation problem in chemicals legislation in the EU and US

Markus Widmer and Christoph Meili

13.    A good foundation? Regulatory oversight of nanotechnologies using cosmetics as a case study

Geert van Calster and Diana M. Bowman

14.    Therapeutic products: regulating drugs and medical devices

Rogério Sá Gaspar

15.    Regulatory perspectives on nanotechnologies in foods and food contact materials

Anna Gergely, Qasim Chaudhry and Diana M. Bowman

16.    Regulation of nanoscale materials under media-specific environmental laws

Linda Breggin and John Pendergrass

17.    Military applications: special conditions for regulation

Jürgen Altmann

18.    Regulating nanotechnology through intellectual property rights

Gregory N. Mandel

PART IV:    The Future Regulatory Landscape

19.    The role of NGOs in governing nanotechnologies: challenging the ‘benefits versus risks’ framing of nanotech innovation

Georgia Miller and Gyorgy Scrinis

20.    Voluntary measures in nanotechnology risk governance: the difficulty of holding the wolf by the ears

Christoph Meili and Markus Widmer

21.    The role of risk management frameworks and certification bodies

Thorsten Weidl, Gerhard Klein and Rolf Zöllner

22.    Risk governance in the field of nanotechnologies: core challenges of an integrative approach

Ortwin Renn and Antje Grobe

23.    International coordination and cooperation: the next agenda in nanomaterials regulation

Robert Falkner, Linda Breggin, Nico Jaspers, John Pendergrass and Read Porter

24.    Transnational regulation of nanotechnology: reality or romanticism?

Kenneth W. Abbott, Douglas J. Sylvester and Gary E. Marchant

25.    From novel materials to next generation nanotechnology: a new approach to regulating the products of nanotechnology

J. Clarence Davies

PART V:    Conclusion

26.    Conclusions: triggers, gaps, risks and trust

Andrew D. Maynard, Diana M. Bowman and Graeme A. Hodge

More information on the International Handbook on Regulating Technologies can be found here.  The anticipated publication date is late November.

Sometime in the past couple of weeks – I’m not entirely sure when as accounts are conflicting – the World Technology Evaluation Center (WTEC) posted a draft of a new report examining the long-term impacts and research directions of nanotechnology.  The “Nano2″ study was supported by the National Science Foundation under the direction of Mike Roco, and included input from an impressive array of nano-experts from round the world.  What resulted was a 13 chapter behemoth of a report on the current state and next ten years of nanotechnology worldwide.

Having just started to look through the report (I was traveling when it was posted … I think) I can’t really comment on it’s overall relevance and authority.  But if the chapter dealing with environment, health and safety (EHS) issues is anything to go by, this is a report to take seriously…

The EHS chapter (chapter 4) is authored by twelve recognized experts in the field of nano-risks, and presents a comprehensive perspective on near-term research challenges and opportunities.  The chapter is far from perfect – as you would expect, it reflects the perspectives and interests of the authors – but then most reports of this type do.  It also contains some rather jangling statements. For instance on the first page the definition of “the environmental, health and safety (EHS) of nanomaterials” seems to miss out environmental impact beyond “animal health”.  And a rather outmoded focus on educating the public on page 25, where the authors state

“A key issue therefore is for academia, industry and government is to find appropriate mechanisms to reach consensus, and effectively communicate and educate the public on the beneficial implications of nanotechnology, the potential for risk, and what is being done to ensure safe implementation of the technology.”

Mmm, not quite what they are teaching in engagement 101 these days!

But this is a draft, and these and other questionable statements do not detract from the overall usefulness of the chapter.

In many ways, the chapter reflects challenges that have been raised before.  Many of the issues highlighted can be traced back to the 2006 commentary in Nature I co-authored on nanotechnology safety challenges, and a number of reports that preceded it.  So questions surrounding exposure monitoring, toxicity screening, predictive modeling, safety by design and taking a life cycle approach to emerging nanomaterials abound.  But many of these are unpacked and explored in a fresh and useful way in this document. There is also a very welcome tie-in to risk-governance [a topic near and dear to my heart, having just co-edited a forthcoming book on the subject], reflecting the need for integrative approaches to understanding and addressing the challenges presented by engineered nanomaterials.

That said, the report fails to break out of old ruts when it comes to identifying materials of concern.  The old chestnuts are there – carbon nanotubes, zinc oxide, titanium dioxide, nano-silver and the like.  But there’s little mention of the next wave of emerging nanomaterials – nanoscale cellulose for instance, or active nanomaterials.  Neither do prevalent but poorly studied engineered nanomaterials like platinum/palladium nanoparticles in auto catalysts get a look-in.  Granted that the document is only looking forward 10 years, but it would have been good to have seen more thought given to complex nanomaterials, and novel approaches to exploring whether they present emergent risks, and how to handle them.

That aside though, this chapter is a strong addition to the literature on nanomaterial risks, and how we need to start addressing them – from risk identification and assessment through to risk management, mitigation and avoidance.  The areas highlighted for further research/action aren’t comprehensive, but they are important.  These include:

• Developing validated nano-EHS screening methods and harmonized protocols that promote standardized engineered nanomaterials risk assessment at levels commensurate with the growth of nanotechnology.
• Developing risk reduction strategies that can be implemented incrementally through commercial nanoproduct data collection, regulatory activity, and EHS research directly linked to decision-making.
• Developing a clearly defined strategy for nano-EHS governance that is compatible with incremental knowledge generation and stepwise decision-making
• Developing computational analysis methods capable of providing in silico modeling of nano-EHS risk assessment and modeling.
• Developing high-throughput and high-content screening as a universal tool for studying nanomaterial toxicology, ranking hazards, prioritizing animal studies and nano-Quantitative Structure Activity Relationship models, and guiding the safe design of nanomaterials.
• Improving safety screening and safe design of nanomaterials used in therapeutics and diagnostics.
• Developing advanced instrumentation and analytical methods for more competent and reliable engineered nanomaterial characterization, and detection in complex biological and environmental media.
• Development of computational models, algorithms, and multidisciplinary resources for increasingly sophisticated predictive modeling.
• Developing workforce capacity through interdisciplinary education and training, particularly in the nano-EHS field, where a large number of research areas are converging.

If you have an interest in nanotechnology impacts, I would definitely put the chapter on your reading list.  If you are actively involved in the field – it’s a must-read.

I mentioned that this is a draft report, and it’s actually open for public comment – you can sign up to comment here.  But you’d better be fast – just as there is some ambiguity over when the draft was posted, there is also ambiguity over when the comment period closes.  One source suggests it could be the end of this week – but I couldn’t find any confirmation of that.  So the sooner you get reading and commenting, the better!

Most manufacturers of nanomaterial-based sunscreens try to make sure that the material they use doesn’t generate harmful chemicals in the presence of sunlight.  But the paper this piece was based on suggested that some photoactive materials might be slipping through the net.

Originally posted June 21 2008.

Painted metal roofs are cheap, convenient, and usually very durable.  But over the past two years, a rash of accelerated ageng has blighted pre-painted steel roofing in Australia.  And intriguingly the aging—which affects the coating—seems to be localized to small patches, taking on the form of fingerprints, handprints and even footprints.

The culprit it seems is sunscreen that is spilt or otherwise transferred to the roofing by construction workers during installation. And not any old sunscreen—this would appear to be a uniquely nano phenomenon.  But I get ahead of myself…

Pick up a bottle of sunscreen and there is a fair chance these days that it contains nanoparticles, engineered to absorb and reflect away harmful UV radiation.  Many manufacturers are introducing lines of nanoparticle-containing sunscreens as alternatives to those using more conventional organic chemicals, and it’s not hard to see why: the active ingredients in these nano sun blocks are generally more gentle on the skin than their non-nano counterparts; they are made to sit on the surface of the skin rather than penetrate into it; and if designed well, they continue to block UV radiation for several hours after application.  And of course, they go on clear, giving a product that works well and looks good.

But each year as the sun and the sunscreen come out, questions over the safety of nano-formulations are raised.  Can these nanoscale particles penetrate through the outer layers of the skin to the underlying living cells, and even the bloodstream? And if they get there, what harm could they cause?  So far, most studies suggest that nanoparticles in sunscreens stay where they are supposed to—on the skin, not in it.  Yet there is another question that has been bobbing along just under the surface for the past few years: could mixing nanoparticles, sun and moisture lead to a chemically corrosive mix that is bad for the skin?

The issue in question is photocatalytic activity.  Titanium dioxide, and to a lesser extent zinc oxide, are photoactive—they have the ability to absorb UV, and in the presence of moisture convert benign water molecules into chemically active hydroxyl free radicals.  These highly reactive chemicals could spell bad news for sunscreen users if they are generated in large amounts—eating away the components that hold the sunscreen together, and even possibly causing skin damage if they get below the surface and into cells.

Fortunately, manufacturers and users of titanium dioxide have long been aware of this propensity to generate free radicals, and have found ways of suppressing it in sunscreens. Photocatalytic activity depends on the crystalline structure of titanium dioxide.  Anatase and rutile forms of titanium dioxide have the same chemical formula but different crystalline structures. And, as it turns out, different properties. Make nanoparticles from anatase titanium dioxide, or a mix of anatase and rutile, and you have a powerful source of harmful hydroxyl radicals in the presence of water and UV. But make nanoparticles out of rutile titanium dioxide alone, and photocatalytic activity is reduced substantially.

However, even rutile titanium dioxide particles show some photocatalytic activity.  Early uses of rutile titanium dioxide as a white pigment in outdoor paint were plagued by the paint turning chalky after too much sun exposure. The problem was tracked down to hydroxyl radicals being produced and degrading the paint’s binder.  The solution: coat the particles with a material that prevents free radical formation—no more chalky paint, and coatings that will last for years in the fiercest sun.

Makers of titanium dioxide-based sunscreens use a similar trick to retain the functionality of nanoparticles while avoiding the potentially harmful photocatalytic properties. For instance Optisol—a UV blocking agent made by the company Oxonica—incorporates a minute amount of manganese into the crystal lattice of rutile titanium dioxide nanoparticles.  This doping allows the absorbed UV energy to be dissipated while virtually eliminating the formation of free radicals.  Not only does this make sunscreens using Optisol potentially safer; they also last longer in the sun, as there are fewer free radicals to break down other ingredients in the product.

So all looks rosy for nano-enabled sunscreens.  At least, it did until the publication of a recent paper.  And this is where we get back to pre-painted steel roofs. Since mid 2006, researchers in New South Wales Australia have noticed unusual defects developing in newly installed pre-painted steel roofs.  The damage is typically localized to areas of pressure contact, often taking the form of fingerprints or shoe impressions.  And it results in accelerated weathering—in one example, patches of a roof appeared to age an equivalent of 15 years in only 18 months. The culprit?  Nanoparticle-containing sunscreens, which are accidentally transferred to the roof during installation by touching or splashing.

In the paper “The interaction of modern sunscreen formulations with surface coatings,” [Progress in Organic Coatings62: 313:320. 2008] authors Phil Barker and Amos Branch systematically track down the underlying cause behind the unsightly blemishes.  Out of ten sunscreens tested—four containing no nanoparticles, five containing titanium dioxide nanoparticles, and one containing zinc oxide nanoparticles—all but one of the nanoparticle-based sunscreens consistently degraded samples of pre-painted roofing surface exposed to sunlight for 12 weeks.  In contrast, the non-nano products had no obvious deleterious effect.  In the worst case, the roofing lost over 85% of its gloss (a measure of degradation) in just six weeks.

Digging a little deeper, Barker and Branch pinned the effect to nanoparticles in all but one sunscreen acting as photocatalysts, and generating hydroxyl radicals in the presence of UV radiation and water.  Despite assumptions that nanoparticles in sunscreens are engineered not to produce significant amounts of free radicals, these products were generating them fast enough to significantly damage roof coatings in a matter of weeks!

So have we had the wool pulled over our eyes?  Are these supposedly benign nano-sunscreens we are slathering on our skin adding to our wrinkle-count before our time, and perhaps more besides?

Before jumping to conclusions, it is worth taking stock of what is known, and what is not.  While the study showed all but one of the nanoparticle-based sunscreens had some adverse effects on the roofing, these effects varied greatly between products.  The sunscreen using nano-zinc oxide particles led to a 55% reduction in gloss over 12 weeks, while in the worst case, a sunscreen containing 4% titanium dioxide led to a 95% reduction in gloss over 12 weeks.  Assuming that the reduction in gloss is associated with the formation of hydroxyl radicals (and the evidence presented by Barker and Branch arising from a logical sequence of laboratory experiments is pretty convincing), there is still uncertainty over how harmful these would be when generated on the skin of a sunscreen-user.  To cause damage, the hydroxyl radicals would need to penetrate deep into the skin and into cells before loosing their potency, and if the nanoparticles stay on top of the skin where they are supposed to, significant penetration may not occur.

Then there is the anomalous nano-sunscreen that didn’t show an appreciable effect.  A nifty piece of X-ray diffraction analysis in the Barker and Branch paper showed that the titanium dioxide nanoparticles in the roof-damaging sunscreens were an anatase/rutile mix, while the nanoparticles in the benign sunscreen were comprised of rutile titanium dioxide alone.  Clearly crystalline form matters, as Oxonica realized when they selected the less-active rutile form of titanium dioxide as the basis for Optisol.

This study demonstrates that it is possible to create nanoparticle-based sunscreens that do not generate significant amounts of hydroxyl free radicals.  But the bottom line here is that some nano-based sunscreens are being sold (in Australia at least) that contain photoactive nanoparticles which generate hydroxyl radicals in the presence of water and sunlight.  This raises questions about the impact of these products on users over time and, perhaps more significantly, their impact on the environment.  A photocatalytic titanium dioxide particle released into the environment will continue to generate hydroxyl radicals as long as it is exposed to UV radiation—because this is a catalytic process, the particle is not destroyed in the process, but just carries on doing its stuff; day after day, year after year.

But perhaps the biggest question here is one of regulation.  In the US, the Food and Drug Administration does not currently discriminate between anatase and rutile titanium dioxide particles in sunscreens, or doped and un-doped particles [Sunscreen Drug Products For Over-The-Counter Human Use: Final Monograph.  May 21 1999.  PDF, 424 KB].  But in the meantime, what is to stop manufacturers using potentially harmful forms of titanium dioxide in sunscreens?  And how will consumers be able to distinguish between companies that have got it right, and those that have not?

It seems that if we are not careful, nano-sunscreens could be making their mark on more than just pre-painted steel roofing.

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The full August in the Archives 2010 series can be browsed here

This was based on a piece I originally wrote for Nano Today – the blog was a slightly extended version of what was published.  Although it was written two years ago, it’s still surprising how few people realize that breathing in nanoparticles is an everyday fact of life, and that to make sense of new risks from engineered nanoparticles, we need to understand what we are already experiencing.

Originally posted April 5 2008

Read some accounts of nanotechnology risks, and you might be forgiven for concluding that a single engineered nanoparticle can kill you.  Of course, a little critical thinking soon dispels this notion—we are constantly bombarded with incidental nanoparticles from sources that include cars, incinerators and fires; we have been since birth.  And as critics of “risk extremists” often point out, we seem to be doing just fine in this nano-rich environment.  But does this mean that the potential risks associated with engineered nanoparticles are little more than a myth?

This was the question I faced while writing an opinions piece for the latest issue of Nano Today.  It’s a question that’s constantly popping up, either because someone has forgotten (or never realized) that nanoparticle exposure is a fact of life, or as a justification for not worrying about the engineered varieties of nanoparticles.

As you might expect, the truth is somewhat more complex than either of these extremes, and still remains unclear.  But to get back to the article; as an “ambience-hack” (the literary equivalent of a “character actor”), I felt it important to start off in a place particularly laden with nanoparticles—my local coffee shop.  Armed with a model 3007 portable condensation particle counter, kindly on loan from TSI Incorporated, I resolutely set out to sample the local nano-aerosols over a good cappuccino.

As coffee and breakfast were being prepared, the particle counter indicated I was inhaling somewhere around four billion particles per minute.  That’s not far off one nanoparticle for every man, woman and child on the planet entering my lungs every sixty seconds.  Yet I was feeling fine.  Clearly my body was doing a good job of handling them—thanks to millennia of Darwinian natural selection giving me lungs that know a thing or two about airborne nanoparticles.

But I don’t buy into the idea that my surviving the coffee shop naturally means all nanoparticles are safe. The trouble is; all nanoparticles are not created equal, and to generalize will be to make mistakes—perhaps costly ones.

And the idea that we are perfectly adapted to breathing in particles is somewhat flawed. Consider these rather sobering facts associated with inhaling particles having a range of sizes: Between 1990 and 1999, there were over 30,000 deaths in the U.S. associated with occupational exposure to airborne materials [1]. Estimates of worldwide deaths from asbestos exposure lie between 250,000 and 400,000; and in the U.K., deaths due to asbestos-related mesothelioma are not expected to peak for another ten years—despite imports and use of asbestos peaking in the 1960’s [2].  In the general environment, estimates of the number of people who died from inhaling particles in the London Smog of 1952 are as high as 12,000 [3]. At a more subtle level, exposure to fine airborne particles has been associated with an elevated likelihood of dying, and there is increasing evidence linking nanoscale particle exposure with impacts on the cardiovascular system [4].

The bottom line is that our lungs, incredible as they are at dealing with each day’s dust burden, have their limitations. Our knowledge of airborne particles in general and incidental nanoparticles in particular can illuminate our approaches to engineered nanoparticles.  But just as the health risks from asbestos, vehicle emissions and welding fume differ, we will not be able to derive everything we need to know about engineered nanoparticles just by looking at the incidental varieties.

It’s interesting to push this idea of differences between particle types further.  Clearly our lungs have evolved to handle naturally occurring nanoparticles.  But does this mean we also have the ability to deal with engineered nanoparticles never previously encountered, and as a species have not had the chance to acclimatize to?  We know that our bodies have a hard time dealing with chemicals that do not occur naturally—will the same hold true for engineered nanomaterials?

And then there is the comparison between the veritable cocktail of ambient nanoparticles we all breathe, and the precision of many engineered nanoparticles. Does exposure to a complex mixture of particles cause harm through synergistic interactions, or does the “soup” we breathe dilute the impact of the relatively few dangerous particles that might be present?  And—if a manufacturer hits on a particular combination of physical and chemical properties that is less than compatible with a long and healthy life—how much more dangerous is an aerosol of this “pure nanomaterial” than the nanoparticles you and I are breathing now?

This leads to the tricky issue of dose—how much material is needed to cause damage.  “The dose makes the poison” is the mantra of toxicologists worldwide—acknowledging that the most toxic substances can be harmless (or even beneficial) at low enough doses, while nothing is good for you in excess.  Four billion particles per minute might sound like a lot, but it is a minuscule amount of material when you consider how much mass there probably is in those particles.  Scribbling out some rather crude back-of-the-envelope calculations, I am probably inhaling no more than 50 nanograms of nanoparticles per minute in the coffee shop.  In contrast, a highly toxic dust like crystalline silica has an occupational exposure limit that equates to inhaling around 1,000 nanograms per minute over eight hours, and the equivalent limit for a material like titanium dioxide is a whopping 300,000 nanograms per minute.  Yet which is the appropriate way to measure dose—the mass of particles, their number, or something else; like surface area?

At the end of the day, I can drink my coffee and inhale the local nanoparticles with no obvious ill effects because I’m not exposed for that long and my body knows how to deal with them.  And there are probably plenty of engineered nanomaterials I could do the same with.  I know that a single nanoparticle won’t kill me—probably a few billion wouldn’t be enough to do much damage.  But I’m under no illusion that all engineered nanoparticles will be safe, just because I’m breathing in incidental nanoparticles all the time.  It all comes down to understanding what causes a new material to be harmful, and how to avoid harm—which means we need to get on and do more research if questions like the ones above are going to be answered.

Now, back to my four billion particles a minute with a cappuccino on the side…

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The full August in the Archives 2010 series can be browsed here

A few weeks ago, I set Friends of the Earth a challenge - What is your worst case estimate of the human health risk from titanium dioxide and/or zinc oxide nanoparticles in sunscreens?

The challenge came out of an article from FoE on nanomaterials and sunscreens, which I subsequently critiqued on 2020 Science.  Georgia Miller and Ian Illuminto from FoE kindly responded to my challenge – not by rising to it as such, but by fleshing out the justification for the position that they take on nanomaterials and sunscreens.

That post led to a useful discussion on the issues, with comments from the NGO community, regulators and respected scientists – it’s one that I would highly recommend anyone interested in nanomaterials and sunscreens reading.

To wrap things up (for the time being), I thought it would be worth reflecting on some of the issues raised by Georgia and Ian in their response, and the ensuing discussion:

Getting nanomaterials’ use in context. First, Georgia and Ian, very appropriately in my opinion, brought up the societal context within which new technologies and products are developed and used:

“why not support a discussion about the role of the precautionary principle in the management of uncertain new risks associated with emerging technologies? Why not explore the importance of public choice in the exposure to these risks? Why not contribute to a critical discussion about whose interests are served by the premature commercialisation of products about whose safety we know so little, when there is preliminary evidence of risk and very limited public benefit.”

This is a legitimate issue, and one that is touched on by a number of people in the comments.  Decisions on what is developed, what people are exposed to, who decides what is appropriate and what is not, and who pays the consequences while who reaps the benefits, go far beyond the science and technology itself.  This is touched on by Jennifer Sass from NRDC:

I strongly support a dialogue that has space for both scientific calculations and values and perceptions of risk. We need to make that dialogue public, inclusive, transparent, and thoughtful. Risk is more than a number – its a face, a person, a community.

Guillermo Foladorio also touches on this broader societal context:

We have here 2 kind of issues. One is the “scientific” knowledge (are nano-sunscreens harmful?). This is a never endend issue. Science is a process and not a fact. The other issue, although hidden, is of great importance: focusing on a never ended scientific discussion is the field that corporations like, in the meanwhile the market of such products grows and consolidates, aside from any wondering of the needs for such new stuff; or better which percentage of the population will benefit in the case.

I would suggest that forcing a technology on society has never been acceptable behavior.  But it has certainly been easier to do in the past.  These days though, we live in a much more crowded, resource-constrained and interconnected world than ever before.  Which means that the consequences of ill-conceived technology implementation are magnified, and the dynamics of introducing new – and possibly beneficial – technologies – are far more complex than they were in the past.

This means that we need to think critically about the broader societal issues associated with technology innovation, and we need to push the dialogue further upstream in the development process – a point Jeff Morris from EPA makes.  This means rethinking how we make decisions in partnership across society, and how we begin to apply ideas like the precautionary principle in a complex world – a point eloquently made by Richard Jones.

But it also means that we need to think carefully about how we use scientific knowledge and data – “evidence” – in making decisions.

Evidence-informed decision-making. At some point, decisions need to be based on information, and in the long run you cannot get away with making that information up!  It’s one thing to evaluate critically the current state of evidence in making decisions, but quite another to preferentially select evidence that supports a predetermined position.  Yet the latter is often the default position when it comes to influencing decisions – whether by policymakers or consumers.

Having worked at the heart of science-based policy in the US for a number of years, I’m all too familiar with the line of argument that goes “what do we want to achieve?” followed by “what evidence can we find that supports us?”.  Yet this is an approach that ultimately devalues the importance of evidence in making decisions, one that can have serious adverse consequences when decisions are made on dodgy information, and one that is patently unsustainable in the long run.

My original critique of FoE’s article challenged their use of “evidence” in supporting the position they took.  To me, they showed a tendency to use selective pieces of information to sow seeds of doubt in the mind of the reader, rather than to empower the reader to make informed decisions. The social agenda was a laudable one – the use of selective science sound-bytes, less so.

This begins to come out when you read the comments on Georgia and Ian’s response from three scientists who have worked on nanoscale materials on the skin.  Despite FoE’s implications that nanoparticles in sunscreens might cause cancer because they are photoactive, Peter Dobson points out that there are nanomaterials used in sunscreens that are designed not to be photoactive. Brian Gulson, who’s work on zinc skin penetration was cited by FoE, points out that his studies only show conclusively that zinc atoms or ions can pass through the skin, not that nanoparticles can pass through.  He also notes that the amount of zinc penetration from zinc-based sunscreens is very much lower than the level of zinc people have in their body in the first place.  Tilman Butz, who led one of the largest projects on nanoparticle penetration through skin to date, points out that – based on current understanding – the nanoparticles used in sunscreens are too large to penetrate through the skin.

These three comments alone begin to cast the potential risks associated with nanomaterials in sunscreens in a very different light to that presented by FoE.  Certainly there are still uncertainties about the possible consequences of using these materials – no-one is denying that.  But the weight of evidence suggests that nanomaterials within sunscreens – if engineered and used appropriately – do not present a clear and present threat to human health.

Yet, because there are uncertainties still, we cannot afford to be complacent here.

Handling uncertainty. And this brings me to the thorny issue of uncertainty.  When we are lacking absolute evidence on safety or risk, what do we do – do we halt progress until we are sure about how safe something is, or do we muddle along until more information is available?

This question is becoming increasingly important as the rate of technology innovation – and the complexity of emerging technologies – accelerates.  Consumers, regulators, businesses and others are being forced more and more to make decisions in the face of increasing uncertainty.  At the same time, we are dependent on technology innovation as a global society – although the idea of “going back to basics” is an attractive one, it’s not going to help the marginalized in an overcrowded and resource-constrained world.  Rather, we need new ideas on how to use science and technology in ways that ensure as many people as possible have an acceptable quality of life.

The question is, how do we do this when we cannot be sure of how safe or dangerous a new technology is?

The Precautionary Principle is one approach – and a very misunderstood and misused one – to addressing this, and one brought up by FoE and others in the context of sunscreens.  It has many formulations – it’s not a hard and fast principle.  But it is currently described in the European Union in this way:

The precautionary principle should be informed by three specific principles:

• implementation of the principle should be based on the fullest possible scientific evaluation. As far as possible this evaluation should determine the degree of scientific uncertainty at each stage;
• any decision to act or not to act pursuant to the precautionary principle must be preceded by a risk evaluation and an evaluation of the potential consequences of inaction;
• once the results of the scientific evaluation and/or the risk evaluation are available, all the interested parties must be given the opportunity to study of the various options available, while ensuring the greatest possible transparency.

Besides these specific principles, the general principles of good risk management remain applicable when the precautionary principle is invoked. These are the following five principles:

• proportionality between the measures taken and the chosen level of protection;
• non-discrimination in application of the measures;
• consistency of the measures with similar measures already taken in similar situations or using similar approaches;
• examination of the benefits and costs of action or lack of action;
• review of the measures in the light of scientific developments.
• The burden of proof

This is a pragmatic principle, that looks to using evidence and an evaluation of consequences in making informed decisions in the face of uncertainty.  It certainly does not preclude the development or implementation of a new technology until there is certainty on safety.

The emphasis on the potential consequences of inaction are particularly relevant to today’s world, where we are stuck on a technological tight-rope, and where the consequences of not doing something may be more harmful than taking action.  Richard Jones picked up on this in his suggestion for a more relevant application of the Precautionary Principle to emerging technologies:

what are the benefits that the new technology provides – what are the risks and uncertainties associated with not realising these benefits?

what are the risks and uncertainties attached to any current ways we have of realising these benefits using existing technologies?

what are the risks and uncertainties of the new technology?

This seems a useful place to start from when faced with the reality of having to make the best possible decisions in the face of uncertainty, and where inaction isn’t a option.

But to make decisions – even when there are gaping holes in the data – you need something to go on.

So why did I pose the challenge in the first place? Despite suspicions from some that I was merely being provocative with this question, I asked it in all seriousness.  In the face of uncertainty, playing out different potential scenarios is a powerful tool in helping identify the magnitude and nature of the consequences of different choices.

When it comes to using nanomaterials in sunscreens, I genuinely would like to know whether in the worst case we are looking at mass illness and death, isolated cases of skin rashes, or something in between.  Because the likely implications of the use of such materials in the future have profound implications on the actions we take now.

If decisions are made now on futures that are unlikely to be realized, not only do we waste resources and effort, but we potentially endanger people’s lives through ill-informed choices.  This cuts both ways – if TiO2 and ZnO nanomaterials in sunscreens are likely to harm a significant number of people to a significant degree, action should be taken to avoid this as soon as possible.  But if the benefits are positive and the impacts likely to be inconsequential, inhibiting the use of such materials could cost lives.

Using the best available information to work through possible scenarios provides insight into which futures are more likely, and where efforts are best focused.  This isn’t about setting exposure levels or conducting quantitative risk assessments – it’s about helping people making informed choices.

And who should do this?  I think any group that has a stake in how contemporary decisions affect future outcomes has a part to play.  I focused on FoE because they were pushing the issue.  And I think they have sufficient people they can draw on to make a stab at working through some scenarios and estimating likely impact.

But at the end of the day, this is something that all stakeholders should be involved in.

Because these are decisions that we are all going to have to live with the consequences of.

Last week, I posed Friends of the Earth a challenge – “What is your worst case estimate of the human health risk from titanium dioxide and/or zinc oxide nanoparticles in sunscreens?”  Georgia Miller of FoE Australia and Ian Illuminato of FoE in the US have kindly provided a detailed response.  Rather than just keep this as a comment on the original blog, I thought it deserved a wider airing – and so am posting it here.

I will respond to the response in a few days time.  In the meantime, I would be extremely interested in what others think of the use of nanoparticles in sunscreens, based on my original piece and Georgia and Ian’s piece below.  Please do comment – this seems to be an area that desperately needs some good and open discussion.

Andrew – thanks for the invitation to perform some complex risk assessment using several poorly understood variables. However we do have to point out that the world’s best minds don’t yet have enough information even to design reliable nanomaterial risk assessment processes, let alone to come up with a single ‘worst case scenario’ figure for long term health impacts of using nano-sunscreens.

The huge knowledge gaps plaguing nanomaterials toxicity and exposure assessment (along with preliminary studies suggesting the potential for serious harm) are key reasons for calls by Friends of the Earth Australia and United States for a precautionary approach to management of nanotoxicity risks.

We explain below why your risk assessment challenge is impossible given these data gaps. We also point out that given that different people with different skin types are likely to experience different exposure levels, positing any single ‘worst case scenario’ figure is inappropriate. Obviously you are aware of these serious limitations. This does prompt us to question the intent of your challenge.

Further, we strongly suggest that your challenge is directed to the wrong people. Why not demand that the manufacturers of nano-sunscreens provide you with the data to demonstrate that their products are safe? Why not challenge the regulators to explain their failure to keep nanomaterials that behave as extreme photocatalysts out of sunscreens?

Better yet, why not support a discussion about the role of the precautionary principle in the management of uncertain new risks associated with emerging technologies? Why not explore the importance of public choice in the exposure to these risks? Why not contribute to a critical discussion about whose interests are served by the premature commercialisation of products about whose safety we know so little, when there is preliminary evidence of risk and very limited public benefit? Transparent micron-particle sized zinc oxide sunscreens are commercially available; a recent article suggests most titanium dioxide nano-sunscreens on the market could be doing more harm than good. No-one need use nanoparticles in order to produce a cosmetically and functionally acceptable sunscreen.

Andrew, we respectfully suggest that someone of your expertise and stature could play a more constructive role in these debates – debates which should not be limited to a question of technical risk assessment.

Georgia Miller and Ian Illuminato
Friends of the Earth Australia and United States
http://nano.foe.org.au
http://www.foe.org/healthy-people/nanotechnology-campaign

Why determining a single figure for ‘worst case scenario’ health harm associated with using nano-sunscreens is not possible

In 2004 the UK’s Royal Society recommended that nanoparticles be treated as new chemicals, subject to new safety testing before they could be used in products, and face mandatory labelling. Six years on, none of those things have happened.

The development and validation of nano-specific risk assessment processes may take years. As the European Food Safety Authority pointed out last year in relation to the risk assessment of nano-foods: “Although, case-by-case evaluation of specific ENMs [engineered nanomaterials] may be currently possible, the Scientific Committee wishes to emphasise that the risk assessment processes are still under development with respect to characterisation and analysis of ENMs in food and feed, optimisation of toxicity testing methods for ENMs and interpretation of the resulting data. Under these circumstances, any individual risk assessment is likely to be subject to a high degree of uncertainty. This situation will remain so until more data on and experience with testing of ENMs become available” (EFSA 2009, p2-39).

When it comes to sunscreens, a key component of risk assessment – determining likely exposure – is not yet possible because we do not yet understand what quantities of nanomaterials may be absorbed into the skin from sunscreens and in what circumstances. Skin penetration studies to date have largely failed to look at important variables such as skin condition (including damage through sunburn, injury or eczema, or thin skin present in the young or elderly), skin flexing (eg through exercise) and the role of substances in sunscreens that can act as penetration enhancers by increasing skin permeability. Further, most skin penetration studies have used excised skin in in vitro studies which is likely to underestimate actual penetration.

In your earlier blog you point out that research by Professor Brian Gulson at Macquarie University and by scientists at Australia’s CSIRO which shows radio-isotope labelled zinc from sunscreens in the blood and urine of human volunteers is not yet published. True enough – also that these researchers are not yet able to say whether or not the absorbed zinc they detected is in particle or ionic form. Nonetheless, the results do show that zinc in sunscreens does not simply remain on the outer layers of dead skin cells, as some have claimed. Many questions remain: the one clear answer is that more research is required.

One interesting point about Brian Gulson’s study underscores the impossibility of determining any single ‘worst case scenario’ figure for health harm. Professor Gulson told the ICONN conference in Sydney this year that one woman with sensitive skin suspended her participation in the trial after four days due to an adverse reaction. The levels of isotope labelled zinc in her blood were also substantially greater than that of other people in the trial. Are people with sensitive skin more likely to experience substantially greater skin penetration by nano-ingredients in sunscreens? Could this put a minority of the population at greater health risk? We don’t yet know.

A further constraint on calculating your requested ‘worst case scenario’ figure is the paucity of long-term and multi-generational nanotoxicity studies. This is a very serious limitation. Potential health harm from exposure to many nanomaterials may be more likely to manifest in the long term, rather than immediately. This point was made in 2004 by global reinsurance giant Swiss Re (2004). Swiss Re emphasised that as with asbestos, the significant time lag between exposure to nanomaterials and the onset of health harm is the greatest challenge for insurers attempting to calculate risk.

You ask for a ‘worst case scenario’. One worst case scenario is the accelerated development of skin cancer in people using nano-sunscreens, despite their wearing sunscreens for sun protection. We are copying below an extract of comments made by Dr Maxine McCall of the Australian CSIRO to the ABC’s 7.30 Report in late 2008.

“There’s the concern that there could be free radical generation on the skin, potentially damage, when the nano particles get into cells in the body if they don’t dissolve,” Maxine McCall, head of the CSIRO’s nano safety research, said. “Because they could interact with proteins in the cell or with DNA which codes – which has the genetic information – the worst case scenario, I suspect, could be development of cancer. We don’t know. That’s what we’re trying to find out.”

Dr McCall told the 7.30 Report that it would be two to three years before the CSIRO could reach a conclusion on nano sunscreens. “At the moment, we just don’t have enough information to make informed decisions,” she said.

Nanomaterials that behave as photocatalyts have been found in five of six Australian nano-sunscreens tested by Barker and Branch (2008). Sunscreens containing both nanoparticle titanium dioxide and zinc oxide were demonstrated to have a photocatalytic effect. Some of these photocatalysts were so extreme that they accelerated sun damage to pre-painted steel roofs by up to 100 times. Clearly the effects on human skin of nano-sunscreen use will differ from a pre-painted steel roof. Will these extreme photocatalysts penetrate human skin and persist in particulate form in sufficient quantities to cause long-term health harm? We don’t know.

Another worst case scenario is harm to the developing brains and reproductive systems of unborn babies, following maternal exposure to sunscreens. If nanoparticles from sunscreens are absorbed into a pregnant woman’s bloodstream, it is possible that they could pass across the placenta to the unborn baby. A recent study showed that polystyrene nanoparticles up to 240nm in size can be transported through a human placenta [note to Andrew: in your earlier blog you state that this “research was aimed at working out how to get beneficial drugs to the fetus”. The motivation of the study is arguably irrelevant. However in this instance the study is clearly designed to explore the potential for risky nanoparticle exposure in utero].

Animal studies have found altered gene expression, harm to the brains and reproductive systems and minor neuro-behavioural alterations in mice born to mothers exposed to titanium dioxide nanoparticles. Will nanoparticles of titanium dioxide be absorbed from sunscreens into the bloodstreams of pregnant women in sufficient quantities, and will they persist in particulate form in sufficient quantities, to harm unborn babies? Again, we don’t know. This will require much further research.

In the meantime, regulators faced with substantive knowledge gaps struggle to formulate an appropriate public policy response to uncertain but potentially serious risks. Challenging community groups to calculate the technical risk of a worst-case scenario of wearing nano-sunscreens to justify their asking product manufacturers to undertake basic safety research seems more than a little retrograde.

Following up from my previous post, here’s an open question to Friends of the Earth:

What is your worst case estimate of the human health risk from titanium dioxide and/or zinc oxide nanoparticles in sunscreens?

What I am interested in is a number – a probability of a specific human health impact being caused by using a given amount of nano-sunscreen over a certain amount of time.  Something like:

“In the worst case, it is estimated that using [number] grams per day of sunscreen comprising [percent] TiO2/ZnO nanoparticles over [number] days could lead to an [percent] risk of the user developing [disease].”

This can be based on an extrapolation of the current state of the science to a worst case scenario.  But it must be plausible.  And the calculations/sources to get to the end number must be transparent.

I’m asking because I am interested to see whether it is possible to place an upper bound on the safety of nanoparticle-based sunscreens, and whether this will be useful in moving the dialogue over nano-enabled sunscreens away from ungrounded speculation, towards evidence-based discussion.

So that’s the challenge.  I’m hoping my good friends at Friends of the Earth will rise to it.

Friends of the Earth (FoE) do not like nanoparticle-based sunscreens.  This has been evident for some years – back in 2006 the organization published the report Nanomaterials, Sunscreens and Cosmetics: Small Ingredients, Big Risks, and every year since then they have had something to say on the subject.

This year’s web-based piece leaves now doubt about FoE’s stance on nanotechnology-enabled sunscreens.  The recently posted article starts:

While you’re planning your summer vacation and thinking about what to pack, don’t forget the sunscreen — but make sure it doesn’t have manufactured nanoparticles in it!

But what is the reasoning behind this stance?  Helpfully, FoE have also posted six cases of what they describe as evidence “of risks from manufactured nanomaterials in sunscreen.”

As these are evidence-based statements, I thought it would be worth while going through them, and taking a look at the evidence they are based on:

FoE: “Manufactured nanomaterials used in sunscreens (such as zinc oxide and titanium oxide) can Damage human colon cells: A study from the University of Utah showed that nano zinc oxide is toxic to colon cells even in small amounts. The scientists called for more research and warned that the evidence is especially concerning for children who are more likely to accidently ingest sunscreen. The colon is vital because it eliminates food waste and absorbs important nutrients.”

This was a study that looked at interactions between zinc oxide (ZnO) particles and cells derived from the human colon, and was carried out in vitro (i.e. in a cell culture rather than in animals or people).  It did indeed indicate that nanometer scale ZnO particles were around twice as potent as larger ZnO particles in their ability to kill these cells under idealized conditions.  But the research also emphasized that direct contact with the cells was needed for a nanoscale particle-related effect.  In fact, the title of the paper was “ZnO Particulate Matter Requires Cell Contact for Toxicity in Human Colon Cancer Cells,” emphasizing this point above the higher potency of the more finely structured particles.

The research was interesting, but did not resolve whether zinc oxide particles could survive long enough in the gut to come into contact with cells lining the colon, whether interactions like those observed in the laboratory are plausible under real-world conditions, and what levels of exposure would be needed to cause significant harm.  The research also indicated that larger particles of zinc oxide – similar to particles that have been used in sunscreens and other topical creams for decades – were toxic to cells under the conditions of the study.

FoE: “Manufactured nanomaterials used in sunscreens (such as zinc oxide and titanium oxide) can Damage brain stem cells in mice: A study from China found that zinc oxide nanoparticles can damage the brains of mice by killing important brain stem cells. In another study, Japanese scientists injected pregnant mice with nano titanium dioxide and recorded changes in gene expression in the brains of their fetuses. These changes have been associated with autistic disorders, epilepsy and Alzheimer’s disease. Though more studies are necessary to know if this damage to would occur in humans, these studies with mice serve as important warnings. Such studies have encouraged scientists in the United Kingdom to explore the link between manufactured nanomaterials and Alzheimer’s disease. At the end of last summer, scientists at the University of Ulster were funded by the European Union to conduct more research.”

The China study was once again carried out using cell culture rather than in animals, and as a consequence the results are very hard to interpret.  What the researchers did find is that, under rather idealized conditions, it is possible to cause neural stem cells from mice to undergo apoptosis (controlled cell death) if they are exposed to enough zinc-containing material.  Importantly, the study did not indicate that cell death was associated with particle size – large particles, small particles and even dissolved Zinc all gave similar results.

The Japanese study on the other hand injected mice with extremely high concentrations of titanium dioxide (TiO2) particles – way, way higher than levels likely to get into people’s bloodstream.  Researchers saw qualitative changes in gene expression in fetuses and mice pups that are indicative of a number of disorders.  But – and this is important – there is no direct link between gene expression as measured in this study, and the onset of the neurological diseases mentioned above.  All this study indicates is that injecting TiO2 nanoparticles directly into the blood at extremely high levels causes brain cells in fetuses and pups to respond in some way.  Without knowing how those responses translate into disease (if they do at all), and what the relationship between dose and response is, this study does not provide information on the likelihood of TiO2 nanoparticles impacting the brain.

FoE: “Manufactured nanomaterials used in sunscreens (such as zinc oxide and titanium oxide) can Penetrate healthy adult skin: Isotope-labeled zinc used in nanosunscreens can potentially reach the blood stream and urine of humans, suggests an Australian study by Macquarie University’s Professor Brian Gulson. This study undermines claims that nanosunscreens will stay on the outer layers of dead skin.”

This study by Brian Gulson and colleagues has yet to be published, and so it is a little premature to draw conclusions from the findings.  However, from what has been discussed in the public sphere, the study does not show conclusively that manufactured nanoparticles used in sunscreens can penetrate healthy adult skin.  The study cleverly used sunscreens containing nanoparticles incorporating a stable isotope of zinc – one that is found naturally at very low concentrations.  This meant that, by applying the specially formulated sunscreens to volunteers and monitoring their blood and urine, researchers could tell conclusively whether the zinc from the sunscreen was getting into the body.  What they could not tell was whether it was particles or dissolved zinc getting through the skin.  And as zinc oxide is soluble, there’s a high chance that the very low levels of sunscreen-related zinc that were found in body fluid samples were associated with the stuff dissolving, rather than the penetration of nanoparticles.

We’ll have to wait for the paper to be published before any firm conclusions can be drawn from this work.  But if dissolution is the dominant mechanism here, it suggests that sunscreens relying on larger ZnO particles (and, coincidentally, recommended by Friends of the Earth), may lead to just as much zinc getting into the body as those using nanoscale ZnO particles.

It should also be noted that the results of this study are specific to ZnO – they cannot be extrapolated to other materials, such as TiO2.

FoE: “Manufactured nanomaterials used in sunscreens (such as zinc oxide and titanium oxide) can Travel up the food chain from smaller to larger organisms: A study by researchers at Arizona State University, the Georgia Institute of Technology, and Tsinghua University in China found through a dietary experiment that Daphnia (a “water flea” that provides important nutrition for aquatic life) can transfer nano titanium dioxide to larger organisms (in this case Zebrafish). This study is of great concern because it shows that manufactured nanomaterials with toxic properties could end up in the animal food chain at large.”

This is very true for the material that was the subject of the cited study – nanoscale TiO2 – although the results do not necessarily hold for other nanoscale materials.  At the same time, the study showed that the higher organisms in this case – zebrafish – accumulated more nanoscale TiO2 directly than they did through eating the lower organism – daphnia.

Where nanoscale materials used in sunscreens go in the environment, where they accumulate, and the impact they have, are all important questions.  But without information on toxicity and amounts of material potentially transferred, it is hard to say whether the transfer of these materials up the food chain is significant or not.

FoE: “Manufactured nanomaterials used in sunscreens (such as zinc oxide and titanium oxide) can Damage important microbes in the environment: Scientists at the University of Toledo found that nano titanium dioxide inhibited the function of bacteria after just an hour of exposure. Manufactured nanomaterials from sunscreens can easily wash off of the body in the shower and end up in wastewater and the wider environment, which could affect microbes that are helpful to ecosystems and sewage treatment plants.”

The link here is to a report from a presentation at an American Chemical Society meeting in 2009.  The full peer reviewed paper can be found here.  The published research indicates that nanoscale TiO2 can compromise the integrity of some (not all) bacterial cell membranes at certain concentrations under certain (laboratory) conditions.  The consequences of this are unknown, and it certainly isn’t possible to extrapolate from the research what the environmental impacts of nanoscale TiO2 releases might be, or at what concentrations in the environment an impact is likely.  More importantly, the published work showed no impact of nanoscale ZnO on bacteria at the concentrations used. In other words, the research does not show that nanoscale zinc oxide can damage important microbes in the environment.

FoE: “Manufactured nanomaterials used in sunscreens (such as zinc oxide and titanium oxide) can Travel from mothers to unborn fetuses: Nanoparticles up to 240 nm in size can cross into human placentas, meaning that the toxicity of manufactured nanomaterials could extend across generations.”

This is an important study, as it shows that particles of a specific type injected into the bloodstream can potentially cross over the placental barrier and into the fetus.  The research was carried out using human placenta, but outside the body and under laboratory conditions.  The particles used were polystyrene particles.  And the research was aimed at working out how to get beneficial drugs to the fetus.  The authors of the work note that high exposures were used, and that transport fro the placenta may well be influenced by particle composition and surface coating.  They go so far as to say that the research cannot be generalized across different types of nanoparticles.  In fact, while polystyrene particles up to 240 nm were observed to cross over the placental barrier in this study, the authors point out that in another study using the same system, polyethylene glycol coated gold particles up to 30 nm in diameter were not able to cross the placenta.

Each of the studies cited above is scientifically interesting.  But none of them seem to provide clear evidence that TiO2 or ZnO nanoparticles in sunscreens present a plausible risk to human health.  In many cases, they are associated with very artificial test systems that shed light on the science of how nanoparticles behave under certain conditions, but are far removed from real world situations.  Specifically, the studies do not shed light on whether nanoparticles in sunscreens can get into the body (the weight of scientific evidence is that they cannot get through the skin), whether the body’s defense mechanisms deal effectively with any nanoparticles that do get through (the evidence is that they can), and how much stuff is needed in the body to cause disease (a number of these studies indicate rather large quantities of material are needed).

In other words, the science is far from compelling in indicating that nanoparticles in sunscreens are a bad thing.  In fact, the current state of the science suggests that nanoparticles in sunscreens stay on top of the skin rather than penetrating it, are an effective and long lasting barrier against Ultraviolet radiation from the sun if applied correctly, and avoid some of the health concerns associated with non-nano sunscreens.  This is probably why another environment group – the Environmental Working Group (EWG) – recently recommended a range of nanoparticle-based sunscreens.   In fact, in a recent review EWG stated

Our top-rated sunscreens all contain the minerals zinc or titanium. They are the right choice for people who are looking for the best UVA protection without any sunscreen chemical considered to be a potential hormone disruptor. None of the products contain oxybenzone or vitamin A and none are sprayed or powdered.

Part of the problem here is that there is a lot of speculation going on about the pros and cons of nanoscale TiO2 and ZnO in sunscreens, and not a lot of analytical thinking.  What would be really helpful is some numbers on how risky these products might be.  Of course, we don’t have the data to state conclusively what levels of nanoparticles in sunscreens are safe – and there is a compelling case for more research here.  But we should at least be able to guestimate the numbers for a worst case scenario, based on the current state of the science.

So here’s a question back to Friends of the Earth – based on the current state of the science, what number would you put on the risk to human health of using nanoparticle-based sunscreens under a plausible worst-case scenario?

I’ll reiterate this question in a follow-up blog.  But it strikes me that, if we can begin to get some numbers on the table – even if they are just rough estimates, we might be able to cut through some of the speculation here and open up a reasonable discussion on the safety or otherwise of nanotechnology-enabled sunscreens.

]]> http://2020science.org/2010/06/08/friends-of-the-earth-come-down-hard-on-nanotechnology-are-they-right/feed/ 11 http://2020science.org/2010/03/02/nanotechnology-and-cancer-treatment-do-we-need-a-reality-check/ http://2020science.org/2010/03/02/nanotechnology-and-cancer-treatment-do-we-need-a-reality-check/#comments Tue, 02 Mar 2010 20:41:38 +0000 Andrew Maynard http://2020science.org/?p=2929

Cancer treatment has been a poster-child for nanotechnology for almost as long as I’ve been involved with the field.  As far back as in 1999, a brochure on nanotechnology published by the US government described future “synthetic anti-body-like nanoscale drugs or devices that might seek out and destroy malignant cells wherever they might be in the body.”  Over the intervening decade, nanotechnology has become a cornerstone of the National Cancer Institute’s fight against cancer, and has featured prominently in the US government’s support for nanotechnology research and development.  And for good reason – nanotechnology holds the promise of treatments that can diagnose cancer earlier in the disease’s development than ever before; treat tumors using lower concentrations of chemotherapy agents, and target malignant cells while leaving healthy cells untouched.  Like many of my colleagues, I have used emerging nanotechnology-based cancer treatments as a compelling example of what is possible when we gain mastery over materials at the scale of the atoms and molecules they are made of.

So I was somewhat surprised to see the eminent chemist and nano-scientist George Whitesides questioning how much progress we’ve made in developing nanotechnology-based cancer treatments, in an article published in the Columbia Chronicle.

According to the article,

George Whitesides, professor of chemistry and chemical biology at Harvard University, said that while the technology sounds impressive, he thinks the focus should be on using nanoparticles in imaging and diagnosing, not treatment.

The problem lies in being able to deliver the treatment to the right cells, and Whitesides said this has proven difficult. “Cancer cells are abnormal cells, but they’re still us,” he said.

Whitesides went on to comment that

“It’s easy to say that one is going to have a particle that’s going to recognize the tumor once it gets there and will do something that triggers the death of the cell, it’s just that we don’t know how to do either one of these parts”

This got me thinking – because George is a smart guy and well worth paying attention to – have we somehow got so caught up in the possibilities of nanotechnology in treating cancer, that we have lost sight of the realities?

To get a better sense of where we are on nanotech-enabled approaches to treating cancer, I asked a handful of experts working in the field the following question: “What are some of the more significant science challenges researchers face in developing nanotechnology-based cancer treatments?” The responses were cautious, and clearly cognizant of the hurdles to taking scientific and technological breakthroughs out of the lab and into the market.  Yet despite this, there was an over-riding sense of optimism running through them.

Steve Rosen, Director of the Robert H. Lurie Comprehensive Cancer Center at Northwestern University commented:

“I feel nanotechnology has the possibility of revolutionizing both in vitro and in vivo cancer diagnostics.  Therapy always remains a greater challenge and in the short term I see nanotechnology as a vehicle to enhanced delivery. The long term prospects are substantial and limited only by the creativity of individuals involve in this area of investigation.”

This was echoed by Tyler Jacks, Director, David H. Koch Institute for Integrative Cancer Research at MIT:

“Nanotechnology holds great promise for cancer therapy, in my view. That said, there is need for more research to learn the best strategies to specifically direct the nanomaterials to cancer cells following systemic administration. This will require overcoming the body’s natural filtration systems as well as optimizing the methods for tumor-specific targeting. It may be that truly tumor-specific targeting will require combinatorial approaches.”

The difficulties of overcoming biological barriers to using nanoparticles effectively in treating cancers were expanded on by Martin Philbert, Senior Associate Dean at School of Public Health, University of Michigan:

“The body’s immune system is primed to recognize particles of the size range encompassed by most therapeutic and imaging nanotechnologies.  Since elements of the immune system are coordinated and disseminated throughout the body, a major challenge is the design and fabrication of nanotechnologies that will either avoid immune cells or use them to achieve appropriate targeting without activation or suppression of immune function.

A second major hurdle is elimination from the body.  Many of the newer nanoparticles are designed to be eliminated from the body by either being ‘small’, i.e., less than 8 nm in diameter to facilitate passage with the urine out of the kidneys, or to dissolve to a size that allows for elimination through the urinary flow.  Nevertheless, the kinetics of elimination are invariably altered by the ability of the reticuloendothelial portion of the immune system to take up these materials and sequester them in lymphatic organs or interstitial spaces for longer periods than anticipated.”

Yet despite thee challenges, progress is clearly being made.  Piotr Grodzinsky, Director, Nanotechnology Cancer Programs at the National Cancer Institute noted that

“Nanotechnologies for medical applications have been maturing. Several therapeutic formulations entered clinical trials and are expected to have an impact on how cancer treatment is done in the future. Similarly, multiplex diagnostic platforms with high sensitivity and specificity are proving themselves in testing of clinical specimens and will contribute to early disease detection.”

Scott McNeil, Director of the Nanotechnology Characterization Laboratory cautioned that

“Developers of nanotech-based therapeutics face preclinical challenges that may be more involved than development of small molecule drugs…”

but went on to add

“…the payoffs are now being demonstrated in clinical trials by several companies. We are observing a consistent trend towards decreased toxicity for nanodrugs compared to their small molecule counterparts.”

And in responding specifically to Whitesides’ comments, Jim Baker, Director of the Michigan Nanotechnology Institute for Medicine and the Biological Sciences, observed that

“[George Whitesides] is correct that this is a very complex problem, with cancer as a variation of self being a central issue.  In addition, the concept of some in the material science community that nanoscale materials would be inherently better ignores potential problems related to biocompatibility and the necessity of this material to function in a wet environment.  Additionally, the concept of a “nanomachine” is fundamentally flawed because having mechanical devices of this size violates the laws of physics.  What is moving forward are bio-inspired materials that will provide incremental improvements in drug delivery and imaging that could not be accomplished with traditional materials.  Each one will be unique, however, and require its own evaluation for efficacy and toxicity, just like any other drug.  This provides a difficult hurdle, given the costs and clinical evaluations that are involved.”

Reading through these comments, I get the sense that we’re only beginning to scratch the surface of what working at the nanoscale can do for cancer treatment.  Certainly there are hurdles to be overcome – some of them significant.  And it’s important to remember that the road between lab-based discoveries and real-world treatments is a long and arduous one – even the most promising therapies can take years or even decades to get to the point where they are widely available.  Yet it’s hard to avoid being caught up in the enthusiasm of scientists working on nanotechnology-enabled cancer treatments, or not to  be inspired by what might be achieved through engineering increasingly sophisticated therapeutics at the nanoscale.

That said, expectations on how nanotechnology will impact cancer treatment clearly need to be tempered.  In this respect, I thought that the comments from Jennifer West, the Isabel C. Cameron Professor of Bioengineering at Rice University, were particularly well-grounded:

“Nanotechnology isn’t a magic solution to cancer, but provides additional tools in the arsenal, some with new and unique properties.  As with any cancer therapy, the key issue is to get the therapeutic agent to tumor sites and metastases at high concentrations, then destroy cancerous cells while minimizing damage to normal cells.”

Nanotechnology is clearly not a panacea.  It provides exciting new opportunities for treating cancer.  But its use also faces many scientific, economic and regulatory hurdles.  Yet the idea of crafting more effective cancer treatments by engineering matter at the nanoscale remains a compelling one – if only we can work out how to translate the idea into practical solutions.

As one of my sources – who preferred not to be named – commented:

“I don’t think that the field needs a reality check but rather ways to move more of the discoveries and developments into humans”

]]> http://2020science.org/2010/03/02/nanotechnology-and-cancer-treatment-do-we-need-a-reality-check/feed/ 16 http://2020science.org/2009/11/05/could-nanoparticles-inflict-harm-across-tight-cellular-barriers/ http://2020science.org/2009/11/05/could-nanoparticles-inflict-harm-across-tight-cellular-barriers/#comments Thu, 05 Nov 2009 18:01:34 +0000 Andrew Maynard http://2020science.org/?p=2362

A new paper published on-line today in Nature Nanotechnology hints that some nanoparticles could cause damage to cells on the other side of normally tight barriers – such as the blood brain barrier or the placenta – without actually crossing the barriers.  It’s a study that could raise concerns over the safe  medical use of nanoparticles, at a time when the first human trials of “smart nanoparticle” therapeutics are being discussed.

Using an artificial system designed to investigate cellular barriers, Gevdeep Bhaba and co-authors show that high concentrations of Cobalt-Chromium alloy nanoparticles on one side of a tightly meshed layer of cells can cause measurable DNA damage to cells on the other side.  And they seem to do this without actually crossing the cellular barrier.

I’m not sure how much attention this paper will get, but given its apparent relevance to harm occurring across the placental barrier, there could be some pickup beyond the usual scientific outlets.  And interestingly, it is being published at the same time as the first human trials for a “smart nanoparticle” based cancer therapy are being reported – that’s a juxtaposition that could drive a substantial amount of interest in the research.

As I was asked to comment on it prior to its release, I thought it worth jotting some notes down here on the work, just in case anyone’s interested (I’ll be in the thick of a workshop on emerging technologies and emerging economies when the paper is published on-line, so this post is being written some time ahead of it going live).

In brief, the paper (Nanoparticles can cause DNA damage across a cellular barrier, by Gevdeep Bhaba et al., Nature Nanotechnology. DOI: 10.1038/NNANO.2009.313) describes a set of experiments carried out using an artificially grown layer of cells on a porous support.  The cells (BeWo cells for the interested, derived from a human trophoblast choriocarcinoma cell line) were grown as a multi-layered barrier, to simulate tight barriers in the body like the placental barrier.  On one side of this layer of cells were placed human fibroblast cells.  On the other side, Cobalt-Chromium alloy particles (CoCr particles) were placed.  Following introduction of the particles, the fibroblasts were checked for DNA damage using an alkaline comet assay.

Schematic of the system used by Bhabra and colleagues to investigate the potential for CoCr particles to cause DNA damage across tight cellular barriers (Nature Nanotechnology, DOI: 10.1038/NNANO.2009.313)

As you would expect in a good study, DNA damage was measured under a number of conditions, to identify what was going on.  Nanometer-scale and larger CoCr particles were used to see whether size was important.  Cobalt and Chromium ions were also used, to see whether the presence of dissolved metals was significant.  Particles were also introduced directly to the fibroblasts, to see what happened in the absence of the cellular barrier.  In addition, the concentration of Cobalt and Chromium was measured below the cellular barrier to see how much stuff (if any) got through.  And the barrier cells were treated with agents designed to block different transmission routes for certain substances, to get a handle on whether DNA damage was being caused by stuff penetrating through the barrier, or being generated (and subsequently released) from within the barrier.

The upshot of all this was that the researchers found evidence that placing Cobalt or Chromium one one side of the barrier caused measurable DNA damage in the fibroblasts on the other side, and that the damage seemed to be associated with chemicals generated within the cellular barrier by the metals.  In other words, the combination of CoCr particles and cellular barrier seemed to lead to DNA damage the other side of the barrier, even though the particles didn’t cross it!

The authors of the paper conclude:

We suggest that an evaluation of nanoparticle safety should not rely on whether they fail to gain access to privileged sites.  Instead there should also be an evaluation of their genotoxic potential for both direct and indirect effects to avoid any potential risks to targets on the distal [far] side of cellular barriers.

However, while this is an interesting paper, it wold be dangerous to speculate too far on what its relevance to nanoparticle safety.  When asked to comment briefly on the paper by the Science Media Center in the UK, this is what I wrote:

This is a study that raises an intriguing question – can foreign materials in the body cause harm across barriers like the placenta and the blood-brain barrier without actually crossing the barriers?  Evidence is presented that suggests there is some possibility of this occurring.  But the results should be treated with a high degree of caution until more is known.  In particular:

The effects seen are do not seem to be confined to nanoparticles alone.  There is some evidence that even large particles containing Cobalt and Chromium – the two specific materials studied here – can exert their influence across barriers in the body.

No evidence is presented to suggest that this is a way in which all nanoparticles can cause harm, as opposed to the specific types of nanoparticles tested.

From these results, it is not possible to say whether the observed effects could occur under real-life conditions, or whether harm could be caused at realistic exposure levels.  The concentrations of material used were very high – the equivalent of the placenta in a 9 months pregnant woman being exposed to approximately 4 – 40 grams of material. Whether such high exposures to materials like the ones used will ever occur is questionable.

While the study opens up new avenues of research, and should be of particular interest to scientists developing new nanoparticle-based drugs and medical devices, it is too early to say whether materials in the body – including nanomaterials – are likely to cause damage across normally tight barriers like the placenta.

In other words, a fascinating piece of science that raises the possibility of a novel way in which materials could cause harm, but which sheds little light on the likelihood of this being a significant concern from real products in real people.

The bottom line here is that, while this is a scientifically interesting study, it is far removed from implying that specific types of nanoparticles in the body could actually cause significant harm in this way.  Certainly, it suggests more research is needed in this area – especially as an increasing number of drugs and medical devices are developed that rely on nanoparticles, and as these products enter the human trials phase.  But at the moment, the data do not support nanoparticle-related DNA damage across the placenta (or any other tight biological barrier) as being a probable cause of serious harm.

]]> http://2020science.org/2009/11/05/could-nanoparticles-inflict-harm-across-tight-cellular-barriers/feed/ 9 http://2020science.org/2009/08/25/sunscreens-alzheimers/ http://2020science.org/2009/08/25/sunscreens-alzheimers/#comments Tue, 25 Aug 2009 14:26:31 +0000 Andrew Maynard http://2020science.org/?p=2089

Could using sunscreen lead to Alzheimer’s, Parkinson’s, or other neurodegenerative diseases?  The association seems far-fetched – given the amount of sunscreens, creams and lotions used every day, surely someone would noticed a link by now if it existed!  Yet a press release from the University of Ulster suggests the nanoparticles used in some sunscreens could potentially cause or exacerbate these diseases.  Drawing on the release, a number of media outlets are now running stories along the lines of “Sunscreen could cause Alzheimer’s” (this from The Daily Mirror in the UK).

This is a rather unfortunate case of a poorly conceived press release leading to sensationalist – and misleading – headlines… The press release is associated with new research funded under the umbrella of NeuroNano – a European project focused on developing nanoscale neuro-implants that will enhance the functioning of the brain.  However this new project, being led by Professors Vyvyan Howard and Dr. Christian Holscher at the University of Ulster, is focusing on how nanomaterials inadvertently entering the brain could cause damage.

The basis of their research is actually quite reasonable.  There is some evidence that exposure to specific types of nanometer-scale particles could lead to them entering the brain, either by traveling up the nerves connecting the nose to the brain, or by crossing over from the blood.  If insoluble nanoparticles do get into the brain they are likely to stick around for a while, as there are limited ways in which the body is able to get rid of foreign material from here.  While there, they could damage neurons by causing the release of reactive oxygen species (ROS) – highly active chemicals.  And there is also research showing that some nanoparticles can cause the type of protein misfolding that has been associated with neurodegenerative diseases like Alzheimer’s – although this was carried out outside the body, under conditions set up to favor misfolding.

These tantalizing snippets of information are like a red rag to a bull as far as scientists go – they suggest there is new knowledge waiting to be discovered; knowledge that could help prevent some forms of brain disease.  Together, they form a sound reason for carrying out more research.

But in no way do they link sunscreens to Alzheimer’s!

The sunscreen link comes about because a number of these lotions use insoluble nanoparticles as the active ingredient.  The thought-process then goes something like this:

The nanoparticles of titanium dioxide or zinc oxide in a sunscreen could conceivably get into someone’s body, by passing through the skin, being eaten, or being inhaled.  Once there, they might be able to get into the blood.  From there, there is a chance that they could pass over into the brain.  Or they might even be inhaled and travel straight up the olfactory nerve and into the brain.  And once there, they could cause vital proteins to misfold that then lead to diseases like Alzheimer’s.

But while this makes an interesting story and a compelling grant proposal, it has little bearing on reality as we currently understand it:

• Most research suggests nanoparticles in sunscreens don’t pass through the skin.
• Even if you could snort sunscreens (a feat in itself), studies showing nanoparticles traveling from the nose to the brain have used rodents not humans – and human noses are very different; they don’t offer the same opportunities for significant exposure through this route.
• It takes a very special type of nanoparticle to cross the blood-brain barrier – you can’t get any old junk across it.
• And research into nanoparticle-induced protein misfolding is at a very preliminary stage – any associations between effects seen in test tubes and brain disease are little more than speculative.

More to the point, we are exposed to billions of nanoparticles each day in the air we breathe; from car exhausts, fires, even sea spray.  If any nanoparticles are going to find their way to our brains in large numbers, it will be these – not those used in some sunscreens.

This is not to detract from the importance of this new research project.  If there are links between nanoparticle exposure and neurodegenerative diseases, we need to know.

But linking sunscreens to Alzheimer’s in the absence of any hard scientific data?  Given what we currently know, that just seems irresponsible!

Update, 8/27/09.  Since posting the original press release, the University of Ulster have changed the headline – without, apparently, telling anyone.  What was “Groundbreaking Research Links Sunscreen and Alzheimer’s Disease” is now “Groundbreaking Research Into Nanoparticles And Alzheimer’s Disease.”

Makes you wonder how much of the sensationalist coverage could have been avoided with a bit of forethought, rather than post-thought.

Thanks to @silentypewriter for the archive link

For more information…

Information on the NeuroNano program can be found here

Nanoparticles traveling from the nose to the brain: There have been a number of studies showing that this is possible in rodents, although little is known about how many particles are likely to get to the brain after being inhaled.  Three useful papers are:

Oberdörster, G., Z. Sharp, V. Atudorei, A. Elder, R. Gelein, W. Kreyling and C. Cox (2004). “Translocation of inhaled ultrafine particles to the brain.” Inhal. Toxicol. 16(6-7): 437-445.

Elder, A., R. Gelein, V. Silva, T. Feikert, L. Opanashuk, J. Carter, R. Potter, A. Maynard, J. Finkelstein and G. Oberdorster (2006). “Translocation of inhaled ultrafine manganese oxide particles to the central nervous system.” Environmental Health Perspectives 114(8): 1172-1178. [PDF]

and

Oberdörster, G., V. Stone and K. Donaldson (2007). “Toxicology of nanoparticles: A historical perspective.” Nanotoxicology 1(1): 2 – 25.

For information on nanoparticles and protein misfolding, the following is a key paper:

Linse, S., C. Cabaleiro-Lago, W.-F. Xue, I. Lynch, S. Lindman, E. Thulin, S. E. Radford and K. A. Dawson (2007). “Nucleation of protein fibrillation by nanoparticles.” Proc. Natl. Acad. Sci. U. S. A. 104: 8691-8696.

The Mexico City study mentioned in the University of Ulster press release is:

Calderon-Garcidueñas, L., B. Azzarelli, H. Acune, R. Garcia, T. M. Gambling, N. Osnaya, S. Monroy, M. R. DEL Tizapantzi, J. L. Carson, A. Villarreal-Calderon and B. Rewcastle (2002). “Air Pollution and Brain Damage.” Toxicol Path 30(3): 373-389.

When it comes to crossing the blood brain barrier, there has been a lot of research on engineering nanoparticles to do exactly this – for delivering drugs.  Most research has shown that fancy materials science and chemistry are needed to engineer nanoparticles to move across the barrier – it’s pretty effective at keeping bad stuff out of the brain.  However, there are indications that small quantities of very small nanoparticles could inadvertently cross over from the blood – more more research is needed to understand whether early findings have any significance though.

Less is known about the possibility of ingested nanoparticles getting into the bloodstream.  Again, the barrier between the guts and the blood is a complex one, and it is unlikely that any old nanoparticle will be able to fool the body into getting where it isn’t wanted.  But this is an area where more research would be useful.

For more info on nanoparticles and sunscreens, check out Industry critics give nanotechnology sunscreens the thumbs up

For more papers on nanoparticles and the brain, check out the nanoEHS Virtual Journal

]]> http://2020science.org/2009/08/25/sunscreens-alzheimers/feed/ 11 http://2020science.org/2009/08/18/new-study-seeks-to-link-seven-cases-of-ocupational-lung-disease-with-nanoparticles-and-nanotechnology/ http://2020science.org/2009/08/18/new-study-seeks-to-link-seven-cases-of-ocupational-lung-disease-with-nanoparticles-and-nanotechnology/#comments Tue, 18 Aug 2009 22:16:37 +0000 Andrew Maynard http://2020science.org/?p=2032

A new study about to be published in the European Respiratory Journal links workplace nanoparticle exposure to seven cases of serious and progressive lung disease in China – leading to two patient deaths – and presses a number of “hot” buttons when it comes to the safety of emerging nanotechnologies. To help place the study in context, I have posted separately the following pieces on 2020 Science, and also on the SAFENANO blog:

Nanoparticle exposure and occupational lung disease – six expert perspectives on a new clinical study
Observations from six leading experts on the study, and it’s significance

Is nanotechnology posed for the ride of its life?
A caution against overlooking the study’s true relevance in the rush to use it to justify pre-existing positions on nanotechnology

Further links to useful resources are included at the end of this blog.

Study Overview

In brief, the paper by Song et al. that appears in the European Respiratory Journal is a clinical study of 7 female Chinese workers who were diagnosed with unusual and progressive lung damage. Two of the women died as a result of the damage. All had been working for some months in a facility spraying a polyacrylic ester paste onto a polystyrene substrate that was subsequently heat-cured. The work was carried out in an enclosed space with little natural ventilation. Five months before the lung disease was identified, the local exhaust ventilation in the facility broke down – and from the account given was never mended.

All seven patients were suffering from shortness of breath, and pleural effusions (an excess of liquid in the cavity surrounding the lungs).  Lung tissue samples showed non-specific inflammation, pulmonary fibrosis, and foreign-body granulomas of the pleura – the membrane surrounding the lungs.  Five of the patients were found to have pericardial effusions – an excess of liquid around the heart.

On examination, investigators found ~30 nm diameter particles in fluid surrounding the lungs of the patients, and in the cytoplasm and nucleoplasm of cells lining the inside and outside of the patients’ lungs. They also found evidence of similar sized nanoparticles in the polyacrylic ester paste, and in the (defunct) workplace ventilation system. There were accounts of smoke being produced as the coated polystyrene was heat-cured.

Based on the presence of the nanoparticles in the workplace and the patients, the nature of the disease observed and previously published cell culture and animal exposure studies on the impacts of nanoparticles, the authors speculated that the lung disease – and the two deaths – were a direct result of the nanoparticle exposure. They conclude that

this may be the first study on the clinical toxicity in humans due to long-term exposure to nanoparticles, and so many questions need to be answered, more studies on the possible mechanisms, diagnosis, treatment and prevention of the ‘nano material-related disease’ are needed. These cases arouse concern that long-term exposure to some nanoparticles without protective measures may be related to serious damage to human lungs. It is impossible to remove nanoparticles that have penetrated the cell and lodged in the cytoplasm and caryoplasm of pulmonary epithelial cells, or that have aggregated around the red blood cell membrane.

In the press release accompanying the paper from the European Respiratory Journal, more explicit associations with the safety of nanotechnology are drawn:

While nanoparticles’ diminutive size means they have unprecedented physical properties (such as diffusion, resistance or flexibility of use) that are invaluable in industrial applications, it also raises the question of their toxicity for consumers and the workforce. Their tiny diameter means that they can penetrate the body’s natural barriers, particularly through contact with damaged skin or by inhalation or ingestion. Moreover, their toxicity has already been established in animals: mice were found to develop symptoms of inflammation and pulmonary fibrosis following application of carbon nanoparticles to the trachea. But until now no cases had been reported in humans. The revelations to be published in the ERJ by a Beijing team will thus break new ground and relaunch the debate on the dangers of nanotechnologies.

Given the buttons this paper and the associated press release hit – including nanoparticle safety, worker deaths and (in the press release) parallels with asbestos, this is a paper that could garner a lot of attention. I suspect that it will refocus attention on what is and isn’t known about the safe use of nanomaterials. Even though the logic is suspect from a purely scientific perspective, the two deaths and their association with nanoparticle exposure will most likely lead to some tough questions being asked by consumers and others on the safety of other nanomaterials. This may not be a bad thing, but at the same time it is important to understand the limitations of the study:

This is a clinical study and not a toxicology study: The investigators did not have the luxury of conducting controlled and well-designed experiments, but were placed in the position of detectives piecing together a series of events after the fact.  Inevitably, this leaves gaps in the information presented, but does not necessarily detract from the usefulness of the study.

The paper adds to the general knowledge base of how nanoparticle exposures might impact on human health. In this respect, it is an important addition to the literature.However, in isolation it tells us very little beyond this particular incident, and great care should be taken in extrapolating the findings to the handling of nanoparticles in general.  It is not possible to draw any general conclusions on the safe use of nanotechnologies from the study.

Interpretation of the study is hampered by a lack of exposure data. Nothing concrete is known about the nature or magnitude of the workplace exposures. It can be speculated (reasonably up to a point) that the workers were exposed to high airborne concentrations of a cocktail of materials that probably contained nanometer-scale particles in some form. What is not known is what the particles were made of of, whether they were inhaled as single particles or as large agglomerates or aggregates, or whether there was anything unusual about their surface–including the presence of adsorbed chemicals.  All of these pieces of information are important in making sense of the health effects seen.

There are no electron microscope images of the nanoparticles found in the workplace. The researchers note the presence of ~30 nm particles in the polyacrylate paste and the ventilation system.  But without images, this information isn’t much help in working out whether the presence of these particles was significant.

There is no chemical analysis of the particles found in the workplace or biological samples. This is a critical data gap – the information is needed to link the workplace material to the material found in the patients, and to establish whether these were polyacrylic particles, an inorganic additive to the paste, or something else.

There is no assessment of other plausible causes of the symptoms seen. The authors are quick to dismiss other possible causes (such as other fumes and vapors from the polyacrylic paste or the polystyrene substrate) and focus in on the nanoparticles.  But without further research, it is difficult to rule out the possibility of other factors playing a role here.

In discussing the relevance of the study, no distinction is made between different types of nanomaterials and their potential impacts. The authors cite the in vitro and in vivo behavior of a range of nanomaterials observed in previous studies and relate these findings to their own observations,.  But they fail to recognize that different nanoparticles behave in very different ways.  For instance, they refer to lung damage associated with inhaling carbon nanotubes in animals as being similar to some of the symptoms observed in their patients, without acknowledging that the particles they observe bear no resemblance to carbon nanotubes.   As a result, the authors propagate the idea that nanoparticles are a generic class of material – which research suggests they are not.

Despite these limitations, this is a strong clinical study, and if viewed appropriately, will most likely help avoid similar incidents in the future.

And as a final observation, it is worth noting that the illnesses and deaths observed would most likely not have occurred if long-accepted occupational practices had been followed.  The tragedy here is that, irrespective of the presence of nanoparticles, the illnesses and deaths could have been prevented if simple steps had been taken to reduce exposures.

Additional resources:

GoodNanoGuide
A community resource for working safely with engineered nanomaterials

SAFENANO
Further information on the Song study

ICON Blog
Further comments and reflections on the study from ICON

[8/20/09: link to paper updated]

In the wake of a new study linking “nanotechnology” to two deaths and five additional cases of lung disease, the emerging technology of the ultra-small could be in for a rough ride.  Yet the real risk is that in the rush to use or even abuse the findings, the science and it’s true relevance are overlooked.

It’s never good news when a new technology is associated with a death.

The emerging area of nanotechnology has had a fairly smooth ride so far.  Sure, there have been questions over possible new health risks associated with some of its more esoteric offerings.  But no one has actually got sick from the technology.

Until now it seems…

A new study to be published in the European Respiratory Journal describes seven cases of unusual and progressive lung disease and two deaths amongst workers at a Chinese factory, and pins the likely cause on nanoparticles—which the authors link inextricably with nanotechnology.

The study presses a number of emotional and political buttons that are likely to elevate its significance—workers died; a new class of material, already under suspicion, is implicated; and in the journal’s press release, parallels are drawn with asbestos—a material that continues to be associated with tens of thousands of deaths around the world each year.

As news coverage surrounding the study gathers momentum, there will be the temptation for opponents and proponents of nanotechnology to either parade it as proof of nanotech’s dangers, or to dismiss it as ill-conceived, flawed and irrelevant.  But either approach would be a serious mistake, and in the long term could jeopardize the safe, successful and beneficial development of nanotechnology.

For years it’s been speculated that nanotechnology-derived materials—including nanoparticles—could present new health risks.  Some materials begin to exhibit novel physical and chemical properties at the nanoscale.  Nanometer-sized particles can get to places inaccessible to larger particles.  And particle size, shape and surface area have been linked to unusual biological behavior for some materials.  Backed by an increasing number of lab studies, it’s becoming increasingly clear that the potential health impact of some nanomaterials depends on more than just chemistry.

But hard data on any actual risks associated with nanomaterials remain tantalizingly elusive.  More to the point, no one has knowingly got sick after being exposed to an engineered nanomaterial yet.  And while proactively avoiding potential nanomaterial-related risks sounds awfully laudable, industry and governments are notoriously loath to take serious action on avoiding possible dangers in the absence of actual bodies.

This presents groups advocating proactive risk management or a precautionary approach to emerging technologies with a dilemma—how do you convince decision-makers to take action before people fall ill, rather than in response to a tragedy?  To some of these groups, this new study could well be seen as just the leverage they need to press for more risk research, stronger regulation, and less rapid nanotechnology commercialization.

On the other hand, industries and governments have a vested interest in ensuring the tens of billions of dollars they have invested in nanotechnology turns a profit—financially, politically and socially.  I may be being over-cynical here, but I can’t see them passively sitting by while a study associating nanotechnology with lung disease threatens to undermine this investment.  At the very least, the scientific integrity of the new study will be examined minutely.  And if it is found wanting, the temptation will be to dismiss it as flawed and irrelevant.

Unfortunately, neither of these approaches will help avoid similar incidents occurring in the future, or support the development of safe nanotechnologies in the long run.

This new study adds to a growing body of research into the potential health impacts of nanoparticles.  Eventually, it will no doubt play a role in helping to understand and avoid the potential dangers associated with some nanomaterials under some conditions. But on its own, it is limited and incomplete.  At the end of the day, the study says little about the potential hazards of nanoparticles in general, and next to nothing about the possible dangers of nanotechnology.  If the sad deaths of the two workers and the lung disease of their five colleagues were used to press home a preordained nanotechnology agenda, it would amount to little more than a cynical misuse of the data—not a move that is likely to encourage evidence-based decisions on either workplace safety or safe nanotechnology.

Yet to dismiss the study as flawed and irrelevant would be equally foolish.  The reality is that two workers died and nanoparticles were implicated, at a time when increasing numbers of nanoparticle-containing products are entering the market.  As the details of the study become known, people are going to want to know what the findings mean for them—whether there are risks associated with emerging nanotechnologies, and what government and industry are doing about it.  If nanotech-promoters downplay or even discredit the work, the move is more likely to engender suspicion than allay fears in many quarters.  And once again, evidence-based decision-making will be in danger of being sacrificed in favor of maintaining a set agenda.

Fortunately, there is a middle way; one that hopefully the proponents and opponents of nanotechnology—and all those in between—will take.  And this is to be science-grounded yet socially responsive in how the study is assessed and acted upon.

This is not a perfect study.  There are key pieces of information missing that prevent its application to nanoparticles more generally.  Yet I believe the questions it raises on the safe development of nanotechnology transcend its limitations.  The study places emerging nanotechnologies in the spotlight, and forces consumers, developers and decision-makers to think afresh about how they might be used safely.  Irrespective of the circumstances surrounding the tragic illnesses and deaths reported, the study will prompt people to ask how safe they are while working with and using products based on nanotechnology.

And where there are no satisfactory answers, these same people are going to want to know why.

Posturing in response to the study will only alienate people and hamper progress towards the science-informed development of safe and beneficial nanotechnology.  Rather, this is a chance for everyone with an interest in safe and beneficial nanotechnologies start working together towards science-grounded progress that ultimately serves everyone’s needs.

Talking together about the way forward is a good start, but to be effective it must lead to informed actions. Given the current lack of knowledge on the potential risks of some nanomaterials, these will depend on well-funded, strategic research that addresses the many existing information gaps.  While this new knowledge is being generated—a process that could take decades—innovative new approaches will be needed for working with and using the products of nanotechnology as safely as possible.  And to cap it all, decision-makers—from manufacturers to workers to policy-makers to consumers—will need access to clear, relevant and understandable information on nanotechnologies, and what they mean to them.

Working together along these lines, the groundwork will be laid for making progress that is based on the best possible science, yet doesn’t ignore the concerns and aspirations of the people it touches.

Tragically, the lung damage experienced by the seven Chinese workers in the European Respiratory Journal study could most likely have been prevented if accepted occupational hygiene practices had been followed. Ultimately, this is a story of a human failing, not an emerging technology.  Yet it does stimulate important questions that will need addressing if the long-term benefits of nanotechnology are to be realized.  The question is, are we prepared to put aside preconceived notions and work together to find effective answers?  I hope we are.

The Environmental Working Group (EWG) – a US-based non-profit organization committed to using public information to protect public health and the environment – has just released what is probably the most comprehensive evaluation to date of the safety and effectiveness of using titanium dioxide and zinc oxide nanoparticles in sunscreens.  And their conclusion?

On balance, EWG researchers found that zinc and titanium-based formulations are among the safest, most effective sunscreens on the market based on available evidence.

In other words, not only are zinc oxide and titanium oxide nanoparticle-based sunscreens OK, but they are safer and more effective than many non nanotechnology-enabled sunscreens.

What makes this statement so startling is that EWG is not known for treating regulators and industry with kid gloves.  This is how the organization describes it’s way of working:

Our research brings to light unsettling facts that you have a right to know. It shames and shakes up polluters and their lobbyists. It rattles politicians and shapes policy. It persuades bureaucracies to rethink science and strengthen regulation.

EWG is about as far as you can get from a bunch of industry lackeys.  Yet here they are endorsing one of the more controversial products of nanotechnology…

For the past few years, the safety of using nanometer-scale particles in sunscreens has been hotly debated.  As manufacturers have  turned increasingly to nanoscale mineral UV-blocking agents in place of more conventional chemicals, speculative questions over whether the nanometer-scale particles of titanium dioxide or zinc oxide being used could penetrate through the skin and harm people have been asked.  In the absence of conclusive safety-focused research, some groups have suggested that nanoparticle-based sunscreens should be avoided in favor of more conventional products, where there we have a clearer idea of the possible risks.  In 2007, Friends of the Earth published “A consumer guide for avoiding nano-sunscreens,” kicking off with:

Sun worshippers beware.  While slathering up with sunscreens to block dangerous ultra-violet (UV) rays you may be exposing yourself to a new danger.  Sunscreen manufacturers are adding nanoparticles to sunscreens to make sun-blocking ingredients like titanium dioxide and zinc oxide rub on clear instead of white. These nanoparticles are being added without appropriate labeling or reliable safety information.

Even EWG admit that their researchers were skeptical about the use of nanoparticles in sunscreens, and thought the organization would end up advising against their use.

Over the past few years, there has been a growing body of published data addressing the effectiveness and safety of nanoparticle-containing sunscreens.  EWG researchers ploughed through nearly 400 studies in their quest to assess what the upsides and downsides might be for consumers.  Importantly, they also compared these data to what is known about conventional UV-blocking agents like octinoxate and oxybenzone.

The result is a comprehensive, robust analysis that wouldn’t be out of place in a peer reviewed scientific journal.  The conclusions are highly relevant to consumers concerned over which sunscreens to use, companies paranoid over how they present their products, and governments wondering how to regulate nanotech-enabled sunscreens.  The report states:

Our study shows that consumers who use sunscreens without zinc and titanium are likely exposed to more UV radiation and greater numbers of hazardous ingredients than consumers relying on zinc and titanium products for sun protection. We found that consumers using sunscreens without zinc and titanium would be exposed to an average of 20% more UVA radiation — with increased risks for UVA-induced skin damage, premature aging, wrinkling, and UV-induced immune system damage — than consumers using zinc- and titanium-based products. Sunscreens without zinc or titanium contain an average of 4 times as many high hazard ingredients known or strongly suspected to cause cancer or birth defects, to disrupt human reproduction or damage the growing brain of a child. They also contain more toxins on average in every major category of health harm considered: cancer (10% more), birth defects and reproductive harm (40% more), neurotoxins (20% more), endocrine system disruptors (70% more), and chemicals that can damage the immune system (70% more) (EWG 2007).

We also reviewed 16 peer-reviewed studies on skin absorption, nearly all showing no absorption of small-scale zinc and titanium sunscreen ingredients through healthy skin. In a 2007 assessment the European Union found no evidence of nano-scale particles absorbing through pig skin, healthy human skin, or the skin of patients suffering from skin disorders (NanoDerm 2007). Overall, we found few available studies on the absorption of nano-scale ingredients through damaged skin, but nearly all other sunscreen chemicals approved for use in the U.S. also lack these studies.

In contrast to zinc and titanium, the common sunscreens octinoxate and oxybenzone absorb into healthy skin — in large amounts according to some studies. These 2 sunscreens can cause allergic reactions, can lead to hormone-driven uterine damage, and can act like estrogen in the body, raising potential concerns for breast cancer.

On balance, EWG researchers found that zinc and titanium-based formulations are among the safest, most effective sunscreens on the market based on available evidence. The easy way out of the nano debate would be to steer people clear of zinc and titanium sunscreens with a call for more data. In the process such a position would implicitly recommend sunscreen ingredients that don’t work, that break down soon after they are applied, that offer only marginal UVA protection, or that absorb through the skin.

EWG acknowledge that more research is still needed, alongside effective oversight, to ensure that nanotech-enabled sunscreens are as safe as possible.  But the key message is that the current balance of evidence supports their use as a safe and effective alternative to more conventional sunscreens.

I cannot emphasize enough how important this report is.  The analysis is credible and the conclusions drawn are supported by the current state of the science.  It should reduce consumer concerns over using nanoparticle-based sunscreens, and allow them to make informed decisions that will result in better UV protection.  It should also encourage companies developing and selling nanoparticle-enabled sunscreens to stop obscuring  the fact – either by avoiding any mention of nanoparticles, hiding behind silly euphamisms alike “micronized,” or coming up with elaborate explanations of why their product doesn’t actually contain any nanoparticles.  These are good products using an effective technology, and companies shouldn’t be shy to let people know!

That said, there is still work to be done.  There are gaps in our understanding of how titanium dioxide and zinc oxide nanoparticles behave on the skin and in the environment that it would be good to fill.  Approaches to testing these materials need to be fully evaluated. And regulators need to clarify the rules concerning the safe use of these materials.

Given what still isn’t known, EWG cautioned against the use of nanoparticles in cosmetics at the moment, where they are not being used to protect the wearer’s health.  But when it comes to protecting the skin the organization was clear – nanoparticle-based sunscreens.

End Notes

The full EWG report on “Nanotechnology & Sunscreens” can be read here.

This is part of a larger review of sunscreens, which is accessible here.

Something not covered in the EWG report is nanoparticle agglomeration.  Some companies have claimed that, while the basic size of titanium dioxide and zinc oxide particles they use is in the range of 1 – 100 nm, they form much larger agglomerates in the products and should therefore not be considered “nanoparticles.”  While this may be the case for some products, it isn’t universal, and there are still questions over whether large agglomerates could disaggregate when applied to the skin.  However, given the EWG’s findings and conclusions, the question of agglomeration doesn’t seem to be that important from a consumer’s perspective.

One concern over the use of titanium dioxide and zinc oxide nanoparticles in sunscreens is that these materials are photoactive, and could become more harmful when exposed to sunlight.  As the EWG report notes, most manufaturers treat the nanoparticles to supress their photoactivity.  Howere, there is some evidence that products containing photoactive particles could still be entering the market.   Whether this is important from a health perspective is unknown, although the indications are that it probably isn’t a significant concern when the particle-containing sunscreens are appolied to healthy skin.

]]> http://2020science.org/2009/07/03/nanotechnology-sunscreens/feed/ 17 http://2020science.org/2009/05/26/nanotechnology-primer/ http://2020science.org/2009/05/26/nanotechnology-primer/#comments Tue, 26 May 2009 13:08:56 +0000 Andrew Maynard http://2020science.org/?p=1633

Back in April, the folks at the PBS station THIRTEEN asked me to answer 13 questions on nanotechnology and the environment for their website feature Green Thirteen.   The questions ended up covering most of nanotechnology – what it is, what it’s good for, what the downsides might be, and how we might overcome potential problems to use it effectively.  With this in mind, I thought it worth posting the Q&A here as a brief nanotechnology primer…

1. What is nanotechnology?

The chemist and Nobel prize winner Richard Smalley described nanotechnology as “the art and science of making stuff that does stuff at the nanometer scale.”

Nanotechnology involves working with materials at an incredibly fine scale—around the size of the atoms and molecules that they are made of.  But the aim is to achieve something new and useful by working at this scale.

Working at the nanometer scale—where one nanometer is a mere one billionth of a meter long—it becomes possible to tap into some unique properties of matter.  Many of these properties only become apparent when small clumps of atoms and molecules are carefully constructed and used as the building blocks of larger structures.  For instance, some materials can be used in new ways when they are engineered at the nanoscale, simply because they are more versatile than non-nanoscale materials.  Other materials behave in strange new ways that enable innovative uses.  Gold, for example, becomes a highly reactive, red-colored metal when formed into nanometer-size particles.  And working at the nanoscale allows highly sophisticated new materials to be engineered that would be impossible to produce using conventional technologies—everything from super-strong materials to the next generation of computer chips to targeted drugs.

2. What are the benefits of nanotech?

The benefits of nanotechnology are incredibly broad, but generally involve making existing technologies work better, or enabling the development of  new technologies.

Many people see nanotechnology as a tool kit that allows scientists and engineers to do new things, whether they are chemists, physicists, biologists, or working in a hundred and one other fields.  In many cases, the things we use everyday don’t work as well as they could because we haven’t been able to control their structure precisely at the finest level.  But nanotechnology is changing this.  For instance, a growing number of consumer products are being improved through the use of simple nanotechnology-based applications:  Sunscreens that go on clear, but protect against harmful UV radiation; clothing that repels stains; socks that prevent the buildup of odor-causing bacteria; tennis racquets that are stronger and lighter; MP3 players that are smaller while holding more songs; even foods that are supposedly better because they have been engineered at the nanometer scale.

But these consumer products are only the tip of the nanotechnology iceberg.  Because the technology enables other technologies to work better, it has the potential to help address some of the biggest challenges facing us.  These include combating climate change, generating renewable energy, controlling pollution, ensuring access to clean water, and developing highly effective medical treatments.

As nanotechnology is used to make better products and address serious challenges, it is expected to generate jobs and money.  Some estimates put the possible market value of products that depend in some way on nanotechnology as being worth over $3 trillion dollars within the next five years.  While the significance estimates like these are sometimes hard to evaluate, there is little doubt that the “nanotechnology tool kit” will play a major role in underpinning future technological and economic development.

3. How does nanotech improve existing technologies?

Sophisticated as they might seem, many existing technologies are akin to trying to make fine jewelry while wearing boxing gloves.  Nanotechnology is the equivalent of removing the gloves—it gives us the ability to fine tune how materials and products are put together at the finest level.  For example, consider the integrated circuits at the heart of modern computers.  The power of these circuits is limited by how many components can be squeezed onto a single chip.  But it is also limited by how fast the heat generated by the electrons coursing through the components can be removed.  Nanotechnology is enabling components—individual transistors and connectors—to be shrunk to the nanoscale, allowing many more of them to be packed onto single chips.  But it is also improving the materials used to transmit heat away from these components, ensuring they don’t over-heat and stop working.

Sunscreens are another example of where nanotechnology improves an existing technology.  Ten to fifteen years go there were two options to making a sunscreen.  You could either use chemicals that are absorbed into the skin, and protect against harmful UV radiation from the sun.  Or you could use particles of materials like titanium dioxide—the same material used to make paint and some foods a brilliant white—to coat the skin and reflect the harmful radiation.  The particles were generally more effective at protecting the user and had the advantage that they lay on top of the skin rather than being absorbed into it—but they left a pasty white residue on the skin that was cosmetically unattractive.  Nanotechnology has since removed this disadvantage.  But using nanometer-scale particles of materials like titanium dioxide and zinc oxide, manufacturers have developed sunscreens that are transparent to visible light while still reflecting UV radiation—and that don’t rely on chemicals that are absorbed into the skin.  The result is highly effective products that are also cosmetically acceptable.

Almost any technology that can be thought of which relies on physical materials can be improved using nanotechnology—simply because nanotechnology provides increased control over the atoms and molecules that make up any material and determine its properties.  However, the economic, social and personal advantages of the improvements will not always outweigh the time, effort and resources needed to make them happen.

4. What kinds of industries are involved? How and where are nanomaterials made?

There are many types of industries involved in nanotechnology, ranging from small startup companies to major multinational corporations.  The types of materials being made are also very diverse.  The NanoMetro map published by the Project on Emerging Nanotechnologies gives a feel for the range and location of nanotech businesses in the US, although it probably doesn’t capture everything that is happening.  The map identifies industries using nanotechnology in the broad areas of electronics, energy and environmental applications, imaging and microscopy, tools and instruments, medicine and health, and materials.  One important point here is that nanotechnology is as much about the tools needed to see and manipulate matter at the nanometer scale—electron microscopes and scanning force microscopes for instance—as it is about creating and using new materials.

Many nanotechnology applications rely on nanomaterials—materials that have been engineered with nanometer-scale structures.  A lot of the nanomaterials currently in use are simply nanometer-scale forms of materials that have been used for many years—such as the titanium dioxide nanoparticles used in sunscreens and elsewhere.  As a result, it is common to find companies with experience developing chemicals and materials using more traditional methods beginning to develop nanomaterials.  At the same time, there are a number of smaller companies that are developing increasingly sophisticated and unique nanomaterials.  In many cases, these are being spun out of University-based nanotechnology research.

Approached to making nanomaterials are as diverse as the materials themselves.  Some of the simplest nanomaterials are made by reacting chemicals together, either in a liquid—to produce suspensions of nanoparticles—or in a gas, essentially burning materials in a controlled manner to produce nanometer-scale particles.  These are then collected, purified, and further processed before being added to products.  At the other end of the spectrum, researchers are modifying viruses, and re-programming them to build nanomaterials.  Recent research has led to new batteries that are based on virus-constructed electrodes.  In between, there are many different ways of engineering matter to form nanostructured materials that can be used to add value to products.

5. What kinds of nanomaterials are appearing in consumer goods?

Most nanotechnology-enabled consumer products currently available rely on relatively simple nanomaterials.  A survey by the Project on Emerging Nanotechnologies indicates that silver nanoparticles are one of the most the dominant nanomaterials currently in use, appearing as an antimicrobial agent in everything from clothing to cooking utensils.  Carbon nanotubes—a unique form of carbon with unusual mechanical and electrical properties—is also appearing in a number of products, predominantly in sporting goods as a way to make them stronger and lighter.  Nanoparticles of zinc oxide and titanium dioxide are widely used in sunscreens and cosmetics, while silica nanoparticles are also being used in a number of products.  In addition there are a number of products using “soft” nanomaterials, which rapidly fall apart when they have done their job.  For instance, some cosmetics use nanometer scale liposomes—very small capsules containing specific materials—to deliver nutrients and other ingredients to the outer layers of the skin.  These disintegrate when they reach their destination, delivering the encapsulated material to where it is needed.

With the exception of carbon nanotubes, these and other nanomaterials being used in consumer products tend to be nanostructured versions of materials that have been used for some time.  However, over the next few years it is likely that increasingly sophisticated and complex nanomaterials will find uses in consumer products.

6. What are the negatives of nanotech?

Like any technology, nanotechnology has its plusses and minuses.  These will generally be specific to different uses of nanotechnology.  For instance, the potential downsides of a nanotechnology-enabled memory chip in an MP3 player will be very different from using nanoparticles in food.

Because of the new and unusual behavior of many engineered nanomaterials, questions have been raised about their safety.  If something can be used in new ways, get to new places, or has new and unusual physical and chemical properties, it is reasonable to ask whether these might also lead to new ways of causing harm—either to humans or the environment.  Evidence to date is sketchy, but it does suggest that some nanomaterials might cause harm in unexpected ways if exposure occurs.  For some nanomaterials, their potential to cause harm will be negligible.  In other situations, more care will need to be taken to ensure safe use—a lot depends on whether exposure is likely, and how toxic the material is.  Common sense and current knowledge go a long way to reducing possible risks.  But more work is still needed to determine the best ways of using these new materials as safely as possible.

Other concerns about nanotechnology are more social and ethical in nature.  Will nanotechnology lead to personal rights being infringed—perhaps through ubiquitous surveillance?  Who will benefit from these emerging technologies, and who will pay the price?  At what point should the use of nanotechnology in enhancing human abilities be questioned?  These and similar questions are not unique to nanotechnology.  But they are an important component of the debate surrounding its development and use.

7. Are there any health side-effects associate with nanotechnology? (e.g. carbon nanotubes causing lung cancer, unexpected in-vivo reactions)

Nanotechnology in and of itself does not lead to health impacts, simply because it is a toolbox of different techniques rather than one specific technology.  However, some uses of nanotechnology could affect people’s health if used inappropriately.

For a material to cause harm to humans, it must first get into the body.  Once there, it’s toxicity will determine how severe any response is.  A high exposure to a low toxicity material (and many nanomaterials will have a low toxicity) may result in a negligible impact.  On the other hand, a low exposure to a highly toxic material could cause a lot of damage.

Two materials that have been researched quite a bit are titanium dioxide nanoparticles, and carbon nanotubes.  In both cases, the materials have been studied in cell cultures and in animals but not humans, and so estimating the toxicity of the materials to people is a little difficult.

Research has shown that inhaled titanium dioxide nanoparticles are more toxic than larger particles of the same substance.  In this case, size makes a difference it seems.  However, as titanium dioxide has a very low toxicity to begin with, the nanoparticles—even though they appear to be more toxic—still seem to be reasonably safe.

Carbon nanotubes appear to be harmful if inhaled, but the harm seems to depend on the type of nanotubes—and there are many types of carbon nanotubes.  Recent research has indicated that long, straight, stiff carbon nanotubes that look like asbestos fibers under the microscope, could be as harmful as asbestos if inhaled.  However, many types of carbon nanotubes don’t have the right shape for this to be a serious concern.  Other research has shown that tangled clumps of carbon nanotubes could also harm the lungs if inhaled, although it unclear how much material is needed for harm to occur.

In both these cases, the critical factor is exposure.  If exposures are low—either while making the materials or using products containing them—risks of health effects will also be low.  The good news is that it seems exposure to carbon nanotubes probably will be low—this is a material that doesn’t readily become airborne as fine fibers.  However, more research is needed to work out how low an exposure is low enough.

8. What kinds of threats to the environment might nanotech pose? (e.g.metal oxide nanoparticle toxicity to fish and frogs)

It’s not clear how harmful different nanomaterials will be if they get out into the environment, although it is clear that some nanomaterials will be more harmful than others.  Important questions that still needs answers include how much material is likely to be release, and from where; whether this material is in the form of nanoparticles, or whether it clumps up into larger particles; how far it is transported, and whether it changes as it moves through the environment; where it accumulates, how long it lasts in the environment, which plants and animals will become exposed, and what the impacts might be.

The good news is that nanoparticles from sources like fires and volcanic eruptions have been ubiquitous in the environment as long as living organisms have been around, and so they have evolved over time to deal with them.  That said, no-one is quite sure how the environment will respond to novel engineered nanomaterials—especially precisely engineered nanoparticles.

One particular potential threat that has already been raised concerns the use of nano-silver in products.  Silver is very effective at killing microbes, which is why it is being used in an increasing number of products.  But it is also highly toxic to a number of organisms as well as microbes.  What is not clear at present is what the impact of silver nanoparticles washed out of products and into the environment might be.  The amounts used may be low enough for the impact to be negligible—or they may not.  It’s a question that can’t be answered well without more information on how much nano-silver is being used, where it is being used, and the likely impacts on the environment if it is released.

9. Who regulates nanotechnology products?

There is no one agency or organization that regulates nanotechnology products.  Rather, they are regulated according to the type of product.  For instance, the US Food and Drug Administration (FDA) is responsible for drugs, food additives and cosmetics that contain engineered nanomaterials.  The US Consumer Protection Safety Commission covers consumer product safety.  The US Department of Agriculture covers food safety—except where FDA has jurisdiction.  And the US Environmental Protection Agency is responsible for chemicals and pesticides.  Each part of this patchwork of regulations and regulatory agencies has different levels of regulatory authority when it comes to nanotechnology products.

10. How much is still not known about the safety of nanotech products, and what needs to be done to fill in the gaps?

From a scientific perspective, there is still a tremendous amount that we don’t know about how to develop and use nanotechnology products safely.  Specific research question that need answers have been raised by a number of organizations, including the Project on Emerging Nanotechnologies and the US government National Nanotechnology Initiative.  There is broad agreement that if nanotechnology is to succeed—and succeed safely—there needs to be a major strategic research program that identifies and fills the outstanding research gaps.  This will require a clear set of goals and objectives, additional research funding, and greater coordination between the organizations that fund research, and those that use the information to ensure material and product safety.

That said, we are not starting out with a blank slate when it comes to using nanotechnology products safely.  Knowledge from other materials can be used to reduce potential risks in many cases, and existing regulations can be applied to nanomaterials—although their implementation may be less than perfect.  However, strategic research will be essential to underpin the long-term safety of increasingly sophisticated nanotechnology-based materials and products.

11. What kinds of recycling challenges are there for nanotech materials? What about nanolitter?

Recycling nanotechnology products presents a number of challenges.  First, there is the problem of stuff that isn’t recycled, either because no-one thinks about it, or because including nanomaterials in a product makes recycling difficult.  This leads to the possibility of nanomaterials being released into the environment as products are disposed of in landfills and slowly degrade, or are incinerated.

Where nanotechnology products are recycled there are two challenges:  Is it worth attempting to extract and reuse the nanotechnology components of the products, and how might this be done; and does the inclusion of a nanomaterial in a product make conventional recycling harder?  To illustrate this second point, imagine nanoparticles of some substance were added to plastic bottles to make them perform better, but that these nanoparticles interfered with the quality of material recycled from conventional plastic bottles.  Would it be better to separate out the nano and non-nano bottles, and how would that be achieved in practice.  The first challenge is perhaps a little easier to address, as it is unlikely that nanomaterials could be recycled from nanotechnology products in a useable state.  Rather, it is more likely that the substances forming the nanomaterials—the silver in nano-silver socks for example—would be reclaimed and used to form new nanomaterials.

12. What are some of the future uses for nanotechnology? How likely is a nano-fabricator?

The next few decades will most likely see some tremendous advances that are based in part on controlling matter at the nanometer scale.  These could well include new forms of generating and storing energy; lighter stronger materials; targeted cancer treatments; treatments for degenerative diseases; efficient ways to purify water; faster more powerful computers; computers that run on light, not electricity; biological organisms that are programmed to make new materials and devices; metamaterials that channel light in highly unusual ways.  We will definitely see a shift from the rather simple nanomaterials being used today to increasingly complex multifunctional nanomaterials.  And associated with this will be an increasingly sophisticated suite of instruments for observing and manipulating the world at the nanoscale.

Based on current research, there will further advances in developing new molecules and nanoscale systems that mimic or reflect what happens in biology (biology, after all, operates very effectively at the nanoscale).  These will move us closer to building new materials and devices molecule by molecule.  But the end result will be much closer to conventional chemistry or biology than the “nano-fabricator”—a speculative machine that can construct complex products out of their constituent atoms, much like the replicators of Star Trek.

13. How can we prevent future problems with nanotechnology? (e.g. grey goo)

Nanotechnology will come with its own set of problems—just as every technology preceding it has.  The trick here will be to have the foresight to spot the problems before they get too large and to navigate a course around them.  This is a tough task.  It will require strategic research to address plausible issues, and ways of translating the results of this research into proactive action.

Even with such an approach, there will be mis-steps.  But hopefully, with the right strategies in place, corrective action will be able to taken fast enough to prevent either major human health or environmental impacts, or the hopes of nanotechnology to address critical challenges being dashed.

In the long term, there may be challenges that are outside our current ability to comprehend the potential dangers, and how to avoid them.  Not self-replicating nanobots perhaps—the so-called “grey goo” that is more science fantasy than science fact—but other technological breakthroughs that take us places unimaginable a few years ago.  The only way to deal with such challenges is to develop institutions that are sufficiently fleet footed and forward-looking to respond to the challenges as they come over the horizon.

The one thing we cannot afford to do is to stick our heads in the sand and ignore potential of nanotechnology to do great good and possibly great harm.

These questions and answers first appeared in their original form at THIRTEEN.ORG on April 28 2009

Part 5 of a series on rethinking science and technology for the 21st century

Last time in this series of occasional blogs, I made the rather bold statement that while science and technology are going to have a highly visible impact on our lives over the next few decades, progress is going to be underpinned in most cases by our increasing control over materials at the invisible nanoscale. It isn’t exactly intuitive why this should be the case though—how on earth can engineering matter on a scale a billion time smaller than the average person be so important?

In trying to answer this question, I want to take a rather unconventional approach and explore three advantages of working at this scale: Smallness, strangeness and sophistication.

Smallness. Size matters—it’s something we all understand intuitively.  There are occasions when you can do something with a small object or device that would be impossible otherwise.  This photo from Ilan Kelman for instance illustrates the idea perfectly: There are times that “smallness” gets you to places that larger objects can’t reach—like parking spaces!

It’s easy to see how making things that we can see and touch small can enhance their value.  But the utility of smallness doesn’t stop when things become invisible to the naked eye.  All the way down to the nanometer scale, there are opportunities to make things work better or work differently by making them small.

Here’s a very trivial example of smallness making a difference at the nanometer scale, but it’s a useful illustration of why size matters:

Silver is a great antimicrobial agent.  It’s been used for millennia to prevent infections from spreading and is one of the reasons why “silverware” is—or used to be—made of the metal.

But it’s not that easy to use.  Large lumps of metal aren’t always that easy to incorporate into products that you want to keep sterile or have antimicrobial properties.

One solution is convert the individual silver atoms into charged ions that can be dissolved in liquids and incorporated into other substances.  As its the ionic form of silver that is most harmful to microbes, this makes a lot of sense.  But ionic silver isn’t that easy to use either.  Say you have a silk scarf or a wound dressing you want to imbue with antimicrobial properties.  Getting those silver ions in there without changing the physical feel and nature of the material is a tough challenge.

This is where smallness comes in.  Make the silver metal into nanometer-sized particles, and it becomes relatively easy to get it into a wide range of products.  Because these are particles we are dealing with, there isn’t so much complex chemistry behind using them.  And because they are so small, they don’t unduly affect the feel and performance of the products they are used in.  As an added advantage, replacing a few large particles with millions of small ones increases the chances of microbes coming into contact with them manyfold.

Because of the advantages of smallness when it comes to using silver as an antimicrobial, there has been an explosion of products using silver nanoparticles—everything from refrigerators to socks to toothpaste.  And all because smallness gets you to new places.

It’s a trivial example, but it does illustrate an important way in which “smallness” through increased control over matter at the nanoscale leads to added value.

It’s not the only way though—there is also strangeness.

Strangeness. No two questions about it, things can get a little weird down at the nanoscale. This is good – it means that controlling matter at this scale opens up a whole new toolbox of material properties that can be put to good use.

Vicki Colvin at Rice University came up with a great analogy for strangeness a few years back.  It went something like this:  Imagine you have a cat.  It looks like a cat, sounds like a cat, smells like a cat.  Now, imagine you have a technology that allows you to make that cat smaller.  As you shrink your cat down, it gets smaller and smaller, but still retains its essential cat-ness.  But imagine reaching a point where suddenly, instead of looking, smelling, sounding like a cat, your cat becomes a dog!

This is the very essence of strangeness—materials behaving in unexpected and sometimes radically different ways when they are engineered at a nanometer scale.  This doesn’t always happen—it depends on the material and the scale on which the material is being engineered—but in some cases the changes in behavior can be startling.

A good example is found in the metal gold.

Gold is an inert, yellowish metal—everyone knows this.  It’s lack of reactivity is why so much jewelry is made from the stuff (it doesn’t tarnish), and in part why it holds its value.  But form gold into particles just a new nanometers across, and everything changes—the metal does the equivalent of transforming from a cat into a dog.  Instead of appearing yellowish in color, the particles now appear red, and become highly chemically active.

This change in color has been exploited for millennia in glass-making (unbeknownst to the glass-makers, who had no idea they were making and using nanoparticles), with perhaps the most famous example being the Lycurgus cup from Roman times.  Illuminated from behind, the gold nanoparticle-containing dichroic glass that the cup is made from appears deep red in color.

This strange behavior has a lot to do with how the movement of electrons in materials is affected when they are engineered at a nanometer scale.  As these movements affect everything from electrical conductivity and interactions with electromagnetic radiation—including visible light—to how a material conducts heat, nanometer-scale engineering allows scientists and engineers to tap into material properties that are rarely accessible without control at this level.

But it’s not enough to have a smorgasbord of strangeness at out fingertips—we also need the ability to use these unusual properties.  And this is where sophistication comes in.

Sophistication. As humans, we are pre-programmed to build things.  As kids, we start early—usually with large blocks.  But we soon learn that there are limits to what can be made with these rather awkward building blocks, and so we progress on to finer blocks—think of it as graduating from wooden blocks to Duplo.  However, it isn’t long before we outgrow these bricks and crave something smaller with which to create increasingly sophisticated structures.  And so we discover that ultimate building medium—Lego.

It’s a rather tongue in cheek analogy, but it illustrates something we all know: The smaller the building blocks we use, the more sophisticated the products we can make.  This applies at the human scale, but it just as equally applies at the nanometer scale.  In fact, being able to build with nanometer-scale clumps of atoms and molecules gives us perhaps what is the ultimate construction set.  And before anyone interjects with “surely that’s just chemistry,” the distinction here is the ability to put these small clumps where we want them with nanometer scale precision.  This is sophistication at the nanometer scale, and opens up new possibilities in engineering materials and products with enhanced or unique properties.

It’s probably fair to say that we are just beginning to scratch the surface of what can be achieved through sophisticated nanometer-scale engineering, but already there are examples that hint at the potential that is opening up.

Here you see a schematic of an actual nanometer-scale particle developed by Raoul Kopelman and Martin Philbert at the University of Michigan.  What is particularly interesting is the sophisticated way this particle has been engineered at the nanoscale to carry out a number of tasks.

The core particle is coated with a thin layer of PolyEthylene Glycol (PEG) to make it invisible to the body’s defense systems.  It is also covered with molecules that enable it to attach to a specific target cell—a particular cancer cell in this case.  Internally, the nanoparticle has been engineered with a contrast-enhancing agent, meaning that when sufficient particles are attached to the tumor being treated, they can be seen using imaging techniques like MRI.

Then the really clever bit—the particles have been engineered with a sensitizer.  In essence, this is a component that causes the particle to do something when it receives a signal.  In this case, when the particle is illuminated with a particular wavelength of light, it releases chemicals to kill the cancer cell it is attached to.

This “smart” particle represents an incredible degree of sophistication at the nanometer scale, and does what it does—destroys cancer cells without affecting healthy cells—because of this sophistication.  And it’s only one example from an increasing number of applications that demonstrate what can be achieved when we have the sophistication to build things at close to the scale of individual atoms and molecules.

At the end of the day, smallness, strangeness and sophistication don’t tell you everything you need to know to understand why an increasing ability to control matter at the nanoscale is so important.  But they do provide a pretty good insight—dare I say, a sophisticated insight—into what can be achieved by working at this scale.

They also create a bridge between two largely separate spheres that is poised to take our control over the world in which we live to an entirely new level.  But more of that next time.

Notes

Rethinking science and technology for the 21st century is a series of blogs drawing on a recent lecture given at the James Martin School in Oxford.  This is a bit of an experiment—the serialization of a lecture, and a prelude to a more formal academic paper.  But hopefully it will be both interesting and useful.  I’ll be posting a “rethinking science and technology” blog every week or so, interspersed with the usual eclectic mix of stuff you’ve come to expect from 2020science.

Previously: Control: Gaining mastery over the world at the finest level

Next: Nanoscale control: Leveraging biology

A guest blog by Dr. Frans Kampers, director of the Wageningen biotechnology center for food and health innovation (BioNT) at the Wageningen University and Research Center in the Netherlands.

Using nanotechnology to make food better—it seems like a good idea, but does it have its downsides?  Questions over the safety and wisdom of using nanotech in food products and during their production have been bubbling along for some time.  Earlier this year, the UK House of Lords launched an inquiry into the use of nanotech in the food sector, while in March the European Food Safety Agency (EFSA) published a scientific opinion on the potential risks arising from nanotechnologies on food and feed safety.  And in the past few days, media coverage in Australia has raised questions over the safe use of nanotechnology in food products.

So far the question of safety has been rather confused (especially in the media)—partly because some commentators have been unclear over what types of nanotechnology will potentially be used in food products, and how these specific uses will lead to possible benefits and risks. There’s also been a certain amount of mixing and matching of the data, with data having nothing to do with food being used to raise concerns – not good science!

In March, Dr Frans Kampers, an expert in food and nanotechnology from the University of Wageningen in the Netherlands, gave an excellent overview of why nanotech is of interest in the food sector as part of a symposium at the annual meeting of the American Association for the Advancement of Science.  Given some of the confusion in this area, I asked him whether he would mind me posting his notes from the presentation here on 2020science.

He kindly agreed.

Nanotechnology is a rapidly developing innovative technology with applications in very many areas, including food, nutrition and food industry. Many people associate nanotechnology with nanoparticles and link the hazards of nanoparticles to all applications of nanotechnology. However, most nanotechnology does not result in nanoparticles and many nanoparticles are from natural origin and therefore should not be considered nanotechnology. The opportunities of doing business at the nano-level in food applications arise from the realization that foodstuff usually has a structural hierarchy that starts at the molecular and supramolecular level. Creating new functionality in a food product therefore often means starting the modifications at the nano-level…

There are four global challenges regarding food where state-of-the-art technologies like micro- and nanotechnologies can contribute:

• Feeding the increasing world population in a sustainable way;
• Improving the quality and safety of foods;
• Delivering those nutrients to individual consumers that are required for good health; and
• Helping in the prevention of welfare diseases like obesity.

These will be discussed next.

The increasing levels of welfare in large populations will result in shifts in diets towards more protein rich components (meat and fish). Our planet is not big enough to produce the corresponding amounts of meat and/or fish in the traditional way. New technologies will have to be developed to utilize the plant protein sources more efficiently than via animal production. The realization that meat is a material with structural elements also at the nano-level implies that developing a good meat replacement from plant or dairy protein sources requires structuring the product at the nano-level and constructing the structural hierarchy all the way up to the macro-level. Ongoing research at Wageningen UR (Atze Jan van der Goot, Food and Bioprocess Engineering) has delivered first results of such a development.

Creating “artificial meat” by constructing materials with a hierarchical structure, starting from the nanoscale

Although food never was as safe as it is now in industrialized countries, a report from the WHO from 2002 shows that there is still much room for improvement. The food industry is always looking for opportunities to monitor food quality in various stages of the chain more accurately. However, they are handicapped in the sense that measuring microbial activity on a food material requires a well-utilized lab, qualified personnel and time. And time is something that is valuable in chains where quality deterioration occurs rapidly. Food industry would like to have fast, cheap, easy to use, sensitive and accurate devices that can be used close to the production line of foods for the detection of pathogens or the quantification of spoilage organisms. Nanotechnology can contribute to the fulfillment of this demand. The method could be based on the detection of specific DNA fragments developed by Wageningen UR (Aart van Amerongen, AFSG).

Nanotechnologies are also used to improve packaging materials in such a way that the quality of the packaged products is maintained for longer periods in time. Creating better barriers to reduce oxygen leakage in modified atmosphere packaging systems, is a low tech application of nanostructured clay materials. Adding nanoparticles with antimicrobial properties to the packaging material helps to reduce the bacterial pressure inside the package and therefore slows down spoilage. Radio Frequency Identification (RFID) technology in combination with head space sensors can directly communicate information about the real quality status of the product to the logistical systems, the cash desk or even the refrigerator. This will become economically viable in combination with printable electronics, another result of nanotechnologies.

People evolved to thrive on a mix of foods much less calorie-less rich than those found in today’s diet

If everybody eats a varied diet with 200 g of vegetables and two pieces of fruit a day we all would get all the nutrients we need to stay healthy. Unfortunately there are very few people who eat this sensibly. Large groups in society have one-sided diets and run the risk of missing out on certain nutrients. Especially since our food is extremely rich in calories while our digestive system—evolved in times when periods of food scarcity where abundant—is optimized to store as much of the calories as possible. This effect in aggravated because of our life styles that require virtually no exercise to get the food and in which much less energy is required to maintain our body temperature. The result is that we eat much less high calorie food that does not contain very many other components. Our gastro-intestinal tract, designed to process large quantities of low calorie foods, has very little possibility to extract all the necessary nutrients. The food industry therefore develops novel food products that are fortified with specific ingredients.

Nanotechnology-based encapsulation can be used to get essential nutrients into the body efficiently

Nanotechnology can provide microsized containers that can contain various nutrients. The supramolecular structures used for this purpose can mask undesired flavors that would spoil the flavor of the product, can protect the substances from inactivation, can improve the bio-availability of the nutrients and can deliver them to specific parts of the Gastro-Intestinal tract where they are most effective. Creating these structures in a cost effective way is not trivial and requires intricate knowledge of self-assembly mechanisms. At Wageningen UR (Physical and Colloid Chemistry) fundamental research is being done to understand these mechanisms and to find new ways to create these innovative encapsulation systems.

It is well known that welfare diseases like obesity rapidly develop in an epidemic that could threaten the healthcare system in the industrialized world. Apart from the lack of exercise, the main problem is the fact that our food contains too many calories. The intricate understanding of processes at the micro- and nano-level allow us to re-engineer processes in the food industry and to create new products that taste and feel the same, but contain less calories. As an example Wageningen UR research on double emulsions (Food and bioprocess Engineering) was presented where the core of oil droplets of an oil-in-water emulsion is replaced by water. This could result in a mayonnaise that tastes and feels like the full fat kind, but contains much less calories.

Using nanotechnology, emulsions are possible that have the taste and texture of rich foods, but without the calories

At Wageningen UR we are very well aware of the discussions within society about applications of nanotechnologies in food. Societal acceptance is a condition sine qua non to be able to make use of the opportunities discussed above. One of the key aspects of that is the risk/benefit evaluation of these applications. Unfortunately the general public lacks the technical ability and the information to make a good risk assessment, and partly as a result ends up focusing on the hazards alone, rather than a combination of hazard and exposure. Moreover, since the general perception is that “nanotechnology” equals “nanoparticles,” the hazards of “nanoparticles” are equated with risks of “nanotechnology.” But the hazards of nanoparticles concentrate on the non-dissolvable, persistent particles often made of metals or metal oxides. These particles can sometimes traverse barriers, get in the blood stream and enter certain tissue.

The “nano” in many nanotechnology and food applications is in the structure of ingredients and additives, rather than in their overall size

Persistent nanoparticles are rarely used in food products for the very simple reason that the body cannot benefit from them. The nanotechnology in products largely is used to create encapsulation systems that are designed to fall apart in the Gastro-Intestinal tract and release their contents. Afterwards only molecules of food-grade materials remain and no particles are found in the feces of the consumer. Moreover, these encapsulates are usually larger than 100 nm and therefore do not constitute nanoparticles in the usual sense. The nanotechnology is in the wall of these particles to create the specific functionality that offers the new properties to the product.

The full set of slides from Dr. Kampers’ AAAS lecture can be downloaded here.  (PDF, 6 MB).

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.

Nanotechnology: What is it, what can it do, what are the downsides, and how can we ensure it reaches its full potential?

Managing the Small Stuff. Also available in High Definition on Vimeo

The promise and challenges of nanotechnology is something I lecture on a lot.  And when I do, I’m inevitably asked for a copy of the slides.  But here I have a problem: I have a rather idiosyncratic lecture style that moved on from the 3-bullet point PowerPoint straitjacket some years ago—which is great for the live performance, but lousy when it comes to handing out intelligible PDF’s of the talk.

So with the help of my trusty Mac and YouTube, I’ve been experimenting with other ways to capture the essence of these lectures.  The video above is the first result—a short primer on nanotechnology:

First, let me stress that this is an experiment… I’m not sure whether it succeeds in conveying anything useful about nanotechnology, or whether it ends up being rather crass and unintelligible.  But I would love some feedback.

You’ll notice as you watch the video above (if you are observant) that I eschewed a simple movie of myself giving a lecture.

Why?

Well, would you sit and watch me droning on about nanotechnology for more than a few seconds?  I wouldn’t!

Actually, this would have been easier to pull off than what I ended up doing, but I was more interested in how the presentation medium (Keynote on the Mac) and the internet (YouTube in particular) could be used to convey information in a more innovative and accessible way.  If you are reaching out to a non-specialist audience, to what extent do eye-catching visuals and a soundtrack make the experience more informative and enjoyable?  Again, I’m not sure—but that is all part of what I am trying to find out.

(I should add here that rumors of this whole exercise just being an excuse to play with Keynote’s fancy graphics capabilities are entirely unfounded…)

The resulting video is rather short—it’s an unashamedly high-level view of nanotechnology that avoids specifics, and instead focuses on underlying concepts.  This seems to be a format that lends itself to conveying general information in small chunks.  I’m still tossing up whether to try formatting and posting a full 60 minute lecture in this style, but my gut tells me that this could end up being the YouTube equivalent of Vogon poetry—something no-one should have to endure!

The bottom line here (to get serious for a second) is that compiling animated movies from presentations and posting them on the web does seem to offer new opportunities for us amateur communicators to convey information on science in an accessible and informative way, using readily available tools.  I suspect that if it’s done well, this could be an effective way of packaging information to reach a broad audience.

I’m not sure how successful the movie above is in conveying what nanotechnology is all about to a lay audience.  But I do think it demonstrates the possibility of using today’s digital technology to convey complex information in new ways.  And as science and technology become increasingly important within society, we certainly need innovative ways to bridge the gap between those who generate new knowledge, and those who use it.

__________________________

Technical Stuff

The original presentation was developed in Keynote on a MacBook Pro.  A confession here—I really like the simplicity, utility and visual appeal of Keynote, and develop all of my presentations using the package.  Using PowerPoint just makes me miserable in comparison.

Most of the slides in the presentation were culled from previous lectures I have given, but were formatted specifically for this video.  In particular, animations within and between slides were added to help the story develop as the video progresses.  The slides were formatted at a resolution of 1280 by 720 pixels, allowing them to be saved as a high definition video.

The final presentation was exported as a movie and—you’ve got to love the integration on Macs—imported into GarageBand to allow soundtrack and commentary to be added.  The soundtrack is from my own doodling within GarageBand—for which I must apologize.  The end movie was exported, and uploaded to YouTube.

Finally, first time round I did this, I just included the slides and the soundtrack in the movie.  The result was artistically intriguing—but surreal, cryptic, and ultimately unfathomable – if you don’t believe me, check out the video below.  Which is why I ended up adding the commentary.  But it still makes interesting, if somewhat obscure, viewing.  Whether it makes any sense or not, I hope you enjoy it!

Managing the Small Stuff – without the commentary. Also available in High Definition on Vimeo

I spend quite a bit of my time talking to different groups about nanotechnology, including its potential and its challenges. And as a result, I’m constantly on the prowl for new ways of illustrating why nanotechnology is important. In particular, I’ve been keeping my eyes peeled for a quick and dirty (and fun) demonstration to show that size matters.

Which is why I finally cracked this weekend and started messing around with packs of Mentos Mints and bottles of Coke.

One of the important ideas underpinning nanotechnology is that, as stuff gets smaller, things change. It may be that the smaller stuff can get to new places or be used in new ways. It may just be that the stuff is able to do more of its “stuff” when it’s smaller. Or it may be that the original stuff starts behaving like completely different stuff when it gets really small.

Whatever, when it comes to nanotechnology, size matters.

But how do you convince someone of this when they can’t see or experience what is happening at the nanoscale? After all, we are all endowed with brains that have evolved to handle things we can see and touch—not stuff that is invisible to the naked eye.

One approach is to use analogies between stuff that can be seen and touched, and nanoscale materials that cannot be experienced so readily. Along these lines, I’ve been wondering for some time whether the notorious reaction between Mentos and Coke could be exploited in some way to demonstrate aspects of nanotechnology.

Dropping Mentos into a bottle of coke causes a rapid release of carbon dioxide from the liquid, and a frothy geyser to erupt from the container. (For those of you who have no idea of what I’m talking about, just check out the videos at Eepybird.com). If it’s particle surface that drives the reaction between the Mentos and the Coke, grinding the candy up into smaller bits before adding it to should lead to more vigorous “eruption.”

The result—if it works—lots of fun, and a great illustration of one way in which size matters.

Having nothing better to do this weekend, I drafted my kids and an unwitting friend of my daughters into testing the idea. The concept—crush a couple of Mentos into medium and small bits, add to a 2 liter bottle of Coke, and watch what happens.

Saved for posterity, here’s the video of the great event:

Unfortunately, the finely crushed Mentos didn’t create as stunningly superior a geyser as I had hoped. Lesson number one—there’s often a yawning chasm between hypothesis and reality. However, there was a clear size-effect: The medium sized chunks of candy gave the highest geyser, while the finest chunks led to the longest reaction.

Clearly size mattered—just not in the way that might have been predicted…

Despite the disappointing performance of the fine stuff in this instance, the experience has convinced me there’s considerable mileage in using Mentos to explore some of the ideas underpinning nanotechnology. The experiment clearly demonstrates to those involved that making something into smaller pieces changes how it behaves—that’s a pretty important concept.

But that’s just the beginning. Mentos are a great example of a particle with a core-shell structure—the outside of each Mento is different to the inside. Many engineered nanoparticles have a similar structure, so we’re on good analogy ground here.

It’s likely that the Mentos’ outer shell has something to do with the vigor of the reaction with Coke—as New Scientist reported last year, surface roughness and chemistry probably play a role in making the whole Mentos-Coke thing work. So just crushing the candy up wouldn’t necessarily make the reaction go that much faster, as you’re not adding any more of the outer coating to the mix.

However, what if that outer coating was removed? I haven’t tried this, but it would be a cool experiment to wash (or suck perpahs) the outer coating off the Mentos, and see how it affects their geyser-forming properties. You could even go one step further, and see how crushing the denuded Mentos into increasingly finer particles changed things.

This could have the makings of a fun experiment for exploring the importance of size and surfaces—and all with a pack of mints and a bottle of Coke. How much simpler could things get?

Of course, the down-side is that someone needs to clear the mess up afterwards!

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.

Introducing MINChar—a new community initiative to support effective material characterization in nanotoxicity studies.

Here’s a tough one:  Imagine you have a new substance—call it substance X—and you run some tests to see how toxic it is.  But you’re not quite sure what substance X is.

You know that it is a powder, and it is supposed to have chemicals x y and z somewhere in it.  But you don’t know how small the particles are, what shape they are, whether chemical z is on the surface of the particles or inside them, whether the particles all clump together when shoved into the test system or whether they can’t get far enough away from each other after being administered, or whether there is something else present in substance X that really shouldn’t be there.

Now imagine your tests show that substance X looks like it could be rather dangerous.  How do identify which aspect of the material is causing the problem, so you can go about fixing it?

Or imagine someone else wants to repeat your work.  Or they want to compare your data with another study.  How do you know that the substance being used in other studies is the same as substance X, and not simply a crude approximation?

The scenario is somewhat hypothetical, but the issues are very real.  And they have dogged the field of nanotoxicology for over a decade.

The problem is, toxicologists are used to working with substances where chemical identity and mass of material are all that are needed to establish the concentration at which the material becomes harmful.  These folks aren’t used to dealing with materials that “do what they do” because of a complex set of physical and chemical characteristics, and that may change from one environment to another.

But the toxicology community is becoming increasingly aware of the new challenges of studying the harmfulness of engineered nanomaterials.  Which is why a new grass-roots initiative has just been launched to try and change things for the better.

The Minimum Information on Nanomaterial Characterization initiative—MINChar for short—has its roots in a workshop held in Florida back in 2004.  At the time, materials scientists and toxicologists were well aware of the disconnect between conventional toxicology and the new challenges presented by engineered nanomaterials.  But they weren’t clear what to do about it.  And it rapidly became apparent that the research community wasn’t ready to take radical action to change the habits of a lifetime—the ideas were there, but the timing wasn’t right.

Four years on though, the landscape has changed—an increasing amount of nanotoxicology research is being funded and published, and more people are realizing that for the work to be useful, the materials being tested need to be characterized appropriately.

But there is a problem: what constitutes “appropriate.”  Or rather, to the toxicologist who is easily scared by long lists of incomprehensible parameters that require fancy (and expensive) instruments to measure—what is the minimum material characterization that is achievable in practice.

This is what the MINChar initiative set out to address.  Over the course of two days in October, a group of people involved with generating, assessing and using toxicology data got together and hashed out a minimum set of information they thought was necessary for effective studies.  The idea was to put something in place as a community that would compliment initiatives from more august bodies—and start to improve the quality of nanotoxicology studies from the laboratory outward.

The result was a list of nine physical and chemical parameters, and three overarching considerations—available on the MINChar website.

But just as importantly, the meeting spawned a community of people interested in improving the state of material characterization in nanotoxicology studies.

And if you are involved in any way with nanotoxicology—as a researcher, a reviewer, a program manager, a data-user—you can sign up as a member of MINChar Community.  This is something that is being strongly recommended by the organizers of the October workshop—because the more people there are involved in improving the quality of nanotoxicology research, the more likely it is that approaches to using new and potentially useful nanomaterials safety will be developed.

And understanding how to use substance X safely will no longer be like groping in the dark.

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Endnotes

• Further information on the MINChar initiative can be found at http://characterizationmatters.org
• If you are interested in being a part of the MINChar community, you can sign up at http://characterizationmatters.org/community/
• This week’s copy of Chemical & Engineering News has a great article on MINChar [accessible from here]

]]> http://2020science.org/2008/12/15/getting-to-grips-with-nanomaterial-toxicity/feed/ 1 http://2020science.org/2008/11/23/toxic-particles-and-trivial-pursuits/ http://2020science.org/2008/11/23/toxic-particles-and-trivial-pursuits/#comments Mon, 24 Nov 2008 03:44:34 +0000 Andrew Maynard http://2020science.wordpress.com/?p=487

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 cataloguing 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.

On the widget’s web page, choose “Time Progressive Distribution Analysis” and hit go, and you get the number of papers published per year in each category, displayed as a bar chart.  You can also narrow or widen the number of years covered by each bar—the example below shows the number of publications every two years. (“Series 1″ represents dermal/mucosal exposure – a niggling aspect of the widget display I tackle further down the page).

As well as providing hours of fun for the socially-challenges (regrettably, I suspect I fall in this group), the widget is a great gateway into the rich publications database ICON are amassing.  One trend it shows readily is an apparent exponential increase in the number of nanomaterial environment, health and safety papers being published.  The following plot is the time series from 1981 to 2008 for papers covering any exposure pathway, summed up in two year blocks.

More interestingly, this trend can be separated out by exposure route—ingestion, inhalation, dermal, multiple routes, or the catch-all category “other/unspecified.”  And when the data are plotted out (see below), things get interesting—the exponential rise in publications is only seen for the “other/unspecified” category.  Publication rates for papers dealing with inhalation or dermal uptake seem somewhat static.

Further exploration reveals that the rise in papers within the “other/unspecified” category is predominantly associated with in vitro studies.

Even after just an hour or so playing with the widget, it is clear that it is a powerful tool for assessing trends, and beginning to identify deficiencies in the global research agenda.  Beyond producing useful web graphics, each analysis can be downloaded as a PDF or Excel spreadsheet—a useful feature.  And as has been mentioned, the papers each analysis is based on can be listed and examined in more depth.

But the widget isn’t perfect.  Like any data analysis tool, how the numbers are interpreted is everything (remember the old computer adage—garbage in, garbage out)—and it’s easy to generate numbers that can be misleading.  Just one example: plot the numbers of papers on inhalation exposure between 1983 and 2008, averaging over every five years, and you will be shocked to see that there seems to be a dramatic decrease in publications over the past five years.  Until you realize that the last bar on the plot represents just one year (January 2008 – December 2008), and not five.  Artefacts like this can be misleading if a weather-eye isn’t trained on what is actually being shown.

Another example is the pie chart shown earlier in this post.  It’s tempting to read the percentages shown on the plot as the fractions of papers published on either inhalation, ingestion or dermal exposure.  Whereas they are only the fractions of papers within this particular grouping—add other possibilities into the mix (injection, multiple exposure pathways, the catch-all “other/unspecified” category), and the percentages change.

And there are some niggling things about how the widget does its stuff, like a tendency for the plot legend to revert to “series 1” or “series 2” etc. when the full descriptor is too long (as on the chart above).  Or a pet peeve of mine—referring to a bar chart as a “histogram!”

But despite these potential pitfalls and minor irritations, this is a powerful tool that is extremely useful for mining the nanoEHS Virtual Journal’s extensive data.

And, of course, the widget is the perfect resource for that last-ditch game of “toxic particles trivial pursuit.”

Go on, give it a whirl—I dare you!

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* Of course, I must point out that not all nanoparticles are necessarily more toxic than their larger counterparts, and that some nanoparticles seem to be pretty benign compared to others.  But the title “Particles of indeterminate toxicity and trivial pursuits” just didn’t seem to scan quite so well…

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.

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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.

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!

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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

The blogging community is no stranger to the use (and possible abuse) of nanometre-scale silver—products ranging from silver-enhanced socks and toothpaste to plush toys and cure-alls have all appeared in the spotlight recently. With each passing month, the number of nano-silver gizmos on the market is growing.

Back in March 2006 when the Project on Emerging Nanotechnologies Consumer Products Inventory was launched, there were 25 products claiming to use nanoscale silver. In contrast, the August 2008 update of the inventory brought the number of nano-silver containing products to 235—an increase of nearly ten times over two and a half years!

This fashion for a splash of silver in consumer products has quite naturally led to questions being asked—how much silver is being used, where does it go, and what harm does it do (if any) when it gets there? Unfortunately, answers to these questions have been less than forthcoming; leading to a lot of speculation and rather less science in the ensuing discussions. But this is hopefully about to change…

Some time ago, the Project on Emerging Nanotechnologies asked Dr. Sam Luoma—an internationally respected expert on silver in the environment—to turn his thoughts to the possible impacts of nano-silver. The result—just published—is a thorough exposition of what is known about silver in the environment, how this applied to nanoscale silver, what new potential challenges the use of nano-silver raises, and how these challenges might be addressed.

The report (available here. PDF, 1.1 MB), which includes a highly recommended foreword by J. Clarence Davies on the policy implications arising from Sam’s science-based analysis, is probably the most comprehensive assessment to date of the current state of knowledge on silver and nano-silver in the environment. By my reckoning it covers everything you ever wanted to know about silver, and then some…

Luoma starts off by looking at what is already known about silver in the environment; what happens to it, where it accumulates, its bioavailability, and its toxicity. He then goes on to ask how much of this can be applied to nanoscale silver, and where the nanoscale form of the material leads to new behaviour and new challenges.

The discussion follows a logical progression, using the “source-pathway-receptor-impact” principle for risk assessment suggested by Richard Owen and Richard Handy in 2007 (PDF, 428 KB). In essence, this deals with the questions:

• Where does the silver come from?
• Where does it go and how does it get there?
• What is exposed to it? And
• What happens then?

This turns out to be a smart move, because when the discussion moves from silver (about which we know quite a bit) to nanoscale silver (about which we know not a lot), a clear framework has been established for thinking about where nano-silver can probably be treated as other forms of silver, where its “nano-ness” likely leads to shifts in behaviour away from the established baseline, and where the critical data gaps and challenges lie.

This is a report that has to be read from cover to cover to get the full flavour of Luoma’s analysis. Fortunately, the 60 pages (72 with foreword, appendix and references) are written in a highly accessible style—never have marine clams been so engaging! However, here are a few things in particular that struck me as I read through the work:

• First, Sam eloquently establishes that we know a lot about silver in the environment; we are not starting from zero knowledge, but have a solid baseline from which to build on. This is a timely reminder that dealing with nanotech risks will often mean building on existing knowledge, rather than starting from scratch.

• Second, the physical, chemical and biological behaviour of silver in the environment is complex—this is not a substance that can be dealt with through sweeping generalizations. The transport, bioavailability and toxicity of the material depends to a significant degree on the chemistry of the environment it is within, and the potential to cause harm may decrease as well as increase depending on this environment. There is no reason to believe that things get any simpler when dealing with nanoscale silver.

• Third, while somewhat speculative, it is possible to imagine scenarios where the distributed use and release of nanoscale silver could lead to relevant environmental loadings. In other words, just because the individual release rates from one washing machine or a single pair of nano-silver socks are extremely low, does not mean that the cumulative release rates from many nano-silver products will not be important. While I suspect that some of the usage figures in Sam’s scenarios may be on the high side of realistic, it is possible to show that the widespread use of nano-silver containing products could lead to environmental contamination levels comparable with those associated with the analogue photographic industry at its peak.

• Fourth, silver nanoparticles could conceivably act as a “Trojan horse” for getting toxic silver ions into cells—essentially increasing the toxicity of the material by transporting it to places that are normally off-limits.

• And finally, there are sufficient gaps in our knowledge over the release, fate and impact of nano-silver that, when coupled with what is known, demand strategic research into potential risks and their management at a level which currently does not exist.

But these are fleeting impressions that do not do the report justice, and are certainly no substitute for reading the report itself.

I suspect that nano-silver is here to stay—the value it adds to products is too real to ignore. But its safe use will depend on grappling with the new challenges it presents. And Luoma’s report provides what is probably the most thorough resource to date for identifying these challenges, and developing a plan of action for dealing with them.

Clearly, essential reading for anyone with a stake in ensuring a responsible and successful nano-silver business!

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Notes

The report “Silver Nanotechnologies and the Environment: Old Problems or New Challenges?” (PEN 15) is freely available at www.nanotechproject.org/publications/archive/silver/

In the spirit of full disclosure, I could be accused of having a biased perspective on this report; having worked closely with Sam through its development. So you probably shouldn’t take too much notice of me when I claim that this is a seminal report on nano-silver in the environment, and one that is destined to become the reference work in the field for some years.

Sam’s report is augmented by a database of silver nanotechnology used in commercial products, published on the Project on Emerging Nanotechnologies website (available here). This was compiled by Emma Fauss at the University of Virginia, and complements the PEN Consumer Product Inventory by including more extensive information on the use of nanoscale silver in products.

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This post first appeared on the SAFENANO blog in September 2008

If you evaluate the toxicity of an engineered nanomaterial, how far can you trust your results?  If someone else repeats your tests and gets a different answer, did they do it wrong? Did you?  Or was the material used different in some subtle but nevertheless important way?

These are questions that have dogged nanotoxicologists for years, and have undermined many a study.  But help is at hand—a group of scientists have decided to grasp the nettle and start working together to unravel these rather knotty challenges.

Behind the rather grand-sounding title, the International Alliance for NanoEHS Harmonization (IANH) is a serious attempt by toxicologists around the globe to get together and start to dismantle some of the barriers to exploring and evaluating the potential toxicity of nanomaterials.  The current team represents some of the foremost thinkers and researchers in the field of nanotoxicology, including Kenneth Dawson from University College Dublin, Vicki Colvin from Rice University, André Nel from UCLA, Vicki Stone from Napier University, Mark Wiesner from Duke University and Günter Oberdörster from the University of Rochester (a complete list of members can be found here).  The Alliance was announced today at the Second International Conference on Nanotoxicology, in Zurich.

The idea behind IANH is first and foremost to establish testing protocols that will enable reproducible toxicological testing of nanomaterials at the cell and animal levels.  Central to this will be a set of round robin experiments, where researchers share materials and compare the results of independently conducted tests, then work out why some agree and some don’t.  The Alliance then intend to build on this to address correlations between in vitro and in vivo studies—funding-willing.

My gut feeling is that the broader nano-risk research agenda will still need to be set by authoritative national and international bodies if significant progress is to be made in developing safe and sustainable nanotechnologies—bodies such as the Organization for Economic Cooperation and Development, national scientific academies, and governments.  But this new group brings three important things to the table:

• Communication and coordination between researchers that will enable responsive, targeted and synergistic research;
• a research community that can work together on problems that seem to have slipped off other people’s agendas—like developing and refining common approaches to toxicity testing that are both meaningful and reproducible; and
• an international community of scientists who can deliver the highest quality research in response to calls for targeted information on the potential impacts of emerging engineered nanomaterials.

Of course, all this depends on research funds being available.  But if national and international funding organizations get their act together and start to fund strategic nanotech risk research at the levels needed, the chances are that this self-assembled group of leading nanotoxicologists will help ensure research investments deliver the goods.

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More information on International Alliance for NanoEHS Harmonization  is available at www.nanoehsalliance.org

Contacts for further information include:

Europe: Iseult Lynch, iseult@fiachra.ucd.ie

Americas: Vicki Colvin, colvin@rice.edu; André Nel, anel@mednet.ucla.edu; Günter Oberdörster, Gunter_Oberdorster@URMC.Rochester.edu; Mark Wiesner, wiesner@duke.edu

Japan and Asia: Masahiro Takemura, TAKEMURA.Masahiro@nims.go.jp

This post first appeared on the SAFENANO blog in September 2008

How cool is this: A nanotech-enabled labcoat to protect the user against… well, nanomaterials presumably, amongst other things!  

The labcoat—which uses Nanotex technology to make it stain resistant—is part of a major update to the Project on Emerging Nanotechnologies Consumer Products Inventory that tracks manufacture-identified nano-products.  Other eye-catchers in the update include a hunting shirt that resists bloodstains, a nanotech-based adhesive for McDonald’s burger containers, and an oven-like device for sanitizing whiffy shoes.

Of course, there are plenty of people who feel that consumer products represent an altogether too trivial side of nanotechnology.  And I have to agree that on the scales of virtue, a nano-silver bidet would find it hard to compete with the next generation of nano-enabled solar cells or targeted cancer drugs.  Yet trivial as many of the 800+ products in the updated inventory may seem, this is where most people will probably first come across the technology, and start to form their early opinions on whether it’s a good thing, or not so good.  

And in this bizarrely-connected world within which we live, good experience with nano-bidets (for example) are more likely than not to make the introduction of nano-cancer drugs go just that little bit smoother.

But beyond initial impressions, consumer products in their broadest sense are where some of the first widespread exposures to engineered nanomaterials are likely to occur.  And this means that care is needed over how nanomaterials are used in these products, and how that use is monitored and regulated.  

In the US, the Consumer Product Safety Commission (CPSC) is responsible for protecting the public against unreasonable risks of injury or death associated with consumer products.  But recently, the CPSC has been struggling with low-tech problems like lead in children’s toys, and there is concern that this doesn’t bode well for the agency’s ability to tackle high tech nanotechnology-based products.

This is the conclusion of a new report by E. Marla Felcher of Harvard University’s Kennedy School.  In “The Consumer Product Safety Commission and Nanotechnology,” published by the Project on Nanotechnologies, Felcher paints a picture of CPSC as an agency of lofty ideals, crippled by a lack of political support, dwindling resources, inadequate scientific expertise and inadequate authority.  In the report’s executive summary, she writes

“CPSC’s inability to carry out its mandate with respect to simple, low-tech products such as Thomas the Tank Engine toy trains, Barbie dolls and Easy-Bake Ovens bodes poorly for its ability to oversee the safety of complex, high-tech products made using nanotechnology. The agency lacks the budget, the statutory authority and the scientific expertise to ensure that the hundreds of nanoproducts now on the market, among them baby bottle nipples, infant teething rings, teddy bears, paints, waxes, kitchenware and appliances, are safe. This problem will only worsen as more sophisticated nanotechnology-based products begin to enter the consumer market.”

The critique is harsh—all the more so because CPSC staff are clearly trying hard to get their heads around the challenges that nanotechnology is presenting them with.  Yet according to Felcher, the problems lie not so much with the staff as with the agency’s lack of information, resources and authority.  To ensure CPSC is nano-ready (and more broadly, emerging technology-ready), she recommends that:

• The agency’s knowledge-base is built-up,
• that CPSC work closely with other health and safety agencies,
• that information on nano-products is solicited from companies,
• that a Chronic Health Advisory Panel is convened to evaluate potential risks associated with nano-products for children,
• that the agency appeal to industry to develop voluntary safety standards for children’s products,
• and that the US congress take action on the Consumer product Safety Act bill to increase CPSC’s authority to address products based on new and emerging technologies.

There’s a good chance that many of the allegedly nanotechnology-enabled products entering the market are harmless (or at least, mostly harmless).  But a combination of novel and sometimes unpredictable material behaviour, few checks and balances to use and an inadequately resourced and empowered regulator seems like a dangerous combination; when a potentially harmful nano-product does come along, there aren’t, it seems, many barriers to prevent problems from occurring.  

And we are still dealing with very simple nanotechnologies—nanoparticles of silver, titania and carbon in the main.  What happens when consumer product manufacturers start to use more complex nanotechnologies?

OK so nano-consumerism may seem rather trivial in the grand scheme of things.  But the impacts of nano-consumerism gone wrong could be far from inconsequential.  So if we want to see the less trivial products of nanotechnology—the renewable energy sources, the high performance batteries, the smart drugs—now might be a good time to make sure the first waves of products perform well without causing harm.

Now, back to that shoe de-whiffer—I think my “nano  silver far infrared  anti-odor healthy socks” need a little help…

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This post first appeared on the SAFENANO blog in August 2008

Painted metal roofs are cheap, convenient, and usually very durable.  But over the past two years, a rash of accelerated ageing has blighted pre-painted steel roofing in Australia.  And intriguingly the ageing—which affects the coating—seems to be localized to small patches, taking on the form of fingerprints, handprints and even footprints.

The culprit it seems is sunscreen that is spilt or otherwise transferred to the roofing by construction workers during installation. And not any old sunscreen—this would appear to be a uniquely nano phenomenon.  But I get ahead of myself…

Pick up a bottle of sunscreen and there is a fair chance these days that it contains nanoparticles, engineered to absorb and reflect away harmful UV radiation.  Many manufacturers are introducing lines of nanoparticle-containing sunscreens as alternatives to those using more conventional organic chemicals, and it’s not hard to see why: the active ingredients in these nano sun blocks are generally more gentle on the skin than their non-nano counterparts; they are made to sit on the surface of the skin rather than penetrate into it; and if designed well, they continue to block UV radiation for several hours after application.  And of course, they go on clear, giving a product that works well and looks good.

But each year as the sun and the sunscreen come out, questions over the safety of nano-formulations are raised.  Can these nanoscale particles penetrate through the outer layers of the skin to the underlying living cells, and even the bloodstream? And if they get there, what harm could they cause?  So far, most studies suggest that nanoparticles in sunscreens stay where they are supposed to—on the skin, not in it.  Yet there is another question that has been bobbing along just under the surface for the past few years: could mixing nanoparticles, sun and moisture lead to a chemically corrosive mix that is bad for the skin?

The issue in question is photocatalytic activity.  Titanium dioxide, and to a lesser extent zinc oxide, are photoactive—they have the ability to absorb UV, and in the presence of moisture convert benign water molecules into chemically active hydroxyl free radicals.  These highly reactive chemicals could spell bad news for sunscreen users if they are generated in large amounts—eating away the components that hold the sunscreen together, and even possibly causing skin damage if they get below the surface and into cells.

Fortunately, manufacturers and users of titanium dioxide have long been aware of this propensity to generate free radicals, and have found ways of suppressing it in sunscreens. Photocatalytic activity depends on the crystalline structure of titanium dioxide.  Anatase and rutile forms of titanium dioxide have the same chemical formula but different crystalline structures. And, as it turns out, different properties. Make nanoparticles from anatase titanium dioxide, or a mix of anatase and rutile, and you have a powerful source of harmful hydroxyl radicals in the presence of water and UV. But make nanoparticles out of rutile titanium dioxide alone, and photocatalytic activity is reduced substantially.

However, even rutile titanium dioxide particles show some photocatalytic activity.  Early uses of rutile titanium dioxide as a white pigment in outdoor paint were plagued by the paint turning chalky after too much sun exposure. The problem was tracked down to hydroxyl radicals being produced and degrading the paint’s binder.  The solution: coat the particles with a material that prevents free radical formation—no more chalky paint, and coatings that will last for years in the fiercest sun.

Makers of titanium dioxide-based sunscreens use a similar trick to retain the functionality of nanoparticles while avoiding the potentially harmful photocatalytic properties. For instance Optisol—a UV blocking agent made by the company Oxonica—incorporates a minute amount of manganese into the crystal lattice of rutile titanium dioxide nanoparticles.  This doping allows the absorbed UV energy to be dissipated while virtually eliminating the formation of free radicals.  Not only does this make sunscreens using Optisol potentially safer; they also last longer in the sun, as there are fewer free radicals to break down other ingredients in the product.

So all looks rosy for nano-enabled sunscreens.  At least, it did until the publication of a recent paper.  And this is where we get back to pre-painted steel roofs. Since mid 2006, researchers in New South Wales Australia have noticed unusual defects developing in newly installed pre-painted steel roofs.  The damage is typically localized to areas of pressure contact, often taking the form of fingerprints or shoe impressions.  And it results in accelerated weathering—in one example, patches of a roof appeared to age an equivalent of 15 years in only 18 months. The culprit?  Nanoparticle-containing sunscreens, which are accidentally transferred to the roof during installation by touching or splashing.

In the paper “The interaction of modern sunscreen formulations with surface coatings,” [Progress in Organic Coatings62: 313:320. 2008] authors Phil Barker and Amos Branch systematically track down the underlying cause behind the unsightly blemishes.  Out of ten sunscreens tested—four containing no nanoparticles, five containing titanium dioxide nanoparticles, and one containing zinc oxide nanoparticles—all but one of the nanoparticle-based sunscreens consistently degraded samples of pre-painted roofing surface exposed to sunlight for 12 weeks.  In contrast, the non-nano products had no obvious deleterious effect.  In the worst case, the roofing lost over 85% of its gloss (a measure of degradation) in just six weeks.

Digging a little deeper, Barker and Branch pinned the effect to nanoparticles in all but one sunscreen acting as photocatalysts, and generating hydroxyl radicals in the presence of UV radiation and water.  Despite assumptions that nanoparticles in sunscreens are engineered not to produce significant amounts of free radicals, these products were generating them fast enough to significantly damage roof coatings in a matter of weeks!

So have we had the wool pulled over our eyes?  Are these supposedly benign nano-sunscreens we are slathering on our skin adding to our wrinkle-count before our time, and perhaps more besides?

Before jumping to conclusions, it is worth taking stock of what is known, and what is not.  While the study showed all but one of the nanoparticle-based sunscreens had some adverse effects on the roofing, these effects varied greatly between products.  The sunscreen using nano-zinc oxide particles led to a 55% reduction in gloss over 12 weeks, while in the worst case, a sunscreen containing 4% titanium dioxide led to a 95% reduction in gloss over 12 weeks.  Assuming that the reduction in gloss is associated with the formation of hydroxyl radicals (and the evidence presented by Barker and Branch arising from a logical sequence of laboratory experiments is pretty convincing), there is still uncertainty over how harmful these would be when generated on the skin of a sunscreen-user.  To cause damage, the hydroxyl radicals would need to penetrate deep into the skin and into cells before loosing their potency, and if the nanoparticles stay on top of the skin where they are supposed to, significant penetration may not occur.

Then there is the anomalous nano-sunscreen that didn’t show an appreciable effect.  A nifty piece of X-ray diffraction analysis in the Barker and Branch paper showed that the titanium dioxide nanoparticles in the roof-damaging sunscreens were an anatase/rutile mix, while the nanoparticles in the benign sunscreen were comprised of rutile titanium dioxide alone.  Clearly crystalline form matters, as Oxonica realized when they selected the less-active rutile form of titanium dioxide as the basis for Optisol.

This study demonstrates that it is possible to create nanoparticle-based sunscreens that do not generate significant amounts of hydroxyl free radicals.  But the bottom line here is that some nano-based sunscreens are being sold (in Australia at least) that contain photoactive nanoparticles which generate hydroxyl radicals in the presence of water and sunlight.  This raises questions about the impact of these products on users over time and, perhaps more significantly, their impact on the environment.  A photocatalytic titanium dioxide particle released into the environment will continue to generate hydroxyl radicals as long as it is exposed to UV radiation—because this is a catalytic process, the particle is not destroyed in the process, but just carries on doing its stuff; day after day, year after year.

But perhaps the biggest question here is one of regulation.  In the US, the Food and Drug Administration does not currently discriminate between anatase and rutile titanium dioxide particles in sunscreens, or doped and un-doped particles [Sunscreen Drug Products For Over-The-Counter Human Use: Final Monograph.  May 21 1999.  PDF, 144 KB].   This may change following further consultation on the use of nanoscale titanium dioxide and zinc oxide in sunscreens [see Sunscreen Drug Products For Over-The-Counter Human Use; Proposed Amendment of Final Monograph; Proposed Rule.  August 27 2007.  PDF, 424 KB].  But in the meantime, what is to stop manufacturers using potentially harmful forms of titanium dioxide in sunscreens?  And how will consumers be able to distinguish between companies that have got it right, and those that have not?

It seems that if we are not careful, nano-sunscreens could be making their mark on more than just pre-painted steel roofing.

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This post first appeared on the SAFENANO blog in June 2008

If you want proof that nano is mainstream, just pick up the U.S. May edition of fashion magazine “Elle.”   Sharing cover-space with Madonna is the latest article on nanotech and the beauty business.

Elle might not be your first choice of reading for cutting edge science, but Joanne Chen’s article “Small Wonders” is no slouch when it comes to conveying complex ideas in digestible bites.  Using beauty products as examples (from hair dryers to conditioners to anti-wrinkle cream), Chen takes the reader on a journey through the wonders and worries of nano.   As an exercise in making nanotechnology accessible, the article is a must-read.  

On the benefits of smallness:  

“Once downsized, common materials can take on almost supernatural powers.  Nanogold transforms into a catalytic agent and carbon, Clark Kent-like, suddenly acquires strength 100 times that of steel.”   

And on nanoscale liposomes: 

“If your liposome is your chunky, clunky well-loved first generation iPod, a nanosome is an nth-generation iPod, the hearing-aid size one that Steve Jobs will persuade you to buy in a few years. … But just as that little iPod of the future will inevitably get lost at the bottom of your F/W 2010 Balenciaga Giant purse, nanosomes could shimmy through the dermis, sliding into nerve endings, even into the blood cells, surfing their way through the circulatory system.”

Some dismiss nano-consumer products as trivial; even flippant. But for most people, this is where they will first encounter nanotechnology.  And it is these products that will mould their perceptions and opinions.  Pick up a nano-hair dryer that really works, and you have a nano-advocate.  But slap on a nano-cream that leaves you with nothing but worries, and nano-doubts begin to set in.  

These products are increasing rapidly in numbers and diversity—as Project on Emerging Nanotechnologies director David Rejeski noted while showing U.S. Senate Committee on Commerce, Science and Transportation Chair John Kerry a locally-purchased tube of nano-silver toothpaste yesterday.  The current tally of allegedly nano-enabled consumer products in the on-line PEN inventory is over 600; and these are just the tip of the iceberg.  Rejeski’s Ace Silver Plus Nano Silver Toothpaste is typical of many entries—using nanotech to “improve” an existing product, but with apparently little attention paid to whether the use is a good idea.

And this raises serious questions in the minds of consumers, regulators and many nanotech businesses.  What safeguards are there to ensure the nano-innovator next door (or South Korea in the case of the toothpaste) is asking the right questions about avoiding adverse impacts?  Not a lot is the answer.  Many nanotechnology industries are still floundering in a sea of uncertainty when it comes to ensuring product safety.  

Matthew Nordan, president of Lux Research, summed it up in testimony submitted to yesterday’s Senate Commerce Committee hearing: 

“Seven years after the NNI’s launch, it’s still unclear to most commercial entities when and how the materials they work with will be treated under the EPA’s Toxic Substances Control Act – forming a real commercialization gating factor.” [written testimony available here.  PDF, 192 KB]

Such uncertainty is bad for business, bad for consumers, and ultimately bad for nanotechnology.

As nanotechnology begins to rub shoulders with pop culture and awareness of its existence grows, more and more people will be asking what it can do for them, and what the down sides are. Yesterday’s hearing (focused on the reauthorization of the U.S. 21st Century Nanotechnology R&D act) asked what is needed to ensure the commercial success of nanotechnology.  And the answers came through loud and clear—understand and avoid risks ahead of the game, ensure transparency, and engage people.  

This month in Elle, nanotechnology just happened to be in the right place at the right time as it shared the cover with Madonna.  But awareness is definitely growing.  And as it does, people will want to know whether it is safe and effective.  

The question is, will we have the answers?  

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Trivia

• Madonna’s 1991 film “Truth or Dare”, documenting her Blond Ambition tour, was released as “In Bed With Madonna” in the UK and Australia.

• In 2004, nanotech commentator and fellow blogger Howard Lovy drew a link between Madonna and nanotechnology in the Salon article Nanotech angels.

• I am not a Madonna fan

Admit it-deep down, your don’t really believe people will be exposed to engineered nanomaterials.  After all, most nanomaterials will be made in enclosed reactors, handled as precious commodities where not a particle can be spared, and irreversibly incorporated into a bewildering array of products.  And those that do start their life as nanoparticles will clump together in the blink of an eye, becoming nano-no-more before anyone can breathe them, touch them or (goodness forbid) eat them!

At least, that is how the argument goes.  But how much if it is based on science rather than wishful thinking?  When Washington Post science writer Rick Weiss visited a nanomaterial production plant, he expected to see a pristine high-tech workplace.  Instead, he describes passing

“…through heavy doors into the … manufacturing area and the future looks a lot like the past. Men in grease-stained blue coats navigate catwalks atop hulking, two-story-tall spray-drying machines. Forklift drivers steer 55-gallon drums of chemicals from one area to another. Other workers attend to noisy milling operations, their face masks gathering a thin film of pale dust as they empty buckets of freshly made powders to be used in nanotech batteries and premium paints”.  (Rick Weiss, Washington Post page A01, April 8, 2006)

Talk to most people actually making engineered nanomaterials, and it quickly becomes apparent that reality is a lot messier than the clean room-like future of our dreams. And this is just in the production process.  How about those products designed to go onto the body, into the body, or out into the environment as nanostructured materials?  Clearly, exposure to these materials will occur; the challenge we face is surely to snap out of denial, and start to ask what the nature of the exposures will be, and whether they will lead to harm (realizing of course that not all nanomaterials are made equal, and some may be as “safe” as the air we breathe).

This is my first foray into the “blogosphere”, courtesy of the brave souls at SAFENANO, who are under the delusion that I may have something interesting to say!  Expect an eclectic commentary on all things nano over the coming months, with an emphasis on combating speculation with science.  Getting back to the issue of exposure, this first entry is accompanied by an article on SAFENANO that addresses the “myth” of particle agglomeration.  Do you think that rapidly agglomerating airborne nanoparticles will prevent exposure?  Read the article, and think again (or at least, let me know where I’m going wrong).  Of course, predicting what might happen from established science is a form of speculation in itself, and needs to be backed up by hard evidence of exposure.  But that’s a story for another day.

And for those of you still puzzling over the title of this entry, it’s an obscure reference to the person credited with planting the idea of nanotechnology in people’s heads, who’s autobiography-which if I remember correctly says nothing about nanotechnology-was titled “Surely You’re Joking Mr Feynman!”.

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This entry first appeared on the SAFENANO blog in October 2007