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Andrew Maynard

  • Ten things everyone should know about nanotechnology safety

    [2020Science]: Asked to conclude the Fourth International Conference on Nanotechnology, Occupational and Environmental Health in Helsinki this year, I rather rashly came up with the above title for my talk - thinking that I would find inspiration in the multitude of new research on nanotech safety being presented at the meeting.

    As it turns out, events conspired against me and I ended up unavoidably missing most of the conference!

    Faced with the tricky task of wrapping up a meeting that I had been embarrassingly absent from, I decided to share a rather more personal perspective on nanotechnology safety - my own reflections on things I think people should know.

    This list is far from complete, and is heavily biased towards workplace safety.  And given that it was prepared for a crowd of conference attendees who were most likely maxed out on nano and more interested in where the nearest bar was, it’s a little light on detail.

    Nevertheless, it is hopefully interesting and informative, and causes at least one person other than myself to stop and think afresh about how to ensure safety in the face of a new and rapidly developing technology.

    So without further ado, and in reverse order, here is my highly subjective list of ten things everyone should know about nanotechnology safety…

    10.  There’s no such thing as “nanotechnology safety”

    Actually, this isn’t quite true.  Nanotechnology safety is clearly an important and legitimate goal.  It’s just that when you get down to the business of protecting people and the environment, the big idea of “nanotechnology” can become more of a hindrance than a help.

    These are just two traps that discussing “nanotechnology safety” can open up:

    First, we have the problem of definitions.  If we are going to discuss “nanotechnology safety,” we need to know what we are talking about.  Unfortunately, the generally accepted definition of nanotechnology—“the understanding and control of matter at dimensions between approximately 1 and 100 nanometers, where unique phenomena enable novel applications” is what the US National Nanotechnology Initiative uses—is one of expedience, not of science.  It serves the purpose of stimulating new research and technology innovation in an exciting new area brilliantly.  But it doesn’t clearly define a set of products and processes that have common and specific safety issues; and it was never intended to.

    As a result, attempts to apply the generally accepted definition of nanotechnology to material and product safety ends up in a messy mismatch.  Materials that are probably benign come under suspicion, while others that we should be worried about potentially slip the net.

    Second, there is the problem of generalities.  The products of nanotechnology are infinitely varied; each behaves in a different way and potentially presents a different set of risks.  This is obvious when we think about it.  Comparing the potential benefits and risks of scanning tunneling microscopes, semiconductor chips and smart drugs (for instance) is nonsensical, even though each can legitimately be claimed as a product of nanotechnology.  The trouble is, focusing on “nanotechnology safety” seems to result in rationality by-pass sometimes, leading to the questionable assumption that nanotechnology presents a common set of safety problems, which can be solved by a common suite of safety solutions.

    In the extreme, this type of generalization can lead to experiences with one nanotech product being applied to others—safety concerns over titanium dioxide nanoparticles in sunscreens being driven by inhalation studies using carbon nanotubes for instance; or consumers potentially avoiding “nano” branded goods because they heard that “nanotechnology” isn’t “safe.”

    Perhaps more to the point though, nanotechnology—like most technologies—is safety-neutral.  It isn’t the technology so much as what is done with it that is important.  Which means that rather than talking about “nanotechnology safety,” it makes a lot more sense to talk about the safe handling, use and disposal of specific materials, products and processes that arise from its application.

    9.  We’re living in a post-chemistry world

    Having debunked the idea of “nanotechnology safety,” I should really talk about what might be important when it comes to working with and using the products of nanotechnology as safely as possible—because without a doubt, some of its uses will lead to new safety challenges.

    One class of products that raises some interesting safety questions is “nanomaterials”—materials engineered at the nanometer-scale so they exhibit scale-specific properties.  These materials are intentionally designed to do what they do because of their physical form, as well as their chemical makeup.  So it seems reasonable to ask whether what they look like at the nanoscale also leads to new safety issues.

    Of course, for physical form to be relevant to human health or the environment, the material first has to get to where it can do harm.  For people, this means that chunks of it need to be small enough to be inhaled, ingested, or penetrate through the skin.  No exposure—no harm.

    However, for nanomaterials that can get into the body, there will be some cases where their physical form—their size, shape, physical structure—can lead to them being dangerous above certain concentrations.

    But here’s the rub.  Over the past fifty plus years, we’ve got used to assessing the likely risks associated with materials by considering their chemistry alone.  As a result we have a bit of a blind spot when it comes to materials that are potentially harmful because of something more than just their chemical composition.

    This is a bit of an oversimplification of course.  In the field of occupational health we have had to deal with asbestos and other fibers that cause harm because of their chemistry and their physical form.  And it’s long been recognized that different sized airborne particles present different risks if inhaled.  But these are the exceptions rather than the rule, and there is still a tendency when assessing risks to ignore physical form, or to struggle with what to do with it.

    However, as engineered nanomaterials become increasingly sophisticated, this will need to change if we are to work with them safely.  We are living in a post-chemistry world, where functionality and safety depend on more than just what something is made of.  And if we are to ensure the safety of emerging engineered nanomaterials, we need to learn how to survive and thrive in this world.

    8.  Current understanding of nanomaterial risks has more holes than a Swiss cheese

    So we know that we might need a new perspective on the potential risks associated with engineered nanomaterials and how to manage them.  But here we hit a problem—when it comes to answering questions that seem to be important, there’s a distinct dearth of information.

    Quantifying the human health risks (for example) associated with a material—a normal step in ensuring their safe use—requires answers to many questions, including:

    • How can the material enter the body?
    • Where does it go and how does it change once it gets there?
    • What aspects of the material end up causing harm?
    • How much material is needed for serious harm to occur?
    • How should the toxicity of the material be assessed?
    • How will people end up being exposed to the material?
    • How should exposure be measured? And
    • Can exposures be adequately controlled?

    When it comes to new nanomaterials, these are just some of the questions we still don’t have complete answers to.  And they only address occupational exposures.  What happens when these same nanomaterials get out into the environment?

    If we are going to get a good handle on working safely with engineered nanomaterials and other products based on nanotechnology, these holes will eventually need to be filled.  And as the diversity and sophistication of engineered nanomaterials continues to grow, research into assessing and managing their possible risks will need to be well funded and strategically targeted if it is to keep up.

    7.  Engineered nanomaterials are accomplished shape-shifters

    It is probably something of an exaggeration to refer to nanomaterials as shape-shifters, but without a doubt, one of the big challenges of ensuring the safety of engineered nanomaterials is that their behavior changes depending on where they are, and where they’ve been.  A freshly minted nanoparticle may have a surface that is crammed full of highly active chemicals.  Ten minutes later, these chemicals may have lost their potency—with a resulting reduction in the material’s ability to cause harm.  Small particles may agglomerate with others to form large particles over time.  Or large agglomerates may separate out into smaller ones once inhaled.  Particles moving through the air might pick up a coating of other chemicals in their vicinity and, if inhaled, will behave differently to “naked” particles.  Nanoparticles in the lungs or blood may become shrouded in specific biological molecules that dictate where they go and how the body responds.  Nanoparticles may be suspended in liquids, compressed into pellets, or embedded in plastics.  Nanotechnology-enabled products may shed material that changes as it moves through the environment, and moves through the environment differently as it changes.  And nano-products disposed of at the end of their life may once again liberate nanomaterials that bear little resemblance to the stuff they were originally made of.

    In short, the qualities that make a nanomaterial potentially harmful change over the material’s lifetime.

    This complicates matters when it comes to ensuring safety.  Just because a nanoparticle in a workplace is considered safe, doesn’t mean that it will still be safe several steps down the road.  The converse is also true—a nanomaterial that needs to be handled with care in the workplace may be relatively benign after it has been incorporated into a product.

    There are no easy answers to dealing with this shifting risk profile.  But one thing is certain: If engineered nanomaterials are to be used safely, their potential for causing harm, and the means to manage this, needs to be considered across their life cycle.

    6.  The technology’s new, but that doesn’t make old safety practices redundant

    In the face of a new and, in some cases, radically different technology, there is a temptation for imaginations to go into overdrive and assume that these new technologies automatically demand new safety measures.

    Fortunately, even though we are facing a nanotechnology safety future that is complex and riddled with holes, we do have some tricks at our disposal for helping to ensure the safer handling of nanomaterials.

    It seems that established occupational hygiene practices go a long way to preventing exposures and reducing risks.  Guidance from the US National Institute for Occupational Safety and Health (NIOSH), BSI, the International Standards Organization (ISO) and others makes it very clear that by taking reasonable precautions with how materials are handled, control measures are established and workers are protected, the chances of something untoward happening are reduced substantially—even if hard data on a new material’s toxicity are lacking.

    Undoubtedly there will be situations where conventional practices don’t go all the way to ensuring the safe use of nanomaterials—just one more reason why more research is needed. But we do know that airborne nanoparticles can be removed from the air with conventional local exhaust ventilation systems; that air filters do a good job of reducing exposures; and that bad workplace practices increase the chances of harm occurring, whether the materials being handled are nanoscale or not.

    So the good news is that we don’t need to throw out decades of experience with working safely with nanomaterials.

    On the other hand, it’s probably not a good idea to be complacent—old tricks may work with new technologies, but probably only up to a point.

    And just to be clear, there is a world of difference between safe and safer.

    5.  Lower exposures mean lower risks

    Continuing the theme of old tricks, reducing risks through controlling exposure does seem to be an area where established wisdom has a role to play with engineered nanomaterials.

    As a rule of thumb, lowering exposure levels is likely to reduce potential risks from nanomaterials, even in the absence of hard toxicity data.  With few exceptions, the human health risks of materials tend to follow a general trend of increasing response with increasing dose.  There are subtleties here involving the shape of the relationship between dose and response, the period over which effects occur, how dose is measured and whether a dose exists below which no response is observed.  But these aside, most of our experiences with harmful agents—whether gases, liquids or particles—suggest that less stuff means lower risk.

    This is helpful when handling new engineered nanomaterials, because we can be reasonably sure that every step towards lowering exposures is a step in the right direction.  It means that equipped with the most basic exposure control technologies and an instrument capable of measuring some aspect of the nanomaterial concentration, potential risks can be reduced.

    But helpful as this approach to reducing risk is, there is a problem: how low is low enough?

    4.  Measurement without meaning is like a car without an engine

    If you measure the concentration of nanoparticles in a workplace—say you measure the number or mass of particles per cubic meter—what does that measurement mean?  And how can you use it to increase safety without impacting unnecessarily on operating costs?

    Exposure measurement is a tricky subject.  Numbers—hard data—can be comforting.  But without a clear idea of their relevance, they can also be misleading. A measurement of airborne nanomaterial concentration can be used to reduce exposure, but how far should it be reduced?  Alternatively, measurements can be used to try and eliminate exposure altogether.  But there’s always that lingering doubt that exposures are occurring below the instrument’s detection threshold.  And rather annoyingly, the lower the concentration of material an instrument will detect, and the harder it will be to get a zero reading.

    In other words, measurements without the means to interpret and use them are a bit like a car without an engine—pretty, but useless!

    The reality is that without guidance on how to interpret and act on them, measurements can cause more problems than they solve—especially if the cost of reducing exposures to some arbitrary level becomes prohibitively expensive.

    What would be helpful here is a benchmark against which exposure measurements can be assessed—a reference that enables measurements to be translated into actions.  Where solid risk-related data are available, these benchmarks are the exposure limits set by governments and other organizations familiar to any occupational hygienist.

    But what do you do in the absence of such limits?

    One option is to take a stab at estimating reasonable benchmark limits, based on the best available information. For instance, in “Nanotechnologies – Part 2: Guide to safe handling and disposal of manufactured nanomaterials,” BSI has recommended a series of rules –of-thumb, based on reasonably well-understood materials, which help establish working benchmark levels for new and untested materials.  The idea is that in the absence of any better information, exposure limits for analogous materials are used as a starting point.

    The methodology is rough and ready, and doesn’t sit well with every expert.  But at least it provides a useful way of assigning meaning to measurements; as long at the working benchmark levels do not become set in stone.

    3.  When the data run out – innovate!

    This question of measuring exposure in the absence of well-established exposure limits is just one part of a larger issue—how do you make smart safety decisions in the absence of good information?

    Even if we can use established practiced to lower risks, we are still faced with a barrow-load of unknowns and uncertainties that pull the rug out from under conventional approaches to quantifying and managing risks.  And even if did manage to fill in all the current knowledge-holes, the chances are that we would be facing a whole new set of uncertainties sooner rather than later.

    So what do we do – apart from panic?

    The answer is: Innovate! More than ever in the future, we will have to rely on new and innovative approaches to managing risks; ones that enable decisions to be made in the absence of hard data.  Something of this was seen in the observation that lower exposures mean lower risks—a concept that enables risks to be reduced even in the absence of toxicology data.  Yet more inventive approaches will be needed if engineered nanomaterials are to be used safely in a world where a science-based understanding of the risks looks increasingly like a Swiss cheese, no matter how hard we try.

    Vladimir Murashov and John Howard recently highlighted some possible innovations in the journal Nature Nanotechnology. Writing on essential features for proactive risk management, they discussed a number of ways to manage risk in a data-deficient world.  In particular, they stressed the need to consider “soft” (or qualitative) approaches to assessing and managing risks such as using expert judgment, and control banding.

    These recommendations are a good start.  But much more is needed if we are to learn to make smart choices in the face of uncertainty.

    2.  It’s good to talk

    The adage “a problem shared is a problem halved” is rather a trite one, but it does contain a grain of truth.  Where companies and workers face difficult challenges in ensuring the safety of their workplaces, drawing on the collective wisdom of the community can be a great boon.

    In their article, Murashov and Howard stressed is the need for global stakeholder cooperation in ensuring the safe use of engineered nanomaterials.  This makes perfect sense.  Safety shouldn’t be a competitive issue—it’s in everyone’s interest to share information and experiences that will prevent harm to people or the environment. Information sharing encourages faster, better solutions to challenges. It allows smaller outfits to tap into a wealth of experience and expertise that would otherwise be beyond their reach. And it reduces the chances of competitors making a mess of “nanotechnology safety” in a way that undermines the credibility of the technology as a whole.

    The good news is that people are talking—not as much as they should perhaps, but at least the lines of communication are open.  The NanOEH2009 conferences is a great example of information sharing, and there are many more—ISO and OECD initiatives for instance, and the work of the International Council On Nanotechnology.

    But I wanted to highlight one initiative in particular, in part because I had a small hand in the initial idea, but mainly because I think it has great potential to get the global nanotechnology safety community working together to find solutions to the challenges they face.  And that is the Good Nano Guide.

    Designed as a community forum and resource, this is developing into an important place for learning about other people’s experiences of working safely with nanomaterials, and for sharing your own.  As people begin to contribute to it and use it, it could turn into an open-access goldmine for know-how on working as safely as possible with engineered nanomaterials.

    1.  People matter

    And finally my number one thing that everyone should know about nanotechnology safety—people matter.

    This may seem simple, or obvious, but it’s something that can get left out of the equation all too easily.

    At the end of the day, human risk research is about protecting people from injury, disease and death, and ensuring a high quality of life.  It isn’t about the buzz of new discovery.  It isn’t about getting rich and famous.  It isn’t about making a profit.  And it isn’t about sustaining ideologies.

    All of these have their place, and in many cases are good and important.  But the primary focus of risk research should be the people it ultimately impacts.

    This is part of the culture of risk-based research professionals who have come up through schools of public health, government research labs and similar institutions.  It may get buried at times.  But generally there is that recognition that the rewards of the work are more safe and healthy people, and fewer injuries, diseases and deaths.

    (It goes without saying that a similar ethos exists for environmental risk research)

    But when it comes to nanotechnology risk research, I am concerned by the influx of researchers and decision-makers into the field that don’t come from this culture of focusing on people’s health and safety.

    This is a very personal perspective, and I may be wrong.  But it seems that with increasing interest in, and funding available, for nanotechnology-related risk research, there has been a shift in emphasis away from traditional risk-research experts and towards researchers with primary expertise in other areas—chemistry, materials science and drug development for example.

    This isn’t necessarily a bad thing.  But it does mean that research programs, strategies and policies are increasingly being influenced by people who lack a professional cultural bias toward focusing on the individuals their work and decisions will affect.

    That is not to imply that these people do not care—in many cases, they clearly do.  But without that ingrained culture of putting others first, I wonder whether there is a danger of nanotechnology risk research being driven more by political expediency and the promise of economic gain, and less by the need to protect people.

    If this isn’t the case, I am willing to stand corrected.  But if it is, we need to work out how to get people back at the center of the nano-risk enterprise.  This may need some careful thought over where research funding goes and how strategic research decisions are made.   But I suspect it will also rely on the willingness of the emerging nanotechnology safety community to rethink and reaffirm its values.

    At the end of the day, despite the clear economic and social justifications, getting nanotechnology “right” will be a hollow achievement if we end up neglecting the very people who will make its success possible.  Let’s hope we don’t.

    Originally posted at 2020science.org


  • Sunscreens and Alzheimer's - solid science or scare-mongering speculation?

    Originally posted on 2020 Science, 25/8/09:

    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!

    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

  • Is nanotechnology poised for the ride of its life?

    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 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.

    This post also appears on the 2020 Science blog

  • Nanoparticle exposure and occupational lung disease – six expert perspectives on a new clinical study

    The recent tragic account of seven Chinese workers suffering—apparently—from nanoparticle-induced lung disease, is likely to raise serious concerns with anyone potentially exposed to similar particles.  Yet without the benefit of insight from scientists and others working on nanoparticles and their potential health impacts, it’s hard to get a handle on the study’s broader relevance.

    When I first found out about the study, I asked six highly regarded experts familiar with the issues to share their thoughts on the work and its broader implications.  Their comments (below) reflect a range of perspectives and opinions, and hopefully provide a deeper insight into an important but far from conclusive piece of research.

    Professor Anthony Seaton MD

    Professor Seaton is a distinguished clinical physician specializing in occupational health, and a highly regarded expert on the potential impacts of inhaling airborne nanoparticles. He is currently emeritus professor in the Department of Environmental and Occupational Medicine at the University of Aberdeen.

    Although this paper has weaknesses, it contains a number of important messages. Essentially it is tragic story of a fatal industrial accident, from the rather sparse description in the text, consequent upon grossly inadequate health and safety measures in a workplace. A small number of unsophisticated young women and one man were exposed to a toxic mixture of dust and fumes in a small unventilated room and developed a progressive lung condition that has so far killed two of them and seriously disabled most. Similar episodes, almost always involving gases, have occurred in the past, but this one has unique features, notably the effect in causing effusion of fluid into the linings of the lung (the pleura) and heart (the pericardium), the finding of nanoparticles in the workplace and in the lungs and lung fluid of the workers, and the finding of a tissue reaction to particles in the lung lining. Most unfortunately, the authors were unable to obtain or report information on the chemical nature of the particles in the lungs or the workplace. While it remains an open question how far the illnesses reported were due to particles and how far to gases, it is my view that an important component must have been due to particles.

    But… the messages:

    1. It is not always known that a fume, by definition, comprises nanoparticles generated by heating. This process involved not only spraying of a powder but also heating of a plastic material and fume would undoubtedly have been produced (the authors describe “smoke”).
    2. Heating of plastics will produce any number of organic chemicals in particulate and gaseous form, depending on temperature and the chemistry of the plastic. Many of these are very toxic to the lung.
    3. In such circumstances, if the particles produced are insoluble, they are likely to be retained in the lung and other tissues. If also they have toxic surfaces, tissue reactions will occur, as apparently in this case.
    4. Such dreadful episodes can be prevented (and generally are prevented) by well-established occupational hygiene measures. Those who decry the attitude of governments in the West to “Health and Safety” need to be aware that our attitude results from many similar experiences throughout our own industrial revolution and even occasionally nowadays.

    So to me the message of this episode is that fumes and dusts are often toxic and if you ignore this, tragedies like this may occur. Appropriate workplace hygiene will prevent this in the nanotechnology industry as elsewhere. Please take note, and let’s not argue about whether this paper’s conclusions are right or wrong – that is not the message.

    Professor Günter Oberdörster

    Professor Oberdörster is considered by many to be the “father” of research into the toxicology of inhaled nanoparticles.  His group at the University of Rochester has led global research in this area for over two decades.

    This is clearly a case of a very complex exposure to a lethal mixture of reactive gases and particles of different chemistry and sizes, including nano-sized particles. But, even more importantly, this is a case of a tragic accident with fatal outcome due to extremely poor industrial hygiene conditions.  To blame the resulting severe pathology and fatalities categorically on “nanoparticles” that were present in a paint paste is scientifically unjustified.  There are a number of potential mechanisms that may have been at play, including the formation of highly reactive gas phase polymer compounds generated by the heating of the spray painted styrene boards combined with immediate formation of condensation aerosols of ultrafine particles (fume) of different larger agglomeration and aggregation states (smoke was visible).  Such freshly heat-generated condensation aerosols can cause highly toxic acute effects. Well known examples include metal fume fever and polymer fume fever, which are generally of a short-lasting nature, but fatalities have been reported following polymer fume exposures.  Fume exposures can also result in an adaptive state and thereby protect the organism from untoward effects of subsequent exposures, which has been described already in the early part of the last century in human zinc metal fume exposed workers (could this explain the many months long exposure duration, until it was too late for the Chinese workers?). Even seemingly harmless actions such as heating ski wax onto ski surfaces has resulted in severe ARDS [Acute Respiratory Distress Syndrome]-like effects due to inhalation of the generated fumes, requiring hospitalization. Thus, fumes of freshly-generated thermodegradation products are clearly a well-recognized occupational hazard, as well as a potential hazard to consumers (e.g., exposure to fumes from heated PTFE in household cooking and other appliances).

    In the tragic industrial accident in the Chinese factory reported here, the paint paste was described as a mix of many organic components that contained additionally nanoparticles of polyacrylate (~30nm) as did the collected dust, but neither detailed characterization nor pictures are provided. Are they identical to the nanoparticles found in fluids and tissues of the patients? Unfortunately, there is a complete lack of the characterization of the nanoparticles found in the effusion fluids and lung tissue, and no attempt was made to compare these to those contained in the paint and dust. Conceivably, when inhaled they could act as carriers of reactive gas phase constituents, or otherwise they could just signal a breakdown of epithelial barriers in the lung, which increased their biodistribution to interstitial, pleural and other sites where they were found, if indeed they were the same. Thus, the question:  “Did polyacrylate nanoparticles cause, or contribute to the cause of, the observed severe pathology, or are they just 'passive bystanders' in this complex mixed exposure scenario?” cannot be answered.  We simply do not know, but what is obvious is that proper industrial hygiene would have prevented such a horrific accident.  Given this clear message it is not obvious why the authors identify a need for "more studies on … prevention of the 'nanomaterial related disease' ". No, we do not need more studies on how to prevent future accidents like this one, just proper well-established common sense industrial hygiene measures will do that. And yes, we need to identify hazardous nanomaterials and the characteristics that make them hazardous; key is, however, to use readily available preventive measures to monitor and avoid exposure until we know better and are able to set scientifically founded safe exposure limits.

    This case should not be used to bedevil nanotechnology, and a conclusion that nanoparticles generically are to blame is very unfortunate.  Because of this, the paper is likely to make a big splash in the media. It is important that terrible incidents like this be published, despite the lack of rigorous scientific analysis that should have been included. Such accidents serve as warnings and grim reminders of the need for workers' protection, whether exposure to nanomaterials is involved or not. Indeed, earlier incidents of severe cases of organising pneumonia including fibrosis resulting in six fatalities in textile paint spraying operations occurred in the early 1990's in Spain (long before the awareness of media and scientists for "nano"). It should have been a strong message for the necessity of precautionary protective measures in paint spraying industrial applications.

    Professor Ken Donaldson

    A toxicologist specializing in workplace lung diseases, Professor Donaldson is one of the world’s leading authorities on the health impacts of inhaling airborne nanoparticles.  His group at the University of Edinburgh has conducted extensive research into the potential health impacts of inhaling nanomaterials.

    This is a puzzling case. There is no conventional particle exposure that does this kind of damage to the lungs. Not even long-term exposure to high levels of the most toxic dusts known. Even when asbestos affects the pleura it takes tens of years of exposure. In the past there was a report of a highly toxic, hot Teflon particle exposure from overheated frying pans where the particles had highly toxic free radicals on their surface that disappeared rapidly with time; that is a possibility here. The damaging exposure was clearly a toxic cocktail of particles and chemicals and so is a highly unusual case that sheds little light on the hazards from the vast majority of nanoparticles used in workplaces, which do not have a reactive surface. It may yet turn out that the particles are a by-product of the chemical reaction and not the main cause of the injury.  If a very toxic chemical exposure involves the formation of nanoparticles as part of its chemistry, which is quite possible, they may not necessarily be the main toxin; they could be just an epiphenomenon. I notice that the cell that was stuffed with particles seemed to be alive and well.

    Chemical exposures in the past might have produced nanoparticles but since no-one looked for them they may never have been implicated. In the current climate of concern over nanoparticles the reverse is true and there may be a rush to judgement implicating the nanoparticles in the adverse effects. I think the paper should never have been published without characterising the exposure and the toxicological reactivity of the nanoparticles before blaming the effects on them. If the effects were due to highly toxic short-lived free radicals on the particle surfaces then it informs a tiny sub-division of nanoparticles that really represent a chemical exposure and certainly no member of the public would ever get a substantial exposure to this material. A well-regulated workplace with proper controls would have prevented this accident. Therefore the paper by Song et al. demonstrates a failure of occupational hygiene and worker protection in the chemical industry, that happened to have involve nanoparticles, rather than a helpful insight into nanoparticle toxicology.

    Professor Vicki Stone

    Editor of the journal Nanotoxicology and a professor of toxicology at Napier University in Edinburgh, Professor Stone is a foremost expert on the mechanisms by which nanoparticles potentially interact with the body and cause harm.

    The publication by Song et al. claims to have identified evidence that nanoparticles can cause adverse health effects, specifically on the lungs of women employed in a poorly ventilated working environment.  Unfortunately the publication contains a number of flaws, which make this conclusion hard to believe or confirm.  Firstly, the cocktail of chemicals and particles to which the women were exposed was very complex, containing many substances which are potentially toxic.  This cocktail was poorly understood as the authors were unable to sample and analyse the actual cocktail mixture directly to determine the real composition.  This is often a problem with studies of this type, but usually authors would acknowledge the limitations that this lack of information imposes when trying to draw conclusions.  These authors do not seem to have fully appreciated these limitations causing them to jump to conclusions.

    The authors also showed some interesting pictures of particles within the lungs of these women.  However, they did not provide any evidence to show that these particles were derived from the working environment – this could have been achieved through microscopes that can analyse the particle chemical composition.  Humans constantly inhale particles from a wide variety of sources, including traffic, domestic and industrial pollution.  It is therefore important to confirm that these particles were gained specifically from the working environment before the fumes associated with their employment can be blamed for the health effects observed.

    Therefore, at this time, this paper does not effectively illustrate adverse clinical effects of nanoparticles in a worker population, but it does raise the issue that we need to be careful and vigilant in future.

    Dr. Rob Aitken

    Director of Strategic Consulting at the Institute of Occupational Medicine in Edinburgh and director of the SAFENANO initiative, Dr. Aitken has a wealth of experience addressing workplace safety and health.  He is a leading international expert in developing safe practices for working with engineered nanomaterials—including nanoparticles.

    This tragic event is a shocking example of what can go wrong if a proper care is not taken with basic industrial hygiene. There can be little doubt that these serious health effects have been caused as a result of a workplace exposure. The workplace, where a complex mixture of chemicals was being sprayed, and heating activities producing smoke being carried out, in an closed room with no effective ventilation and entirely inappropriate personal protective equipment seems inexcusable.

    However, the key question which remains unanswered at this time is “exposure to what?” The exposure assessment in the study is poorly described. It seems from the information provided that these unfortunate workers were handling a paste composed of a complex mixture including butanoic acid, butyl ester, N-butyl ether, acetic acid, toluene, di-tert-butyl peroxide,1- butanol, acetic acid ethenyl ester, isopropyl alcohol and ethylene dioxide and finally some type of nanoparticle,  30 nm in diameter. Although the authors describe the nanoparticles found as being polyacrylate, the characterisation within the study provides no clear information about either the nanoparticles’ composition or their quantity within the paint paste. The nanoparticles seem to have been found in the dust in the air but again no indication of the airborne concentration, or the proportion of the mass attributable to them.  Likewise, the same nanoparticles seem to have been found in the biological samples, but again there is no indication or estimation of in what quantity.

    On the evidence presented is not possible to say with any certainty that the nanoparticles in question caused the effects, and I suspect that on this basis alone the paper will be quickly dismissed by scientific communities.  However neither is it possible to say that they are not responsible, and the alarm that such a paper is capable of raising amongst a broader audience is not to be taken lightly.

    There are some parallels with earlier scares, most notably the infamous “magic nano” incident. Where the Chinese incident seems to be different is that there really are nanoparticles here, albeit of apparently unknown composition. However, just like the earlier event, it is not enough to point the finger of blame at other possible culprits, the seriousness of this event demands further investigation, no matter how difficult that is.

    Was this event caused by exposure to some type of nanoparticles? I don’t know, but it would certainly be ill advised to be too quick to dismiss the possibility.

    Dr. Kristen Kulinowski

    Dr. Kulinowski is Director of the International Council On Nanotechnology (ICON) at Rice University, and a global leader in developing safe and responsible nanotechnologies.  Under her direction, ICON has established the foremost on-line database of nanotechnology health and environmental impact research papers, and the GoodNanoGuide—an initiative to enable people share and develop the best possible practices for working safely with engineered nanomaterials.

    I was impressed by the exhaustive clinical detail presented by the physicians to support their case that exposures in the workplace resulted in harm to these women. What I would have liked to see is more analysis of the particles themselves and how they were produced. What are the particles made of? Is there any corresponding toxicity literature investigating the same particle types in animal models? Were the particles part of the paste or created by the spraying or drying process? Not clear.

    It's also not clear if the answers to those questions really inform the lessons we might draw from this incident. Whether these were incidental or manufactured nanoparticles is somewhat beside the point. The real tragedy here is that these workers could have been protected if a conventional chemical hygiene plan had been implemented that included a working ventilation system and personal protective equipment. Preventing inhalation of 30-nm nanoparticles can be as simple as the proper use of an inexpensive mask sold by your neighborhood home improvement store. But even this basic protective measure was not employed in this workplace.

    We can do better than this. A lot better. The tools are out there; it's up to us to use them.

    (Kristen has also posted further comments on the new study on the ICON blog)

    This post also appears on the 2020 Science blog

  • New study seeks to link seven cases of occupational lung disease with nanoparticles and nanotechnology

    A new study just 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 on the study on the ICON blog

    This post also appears on the 2020 Science blog


  • Industry critics give nanotechnology sunscreens the thumbs up

    [From 2020Science] 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 *** 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.

  • New carbon nanotube study raises the health impact stakes

    From 2020 Science:

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

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

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

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

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

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

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

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

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

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

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

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

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

     

     

  • Working safely with carbon nanotubes

    So you want to make or use carbon nanotubes, but you are worried about handling then safely.  What do you do?  The good news is that the UK Health and Safety Executive has just published an information sheet that addresses just this question.  Risk management of carbon nanotubes is (according to the blurb) “specifically about the manufacture and manipulation of carbon nanotubes, and has been prepared in response to emerging evidence about the toxicology of these materials.”

    But is it any good?  Here’s my initial take: [continued...]
  • Nanotechnology risk research, ten years on

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

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

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

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

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

    Kenny, Maynard et al. 1999

    The introduction to the report starts:

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

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


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

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

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

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

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

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


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

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

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

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

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

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

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

    Electronic applications

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

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

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

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

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

    Coatings

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

    Chemical-mechanical polishing using nanoparticle slurries.

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

    Drug delivery systems.

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

    Nanoparticle catalysts

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

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

    There has been little work in this field to date, so it is difficult to draw meaningful general conclusions from the published data. One of the reasons for this lack of data appears to be the difficulty in generating particles of standard and known size for use in in vitro studies. Particles used in both in vitro and in vivo studies have also tended to be relatively poorly characterised. Different effects both in vitro and in vivo have been observed with different sources of ultrafine particles, so the responses measured may be a function of the particle constituents rather than the particles per se. The differences observed have been attributed to the ability of particles with a particular composition to have different levels of free radical activity at their surface. Whilst there has been some work investigating synergy between acid aerosols and ultrafine particles (see below), there has been no work investigating the synergy between ultrafine particles and other potential airborne contaminants, e.g. allergens, VOC’s and bacteria. Some of the animal models used to demonstrate toxicological endpoints require exposure regimes which are far in excess of any possible exposure in humans (e.g.  6 hours a day, 5 days a week for 3 months). Therefore, the extrapolation of such health effect data to humans should be treated with some caution.

    Interest in possible health effects following inhalation of ultrafine particles is high at present, and research is beginning to follow this interest.  Inhalation toxicology has taken over from epidemiology over the past few years, and dominates the field at present.  Dose response relationships in rodents are being seen that indicate particle number or surface area to be more appropriate metrics than mass.  The possibility of ultrafine particles acting as vectors to transport  acids and metals to the alveolar region of the lung is also being explored.  However it is recognised that many of the current approaches being taken are lacking in various aspects, particularly regarding the significance of chosen endpoints and the characterisation of particle exposure, and a number of groups are now beginning to address these issues.  This is an area that is particularly ripe for good research proposals to sympathetic funding bodies. The need to fully characterise the particles used in exposure and inhalation tests, as well as those that people are exposed to in the workplace and environment, is well understood, although the right combination of technical skills to achieve this seems to be lacking in many establishments.  In particular there would appear to be significant scope for transferring analytical electron microscopy skills used in materials science and nanostructure analysis to the analysis of ultrafine aerosol particles.  There is also a recognised need for in-vitro test systems that allow cell cultures to be exposed to the aerosol, rather than a particulate suspension.  A small number of research groups are currently developing test systems allowing direct aerosol deposition.  Funding for fine particle research (PM2.5 sampling, and mass-based aerosol sampling) still dominates, but all aspects of ultrafine particle research are on the increase, and it is likely that the next few years will see significant funding opportunities and research in this area.  Driven by concerns over environmental exposure, together with the need to address exposure limits for nuisance dusts, there is increasing interest in examining the impact of ultrafine particle exposure in the workplace.

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

    Full quantification of ultrafine aerosol exposure in the workplace:

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

    Targeted epidemiology and toxicology studies.

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

    Instrumentation

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

    Control

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

    Exposure Limits

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

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

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

     

    Endnote

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

    References

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

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

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

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

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

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

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

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

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

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

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



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

  • Getting to grips with nanomaterial toxicity

    From 2020science.org:

    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.

    _______________________________
    Endnotes

     

  • Tough love for science and technology innovation

    From 2020science.org:

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

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

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

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

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

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

     

  • Navigating the minefield of airborne nanoparticle exposure

    From 2020science:

    Nanotechnology—like other emerging technologies—presents a dilemma:  If you're making new substances with uncertain health risks, how low is low enough when it comes to managing exposure?

    The issue is raised in the current edition of Nature Nanotechnology by Vladimir Murashov of the National Institute for Occupational Safety and Health (NIOSH), and former NIOSH-director John Howard.  But the question has been bubbling along for some time.

    And it’s an important one.  Uncertainty over safe workplace practices is bad news for nanotech businesses trying to do the right thing—especially small start-ups that don’t have the resources to work out their own bespoke solutions.  It’s not much better for regulators—as the gap between emerging technologies and solid information on their safe use widens, how do you craft new approaches to protecting people’s health and the environment?

    Back in 2007, the Environmental Defense Fund and DuPont released their Nano Risk Framework... The Framework places a heavy emphasis on pragmatic exposure-based decision-making.  In a nutshell, the message was: Use the best information available. And when that runs out, use every trick in the book to come up with the best possible benchmarks for qualitatively managing risk—until better information is available.  And do all this under “reasonable worst-case” assumptions.

    But the Nano Risk Framework stops short of providing practical guidelines on developing benchmarks for exposure assessment.

    This gap was neatly filled by a guidance document from BSI Inc—the British Standards Organization—in January 2008.  The “Guide to safe handling and disposal of manufactured nanomaterials” (BSI PD 6699-2:2007) takes the bold step of recommending starting exposure values for four different classes of nanomaterials—benchmarks for establishing exposure decision-points in the absence of anything else.  PD 6699-2 refers to them as Benchmark Exposure Levels, and couches them in enough caveats to make the most hardened lawyer proud.  A better moniker might have been Lifeline Exposure Levels—because they quite literally throw a lifeline to anyone completely at sea when it comes to making practical decisions on making sense of airborne nanomaterial exposure measurements.

    But the Benchmark Exposure Levels are based on assumptions and speculation, not hard science.  And while they are firmly grounded in recommendations within the Nano Risk Framework—using available information and reasonable worst-case solutions—they are, in the long-run, no substitute for quantitative risk assessment.

    This is one of the main concerns that Murashov and Howard have about the BSI guidelines in their Nature Nanotechnology commentary.  They argue that exposure limits should be based on generally accepted principles of risk assessment—and I agree with them.  But something is needed in the interim while these limits are established, otherwise the whole emerging technology enterprise is on dodgy ground!

    This is exactly what the Nano Risk Framework and PD 6699-2 address, and hopefully what additional guidance from organizations like the International Standards Organization, and even government agencies, will grapple with.

    But this brings us back to the original question—how low is low enough?  Because recommendations like “keep exposures as low as reasonably practicable” simply don’t cut the mustard without some sense of how to evaluate exposure, and what the numbers mean.

    PD 6699-2
    makes a good stab at helping industries develop internal pragmatic guidelines on how to use airborne exposure measurements when working with new nanomaterials.  Earlier this year, I took a stab at assessing the validity and utility of the Benchmark Exposure Limits for BSIthe full assessment is available here (PDF, 168 KB).  My conclusions: the benchmark levels are far from perfect, but they are a great starting point.

    Assuming that most readers will have better things to do than read through the 12-page assessment, here are the conclusions:

    If effective health and safety plans are to be implemented in research laboratories and workplaces generating and using nanomaterials, guideline exposure limits are essential.  In the absence of further information, the benchmark exposure levels presented in BSI PD 6699-2:2007 appear reasonable.  Furthermore, the context surrounding the levels—which is clearly stated in the document—allows people following the recommendations to adapt the levels to their specific circumstances, depending on the best available information.  In other words, they are not binding, but rather present a clear starting point for an informed process of setting relevant exposure levels.  And thus, where evidence exists to suggest that the benchmark exposure levels are overly stringent or not measurable for a given material, it is left to the discretion of the person setting the levels to adjust the accordingly.

    These suggested levels are not a substitute for workplace exposure limits, and do not remove the need for targeted research leading to the development of evidence-based limits.  But until such levels are developed, they fulfil a role that is essential to underpinning the development of safe and successful nanotechnologies.  As such, BSI should be applauded for publishing them.

    The bottom line here is that industry needs practical guidelines on safe workplace practices where hard information on risks is lacking, and at some point this will mean grasping the bull by the horns and providing advice on how to measure exposures, and what the numbers mean.

    Giving meaning to the numbers might simply require establishing rules of thumb for developing bespoke exposure levels.  Or it might require clear benchmark exposure levels to be suggested for different classes of materials (with suitable caveats of course).  Either way, there will be exposure data, and people will want to know what they mean, and what action to take as a result.

    In the long run however, hard data are still needed to underpin quantitative and authoritative risk assessment that will supersede interim qualitative measures.  And this of course means there needs to be a research plan, plenty of funding, and a willingness to translate new information into informed oversight.

    But that is a story for another day...

     ___________________________

     Note:  See also Rob Aitken's blog on the Murashov/Howard Nature Nanotechnology Commentary

  • Toxic particles and trivial pursuits

    From 2020science.org:

     

    First impressions of the ICON EHS Database Analysis Tool

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

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

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

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

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

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

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

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

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

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

     

     

  • Taking a fresh look at nanomaterials

    From 2020science.org:

    The Royal Commission on Environmental Pollution report on Novel Materials

    Imagine for one naïve moment that we have a pretty good handle on managing the environmental impact of existing manufactured “stuff”.  Then someone comes along and invents some “new stuff” that behaves very differently from the “old stuff.”

    How can we be sure that the frameworks and mechanisms in place for preventing harm to the environment will work for the new stuff?  And where they are strained to breaking point, how do we go about fixing the system?

    These are two questions addressed in a new report from the Royal Commission on Environmental Pollution—an independent British standing body established in 1970 to advise the Queen, government, Parliament and the public on environmental issues... Of course, because this is for the Her Majesty The Queen, phrases like “old stuff” and “new stuff” are conspicuous by their absence in the report—which instead addressed the rather more sophisticated-sounding issue of “Novel Materials in the Environment.”

    This is, in effect, a report on the challenges of avoiding adverse environmental impacts of engineered nanomaterials.  Coming four years after the seminal report from the Royal Society and Royal Academy of Engineering on nanoscience and nanotechnologies, it reflects both how thinking on the challenges and opportunities presented by engineered nanomaterials has advanced, and actions to ensure their safe use have not!

    The report itself draws on extensive interviews with experts around the world, and the depth and quality of the writing reflects this.  Perhaps not surprisingly, many of the recommendations arising from this process will be familiar to readers—the challenges haven’t changed that much over the years, and solutions still seem few and far between in many cases...

    [Follow the link to read more]

  • Nanotechnology and cosmetics

    From 2020science.org:

    UK Consumer Organization Which? Releases New Report

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

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

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

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

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

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

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

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

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

     

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