It looks like the US is heading for some serious action on addressing the safe development and use of nanotechnology-enabled materials, products and processes in 2011.  Reading through the just-released National Nanotechnology Initiative’s (NNI) Supplement to the President’s 2011 budget [PDF, 1.2 MB], there are some noteworthy inclusions:

• The US Food and Drug Administration (FDA) is requesting $15 million in 2011 to address nanotechnology environment, safety and health issues.  This is the first time that the agency has been listed in the NNI budget supplement as requesting nanotechnology-specific funding.  Previously hobbled in its approach to supporting the responsible development of nanotechnology because of a lack of funding, this should go a long way to help the agency get on top of critical oversight-related questions.  The requested funds will support laboratory and product testing capacity, scientific staff development and training, and collaborative and interdisciplinary research to address product characterization and safety.
• The US Consumer Products Safety Commission (CPSC) also joins the FDA in being part of the NNI budget cross-cut for the first time since the NNI was formed.  For 2011, the CPSC is requesting a much-needed $2.2 million to allow it to participate with other agencies in researching safety aspects of nanomaterials use in consumer products.  Planned work includes developing protocols to assess the potential release of airborne nanoparticles from various consumer products and to determine their contributions to human exposure; determining whether nanomaterials can be used for performance improvement in sports safety equipment such as helmets and kneepads without creating other health hazards; and expanding consumer product testing using scientifically credible protocols to evaluate the exposure potential from nanosilver in consumer products, with special emphasis on exposures to young children.
• The National Institute for Occupational Safety and Health (NIOSH) is requesting $16.5 million for nanotechnology safety research in 2011; over 5 times more than the agency’s 2006 nanotech budget, and $7 million above the estimated 2010 budget.  NIOSH has been leading the charge on developing safe workplace practices for handling engineered nanomaterials in recent years – and all on a shoestring budget.  This significant increase in funding should help the agency address critical research needs it been struggling to cover adequately, including much needed work on exposure measurement and characterization.
• The National Institute for Standards and Technology (NIST) budget for nanotechnology safety research is set to double, going from an estimated $3.6 million in 2010 to a requested $7.3 million in 2011.  The agency will target its nanotechnology safety program to measuring the dynamic physico-chemical and toxicological properties of key nanomaterials and the release of these nanomaterials during manufacturing processes and from products throughout full product life cycles.

When requests from other agencies are included, the 2011 budget request for targeted nanotechnology safety research across the federal government for 2011 comes to $116.9 million – three times the amount invested in 2006.

This is an extremely welcome move, and demonstrates that the US government is committed to investing in research that will underpin the development of responsible nanotechnology.

Back in 2006, I estimated that the US government needed to invest at least $106 million per year in research addressing short term nanotechnology safety issues.  More recently in 2008, I set out funding options for addressing critical nanotechnology safety needs – arguing that between $20 million and $100 million per year should be invested over and above existing funding at the time (around $60 million per year).  While I can’t take credit for the apparent convergence between recommendations and budget requests here, it is gratifying to see agency-wide investment come closer to what has been suggested is needed in order to make headway in underpinning responsible nanotechnology.

Interestingly, budget requests for five key agencies align reasonably closely with those 2008 recommendations.

EPA, NIH (specifically, the National Institute for Environmental Health Sciences) and NIOSH requests are not too far from what I estimated as a compromise research investment option that lay somewhere between the minimum and the ideal.  What is particularly encouraging though is the requests for NIST and FDA, which far exceed these estimated budgets.

Of course, these requests only tell half the story.  The other half concerns how the funds are spent, and whether they will enable significant progress to be made towards developing responsible uses of nanotechnology.  In the past, the NNI has been criticized for not having a robust nanotechnology safety research strategy and for being weak on supporting targeted safety research within mission-driven agencies.  While the jury is still out on the strategy, there is no doubt that the 2011 marks a significant shift towards supporting safety research within mission-driven agencies.  In 2006, 21% of the nanotechnology environment, safety and health federal research budget was associated with EPA, NIOSH and NIST. for instance  In 2011, that figure is projected to rise to 37%.

We’re not out of the woods yet on ensuring we have the information needed to develop and use new nanotechnology-based materials and products safely.  But it looks like the US is making progress.  And that’s good news for anyone hoping to see the emergence of strong nanotechnology-based solutions to a whole host of challenges.

Well I guess I set myself up good and proper – I should have realized that in asking people for their questions on nanotechnology safety last week, they would actually want answers!

Having failed miserably to compile a catalog of websites that provide clear and concise answers to the questions asked in last week’s blog (I gave up after the 6th question),  the least I can do is provide some my own answers.  So here they are…

This being a blog and it only being an hour ’till lunchtime,  the answers are rather brief and off the cuff.  Hopefully they are of more use than not.  But if something doesn’t seem right, please check it out – and let me know.

Before I begin though, I must thank the brave souls who did attempt to provide links to answers in the previous blog – thank you!

The Questions, and some Answers:

1.  What sort of nano budget does FDA have?

If you look at the National Nanotechnology Initiative budget – a compilation of US federal agency investment in nanotechnology – FDA does not have a specific nano budget.  That said, the agency does have a number of people working on regulatory issues associated with nanotechnology in general, and engineered nanomaterials specifically.  FDA also supports the National Toxicology Program in the US, which is investigating the toxicity of a number of engineered nanomaterials, and has its own labs at the National Center for Toxicology Research, which are involved in nanomaterial toxicity studies.  So while it is tough to get a handle on the agency’s nano budget, this doesn’t mean they are not working in the area.

2. With something like nanosilver, is it possible to design out the hazard while keeping the “benefits”?

This is a tough one.  It would be nice to be able to do this, and there may be some possibilities here.  The main way silver kills microbes is to release silver ions, which are toxic to many microbes.  Silver nanoparticles are useful in that they release ions (effectively they dissolve) faster than the same quantity of larger particles, and they can be added to a wide range of products.  There is also some evidence that the nanoparticles themselves might be harmful to microbes.  The big problem here is that you have to have the ions to be effective – and if you are releasing the silver ions into the environment, they could do more than just kill the microbes you want them to.  But if there was a way to limit the rate of release and ensure only the microbes you want to get rid of come into contact with the silver ions, it might be possible to reduce possible risks while increasing benefits.  Some of the smarter uses of silver as an antimicrobial seem to be taking this approach.  The thing we really don’t want to do here is release silver nanoparticles into the environment without much thought, where they will continue to release ions and potentially cause damage.

3. What are some of the most interesting nanoparticles found in nature (not manufactured in the lab)?

I guess it depends what is meant by “interesting.”  Certainly, nanoparticles are a fact of life, and were long before humans were around.  Anything that burns and many things that get very hot release nanoparticles – think fires and volcanoes.  Liquid sprays that contain small amounts of dissolved substances can also produce nanoparticles as they evaporate – sea spray for instance is a great source of nanoparticles.  And then you have reactions between different chemicals in the atmosphere that produce nanoparticles.  Photochemical smog is a great example of man-made atmospheric “nanoparticle factories.”  But nature was there before us – terpenes released by trees can form nanoparticles in the atmosphere (the blue haze associated with the Blue Ridge Mountains is a result of naturally occurring nanoparticles).  These are all certainly interesting nanoparticles.  But they usually differ from engineered nanoparticles in that they are usually complex mixtures of nanoparticles and other stuff.

4. When will we know if it’s safe enough? I understand toxicity eg nanotubes. Do we think we can mitigate? What is safe enough?

I’m afraid that “safe enough” is a question that only policy makers, citizens and others can answer.  Science can provide information on how safe – or how risky – something is.  But then it’s up to others to work out when this is okay, and when it is not.  When it comes to nanotechnology, the first step is dividing nanotech into specific materials and products, as each will present different safety questions – including how safe is safe enough.  For example, safe enough for a cancer treatment will be very different from safe enough for a baseball bat.  We then need to work on where the plausible risks are – the materials and products that are more likely to present safety issues that we are not set up to handle well.  Then, we can start to work out where the knowledge gaps are, and how to fill them.  Governments and industry around the world are a good way along this path, although there is a long way to go still before some products of nanotechnology can be deemed “safe enough.”  For instance, we still don’t have a good handle on how to use carbon nanotubes safely, or what the safety issues around developing nanoscale food ingredients are.  On the other hand, there are nanotech-related products that, on the current balance of evidence, appear to be reasonably safe – I would consider sunscreens using well-engineered nanoparticles of titanium dioxide and zinc oxide in this category.  The bottom line though is that we still need to work on defining what is safe enough, and identifying new safety issues that emerge as nanotechnology progresses.

5. Given the nano-size of the particles, are there any effective respirator filters to guard against inhalation?

Yes.  There are some unanswered questions here, but in general, respirator filters are better at capturing nanometer-sized particles from the air than larger particles.  It sounds counter-intuitive, but the secret lies in Brownian motion.  Smaller particles are batted around more than larger particles by air molecules, and as a result are more likely to collide with and stick to the filter fibers or membrane.

6. What do you feel the repercussions are for extended life through utilization of nanotechnology?

Interesting question.  I think there are profound implications associated with the possibility of extending life – especially extending the span of productive/high quality life.  And nanotechnology is one of a suite of technologies that could lead to significant extensions to lifespan. Yet I’m not sure that nanotechnology per se raises questions as much as the implications of extending life – no matter what the technology used.  In thinking about the “repercussions” (I prefer “implications”) of extending life more generally, a lot has been written on this.  The possible implications are both fascinating and challenging – ranging from the possibility of severe planetary over-population, to extreme (and divisive) divides between those with and without access to life-extension technologies, to the possibility of greater environmental and social awareness as people become more aware that they have to live with the consequences of their actions.

7. How are safety tests carried out in nano tech?

There are suites of toxicity tests that are used to determine the hazard associated with chemicals.  Which ones are used depend on the regulations governing the material and how it will be used.  For instance, the toxicology tests on a new drug are substantially more comprehensive than those that would be used on a new cosmetic.  Some of these use cell cultures – in vitro tests.  Some of them are able to provide an indication of hazard without cells, by probing the chemical nature of a substance.  In other cases, computer models are used to get a handle on how toxic a new substance might be.  Most toxicologists agree though that most of these tests only go so far in predicting how a new substance might harm humans, and at some point tests with animals are needed – in vivo tests.  There are moves around the world – and rightly so – to minimize animal testing, and to find alternatives where possible.  Unfortunately, when it comes to brand new materials such as some engineered nanomaterials, it is extremely hard to predict how these materials might behave in a living organism from modeling and cell cultures.  This problem is compounded by some established toxicity tests that have been devised for chemicals not working well for some nanomaterials.  So the toxicologists face a quandary – do they rely on non-animal tests that may not be adequate, and risk allow products on the market that could cause serious harm, or do they test these materials on animals, to minimize the chances of something bad happening?  It’s a tough question.  But the bottom line is that most people involved in ensuring people are not harmed by new products will use the best possible suite of tests to provide them with the best possible information on product safety.

8. Seems that (nano)tech is moving v.fast. Is there a risk that results of safety testing will be out-of-date as soon as printed? How to keep up pace?

This is a challenge for sure.  I don’t think that sound toxicity tests will be quickly out-dated.  But I do think that there is a danger of increasingly sophisticated engineered nanomaterials being produced and used before we have a good handle on how to evaluate their risks, and develop protocols for safe use.  I would argue that in order to keep pace with the technology we need to rethink how we approach safety:  We need to work out how to reduce possible risks before we have all the safety data (by reducing exposures for instance); we need to learn how to predict possible hazards, and work out how to engineer them out of products during development; and we need better ways of tracking new developments so that we can respond quickly to safety issues.  We’re making some progress here.  But we have a heck of a long way to go still.

9. Is it possible/ necessary to regulate the use of materials which don’t yet exist?

It’s tough to regulate something that doesn’t exist!  What we can and probably should do is to use regulation, and other forms of oversight, to create frameworks within which emergent risks will naturally be identified and addressed – more a set of principles than hard command and control regulation.  The trick here is not to think of regulations as a list of “do not’s”, but as sophisticated tools for reducing uncertainty and increasing safety as businesses develop new materials and products.

10. We all want safety decisions to be informed by sound science, yet decisions must be made (indeed are being made) now, in most cases with relatively little useful data. What’s the soundest way to approach such decision making?

The million dollar question, as new materials and products come along faster than the safety science can keep up!  I would argue that we always have to come back to evidence-based decision-making as the foundation of what we do here, but that we desperately need new tools for making decisions in the absence of hard data.  There are a number of approaches to this that are emerging.  Control banding for instance is an approach to reducing risks in the workplace in the absence of good exposure data, and may be extend-able to working with new nanomaterials.  Multi-Criteria Decision-Making is another approach that is being developed to make decisions where data are lacking, or where the data are complex.  Then there are a number of approaches to filling gaps in toxicity and exposure data when trying to develop safety guidelines for new materials.  So we have some tools in the toolbox here for making decisions in the absence of data.  But the reality is that, looking to the future, we are going to be increasingly faced with situations where the data are incomplete, or the evidence is complex, and we are going to have to get increasingly sophisticated with how we make decisions in these cases.

11. Are their any lessons learned (societal/ethical issues) from GM foods that could be applied to the engineering or mechanical manipulation of foods through nanotechnology?

Enough to fill a book is the answer I think.  I’ll just touch on a couple here though.  First, issues associated with nanotechnology is very different from the issues surrounding genetically modified foods, and it is dangerous to compare them too closely.  For one thing, while GM foods are reasonably well-defined, nanotechnology is an umbrella term encompassing a huge diversity of technologies.  But looking to the GM food debate (some would say debacle), two critical issues were perceived heavy-handed tactics from big industry, and a lack of transparency – it seemed that what people really didn’t like was companies making decisions on their behalf, then not telling them about it!  Looking to nanotechnology, there are a number of important lessons to be learned here about how to engage with people when developing and introducing a new technology, to ensure that it is what people want, that they understand the pros and cons, and that they have

12. What should consumers know about nano-foods that labels won’t tell them?

“Should” is a strong word.  But I do think that many people would like to know that they could find out more about how nanotechnology was being used in the foods they were eating – and I’m sure regulators would like a better handle on this as well.  In terms of information that would be useful, I think you have to look at the ingredients list – a simple “nano-inside” sticker is a non-starter as it contains no useful information, while possibly raising speculative and in many cases unsubstantiated concerns.  On that ingredients list, I think it would be useful to identify where something has been specifically engineered at the nanometer scale and added to the food to add value to the product.  This could simply be a case of adding a “n” before the ingredient – nSiO2 for instance.  But this in itself isn’t of much use to the user – without more information, they won’t be able to tell whether that “n” is a good thing, a worrisome thing, or nothing worth fretting about at all.    What I think would be far more helpful is finding a way to link from product labels to more detailed information on the web.  Imagine for instance that you could take a snapshot of the bar code on a product using your smart phone, and be taken to a database that let you know what was in the product and why.  This would be a farm more effective way of providing people who were interested with useful information on the nano in their food – if and when it gets there (and there are remarkably few food products on the streets that clearly and unambiguously contain engineered nanomaterials).  The good news is that this is a technology which is already gaining ground.

13. Nanotech pervades all sectors and there is a huge range in riskiness between the applications. How can we develop a meaningful triage system to prioritize sectors, product classes, products and materials with respect to safety?

Short answer – stop talking about nanotechnology, start talking about specific technologies and the products that use them, and make sure we ask scientifically plausible questions about potential risks, rather than being driven by speculation.  This is a huge issue – not just for nanotechnology – and more thinking is needed on how we begin to identify and address plausible safety issues, without being side tracked by questions that, while interesting, are more speculative than scientifically sound, and run the risk of distracting attention from more important issues.

14. How will we deal with imported nano products and how will we know they are nano?

With great difficulty I think.  Oversight of imported products – whether nano or not – is a major issue in today’s globalized market.  It’s a problem that has got regulators the world over worried.  Add nanotech in, and the problem becomes even greater – because now you have products with components that may lead to new safety issues, that do not have to be identified, and are not easy to detect!  I suspect though that part of the solution is to avoid getting too hung up on nanotechnology, and to start focusing on specific materials that raise new safety issues, and develop ways of detecting and overseeing the use of these materials.

15. What is the risk of NOT developing nanotech (in health care, environmental protection, economic development)?

I suspect that the answer to this question will differ wildly according to who answers it, but my opinion is that we cannot afford not to develop new technologies such as nanotech.  I would argue (and have done so on this blog) that the challenges facing humankind over the next 50 plus years cannot be solved using conventional technologies alone.  Access to nutritious food and clean water; disease treatment and prevention; clean, renewable energy – these are all challenges that we currently do not have the tools to address effectively.  Of course, nanotechnology is one of a number of emerging technologies that can help.  And any emerging technology-based solutions must be integrated with social, economic and conventional technology innovations if we are to ensure the focus remains on solving the problem rather than simply playing with the next new “technology toy.”  That said, I suspect that a failure to develop responsible and sustainable nanotechnologies will have a severe impact on people’s lives and the environment in the future.

16. What is the risk overall? Technology has not made us necessarily healthier and happier – although life expectancy has undeniable risen. Will the advances in 100 sectors be nullified by one “bad sector” (say nano use in weapons)?

I’m not sure you can talk about the overall risk of something as broad as nanotechnology.  Thinking as broadly as possible, there are risks associated with developing nanotechnology without appropriate checks and balances, just as there are risks associated with impeding its development at the expense of people who need food, water, medical treatment, energy…  But it’s far more useful to think about the pros and cons of specific applications of nanotechnology.  Of course, there is always that chance that, because we are working under this “brand” of “nanotechnology”  if something bad happens in one sector – say a new nano drug goes badly wrong – it will have a knock-on effect on other areas where nanotechnology is being used.  This is a possibility as so much has been lumped together under the banner of nanotech.  But I suspect that people are sophisticated enough not to stop using their nanotech baseball bat because the latest nano drug has problems.  Of course, this won’t stop equally sophisticated people from using nano-problems to push other agendas, if they see the opportunity.

17. We may need new bioassays. Can they be designed to simultaneously address animal welfare issues? Can they become models for use in non-nano contexts? Can there development be justified, financed and sped up on that argument?

As new toxicity testing challenges arise with some engineered nanomaterials, I see no reason why this cannot be used to stimulate further research towards minimizing the use of animals in tox testing.  In fact, I would argue that it is important that every opportunity is grasped to find more humane ways to evaluate material and product safety (this was something I highlighted as being important with my colleagues back in 2006 in a commentary in the journal Nature).  Nevertheless, I do feel it is important to ensure whatever assays are used, they lead to the use of products that will not end up inadvertently harming the user.

18. What is the difference between nanotech, biotech and synthetic biology?

Get ten experts in the same room, and they’ll give you at least twenty different answers to this one.  But here’s my take:  Biotechnology is a very broad technology that covers the use of biology in agriculture, food and medicine.  The term often refers to intentionally manipulating the genetic code of organisms – usually at a fairly crude level – to change them in ways that are perceived as being beneficial.  Nanotechnology is about engineering matter at a scale just a little larger than atoms and molecules, and taking advantage of the new and unusual properties that can result from such fine-level engineering.  Nanotechnology is often (but not exclusively) thought of as involving non-living materials.  Synthetic biology on the other hand is all about manipulating the genetic code of organisms at the nanometer scale, to either alter them in useful ways, or to create new organisms.  The truth of the matter is though that each of these terms is a clumsy shorthand for a continuum of science and technology innovation that is providing us with an increasingly sophisticated level of control over matter at the finest level – whether that be in living systems, dead systems, or combinations of the two.

19. Is there sufficient attention to the “soft science” of safety research? Governance, ethics, public relations, process research, organizational research, etc?

I would certainly argue that more need to be done here – much more.  Think about it – we live in a world where not only do we need to make decisions in the absence of information, but the very dynamics of decision-making the world-over are changing.  “Hard” science is not enough on its own to cope in this new world.  We also need to know how it fits in to a complex and shifting social, political and economic environment.  And for this, we need expertise in areas like engagement, governance, social decision-making, and a whole host of other “soft” areas.

20. The problem I have with the whole issue is that nanotech is not a “single” field, like polymers or vaccines, drugs or pesticides, say. Instead it’s a vast area of sci-tech defined rather arbitrarily by the size of the entities/particles involved. We need some way to ensure policy makers are not forced into a corner where they throw a blanket over all nanotech. How can that be achieved?

So true.  I think I touch on this a couple of times above, but somehow we need to decouple the products of nanotechnology from the brand of nanotechnology – so we can have science-informed dialogues on issues that are well-defined.  But how to do this?  We could start making sure that people have access to good information, and that they are fully engaged on the issue for a start.

21. How do we assess long term impacts in short term safety tests & decide it is safe enough?

The unfortunate truth here is that we still struggle to do this with non-nano substances, never mind the products of nanotechnology.  There are ways in which we can get a handle on what some long term impacts might be – the various assays for potential genotoxins, carcinogens etc. are helpful here for instance. But we still have a long way to go.  Maybe we should see this as an opportunity for engineered nanomaterials to stimulate some new ideas and approaches here.

22. Who is accountable if we do miss long term impacts?

Huge question.  I guess, depending on which country you are in, the lawyers would say whoever you can sue is accountable!  But beyond the possibilities of litigation, who is accountable for the impacts of decisions made – or not made – now?  Businesses developing new products are accountable to their shareholders and, perhaps surprisingly to some, their stakeholders in many cases – including customers (a number of businesses have strong value systems and codes of conduct that place stakeholders above shareholders).  This naturally leads to some degree of short to medium term accountability.  On the other hand, looking at government, it is hard to find any true accountability for the medium to long term consequences of actions – especially in an area like nanotechnology which cuts across so many departments and agencies.  Clearly, this is something that needs to be addressed.

23. What % of gov and business budget should be spent on safety?

A few years ago, a number of groups were arguing that 10% of the US nanotechnology research and development strategy should be devoted to health, safety and environmental impact-related research.  These days, I would argue that how the money is spent is at least as important as how much money is spent.  If you don’t start out with the right questions and a reasonable idea of how to get the answers, no amount of funding is going to get you to where you need to be.  That said, once you have a sound strategy, 10% of nanotech R&D is not a bad starting place.  A couple of years ago I was on a congressional testimony panel when a colleague from BASF was asked how much industry invest in ensuring the safety of a new product.  From what I remember, the answer was around 15% of the R&D budget.

24. How do we get companies to share their safety data to add to the body of evidence on safety?

Find mechanisms by which companies can share useful safety data without compromising their business, and develop trust and partnerships between businesses and other stakeholders to make data sharing easier.  This is a tough one though.  Most people in the business think it’s important and should be possible, but no-one’s come up with a viable solution yet.

25. When will 2020 Science learn to count?  (my apologies – realized after posting that I had missed four questions!)

Come off it, I’m a physicist.  Counting’s for engineers!

My apologies for the lack of links and citations here.  Time didn’t allow for more than a quick fire response – maybe this is something that needs to be added in at a later date.

I should warn you in advance – this is an interactive blog – there’s something I want from you!  I have a question – where do ordinary people go to get information on nanotechnology safety?

Feeling a little lazy I thought I would get you – the loyal 2020 Science readership – to help me out here.  Below are twenty questions on nanotechnology safety provided by folks on Twitter and FaceBook (okay so I’m using the term “normal people” in its widest sense).  What I would like is for readers to let me know which websites they feel best answer the questions.  This is how it’s going to work:

1. Pick a question – any question -  from the list below.
2. Do some Googling (you can use another search engine if you fancy).
3. Find a website that provides a decent answer (in your opinion) to the selected question.
4. Post the question number, the link, and anything else you would like to say, in the comments area of this post.
5. Go back to step 1 and repeat until hungry/thirsty/bored.

I’m curious to see whether people really can get satisfactory answers to their questions.  And if they can, which web resources seem to do the best job.  If enough people participate, I’ll post the results later.

So please pitch in – it’ll be fun, honest!

Cheers,

Andrew

And before I go – a big thank you to everyone who send me a question.  Great job.

_________________________

The Questions:

1. What sort of nano budget does FDA have?
2. With something like nanosilver, is it possible to design out the hazard while keeping the “benefits”?
3. What are some of the most interesting nanoparticles found in nature (not manufactured in the lab)?
4. When will we know if it’s safe enough? I understand toxicity eg nanotubes. Do we think we can mitigate? What is safe enough?
5. Given the nano-size of the particles, are there any effective respirator filters to guard against inhalation?
6. What do you feel the repercussions are for extended life through utilization of nanotechnology?
7. How are safety tests carried out in nano tech?
8. Seems that (nano)tech is moving v.fast. Is there a risk that results of safety testing will be out-of-date as soon as printed? How to keep up pace?
9. Is it possible/ necessary to regulate the use of materials which don’t yet exist?
10. We all want safety decisions to be informed by sound science, yet decisions must be made (indeed are being made) now, in most cases with relatively little useful data. What’s the soundest way to approach such decision making?
11. Are their any lessons learned (societal/ethical issues) from GM foods that could be applied to the engineering or mechanical manipulation of foods through nanotechnology?
12. What should consumers know about nano-foods that labels won’t tell them?
13. Nanotech pervades all sectors and there is a huge range in riskiness between the applications. How can we develop a meaningful triage system to prioritize sectors, product classes, products and materials with respect to safety?
14. How will we deal with imported nano products and how will we know they are nano?
15. What is the risk of NOT developing nanotech (in health care, environmental protection, economic development)
16. What is the risk overall? Technology has not made us necessarily healthier and happier – although life expectancy has undeniable risen. Will the advances in 100 sectors be nullified by one “bad sector” (say nano use in weapons)?
17. We may need new bioassays. Can they be designed to simultaneously address animal welfare issues? Can they become models for use in non-nano contexts? Can there development be justified, financed and sped up on that argument?
18. What is the difference between nanotech, biotech and synthetic biology?
19. Is there sufficient attention to the “soft science” of safety research? Governance, ethics, public relations, process research, organizational research, etc?
20. The problem I have with the whole issue is that nanotech is not a “single” field, like polymers or vaccines, drugs or pesticides, say. Instead it’s a vast area of sci-tech defined rather arbitrarily by the size of the entities/particles involved. We need some way to ensure policy makers are not forced into a corner where they throw a blanket over all nanotech. How can that be achieved?
21. How do we assess long term impacts in short term safety tests & decide it is safe enough?
22. Who is accountable if we do miss long term impacts?
23. What % of gov and business budget should be spent on safety?
24. How do we get companies to share their safety data to add to the body of evidence on safety?
25. When will 2020 Science learn to count?  (my apologies – realized after posting that I had missed four questions!)

If you ever wanted proof that the nanotechnology research community is floundering when it comes to safe working practices, look no further than a paper just published in the journal Nature Nanotechnology.  The paper, written by researchers at the Nanoscience Institute of Aragon (NIA) in Spain, surveys nanosafety practices in labs around the world.  Sadly, the flaws in the paper make the point that more needs to be done to raise safety awareness far more eloquently than its content.

The paper “Reported nanosafety practices in research laboratories worldwide” by Balas, Arruebo and Santamaria sets out to survey safety practices used in engineered nanomaterials research.  This is a critical area – anecdotal evidence suggests that good work practices are patchy in research labs, and that dismissive attitudes to safety or lack of awareness of recommended safety measures are not uncommon.  A survey of current safety practices that replaced anecdotes with hard data would have been extremely useful in helping raise the bar here.  Unfortunately, this is not that survey.

NIA is a nanotech research lab – its expertise is in creating new stuff, rather than assessing safety.  In fact the paper’s corresponding author Jesus Santamaria is the laboratory’s Vice Director.  In other words, NIA would have been a perfect participant in a safe practices survey.  But whether they have the necessary expertise to conduct such a survey is another matter entirely.

I would love to deconstruct this paper as I did the Daily Mail nanotech story on “Grey Goo” a few weeks ago.  But due to copyright I cannot reproduce it in full here, so that’s out.  Instead, I thought it would be interesting to extract a few of the key statements and recommendations the authors make, and see how they stand up to scrutiny:

“An online survey shows that most researchers do not use suitable personal and laboratory protection equipment when handling nanomaterials that could become airborne”

This is the top-level summary of the paper.  It’s a sub-heading that wouldn’t look out of place in a Tabloid newspaper.  And its impact hinges on two words – “most” and “suitable.”  Unfortunately, neither seem justified.

The paper reports the results of survey of people selected from the authors of nanomaterial-related publications published between 2007 – 2009.  240 surveys were completed – around 10% of those solicited.  Extrapolating these data to the entirety of nanomaterials researchers with that phrase “most researchers” is a large jump.  But more significant is the term “suitable.”

Out of all those researchers surveyed who thought the materials they were using might become airborne at some stage, 21% didn’t use any form of “special protection” and 30% didn’t use respiratory protection.  Yet there is no way of telling from the survey whether “special protection” (the authors’ terminology) was needed, or indeed whether any respiratory protection was needed.  A researcher handling small amounts of fumed silica for example – used as a food additive amongst other places – might well handle it using established lab safety procedures that are entirely adequate and don’t include the use of a respirator – in this survey they would be classed in the category of “most researchers” not using “suitabe personal and laboratory protection.”

“We find that only about 10% of researchers who are working with nanomaterials reported using nano-enabled hoods, and one in four did not use any form of general laboratory protection.”

The survey question associated with this statistic was “General laboratory safety during synthesis and handling: No special protection; local extraction on lab-bench; standard fume hood; fume hood with nanosized filters (i.e. HEPA); special “nano-safe” fume hood; Other.”

The jump from “no special protection” (which I would interpret as general lab safety procedures were used) to “did not use any form of genera laboratory protection” is eye-poppingly large, to say the least.  And without information on material quantities and characteristics, who knows whether “nano-enabled” hoods were in fact needed by all of these researchers?

“Despite knowing the materials they made could become airborne, about 30% of researchers did not use any type of personal respiratory protection.”

The associated survey questions were “May the nanomaterials become airborne at any stage of the synthesis: Yes; no; I don’t know?” and “Personal protection equipment when handling nanomaterials: None; mouth mask w/o filters; respiratory mask w. standard filters; full face shield w. filter; full body protective equipment; other?”

If a material became airborne in an enclosed part of the process, but not where exposure could occur, a respondent could easily answer “yes” to the first question and “none” to the second – placing them amongst the 30% alluded to.  And yet they would not have been acting inappropriately.

Around 90% of the respondents were either not aware of or did not think there were regulations at the local or national levels for handling nanomaterials… This is not surprising because only a few regulations on nanomaterials have been enacted.

Respondents were asked questions like “Are you aware of any international legislation for handling nanomaterials?”, “Is there applicable a State/Local legislation for handling nanomaterials?” and “Is there applicable a Federal/National legislation for handling nanomaterials?” As no such “legislation” for handling nanomaterials safely in laboratories exist, it’s not surprising that most respondents weren’t aware of them, or didn’t think they had been written.  I’m not sure what useful information was expected out of this question.  But it does worry me that the responses are presented to suggest a lack of awareness amongst researchers, rather than a lack of regulations.

“…nearly three quarters of respondents reported not having internal rules to follow regarding the handling of nanomaterials; approximately half did not have rules and 27.1% were not aware of any internal regulations.”

Despite the potentially confusing use of “rules” and “regulations” this is actually a useful piece of information.  The question was “Does your organization have an internal set of rules or handling nanomaterials: Yes; no; I don’t know?” One would hope that the answer was yes in most cases – clearly this is an area where more effort is needed.

“Regarding general laboratory protection measures, 24% of respondents did not use any type of protection, and 15.2% reported only using local extraction on the lab bench… Taken together this means that nearly 40% of researchers working with nanomaterials reported using none or only weak means of general laboratory protection.”

To recap, the question here was “General laboratory safety during synthesis and handling: No special protection; local extraction on lab-bench; standard fume hood; fume hood with nanosized filters (i.e. HEPA); special “nano-safe” fume hood; Other.” Looking at this, the statement made is patently wrong. “No special protection” is not the same as “did not use any type of protection.”  And local extraction on the lab-bench is not necessarily a “weak means” of control.  As a consequence, this statement is misleading at best.

“When it comes to the use of PPE [Personal Protective Equipment], about 48.8% of researchers reported not using any type of respiratory protection and 24.4% used a mouth mask without filters, which is clearly an ineffective form of protection.”

That 48.8% of researchers not using PPE includes researchers using materials unlikely to become airborne (according to the survey) – so it’s perhaps not surprising the figure is so high.  I’m still trying to work out what a “mouth mask without filters” is – not something I have ever come across.  If, as I suspect, the authors were envisaging a N95 respirator, authoritative organizations like NIOSH do not class this as “an ineffective form of protection.”

About 85% of researchers declared disposing of nanomaterials either without a special procedure (24.3%) or with the same procedure as for other chemicals (61.0%).  This seems at odds with the fact that 81% of researchers stated that nanomaterials should be treated as hazardous waste unless they are known to be non-hazardous.”

There is considerable confusion here, and it stems from an assumption that nanomaterials need to be disposed of in some unique way.  The associated question on the survey was “Do you follow a special procedure for disposing of nanomaterials?  No special procedure; the same as for other chemicals; yes, a special procedure designed for disposing nanomaterials; others?” In answering this, anyone who routinely treated nanomaterials as a hazardous material would answer “no special procedure” or “the same as for other chemicals” – which makes perfect sense.  The interpretation of the survey returns as indicating poor practices here does not hold up well to scrutiny.

51.7% of the researchers reported using the same Materials Safety Data Sheet irrespective of whether they were handling bulk or nanosized material”

The trouble is, 60% percent of researchers were synthesizing their own material, and so wouldn’t have associated Materials Safety Data Sheets – unless they wrote their own.

“Until widely accepted exposure levels and monitoring procedures become available, the general guidelines provided by reliable organizations should be immediately implemented.”

This makes sense – although some help on what defines a “reliable” organization would be useful.

“Finally, scientists should self-regulate, because they are the ones who decide how nanomaterials are handled in the laboratory and are ultimately responsible for implementing nanosafety practices.  One effective way to speed-up the adoption of safety precautions would be for journals to require a specific description of nanosafety measures within the methods or experimental section of all papers dealing with nanomaterials”

So, a survey that appears to suggest that scientists are doing a lousy job of working safely with nanomaterials in the lab suggests that self-regulation is the way to go. And to “enforce” this self-regulation, journals should impose a burden on authors that is not necessary when publishing work on a thousand and one other extremely noxious materials.  I’m still trying to get my head round this one!.

I really don’t want to slam this paper – safe lab practices for working with engineered nanomaterials are critical, and greater efforts are urgently needed.  At the same time though, it’s hard to see how questionable research like this will support progress. The trouble is, this survey seems to have been conducted by team who understand little about crafting effective questionnaires, and who have a poor grasp of what is relevant and what is not when it comes to working safely with engineered nanomaterials.

But here’s the irony – the inadequacies of the paper illuminates more eloquently perhaps than the survey itself that researchers in nanotech laboratories are out at sea when it comes to understanding safety issues: This particular group of asked the wrong questions, didn’t ask the right ones, and interpreted what they got back within a questionable framework.

Clearly, they need help.

And this is perhaps the strongest message to come out of the paper, inadvertent as it is – that more is needed and faster from “reliable organizations” on working safely with engineered nanomaterials in the lab – before someone does themselves an injury.

___________________________

I didn’t want to make a big deal of it above, but I found it worrying that on two of the questions in the supplementary information, the questions and answers are transposed.  What you have in is:

“If dry synthesis, please specify method: Co-precipitation; thermal decomposition; sono-chemistry; polymerization; reverse micelles; other”

“If wet synthesis, please specify method: Laser pyrolysis; CVD/PECVD’ mechanical attrition; electrical discharge; laser ablation; other”

Anyone involved in nanomaterial synthesis will spot that the wrong answers have been mateched with the wrong questions.  Hopefully this was just an error in the supplementary information, and the original survey was correct.  But I guess someone should check…

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

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

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

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

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

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

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

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

The authors of the paper conclude:

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

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

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

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

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

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

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

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

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

]]> http://2020science.org/2009/11/05/could-nanoparticles-inflict-harm-across-tight-cellular-barriers/feed/ 9 http://2020science.org/2009/09/14/nanotechnology-safety-ten-useful-resources/ http://2020science.org/2009/09/14/nanotechnology-safety-ten-useful-resources/#comments Mon, 14 Sep 2009 14:31:10 +0000 Andrew Maynard http://2020science.org/?p=2192

Where’s the best place to look for down to earth information on nanotechnology safety?  Surprisingly, given how much time I spend speaking and writing about the subject, I don’t think I have ever sat down and compiled such a list.  But while preparing for this year’s annual meeting of the Nanotechnology Informal Science Education Network (NISE Net) (surely the coolest nanotech meeting around by the way!) it struck me that such a list might actually be useful.

So here’s my first cut at some places you might want to look if you are interested in nanotech safety.

It’s by no means exhaustive, and it was compiled primarily to support my talk at the NISE Net annual meeting this week.  But it might be of some use – especially if you are interested in the subject, but don’t know where to start.

In putting the list together, I’ve tried to focus on papers and websites that are informative and trustworthy (in my opinion), that you don’t need a PhD in nanotoxicology to get something out of, and that are freely available. In each case, I have tried to provide some idea of what each resource covers, and who might find it useful.

There are bags more good resources out there – this is just a start.  But hopefully, it’s a useful one.

Nano & Me

Nano & Me

What is it? A website targeted at providing readers with clear and accessible information on nanotechnology.  Created by the UK-based Responsible Nano Forum and the Together Agency, and supported by the UK Department for Business, Innovation and Skills (BIS), it covers everything from what nanotech is, to where it’s being used.  The website’s coverage of safety issues is simple, clear and balanced.

Who should use it? Anyone who wants to know more about nanotechnology, but especially newbie’s to the subject.  No science required.

What I like about it: A slick website that puts the information you are looking for at your fingertips, without being condescending or confusing.  Highly recommended.

Link: http://www.nanoandme.org

Nanoscience and nanotechnologies: Opportunities and uncertainties

Royal Society

What is it? An influential 2004 review of the opportunities and challenges of nanotechnology, from the UK Royal Society and Royal Academy of Engineering. Chapter 5 provides an excellent overview of the potential risks presented by some products of nanotechnology, and is still relevant five years on.

Who should read it? The report was written for the UK government, but you don’t need a degree in science to understand it.  A slightly meatier read than the Nano & Me website.

What I like about it: Informed, authoritative, relevant and readable.

Link: http://www.nanotec.org.uk/finalReport.htm

Risk Assessment of Products of Nanotechnology (SCENIHR)

SCENIHR

What is it? A detailed technical report on the current state of the science on nanotechnology safety from SCENIHR – the European Directorate General for Health and Consumers Scientific Committee on Emerging and Newly Identified Health Risks.

Who should read it? This is a technical document, and will probably be more soporific than stimulating to anyone not steeped in nanotechnology safety research and policy.  But if you can get over this barrier, it contains a wealth of information.  There is also a lay version of the report available online though, that is well worth checking out.

What I like about it: Its depth and relevance.

Link: http://ec.europa.eu/health/ph_risk/committees/04_scenihr/docs/scenihr_o_023.pdf [PDF, 500 KB]

Nanotoxicology:  An emerging discipline evolving from studies of ultrafine particles.

Oberdörster, Oberdörster and Oberdörster,

What is it? A review paper on “nanotoxicology” written in 2005 by the father, daughter and son team of Günter, Eva and Jan Oberdörster.

Who should read it? Researchers, regulators, decision makers and anyone else interested in nanoparticle toxicity.  This is an academic review paper, so you probably wouldn’t want to read it if you only had a passing interest in nanotechnology safety.  But for anyone who isn’t scared of a bit of science, it provides an excellent review of the field that is still relevant four years on.

What I like about it: Günter Oberdörster is one of the foremost authorities on nanoparticle toxicity, and this paper expertly sets out the important questions surrounding nanoparticle toxicology.  Highly recommended reading.

Link: http://www.ehponline.org/docs/2005/7339/abstract.html

Nanoparticles, human health hazard and regulation

Seaton et al.

What is it? A recent review paper by Anthony Seaton, Lang Tran, Rob Aitken and Ken Donaldson that provides a unique and highly informative overview of nanoparticle safety from the perspective of the workplace.

Who should read it? Anyone trying to make sense of the possible risks presented by engineered nanoparticles, and how to avoid them.

What I like about it: Well-presented arguments that frame engineered/manufactured nanoparticle risks in the context of what is already known, and what still needs to be known.

Link: http://rsif.royalsocietypublishing.org/content/early/2009/08/31/rsif.2009.0252.focus.full

Approaches to Safe Nanotechnology: An information exchange with NIOSH

Approaches to Safety Nanotechnology

What is it? A compendium of information on nanotechnology safety in the workplace, from the US National Institute for Occupational Safety and Health.

Who should read it? Anyone responsible workplace safety. The report is also a mine of information for readers of all backgrounds who are interested in the safety of engineered nanomaterials.

What I like about it: A comprehensive and periodically updated evaluation of the state of the science on nanomaterial safety, from one of the world’s foremost workplace safety research organizations.

Link: http://www.cdc.gov/niosh/topics/nanotech/safenano/

National Nanotechnology Initiative website

National Nanotechnology Initiative

What is it? The official website of the US National Nanotechnology Initiative (NNI).  The website includes a section on environmental, safety and health aspects of nanotechnology.

Who should read it? Anyone interested in the US government’s take on nanotechnology safety.

What I like about it: It’s a window into what the US government – one of the leading funders of nanotechnology research and development – are doing in this area.

Link: http://www.nano.gov/html/society/EHS.html

International Council On Nanotechnology website

ICON

What is it? A multi-stakeholder organization set up by the Center for Biological and Environmental Nanotechnology (CBEN) at Rice University.  For info. on nanotechnology safety, check out the backgrounders, the news feed (also on Twitter) and the ICON blog.

Who should use it? The ICON backgrounders, blog and news feed are relevant to anyone interested in the latest developments in nanotech safety.

What I like about it: Comprehensive news on nanotechnology safety, and background papers that explain complex science in a simple way.

Link: http://icon.rice.edu/

SAFENANO website

SAFENANO

What is it? An information resource on nanotechnology safety, from the UK-based Institute for Occupational Medicine.  A great source of news, analysis and opinions.

Who should use it? Anyone interested in the latest on nanotechnology safety, with a focus on the workplace.

What I like about it: Down to earth information.  I also contribute to the SAFENANO blog though, so I might be biased!

Link: http://www.safenano.org/

2020 Science website

2020 Science

What is it? OK so this is a little self-serving, but I write so much about nanotechnology safety that I thought I should include 2020 Science here.  For a list of nanotech safety-related blogs, check these out, or start off with Ten things everyone should know about nanotechnology safety.

Who should use it? Anyone who wants to find out more about issues around nanotechnology safety.

What I like about it: Mmm, I don’t think I’m the best qualified person to answer that.

Link: http://2020science.org

In restricting myself to ten resources here, I’m sure I have failed to mention many that others would have included.  So if you have a publicly accessible website, paper or other resource on nanotechnology safety you think people would find useful, please do mention it in the comments below.

Update 09/15/09:  Linked screenshots to respective websites

There’s an absolute killer of a nanotechnology blog post over on placescope, if you are looking for something to brighten your day.  It appears to be based on some old Project on Emerging Nanotechnologies (PEN) press releases.  But the process of translation and re-translation has rendered them so wonderfully bizarre as to make any connection with the original piece entirely coincidental.

Some of the resulting turns of phrase are surely destined to become classics in nanotechnology circles.  But there’s plenty for non-nano affectionados to enjoy here as well, such is the genius of the writer.

The original article can be found here.  But rather than leaving you to plough through it on your own, here’s a guided tour of the juicy bits…

First though, a bit of context.  The piece addresses the regulation of engineered nanomaterials by the US Environmental Protection Agency (EPA), under the Toxic Substances Control Act (TSCA).  It harks back to a program the EPA started a couple of years back to encourage industry to provide information on the nanomaterials they are working on. Key characters in the piece (apart from EPA and TSCA) are J. Clarence (Terry) Davies, one of the original authors of TSCA and an expert on nanotechnology regulation, and David Rejeski, Director of the Project on Emerging Nanotechnologies.  And then there’s nanotechnology itself – but more of that later.  (I also make a cameo appearance, but much to my disappointment, I come across as reasonably sane).

All emphases in the quotes below are mine by the way.

The piece starts off on an positive note, referring to the EPA regulation formerly known as the Toxic Substances Control Act:

The U.S. Environmental Protection Medium (EPA) has published in the Federal Manifest its method for the Nanoscale Materials Stewardship Program under the Toxic Substances Hold back Act (TSCA).

This is followed by a decisive quote from the “Captain” of PEN, David Rejeski:

According to Project on Emerging Nanotechnologies (PEN) Captain David Rejeski, “The information obtained under the stewardship program could help government officials develop a cured understanding of the risks and benefits posed by the story materials.

Pondering how to help regulators cure their understanding (hopefully as in developing a better understanding, rather than treating a diseased one), Terry Davies adds:

Starting the stewardship program is a positive step toward padding in some of the news gaps facing the mechanism.

But then he throws caution to the wind, stating:

A sequential chat up advances will bugger off nanomaterials unregulated fitted afar too long, and choose also be less fruitful than if the two efforts proceed in tandem.

Strong stuff Terry!

The piece then moves back to EPA, and tackles the tricky issue of chemical ripeness:

In its announcement of the voluntary program, EPA also notes that it will not change its policy on what constitutes a unripe chemical under TSCA.

Reading this, I realize I have been under a misapprehension for years.  I thought that nanotechnology brought into question what constitutes a new chemical.  No wonder progress has been slow – I should have been talking to the agency about unripe chemicals all this time.  Doh!

The main article ends by summarizing the conclusions of a report published by PEN back in 2007:

The record recommends more than 25 actions that need to be entranced – by EPA, Congress, the President, the Public Nanotechnology Hustle, and the nanotech industry – to improve the blunder of nanotechnologies.

I’m still trying to work out what the Public Nanotechnology Hustle is – whatever it is, it better get on with improving those nanotechnology blunders!

To round things off, the piece includes some background information under the heading “Helter-skelter Nanotechnology,”  including a definition of nanotech that is worthy of the most exalted international standards committees:

Nanotechnology is the ability to measure, walk, manipulate and manufacture things usually between limerick and 100 nanometers. A nanometer is one billionth of a meter; a soul hair is roughly 100,000 nanometers wide.

It then has this to say about David Rejeski, who you will remember is the “Captain” of PEN, as well as director of the Foresight and Governance Project:

David Rejeski directs PEN and for the past four years he has been the Director of the Perspicacity and Governance Project at the Woodrow Wilson Center. He was a Visiting Fellow at Yale University’s School of Forestry and Environmental Studies and an agency representative (from EPA) to the White Dynasty Council on Environmental Quality (CEQ) … Earlier emotional to OSTP, he was head of the Future Studies Entity at EPA.

I must confess, I’m a little worried about the sound of this White Dynasty!

And what about the two organizations principally involved in the report I think is being reported on here – the Pew Charitable Trusts, and the Woodrow Wilson International Center for Scholars?

The Pew Well-wishing Trusts … is driven by the power of discernment to solve today’s most challenging problems.

What a delightfully quaint re-interpretation of Pew’s name, although I’m not sure they would see it that way!  And finally:

The Woodrow Wilson Cosmopolitan Center over the extent of Scholars … is the living, national memorial to President Wilson established by Congress in 1968 and headquartered in Washington, D.C. The Center establishes and maintains a noncommittal forum for free, undefended, and informed dialogue. It is a nonpartisan sanatorium, supported by public and private funds and engaged in the reflect on of national and global affairs.

Magical stuff!

Enjoy more from placescope here.

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.

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

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

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

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

Study Overview

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Additional resources:

GoodNanoGuide
A community resource for working safely with engineered nanomaterials

SAFENANO
Further information on the Song study

ICON Blog
Further comments and reflections on the study from ICON

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

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…

[More information on this study and its relevance can be found here]

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 posted further comments on the new study on the ICON blog)

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

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

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

Until now it seems…

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

This month’s issue of the magazine Science & Technology takes a closer look at some of the controversies, dilemmas and decisions that will impact on the future development of the science and technology of working at the nanoscale.  Amongst the commentaries is a short piece I wrote about the importance of safety in underpinning successful and beneficial nano-enabled technologies:

Science & Technology, June 2009, Page 66

Over the past few years, scientists and engineers have made huge strides in their ability to manipulate materials at the nanometer scale.  Tapping into novel properties that emerge when substances are engineered at the nanoscale, they have begun to push conventional technologies further than was previously thought possible.  And with this new-found dexterity, they are beginning to develop innovative new technologies that were unimaginable not so long ago.  The result is a rapidly emerging toolkit of scientific knowledge and technical expertise that could have profound economic and social impacts around the world; creating jobs and wealth while addressing challenges that range from disease treatment and prevention to renewable energy and clean water.

As with any new technology, however, the promise of nanotechnology comes at a price. When materials are engineered at the scale of atoms and molecules they can behave in unconventional ways—in effect, the rules that apply to non-nanoscale materials begin to break down.  This is what makes the technology so powerful.  But it raises the possibility of products that can also cause harm in unconventional ways, which may not be captured by the usual approaches to dealing with human health and environmental risks.  Unless these unconventional risks are understood and addressed, the future of nanotechnology could be dogged by uncertainties over safety and dwindling public trust.

Not every product of nanotechnology will present unconventional risks.  But if a nanoscale substance can get to places in the body or the environment that are normally inaccessible, and is able to elicit a response following exposure that is influenced by shape and form at nanometer dimensions, new questions need to be asked on how harmful the substance is and how it can be used safely.  Five years ago, these concerns were raised by the UK Royal Society and Royal Academy of Engineering.  Since then, numerous reports have reiterated and expanded on the challenges being faced to developing safe nanotechnologies.  Sadly, there has been substantially more talk than action.

Fortunately, there have been no documented cases of harm arising from exposure to engineered nanomaterials.  But an increasing body of research indicates that some of these materials are potentially harmful if used without due care.  Yet information is still lacking on what constitutes “due care” in many cases—especially with highly novel substances such as carbon nanotubes.  And while global research into the potential health impacts of engineered nanomaterials is increasing, it still falls far short of what is needed to underpin evidence-based decision-making.

Recently, the US National Academies of Science called for a national research strategy for nanotechnology risk research, drawing on the expertise and perspective of multiple stakeholders.  Coupled with adequate funding, such an approach could help bridge the gap between scientists and policy makers in developing safe nanotechnologies. Yet at the end of the day, even the best risk research strategies will not be of much use if the end users are suspicious of nanotechnology.

Experiences with genetically modified organisms have demonstrated the power of public opinion in determining whether a new technology succeeds or not.  And while the similarities between nanotechnology and GMOs may be slim, it is clear that in today’s hyper-connected world, consumers have an increasingly strong voice.  As a result, it is not sufficient to ensure the safety of nanotechnology-based products; public trust in the technology and the ability of government and industry to manage it safely must also be nurtured.

In many ways nanotechnology is a test-case for other emerging technologies.  Countries and economies around the world are increasingly dependent on technology innovation.  Yet the rules governing success are changing; driven by rapidly evolving global communications, ever-more pressing social and economic challenges, and an increasingly complex knowledge-base.  Proactive risk research and public engagement are key not navigating through this changing landscape.  Get them wrong and we face lost opportunities.  But get them right and there is a chance that nanotechnology—and other emerging technologies—will deliver what they promise.

Originally published in Science & Technology Issue 3, June 2009, pp 66-67

Download the original article [PDF, 312 KB]

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:

HSE recommends a precautionary approach for managing the risks of all carbon nanotubes. This is a good move.  The evidence so far—which admittedly is sparse—points towards all forms of carbon nanotubes being more harmful in the lungs than non-nanotube forms of carbon.  Of course, it depends on how you define “precautionary,” but “looking before you leap” seems a reasonable translation in this case.

No mention is made of possible exposure when working with carbon nanotube-containing products. HSE’s information sheet is clear that exposure to nanotubes can occur when making the stuff, when using it, and when researching its properties.  But there is no mention of what could occur when machining, grinding or cutting a product containing carbon nanotubes.  To be fair, research so far indicates that in most cases, once carbon nanotubes are embedded in a product they are unlikely to come out.  But if a precautionary approach is to be taken, it seems sensible to at least ask whether there is a chance that exposure to the material will occur while working with carbon nanotube-containing products.

The review of new evidence neglects particle-like effects in the lungs. The information sheet revolves around concerns over asbestos-like behavior and certain types of carbon nanotubes, which is understandable given the unpleasantness and latency period of diseases like mesothelioma.  But current research suggests that even clumps of carbon nanotubes that don’t look like asbestos fibers are more toxic if inhaled than might be imagined.  Last July, Anna Shvedova and colleagues published research showing that inhaling non asbestos-like single walled carbon nanotubes at concentrations currently recommended as safe by many manufacturers could be harmful.

In other words, it isn’t just asbestos-like behavior that we need to be concerned with here.

Use of carbon nanotubes appears to be discouraged in the absence of information on inhalation hazards. The information sheet states:

“HSE views CNT’s [carbon nanotubes] as being substances of very high concern.  Although the recent findings only apply to some CNTs we think a precautionary approach should be taken to the risk management of all CNTs, unless sound documented evidence is available on the hazards from breathing in CNTs.  If their use cannot be avoided, HSE expects a high level of control to be used.”

I may be reading this section wrong, but the message seems to be: If you don’t have a good handle on how harmful the substance you are using might be, don’t use it. But if you absolutely must, do everything possible to reduce exposures to a minimum. As there are no definitive data on carbon nanotube toxicity yet, this advice seems to boil down to the use of carbon nanotubes being discouraged.

Given the economic potential here, I’m interested in how this will play with industry.

Recommended qualitative risk management actions will reduce exposures… At the heart of the information sheet is advice on steps to reduce exposure to airborne carbon nanotubes when working with the substance.  These are solid, generic, good occupational hygiene practices—“use appropriate work processes,” “control exposures at source,” “make sure exposures are controlled at all times” etc.  And if followed, they should lead to fewer people being exposed to less material.  But I do wonder how practical some of them are for dealing with certain forms of carbon nanotubes—especially when it comes to working in fume cupboards and keeping material wet where possible.

…But there are few indications of “how much is enough.” Qualitative actions abound in the information sheet: “use appropriate work processes;” “provide suitable work equipment;” maintain “adequate control of exposure at all times.”  But such advice is hard to apply in the absence of any information on what processes are “appropriate,” how suitability is determined, and when “adequate control” is achieved.

I’m sure the point here is that any actions to reduce exposures are better than none.  But without quantitative benchmarks, the chances are that some people will be exposed to worryingly high levels of carbon nanotubes (under the “we tried our best” arguement), while others will struggle to obtain exposure levels that are needlessly low.

On balance, I have to commend the HSE on coming out with the information sheet on the ground that any information is better than no information, and I’m sure that some will find it helpful.  But I do worry that the information provided isn’t specific enough to either protect peoples’ health effectively, or provide nanotech businesses with the help they need to do the right thing without over-doing it.

And unfortunately, the document fails to provide links to other sources of information that may help remove some of the ambiguity (see some of the documents below for instance).

The bottom line here is that the information sheet is great for raising awareness, but seems to falls short of providing much in the way of practical advice.

Of course, I don’t actually have to make hard decisions on what exposures are acceptable for my employees, which controls to put in place, and how to assess their effectiveness.

Maybe if I did, my perspective would be different.

End Notes

I should note that I was asked to informally review a late draft of the information sheet last year.  I suspect I was too late in returning my comments though—the published document isn’t substantially different from my review copy.

For more substantive advice, I would recommend reading the document “Nanotechnologies – Part 2: Guide to safe handling and disposal of manufactured nanomaterials” from BSI Inc.  My review of it can be found here.

More detailed information on working safely with nanomaterials is also published by the US National Institute for Occupational Safety and Health.

Similar advice is available from the standards organizations ISO and ASTM International (see  Alphabet soup hides the secrets of safe nanotech! for further information)

Thoughts on applying Control Banding to working with nanomaterials can be found in this excellent paper by Sam Paik and colleagues.  While not dealing specifically with carbon nanotubes, it does develop a framework for making exposure control decisions:

Application of a Pilot Control Banding Tool for Risk Level Assessment and Control of Nanoparticle Exposures.  Paik et al. (2008) Annals of Occupational Hygiene 2008 52(6):419-428

Paik’s work forms the basis of safe handling guidelines recommended by the Institut de recherche Robert-Sauvé en santé et en sécurité du travail (IRSST), the Commission de la santé et de la sécurité du travail (CSST) and NanoQuébec.

Additional 2020 Science blogs addressing carbon nanotube safety:

• Carbon nanotubes: the new asbestos? Not if we act fast
• Resolving the carbon nanotube identity crisis
• Asbestos-like nanomaterials – should we be concerned?

]]> http://2020science.org/2009/03/17/working-safely-with-carbon-nanotubes/feed/ 1 http://2020science.org/2009/01/23/asbestos-like-nanomaterials-should-we-be-concerned/ http://2020science.org/2009/01/23/asbestos-like-nanomaterials-should-we-be-concerned/#comments Fri, 23 Jan 2009 21:53:33 +0000 Andrew Maynard http://2020science.org/?p=705

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Navigating the minefield of airborne nanoparticle exposure

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 Defence 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 BSI—the 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…

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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Notes

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

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

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

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This post first appeared on the SAFENANO blog in September 2008

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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This post first appeared on the SAFENANO blog in June 2008

The most recent estimate from the U.S. National Nanotechnology Initiative (NNI) puts nanotechnology risk research investment at $68 million for 2006 (the only year complete figures are currently available for—apparently).  Yet theProject on Emerging Nanotechnologies (PEN) has just completed its own assessment—and could only find $13 million associated with research projects primarily focused on addressing nanotechnology risk in the same year.  What gives—are the feds indulging in a bit of creative accounting; or have PEN forgotten the basic rules of arithmetic?

Let’s be honest, I’m not a great fan of bean-counting.  Evaluating research in terms of dollars invested (or Pounds or Euros) is a crude tool at the best of times.  But when it comes to assessing investments and returns, the fact is that bottom-line figures count.  

Faced with counting research dollars, organizations have two choices: use the figures to justify past performance, or employ them to inform future actions.  The former is the easy option—matching what was invested to what was done, rather than what should have been done.  But using past spending as a feel-good exercise is a disaster when it comes to future planning—because the assessment is invariably based on wishful thinking rather than reality.

Admittedly, the U.S. National Nanotechnology Initiative has taken a structured approach to evaluating investment in risk research.  As outlined in its recently-published nano-risk research strategy [PDF, 2.2 MB], nanotechnology risk research needs have been divided into five overarching areas; each consisting of five specific research priorities.  Research funded by the federal government in fiscal year 2006 (running from October 2006 to September 2007) has then been evaluated in terms of its relevance to these research priorities.  

The result: 246 projects that were identified as addressing nanotechnology risks in 2006.

From the report’s executive summary:
 

“In FY 2006, the Federal Government invested $68 million in 246 projects at seven agencies.  Although research categories were not prioritized with respect to each other, there is consensus among members of the NEHI Working Group that research in the Instrumentation, Metrology, and Analytical Methods category is cross-cutting, supporting research in every other category, and therefore is generally a high priority. Among the five research categories, the distribution of projects and spending was: 78 projects ($26.6 million) in Instrumentation, Metrology, and Analytical Methods; 100 projects ($24.1 million) in Nanomaterials and Human Health; 49 projects ($12.7 million) in Nanomaterials and the Environment; five projects ($1.1 million) in Human and Environmental Exposure Assessment; and 14 projects ($3.3 million) in Risk Management Methods. In short, the analysis demonstrated that the Federal Government is supporting more EHS research than has been previously identified, and the research is well-distributed across key priority areas.”

$68 million in one year sounds a lot.  But what does this mean—that all of these projects were dedicated to addressing critical knowledge gaps in the quest to develop safe nanotechnologies, or that 246 projects could somehow be justified as having some relationship to the five research categories?  The distinction is crucial—on the one hand you have a strategically important assessment; on the other, a justification for past actions.

Assessing the value and relevancy of research is not easy—as well as projects dedicated to addressing risk, there are those where risk research is a major component of a more general nanotechnology project; or projects supporting research that could be relevant to understanding risks—if it was applied in the right way.  

Reading through the government’s strategy document, I suspect that the NNI lumped all of these different types of research together without making clear distinctions.  For instance, when assessing research relevant to nanomaterials and human health, the NNI report states:
 

“Much of the research reported for FY 2006 focuses on medical applications. While this focus does contribute to the overall body of knowledge for human health effects, more systematic, targeted study of classes of nanomaterials and the relationship of their physical and chemical properties to biological response would provide better integrated data sets for risk assessment and risk management. These efforts should build upon the existing research whose primary focus is human health and safety.”

But how were these applications-focused projects evaluated in terms of their relevance to risk?  How well does the reported $68 million reflect research that will provide clear answers to well-defined risk questions, and to what extent (if at all) were nano-applications projects used to pad this figure?  Unfortunately, the report does not divulge this—just as it does not list project-specific funding that would enable an independent evaluation of the report’s assessment.

It is this lack of transparency that prompted the PEN analysis of risk-research funding for 2006.  Staring with the 246 projects listed in the NNI document (and removing those projects listed more than once), we matched the projects—where possible—to publicly available information on funding.  We then assessed the summary of each project (available on-line here), and determined whether the research being undertaken was highly relevant to addressing nanotechnology risks, substantially relevant, had some relevance, or was only marginally relevant.  We also classified the research in terms of whether it was primarily focused on engineered nanomaterials, or nanomaterials from other sources (incidental or naturally occurring).

Just to clarify; projects primarily focused on addressing nanotechnology risk (such as toxicity and exposure studies) were classed as being highly relevant.  Those focused on applications (or basic research), but with a major component addressing risk were classed as substantially relevant.  If a project was primarily focused on basic research or nano applications, but was generating information of direct use to understanding and addressing risks, it was classed as having some relevance.  And finally, research that could conceivably be useful to addressing risks—but only if there was increased investment in applying it to environmental health and safety implications—was classed as having marginal relevance.

The results of this exercise are freely available in the PEN Nanotechnology Environmental Health and Safety Research inventory – accessible here.  Although reproducing our assessment of the NNI-listed research is tough because the inventory contains a number of relevant projects that the federal government missed, the data can be searched and evaluated to give a reasonably clear idea of risk-relevant research funded in the U.S. and many other countries. 

Our classification of the NNI-listed projects is also available in testimony to the U.S. Congress House Committee on Science and Technology hearing on the National Nanotechnology Initiative Act of 2008, held 16th April 2008 [testimony available here].  This list contains estimates of annual funding for each project, and may be used to verify the PEN assessment of the NNI’s 246 risk-relevant projects.

And the assessment is revealing.  We could only find $13 million invested in research projects that were highly relevant to nanotechnology risk and received funding in 2006.  These are the projects that directly address environmental, health and safety impact. 

Including substantially relevant projects in the assessment brings this figure up to $29 million—still a little shy of the NNI-reported $68 million!

If these figures look low, take a look at the projects listed in Wednesday’s testimony and see whether the categorization looks reasonable.  To whet your appetite, here are examples of listed projects from each category:

Highly relevant: Example – Monitoring and Characterizing Airborne Carbon Nanotube Particles (NIOSH, Est. funding $400,000 over 3 years). [link to inventory record]

Substantially relevant: Example – Nanoparticles for efficient delivery to solid tumors (NIH, Est funding $333,084 over 3 years).  [link to inventory record]

Some relevance: Example – Nanoscale Science & Engineering Center for Integrated Nanopatterning and Detection Technologies (NSF, Est. funding $12,702,550 over 6 years).  [link to inventory record]

Marginal relevance: Example – National High Magnetic Field Laboratory (NSF, Est. funding $171,883,246 [not a misprint] over an estimated 6 years).  [link to inventory record]

I would be the first to agree that research in the areas of drug development and metrology—which account for many of the projects in the “substantial” and “some” categories—may be very beneficial to addressing risks.  But in the short term, this is not research that is going to answer the questions on the top of most people’s “urgent” list.  To pretend otherwise is like going to the doctor with a headache, and being told that there are millions of dollars being invested on research on cancer drugs that might also offer insight into the underlying mechanisms for head pains—when all you wanted was an aspirin!  

Fortunately, Europe seems to be a little more on the ball—in terms of honest reporting at least!  Risk research listed in the recent document “EU nanotechnology R&D in the field of health and environmental impact of nanoparticles” [PDF, 400 KB] lists projects that are almost all highly relevant to addressing risk (in my assessment at least).  And crunching the figures, you arrive at a European-wide investment in highly relevant nanotechnology risk research for 2006 of around $24 million—not far off twice the U.S. investment.  

These figures are also in the PEN inventory—for anyone to see and verify. 

The NNI’s $68 million may be a feel-good figure; it may be an attempt at international one-upmanship; or it may just reflect a naïve understanding of how to assess the true relevance and value of risk research.  Whatever the explanation, it does little to enable a true assessment of what still needs to be done to find answers to critical questions.

In terms of bean-counting to justify past performance or inform future actions, I have to conclude the NNI is guilty of the former.  The last sentence in the NNI quote above seems to confirm this: 

“In short, the analysis demonstrated that the Federal Government is supporting more EHS research than has been previously identified, and the research is well-distributed across key priority areas.”  

The PEN assessment provides in my opinion a much more honest perspective on what is and is not going on, that has the potential to inform future research strategies.  The good news is that it is also the basis for the OECD Working Party on Manufactured Nanomaterials international database on environment, health and safety research [further details here].  Hopefully the release of this database in June of this year will bring some much-needed transparency and accountability to what has so far been a less than transparent process.

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This post first appeared on the SAFENANO blog in April 2008

A trip through the newly refurbished St. Pancras station in London this week, and home to the widely-proclaimed “longest champagne bar in Europe”, prompted the following thought: At the champagne bar of modern science, are risk researchers the cappuccino drinkers tucked away in the corner?

I’m not sure how far I would dare push such an analogy, but sometimes it seems that scientists who focus on understanding and addressing risks have the less glamorous end of the deal. Attending the European Nanotechnology Occupational Safety and Health (NanOSH) conference in Helsinki, I was struck afresh by the difficulties of evaluating the relevance and importance of risk-related research.  The criteria usually used to assess exploratory and applications-focussed research don’t seem to fit comfortably here.  With some notable exceptions, risk research is more often than not evolutionary rather than original; it doesn’t tend to expand our fundamental understanding of the universe; and there are not that many examples of it making people fabulously rich.  Getting published in a high impact journal like Science or Nature is really tough if you are in the risk research business.  And health and safety Intellectual Property often seems, quite frankly, as common as the proverbial pot of gold at the end of the rainbow.

But does this mean—as some seem to believe—that risk research is somehow second-rate science?  Or is there a danger of applying the wrong criteria when assessing its value, and so coming to the wrong conclusions?

Most risk research is focussed specifically on solving problems and preventing harm.  Where it is successful, the chances of something unpleasant happening are reduced or removed.  On the way, it can be as innovative as other areas of research.  Yet original discoveries are often incidental to its main purpose.  The ultimate aim of risk research is not to be original or to make money (although both may be serendipitous spin-offs). Rather, it is to improve the quality of our lives and the environment in which we live—this is what drives many of its practitioners.

I suspect that this disconnect between the aims of risk research and the criteria under which research in general is evaluated has undermined the importance of investigations that aim to reduce possible harm.  Over the years, the risk research community has grown to accept a reality of meagre funding levels and marginal recognition outside those groups it immediately impacts on.

Yet as nanotechnology moves with increasing rapidity from the lab to the market place, misunderstandings that lead to risk research being evaluated against the wrong end-points are in danger of preventing the right work being done by those best qualified to direct, fund and undertake it.

The need for a strong risk-focussed research program to underpin safe emerging nanotechnologies is almost universally agreed on.  But as decision makers use a generic set of criteria to direct and evaluate risk research, it seems we become increasingly vulnerable to favouring projects that are innovative and profitable, over those that reduce the chances of harm occurring.  More than once, the sentiment has been expressed that nanotechnology risk research proposals are just not up to the mark.  Knowing the quality of researchers in this field around the world, and their struggles to obtain adequate funding, I can only assume this is a mark that is more relevant to exploratory and applications-driven research, rather than preventing harm.

Listening to the presentations in Helsinki, I found it hard to believe that the risk research community is not up to the task at hand.  Here were people that were systematically and expertly chipping away at the unknowns surrounding the safe use of engineered nanomaterials.  In many cases the research wasn’t flashy, it would not lead to IP, it “merely” led to an incremental understanding of potential to cause harm, and it wasn’t always original.  Placed alongside research into the next great nanotech applications, much of it would seem dull and unimaginative.  But none of this detracts from its importance to protecting the quality of life of people working with and using the products of nanotechnology.

Good science is good science, independent of the field of research.  Yet let’s not fall into the trap of confusing good science with original and profitable science.  Risk research may not be as sexy as other areas of research, but that should not prevent us from recognizing its importance or relevance.  Safe and sustainable nanotechnologies need the expertise and perspective of researchers trained in understanding and minimizing risks.  We cannot afford to marginalize them by evaluating what they do against the wrong criteria.  And we cannot afford to starve them by directing funds to more fashionable but less able investigators.

And just for the record, mine was a cappuccino.

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This post first appeared on the SAFENANO blog in December 2007

I have on my desk a plastic bag of carbon nanotubes—2 grams of dry, 60% purity single walled carbon nanotubes to be precise—bought from Cheap Tubes Inc. for the princely sum of $80.  And I am wondering what to do with them.

Despite the cosy assurances of the Manufacturers Safety Data Sheet that these are no more harmful than pencil lead, current research—which is admittedly sparse—is not so certain.  It seems that these thin long fibres can behave in rather unique ways, and not all of them are healthy.  So I am left with a dilemma:  Should I open the bag or not?  Should I put the nanotubes out with the rest of the office rubbish, or should I pour them down the sink?  Or perhaps I should get rid of them the way they came—in a United States Postal Service envelope (unmarked).  (I should note here that the Wilson Center is a policy organization, and isn’t well equipped to deal with hazardous waste).

The problem is, this is a product that anyone can buy, but there is little or no understanding of how to use and dispose of it safely.  I raised this concern at last week’s hearing of the United States Congress’ House Committee on Science and Technology, where I was testifying on nanotechnology environment, health and safety (EHS) research.  But in the course of the meeting, I was told that my fears are unfounded, and that the government has everything under control.

According to Floyd Kvamme, a venture capitalist and co-chair of the President’s Council of Advisors on Science and Technology (PCAST), research is showing that nanomaterials are safe—nanoparticles don’t affect soil, carbon nanotubes injected into the blood are filtered out by the liver, and nanodiamonds are great for delivering drugs.

It did strike me that the examples he cited might have been cherry-picked from the two thousand plus published studies on nanomaterial safety—studies that raise red flags on carbon nanotubes and other nanomaterials in the lungs; that suggest some nanomaterials might interfere with DNA and other proteins; that demonstrate nanoscale materials can get to places in the body other materials cannot; and that indicate particle size-related environmental impacts.

But then I thought: don’t be daft—this guy is a science advisor to the President of the United States!

Of course, the primary challenge is not to understand the risks of nanotechnology, but to develop products that are profitable—getting the “benefit-to-risk ratio” right in Mr. Kvamme’s words.  And here, his message was loud and clear: invest in the applications, and the risks will take care of themselves.

The only problem is, I still have these carbon nanotubes, and don’t know what to do with them…

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This entry first appeared on the SAFENANO blog in November 2007