Friends of the Earth come down hard on nanotechnology – are they right?

by Andrew Maynard on June 8, 2010

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

1 Hilary Sutcliffe June 8, 2010 at 1:56 pm

Excellent Andrew this is very helpful indeed.

I suppose most of the more ‘applied’ research on sunscreens on the human body will have been done by companies, and wonder if this could be an area where businesses might be persuaded to share their testing data without any real IP issues? I know a few companies have done extensive work, which may well be included in some of the studies mentioned in the ‘positive’ list, but I am not sure.

Though I suppose because they are company funded studies, they may not even be considered to ‘count’ in terms of the body of evidence on safety. Which on the one hand is totally understandable because they could be seen to be or actually be biased, but on the other a waste of potentially useful information which can add to the collective knowledge about safety. I suppose this also relies on negative and positive studies being shared and a rationale for the use of a material if there are any negative associations.

Hmm, think I will ask the question.

2 Geoegia Miller June 15, 2010 at 1:19 am

Hi Andrew and other readers,

Sorry for the delayed response – for some reason our posted reply didn’t make it through last week.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

3 Jaydee Hanson June 15, 2010 at 11:33 am

Dear Andrew:

I guess you have been away from Scotland too long to remember that even bulk zinc oxide is NOT an approved ingredient in European sunscreens. My understanding is that it not approved because the companies have not provided the required safety data to the regulatory agencies.

Our organization and many others have petitioned the US FDA to take all of the nano sunscreens off the market until the FDA requires the sunscreen companies to present studies on the safety of the products they are using and for the companies submit the data to the FDA. Why aren’t you asking the companies for that data? Why not ask the FDA why they have not yet responded to our 2006 petition? As far as I know it is not the responsibility of the environmental groups to assure the safety of our sunscreens, but the companies and the FDA. They, not the environmental groups, have let the public down on this issue.

Jaydee Hanson
Policy Director
International Center for Technology Assessment

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