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.

Andrew Maynard