Tag Archives: nanosunscreens

June 2016: time for a post on nanosunscreens—risks and perceptions

In the years since this blog began (2006), there’ve been pretty regular postings about nanosunscreens. While there are always concerns about nanoparticles and health, there has been no evidence to support a ban (personal or governmental) on nanosunscreens. A June 2016 report  by Paul FA Wright (full reference information to follow) in an Australian medical journal provides the latest insights on safety and nanosunscreens. Wright first offers a general introduction to risks and nanomaterials (Note: Links have been removed),

In reality, a one-size-fits-all approach to evaluating the potential risks and benefits of nanotechnology for human health is not possible because it is both impractical and would be misguided. There are many types of engineered nanomaterials, and not all are alike or potential hazards. Many factors should be considered when evaluating the potential risks associated with an engineered nanomaterial: the likelihood of being exposed to nanoparticles (ranging in size from 1 to 100 nanometres, about one-thousandth of the width of a human hair) that may be shed by the nanomaterial; whether there are any hotspots of potential exposure to shed nanoparticles over the whole of the nanomaterial’s life cycle; identifying who or what may be exposed; the eventual fate of the shed nanoparticles; and whether there is a likelihood of adverse biological effects arising from these exposure scenarios.1

The intrinsic toxic properties of compounds contained in the nanoparticle are also important, as well as particle size, shape, surface charge and physico-chemical characteristics, as these greatly influence their uptake by cells and the potential for subsequent biological effects. In summary, nanoparticles are more likely to have higher toxicity than bulk material if they are insoluble, penetrate biological membranes, persist in the body, or (where exposure is by inhalation) are long and fibre-like.1 Ideally, nanomaterial development should incorporate a safety-by-design approach, as there is a marketing edge for nano-enabled products with a reduced potential impact on health and the environment.1

Wright also covers some of nanotechnology’s hoped for benefits but it’s the nanosunscreen which is the main focus of this paper (Note: Links have been removed),

Public perception of the potential risks posed by nanotechnology is very different in certain regions. In Asia, where there is a very positive perception of nanotechnology, some products have been marketed as being nano-enabled to justify charging a premium price. This has resulted in at least four Asian economies adopting state-operated, user-financed product testing schemes to verify nano-related marketing claims, such as the original “nanoMark” certification system in Taiwan.4

In contrast, the negative perception of nanotechnology in some other regions may result in questionable marketing decisions; for example, reducing the levels of zinc oxide nanoparticles included as the active ingredient in sunscreens. This is despite their use in sunscreens having been extensively and repeatedly assessed for safety by regulatory authorities around the world, leading to their being widely accepted as safe to use in sunscreens and lip products.5

Wright goes on to describe the situation in Australia (Note: Links have been removed),

Weighing the potential risks and benefits of using sunscreens with UV-filtering nanoparticles is an important issue for public health in Australia, which has the highest rate of skin cancer in the world as the result of excessive UV exposure. Some consumers are concerned about using these nano-sunscreens,6 despite their many advantages over conventional organic chemical UV filters, which can cause skin irritation and allergies, need to be re-applied more frequently, and are absorbed by the skin to a much greater extent (including some with potentially endocrine-disrupting activity). Zinc oxide nanoparticles are highly suitable for use in sunscreens as a physical broad spectrum UV filter because of their UV stability, non-irritating nature, hypo-allergenicity and visible transparency, while also having a greater UV-attenuating capacity than bulk material (particles larger than 100 nm in diameter) on a per weight basis.7

Concerns about nano-sunscreens began in 2008 with a report that nanoparticles in some could bleach the painted surfaces of coated steel.8 This is a completely different exposure situation to the actual use of nano-sunscreen by people; here they are formulated to remain on the skin’s surface, which is constantly shedding its outer layer of dead cells (the stratum corneum). Many studies have shown that metal oxide nanoparticles do not readily penetrate the stratum corneum of human skin, including a hallmark Australian investigation by Gulson and co-workers of sunscreens containing only a less abundant stable isotope of zinc that allowed precise tracking of the fate of sunscreen zinc.9 The researchers found that there was little difference between nanoparticle and bulk zinc oxide sunscreens in the amount of zinc absorbed into the body after repeated skin application during beach trials. The amount absorbed was also extremely small when compared with the normal levels of zinc required as an essential mineral for human nutrition, and the rate of skin absorption was much lower than that of the more commonly used chemical UV filters.9 Animal studies generally find much higher skin absorption of zinc from dermal application of zinc oxide sunscreens than do human studies, including the meticulous studies in hairless mice conducted by the Commonwealth Scientific and Industrial Research Organisation (CSIRO) using both nanoparticle and bulk zinc oxide sunscreens that contained the less abundant stable zinc isotope.10 These researchers reported that the zinc absorbed from sunscreen was distributed throughout several major organs, but it did not alter their total zinc concentrations, and that overall zinc homeostasis was maintained.10

He then discusses titanium dioxide nanoparticles (also used in nanosunscreens, Note: Links have been removed),

The other metal oxide UV filter is titanium dioxide. Two distinct crystalline forms have been used: the photo-active anatase form and the much less photo-active rutile form,7 which is preferable for sunscreen formulations. While these insoluble nanoparticles may penetrate deeper into the stratum corneum than zinc oxide, they are also widely accepted as being safe to use in non-sprayable sunscreens.11

Investigation of their direct effects on human skin and immune cells have shown that sunscreen nanoparticles of zinc oxide and rutile titanium dioxide are as well tolerated as zinc ions and conventional organic chemical UV filters in human cell test systems.12 Synchrotron X-ray fluorescence imaging has also shown that human immune cells break down zinc oxide nanoparticles similar to those in nano-sunscreens, indicating that immune cells can handle such particles.13 Cytotoxicity occurred only at very high concentrations of zinc oxide nanoparticles, after cellular uptake and intracellular dissolution,14 and further modification of the nanoparticle surface can be used to reduce both uptake by cells and consequent cytotoxicity.15

The ongoing debate about the safety of nanoparticles in sunscreens raised concerns that they may potentially increase free radical levels in human skin during co-exposure to UV light.6 On the contrary, we have seen that zinc oxide and rutile titanium dioxide nanoparticles directly reduce the quantity of damaging free radicals in human immune cells in vitro when they are co-exposed to the more penetrating UV-A wavelengths of sunlight.16 We also identified zinc-containing nanoparticles that form immediately when dissolved zinc ions are added to cell culture media and pure serum, which suggests that they may even play a role in natural zinc transport.17

Here’s a link to and a citation for Wright’s paper,

Potential risks and benefits of nanotechnology: perceptions of risk in sunscreens by Paul FA Wright. Med J Aust 2016; 204 (10): 369-370. doi:10.5694/mja15.01128 Published June 6, 2016

This paper appears to be open access.

The situation regarding perceptions of nanosunscreens in Australia was rather unfortunate as I noted in my Feb. 9, 2012 posting about a then recent government study which showed that some Australians were avoiding all sunscreens due to fears about nanoparticles. Since then Friends of the Earth seems to have moderated its stance on nanosunscreens but there is a July 20, 2010 posting (includes links to a back-and-forth exchange between Dr. Andrew Maynard and Friends of the Earth representatives) which provides insight into the ‘debate’ prior to the 2012 ‘debacle’. For a briefer overview of the situation you could check out my Oct. 4, 2012 posting.

Finding a way to prevent sunscreens from penetrating the skin

While nanosunscreens have been singled out for their possible impact on our health, the fact is many sunscreens contain dangerous ingredients penetrating the skin. A Dec. 14, 2015 news item on ScienceDaily describes some research into getting sunscreens to stay on the skin surface avoiding penetration,

A new sunscreen has been developed that encapsulates the UV-blocking compounds inside bio-adhesive nanoparticles, which adhere to the skin well, but do not penetrate beyond the skin’s surface. These properties resulted in highly effective UV protection in a mouse model, without the adverse effects observed with commercial sunscreens, including penetration into the bloodstream and generation of reactive oxygen species, which can damage DNA and lead to cancer.

A US National Institute of Biomedical Imaging and Bioengineering (NIBIB) Dec. 14, 2015 news release, which originated the news item, expands on the theme (Note: Links have been removed),

Commercial sunscreens use compounds that effectively filter out damaging UV light. However, there is concern that these agents have a variety of harmful effects due to penetration past the surface skin. For example, these products have been found in human breast tissue and urine and are known to disrupt the normal function of some hormones. Also, the exposure of the UV filters to light can produce toxic reactive oxygen species that are destructive to cells and tissues and can cause tumors through DNA damage.

“This work applies a novel bioengineering idea to a little known but significant health problem, adds Jessica Tucker, Ph.D., Director of the NIBIB Program in Delivery Systems and Devices for Drugs and Biologics. “While we are all familiar with the benefits of sunscreen, the potential toxicities from sunscreen due to penetration into the body and creation of DNA-damaging agents are not well known. Bioengineering sunscreen to inhibit penetration and keep any DNA-damaging compounds isolated in the nanoparticle and away from the skin is a great example of how a sophisticated technology can be used to solve a problem affecting the health of millions of people.”

Bioengineers and dermatologists at Yale University in New Haven, Connecticut combined their expertise in nanoparticle-based drug delivery and the molecular and cellular characteristics of the skin to address these potential health hazards of current commercial sunscreens.

The news release then goes on to provide some technical details,

The group encapsulated a commonly used sunscreen, padimate O (PO), inside a nanoparticle (a very small molecule often used to transport drugs and other agents into the body). PO is related to the better-known sunscreen PABA.

The bioadhesive nanoparticle containing the sunscreen PO was tested on pigs for penetration into the skin. A control group of pigs received the PO alone, not encapsulated in a nanoparticle. The PO penetrated beyond the surface layers of skin where it could potentially enter the bloodstream through blood vessels that are in the deeper skin layers. However, the PO inside the nanoparticle remained on the surface of the skin and did not penetrate into deeper layers.

Because the bioadhesive nanoparticles, or BNPs are larger than skin pores it was somewhat expected that they could not enter the body by that route. However, skin is full of hair follicles that are larger than BNPs and so could be a way for migration into the body. Surprisingly, BNPs did not pass through the hair follicle openings either. Tests indicated that the adhesive properties of the BNPs caused them to stick to the skin surface, unable to move through the hair follicles.

Further testing showed that the BNPs were water resistant and remained on the skin for a day or more, yet were easily removed by towel wiping. They also disappeared in several days through natural exfoliation of the surface skin.

BNPs enhance the effect of sunscreen

An important test was whether the BNP-encapsulated sunscreen retained its UV filtering properties. The researchers used a mouse model to test whether PO blocked sunburn when encapsulated in the BNPs. The BNP formulation successfully provided the same amount of UV protection as the commercial products applied directly to the skin of the hairless mouse model. Surprisingly, this was achieved even though the BNPs carried only a fraction (5%) of the amount of commercial sunblock applied to the mice.

Finally, the encapsulated sunscreen was tested for the formation of damaging oxygen-carrying molecules known as reactive oxygen species, (ROS) when exposed to UV light. The researchers hypothesized that any ROS created by the sunscreen’s interaction with UV would stay contained inside the BNP, unable to damage surrounding tissue. Following exposure to UV light, no damaging ROS were detected outside of the nanoparticle, indicating that any harmful agents that were formed remained inside of the nanoparticle, unable to make contact with the skin.

“We are extremely pleased with the properties and performance of our BNP formulation,” says senior author Mark Saltzman, Ph.D., Yale School of Engineering and Applied Science. “The sunscreen loaded BNPs combine the best properties of an effective sunscreen with a safety profile that alleviates the potential toxicities of the actual sunscreen product because it is encapsulated and literally never touches the skin.” Adds co-senior author, Michael Girardi, M.D. “Our nanoparticles performed as expected, however, these are preclinical findings. We are now in a position to assess the effects on human skin.”

So, all of this work has been done on animal models, which means that human clinical trials are the likely next step. As we wait, here’s a link to and a citation for this group’s paper,

A sunblock based on bioadhesive nanoparticles by Yang Deng, Asiri Ediriwickrema, Fan Yang, Julia Lewis, Michael Girardi, & W. Mark Saltzman. Nature Materials 14, 1278–1285 (2015) doi:10.1038/nmat4422 Published online 28 September 2015

This paper is behind a paywall.

Safer sunblock and bioadhesive nanoparticles from Yale University

The skin has a lot of protective barriers but it’s always possible to make something better so a sunblock that doesn’t penetrate the* skin at all seems like it might be a good thing. Interestingly, this new sunblock or sunscreen is enabled by nanoparticles but not the metallic nanoparticles found in what are sometimes called nanosunscreens. From a Sept. 29, 2015 news item on Nanowerk,

Researchers at Yale have developed a sunscreen that doesn’t penetrate the skin, eliminating serious health concerns associated with commercial sunscreens.

Most commercial sunblocks are good at preventing sunburn, but they can go below the skin’s surface and enter the bloodstream. As a result, they pose possible hormonal side effects and could even be promoting the kind of skin cancers they’re designed to prevent.

But researchers at Yale have developed a new sunblock, made with bioadhesive nanoparticles, that stays on the surface of the skin.

A Sept. 28, 2015 Yale University news release by William Weir, whch originated the news item, describes the research in more detail,

“We found that when we apply the sunblock to the skin, it doesn’t come off, and more importantly, it doesn’t penetrate any further into the skin,” said the paper’s senior author, Mark Saltzman, the Goizueta Foundation Professor of Biomedical Engineering. “Nanoparticles are large enough to keep from going through the skin’s surface, and our nanoparticles are so adhesive that they don’t even go into hair follicles, which are relatively open.”

Using mouse models, the researchers tested their sunblock against direct ultraviolet rays and their ability to cause sunburn. In this regard, even though it used a significantly smaller amount of the active ingredient than commercial sunscreens, the researchers’ formulation protected equally well against sunburn.

They also looked at an indirect — and much less studied — effect of UV light. When the active ingredients of sunscreen absorb UV light, a chemical change triggers the generation of oxygen-carrying molecules known as reactive oxygen species (ROS). If a sunscreen’s agents penetrate the skin, this chemical change could cause cellular damage, and potentially facilitate skin cancer.

“Commercial chemical sunblock is protective against the direct hazards of ultraviolet damage of DNA, but might not be against the indirect ones,” said co-author Michael Girardi, a professor of dermatology at Yale Medical School. “In fact, the indirect damage was worse when we used the commercial sunblock.”

Girardi, who specializes in skin cancer development and progression, said little research has been done on the ultimate effects of sunblock usage and the generation of ROS, “but obviously, there’s concern there.”

Previous studies have found traces of commercial sunscreen chemicals in users’ bloodstreams, urine, and breast milk. There is evidence that these chemicals cause disruptions with the endocrine system, such as blocking sex hormone receptors.

To test penetration levels, the researchers applied strips of adhesive tape to skin previously treated with sunscreen. The tape was then removed rapidly, along with a thin layer of skin. Repeating this procedure allowed the researchers to remove the majority of the outer skin layer, and measure how deep the chemicals had penetrated into the skin. Traces of the sunscreen chemical administered in a conventional way were found to have soaked deep within the skin. The Yale team’s sunblock came off entirely with the initial tape strips.

Tests also showed that a substantial amount of the Yale team’s sunscreen remained on the skin’s surface for days, even after exposure to water. When wiped repeatedly with a towel, the new sunblock was entirely removed. [emphasis mine]

To make the sunblock, the researchers developed a nanoparticle with a surface coating rich in aldehyde groups, which stick tenaciously to the outer skin layer. The nanoparticle’s hydrophilic layer essentially locks in the active ingredient, a hydrophobic chemical called padimate O.

Some sunscreen solutions that use larger particles of inorganic compounds, such as titanium dioxide or zinc oxide, also don’t penetrate the skin. For aesthetic reasons, though, these opaque sunscreen products aren’t very popular. By using a nanoparticle to encase padimate O, an organic chemical used in many commercial sunscreens, the Yale team’s sunblock is both transparent and stays out of the skin cells and bloodstream.

This seems a little confusing to me and I think clarification may be helpful. My understanding is that the metallic nanoparticles (nano titanium dioxide and nano zinc oxide) engineered for use in commercial sunscreens are also (in addition to the macroscale titanium dioxide and zinc oxide referred to in the Yale news release) too large to pass through the skin. At least that was the understanding in 2010 and I haven’t stumbled across any information that is contradictory. Here’s an excerpt from a July 20, 2010 posting where I featured portions of a debate between Georgia Miller (at that time representing Friends of the Earth) and Dr. Andrew Maynard (at that time director of the University of Michigan Risk Science Center and a longtime participant in the nanotechnology risk discussions),

Three of the scientists whose work was cited by FoE as proof that nanosunscreens are dangerous either posted directly or asked Andrew to post comments which clarified the situation with exquisite care,

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

However, there may be other ingredients which do pass through into the bloodstream and are concerning.

One other thing I’d like to note. Not being able to remove the sunscreen easily ( “When wiped repeatedly with a towel, the new sunblock was entirely removed.”) may prove to be a problem as we need Vitamin D, which is for the most part obtainable by sun exposure.

In any event, here’s a link to and a citation for the paper,

A sunblock based on bioadhesive nanoparticles by Yang Deng, Asiri Ediriwickrema, Fan Yang, Julia Lewis, Michael Girardi, & W. Mark Saltzman. Nature Materials (2015) doi:10.1038/nmat4422 Published online 28 September 2015

This paper is behind a paywall.

*’teh’ changed to ‘the’ on June 6, 2016.

Risk assessments not the only path to nanotechnology regulation

Nanowerk has republished an essay about nanotechnology regulation from Australia’s The Conversation in an Aug. 25, 2015 news item (Note: A link has been removed),

When it comes to nanotechnology, Australians have shown strong support for regulation and safety testing.

One common way of deciding whether and how nanomaterials should be regulated is to conduct a risk assessment. This involves calculating the risk a substance or activity poses based on the associated hazards or dangers and the level of exposure to people or the environment.

However, our recent review (“Risk Analysis of Nanomaterials: Exposing Nanotechnology’s Naked Emperor”) found some serious shortcomings of the risk assessment process for determining the safety of nanomaterials.

We have argued that these shortcomings are so significant that risk assessment is effectively a naked emperor [reference to a children’s story “The Emperor’s New Clothes“].

The original Aug. 24, 2015 article written by Fern Wickson (Scientist/Program Coordinator at GenØk – Centre for Biosafety in Norway) and Georgia Miller (PhD candidate at UNSW [University of New South Wales], Australia) points out an oft ignored issue with regard to nanotechnology regulation,

Risk assessment has been the dominant decision-aiding tool used by regulators of new technologies for decades, despite it excluding key questions that the community cares about. [emphasis mine] For example: do we need this technology; what are the alternatives; how will it affect social relations, and; who should be involved in decision making?

Wickson and Miller also note more frequently discussed issues,

A fundamental problem is a lack of nano-specific regulation. Most sector-based regulation does not include a “trigger” for nanomaterials to face specific risk assessment. Where a substance has been approved for use in its macro form, it requires no new assessment.

Even if such a trigger were present, there is also currently no cross-sectoral or international agreement on the definition of what constitutes a nanomaterial.

Another barrier is the lack of measurement capability and validated methods for safety testing. We still do not have the means to conduct routine identification of nanomaterials in the complex “matrix” of finished products or the environment.

This makes supply chain tracking and safety testing under real-world conditions very difficult. Despite ongoing investment in safety research, the lack of validated test methods and different methods yielding diverse results allows scientific uncertainty to persist.

With regard to the first problem, the assumption that if a material at the macroscale is safe, then the same is true at the nanoscale informs regulation in Canada and, as far as I’m aware, every other constituency that has any type of nanomaterial regulation. I’ve had mixed feelings about this. On the one hand, we haven’t seen any serious problems associated with the use of nanomaterials but on the other hand, these problems can be slow to emerge.

The second issue mentioned, the lack of a consistent definition internationally, seems to be a relatively common problem in a lot of areas. As far as I’m aware, there aren’t that many international agreements for safety measures. Nuclear weapons and endangered animals and plants (CITES) being two of the few that come to mind.

The lack of protocols for safety testing of nanomaterials mentioned in the last paragraph of the excerpt is of rising concern. For example, there’s my July 7, 2015 posting featuring two efforts: Nanotechnology research protocols for Environment, Health and Safety Studies in US and a nanomedicine characterization laboratory in the European Union. Despite this and other efforts, I do think more can and should be done to standardize tests and protocols (without killing new types of research and results which don’t fit the models).

The authors do seem to be presenting a circular argument with this (from their Aug. 24, 2015 article; Note: A link has been removed),

Indeed, scientific uncertainty about nanomaterials’ risk profiles is a key barrier to their reliable assessment. A review funded by the European Commission concluded that:

[…] there is still insufficient data available to conduct the in depth risk assessments required to inform the regulatory decision making process on the safety of NMs [nanomaterials].

Reliable assessment of any chemical or drug is a major problem. We do have some good risk profiles but how many times have pharmaceutical companies developed a drug that passed successfully through human clinical trials only to present a serious risk when released to the general population? Assessing risk is a very complex problem. even with risk profiles and extensive testing.

Unmentioned throughout the article are naturally occurring nanoparticles (nanomaterials) and those created inadvertently through some manufacturing or other process. In fact, we have been ingesting nanomaterials throughout time. That said, I do agree we need to carefully consider the impact that engineered nanomaterials could have on us and the environment as ever more are being added.

To that end, the authors make some suggestions (Note: Links have been removed),

There are well-developed alternate decision-aiding tools available. One is multicriteria mapping, which seeks to evaluate various perspectives on an issue. Another is problem formulation and options assessment, which expands science-based risk assessment to engage a broader range of individuals and perspectives.

There is also pedigree assessment, which explores the framing and choices taking place at each step of an assessment process so as to better understand the ambiguity of scientific inputs into political processes.

Another, though less well developed, approach popular in Europe involves a shift from risk to innovation governance, with emphasis on developing “responsible research and innovation”.

I have some hesitation about recommending this read due to Georgia Miller’s involvement and the fact that I don’t have the time to check all the references. Miller was a spokesperson for Friends of the Earth (FoE) Australia, a group which led a substantive campaign against ‘nanosunscreens’. Here’s a July 20, 2010 posting where I featured some cherrypicking/misrepresentation of data by FoE in the persons of Georgia Miller and Ian Illuminato.

My Feb. 9, 2012 posting highlights the unintended consequences (avoidance of all sunscreens by some participants in a survey) of the FoE’s campaign in Australia (Note [1]: The percentage of people likely to avoid all sunscreens due to their concerns with nanoparticles in their sunscreens was originally reported to be 17%; Note [2]: Australia has the highest incidence of skin cancer in the world),

Feb.21.12 correction: According to the information in the Feb. 20, 2012 posting on 2020 Science, the percentage of Australians likely to avoid using sunscreens is 13%,

This has just landed in my email in box from Craig Cormick at the Department of Industry, Innovation, Science, Research and Tertiary Education in Australia, and I thought I would pass it on given the string of posts on nanoparticles in sunscreens on 2020 Science over the past few years:

“An online poll of 1,000 people, conducted in January this year, shows that one in three Australians had heard or read stories about the risks of using sunscreens with nanoparticles in them,” Dr Cormick said.

“Thirteen percent of this group were concerned or confused enough that they would be less likely to use any sunscreen, whether or not it contained nanoparticles, putting them selves at increased risk of developing potentially deadly skin cancers.

“The study also found that while one in five respondents stated they would go out of their way to avoid using sunscreens with nanoparticles in them, over three in five would need to know more information before deciding.”

This article with Fern Wickson (with whom I don’t always agree perfectly but hasn’t played any games with research that I’m know of) helps somewhat but it’s going to take more than this before I feel comfortable recommending Ms. Miller’s work for further reading.

Nanopollution of marine life

Concerns are being raised about nanosunscreens and nanotechnology-enabled marine paints and their effect on marine life, specifically, sea urchins. From a May 13, 2015 news item on Nanowerk (Note: A link has been removed),

Nanomaterials commonly used in sunscreens and boat-bottom paints are making sea urchin embryos more vulnerable to toxins, according to a study from the University of California, Davis [UC Davis]. The authors said this could pose a risk to coastal, marine and freshwater environments.

The study, published in the journal Environmental Science and Technology (“Copper Oxide and Zinc Oxide Nanomaterials Act as Inhibitors of Multidrug Resistance Transport in Sea Urchin Embryos: Their Role as Chemosensitizers”), is the first to show that the nanomaterials work as chemosensitizers. In cancer treatments, a chemosensitizer makes tumor cells more sensitive to the effects of chemotherapy.

Similarly, nanozinc and nanocopper made developing sea urchin embryos more sensitive to other chemicals, blocking transporters that would otherwise defend them by pumping toxins out of cells.

A May 12, 2015 UC Davis news release, which originated the news item, includes some cautions,

Nanozinc oxide is used as an additive in cosmetics such as sunscreens, toothpastes and beauty products. Nanocopper oxide is often used for electronics and technology, but also for antifouling paints, which prevent things like barnacles and mussels from attaching to boats.

“At low levels, both of these nanomaterials are nontoxic,” said co-author Gary Cherr, professor and interim director of the UC Davis Bodega Marine Laboratory, and an affiliate of the UC Davis Coastal Marine Sciences Institute. “However, for sea urchins in sensitive life stages, they disrupt the main defense mechanism that would otherwise protect them from environmental toxins.”

Science for safe design

Nanomaterials are tiny chemical substances measured in nanometers, which are about 100,000 times smaller than the diameter of a human hair. Nano-sized particles can enter the body through the skin, ingestion, or inhalation. They are being rapidly introduced across the fields of electronics, medicine and technology, where they are being used to make energy efficient batteries, clean up oil spills, and fight cancer, among many other uses. However, relatively little is known about nanomaterials with respect to the environment and health.

Here’s a link to and a citation for the paper,

Copper Oxide and Zinc Oxide Nanomaterials Act as Inhibitors of Multidrug Resistance Transport in Sea Urchin Embryos: Their Role as Chemosensitizers by Bing Wu, Cristina Torres-Duarte, Bryan J. Cole, and Gary N. Cherr. Environ. Sci. Technol., 2015, 49 (9), pp 5760–5770 DOI: 10.1021/acs.est.5b00345 Publication Date (Web): April 7, 2015

Copyright © 2015 American Chemical Society

This paper is behind a paywall.

While this research into nanoparticles as chemosensitizers is, according to UC Davis, the first of its kind, the concern over nanosunscreens and marine waters has been gaining traction over the last few years. For example, there’s  research featured in a June 10, 2013 article by Roberta Kwok for the University of Washington’s ‘Conservation This Week’ magazine,

Sunscreen offers protection from UV rays, reduces the risk of skin cancer, and even slows down signs of aging. Unfortunately, researchers have found that sunscreen also pollutes the ocean.

Although people have been using these products for decades, “the effect of sunscreens, as a source of introduced chemicals to the coastal marine system, has not yet been addressed,” a research team writes in PLOS ONE. Sunscreens contain chemicals not only for UV protection, but also for coloring, fragrance, and texture. And beaches are becoming ever-more-popular vacation spots; for example, nearly 10 million tourists visited Majorca Island in the Mediterranean Sea in 2010.

Here’s a link to the 2013 PLOS ONE paper,

Sunscreen Products as Emerging Pollutants to Coastal Waters by Antonio Tovar-Sánchez, David Sánchez-Quiles, Gotzon Basterretxea, Juan L. Benedé, Alberto Chisvert, Amparo Salvador, Ignacio Moreno-Garrido, and Julián Blasco. PLOS ONE DOI: 10.1371/journal.pone.0065451 Published: June 5, 2013

This is an open access journal.

Nanotechnology Policy and Regulation in Canada, Australia, the European Union, the UK, and the US: a timeline for us all

The Timeline: Nanotechnology Policy and Regulation in Canada, Australia, the European Union, the United Kingdom, and the United States (PDF; h/t July 10, 2014 news item on Nanowerk) issued by the University of Ottawa’s Institute for Science, Society and Policy (ISSP) takes as its starting point the invention of the field emission microscope in 1936 by Erwin Wilhelm Müller.

This fascinating 40 pp document seems comprehensive to me. While the title suggests otherwise, there are a few mentions of events involving Asian countries and they also include the Berkeley bylaw governing nanotechnology manufacture in the city. From the Timeline, p. 16 (Note: The formatting has been changed significantly),

The City of Berkeley (US)
December 2006

The Berkeley Municipal Code is amended to introduce new measures regarding manufactured nanomaterial health and safety

These amendments require facilities that manufacture or use nanomaterials to disclose in writing which nanomaterials are being used as well as the current toxicology of the materials reported (to the extent known) and to further describe how the facility will safely handle, monitor, contain, dispose, track inventory, prevent releases and mitigate such materials.

Berkeley is currently the only municipal government in the United States to regulate nanotechnology

While searching a month ago (June 2014), I was having difficulty finding information online about the Berkeley bylaw, so this was a delightful surprise.

There is (arguably) an omission and that is the Yale Law School Cultural Cognition Project. The Yale researchers have done some influential work about emerging technologies, including a special nanotechnology project devised in the aftermath of the Berkeley bylaw. Their focus then and now has been on public perceptions and attitudes as they affect policy.

Given how many public perception projects there have been and the timeline’s specific focus on regulation and policy, it’s understandable that not many have been included in the timeline.

Still, I was curious to see if the 2012 nanosunscreen debacle in Australia would be included in the timeline. It was not and, given that this incident didn’t directly involve policy or regulation, it’s understandable. Still, I would like to suggest its inclusion in future iterations. (For the curious, my Feb. 9, 2012 posting titled: Unintended consequences: Australians not using sunscreens to avoid nanoparticles? offers a summary and links to this story about an Australian government survey and some unexpected and dismaying results.)

The timeline appears to have a publication date of April 2014 and was compiled by Alin Charrière and Beth Dunning. It is a ‘living’ document so it will be updated in the future. If you have any comments, issp@uottawa.ca. (I will be sending mine soon.)

It is one of a series which includes two other technologies, Synthetic biology and Bioenergy, at this point (July 10, 2014). You can go here for more about the ISSP.

Finally, bravo and bravo to Charrière and Dunning for a job well done.

Nanoscale metal oxides and lung cells

Bear in mind while reading further that all of this research has not taken place in any situation resembling real life conditions: researchers at the Missouri University of Science and Technology (Missouri S&T; located in the US) have found that metal oxides at the nanoscale can be highly toxic to human lung cells according to a Jan. 28, 2014 news item on Nanowerk (Note: A link has been removed),

Nanoparticles are used in all kinds of applications — electronics, medicine, cosmetics, even environmental clean-ups. More than 2,800 commercially available applications are now based on nanoparticles, and by 2017, the field is expected to bring in nearly $50 billion worldwide.

But this influx of nanotechnology is not without risks, say researchers at Missouri University of Science and Technology.

“There is an urgent need to investigate the potential impact of nanoparticles on health and the environment,” says Yue-Wern Huang, professor of biological sciences at Missouri S&T.

Huang and his colleagues have been systematically studying the effects of transition metal oxide nanoparticles on human lung cells (“Cytotoxicity in the age of nano: The role of fourth period transition metal oxide nanoparticle physicochemical properties”). These nanoparticles are used extensively in optical and recording devices, water purification systems, cosmetics and skin care products, and targeted drug delivery, among other applications.

The Jan. 27, 2014 Missouri S&T news release by Linda Fulps, which originated the news item, describes the research in more detail,

“In their typical coarse powder form, the toxicity of these substances is not dramatic,” says Huang. “But as nanoparticles with diameters of only 16-80 nanometers, the situation changes significantly.”

The researchers exposed both healthy and cancerous human lung cells to nanoparticles composed of titanium, chromium, manganese, iron, nickel, copper and zinc compounds — transition metal oxides that are on the fourth row of the periodic table. The researchers discovered that the nanoparticles’ toxicity to the cells, or cytotoxicity, increased as they moved right on the periodic table.

“About 80 percent of the cells died in the presence of nanoparticles of copper oxide and zinc oxide,” says Huang. “These nanoparticles penetrated the cells and destroyed their membranes. The toxic effects are related to the nanoparticles’ surface electrical charge and available docking sites.”

Huang says that certain nanoparticles released metal ions — called ion dissolution — which also played a significant role in cell death.

Huang is now working on new research that may help reduce nanoparticles’ toxicity and shed light on how nanoparticles interact with cells.

“We are coating toxic zinc oxide nanoparticles with non-toxic nanoparticles to see if zinc oxide’s toxicity can be reduced,” Huang says. “We hope this can mitigate toxicity without compromising zinc oxide’s intended applications. We’re also investigating whether nanoparticles inhibit cell division and influence cell cycle.”

Concerning results? Yes. But, before determining how alarmed you should be, there are a few questions you might want to ask while reading the news release and/or the research paper :

  1. How were these cells exposed to the metal nanoparticles? ‘Breathing’ or were they sitting in a solution?
  2. What was the concentration of metal nanoparticles? (even good things can be bad for you at high concentrations)

This isn’t an attempt to dismiss the findings but rather to point out how much painstaking research has to take place before conclusions of any kind can be drawn. It’s why scientists tend to quite careful in their comments.

In looking at this work, I was reminded of the research into ‘nanosunscreens’ and concerns about the metal oxide nanoparticles (zinc oxides and/or titanium dioxide) penetrating the skin barrier and building up to toxic levels in the body.  In an Oct. 4, 2012 posting about zinc oxide nanoparticles and penetrating the skin barrier, I mentioned this in the context of some then recent research at Bath University (UK),

I missed the fact that this study was an in vitro test, which is always less convincing than in vivo testing. In my Nov. 29, 2011 posting about some research into nano zinc oxide I mentioned in vitro vs. in vivo testing and Brian Gulson’s research,

I was able to access the study and while I’m not an expert by any means I did note that the study was ‘in vitro’, in this case, the cells were on slides when they were being studied. It’s impossible to draw hard and fast conclusions about what will happen in a body (human or otherwise) since there are other systems at work which are not present on a slide.

… here’s what Brian Gulson had to say about nano zinc oxide concentrations in his work and about a shortcoming in his study (from an Australian Broadcasting Corporation [ABC] Feb. 25, 2010 interview with Ashley Hall,

BRIAN GULSON: I guess the critical thing was that we didn’t find large amounts of it getting through the skin. The sunscreens contain 18 to 20 per cent zinc oxide usually and ours was about 20 per zinc. So that’s an awful lot of zinc you’re putting on the skin but we found tiny amounts in the blood of that tracer that we used.

ASHLEY HALL: So is it a significant amount?

BRIAN GULSON: No, no it’s really not.

ASHLEY HALL: But Brian Gulson is warning people who use a lot of sunscreen over an extended period that they could be at risk of having elevated levels of zinc.

BRIAN GULSON: Maybe with young children where you’re applying it seven days a week, it could be an issue but I’m more than happy to continue applying it to my grandchildren.

ASHLEY HALL: This study doesn’t shed any light on the question of whether the nano-particles themselves played a part in the zinc absorption.

BRIAN GULSON: That was the most critical thing. This isotope technique cannot tell whether or not it’s a zinc oxide nano-particle that got through skin or whether it’s just zinc that was dissolved up in contact with the skin and then forms zinc ions or so-called soluble ions. So that’s one major deficiency of our study.

Of course, I have a question about Gulson’s conclusion  that very little of the nano zinc oxide was penetrating the skin based on blood and urine samples taken over the course of the study. Is it possible that after penetrating the skin it was stored in the cells  instead of being eliminated?

Here’s a link to and a citation for Yue-Wern Huang and his team’s latest research,

Cytotoxicity in the age of nano: The role of fourth period transition metal oxide nanoparticle physicochemical properties by Charles C. Chusuei, Chi-Heng Wu, Shravan Mallavarapu, Fang Yao Stephen Hou, Chen-Ming Hsu, Jeffrey G. Winiarz, Robert S. Aronstam, Yue-Wern Huang. Chemico-Biological Interactions, Volume 206, Issue 2, 25 November 2013, Pages 319–326.

This paper is behind a paywall.

Anatase and rutile titanium dioxide and nanosunscreens

The American Chemical Society (ACS) features some research into nanoscreens and the anatase form of titanium dioxide in a Sept. 25, 2013 news release,,

Using a particular type of titanium dioxide — a common ingredient in cosmetics, food products, toothpaste and sunscreen — could reduce the potential health risks associated with the widely used compound. The report on the substance, produced by the millions of tons every year for the global market, appears in the ACS journal Chemical Research in Toxicology.
Francesco Turci and colleagues explain that titanium dioxide (TiO2) is generally considered a safe ingredient in commercially available skin products because it doesn’t penetrate healthy skin. But there’s a catch. Research has shown that TiO2 can cause potentially toxic effects when exposed to ultraviolet light, which is in the sun’s rays and is the same kind of light that the compound is supposed to offer protection against. To design a safer TiO2 for human use, the researchers set out to test different forms of the compound, each with its own architecture.

They tested titanium dioxide powders on pig skin (which often substitutes for human skin in these kinds of tests) with indoor lighting, which has very little ultraviolet light in it. They discovered that one of the two most commonly used crystalline forms of TiO2, called rutile, easily washes off and has little effect on skin. Anatase, the other commonly used form, however, was difficult to wash off and damaged the outermost layer of skin — even in low ultraviolet light. It appears to do so via “free radicals,” which are associated with skin aging. “The present findings strongly encourage the use of the less reactive, negatively charged rutile to produce safer TiO2-based cosmetic and pharmaceutical products,” the researchers conclude.

It should be noted that the researchers used pig skin, i.e., the skin was not on a pig and, therefore, not part of a living organism with its various biological systems coming into play. As well, the testing was done indoors not under direct sunlight which is the condition under which most of us use sunscreen. This research points to problems  with using anatase nanoscale titanium dioxide in sunscreens but it doesn’t provide unequivocal proof.

The Danish Environmental Protection Agency report (this Oct. 3, 2013 posting of mine) on the state of the art of research into nanomateial dermal absorption does refer to research in this area, although it does not include Turci’s work (Note: The numbers n the excerpted text are reference numbers for the bibliography)),

When looking at bulk composition and the level of dermal penetration noted in studies using a specific material type, there appears to be very little pattern between bulk composition and penetration depth. Taking for example TiO2 as one of the most widely studied nanoparticles, we see reports of penetration no further than the SC [subcutaneous skin layer] 78, 86, 91 but also several studies suggesting deeper penetration (basal cell layer) and even penetration into the dermis 63, 84 although this is often reported as being a very small fraction/infrequent. Another compositional issue in relation to nanoparticles and in particular TiO2 is the crystalline structure. TiO2 is often used in either its anatase or rutile form or as mixture of both. Within the literature, there are studies using both the anatase form 86, 94, the rutile form 91, 114 or a mixture 84, 114 although we were unable to find any studies which appear to systematically evaluate the role of crystal form in TiO2 absorption into the skin. [emphasis mine] (p. 44 of this report: Dermal Absorption of Nanomaterials Part of the ”Better control of nano” initiative 2012 – 2015 Environmental Project No. 1504, 2013).

For those who would like to read Turci’s research for themselves,

Crystalline Phase Modulates the Potency of Nanometric TiO2 to Adhere to and Perturb the Stratum Corneum of Porcine Skin under Indoor Light by Francesco Turci, Elena Peira, Ingrid Corazzari, Ivana Fenoglio, Michele Trotta, and Bice Fubini. Chem. Res. Toxicol., Article ASAP DOI: 10.1021/tx400285j Publication Date (Web): September 12, 2013
Copyright © 2013 American Chemical Society

This research is behind a paywall.

Amid controversies, Australian government spends big bucks on Australian Institute for Nanoscience

Kim Carr, Australia’s Minister for Innovation, Industry, Science and Research, delivered  an extraordinary speech, by Canadian standard (ours tend to remarkable blandness), at the sod-turning event for the new Australian Institute for Nanoscience (AIN) due to open in May 2015. Before getting to the speech, here’s a bit more about the event from a July 24, 2013 news item on Global Times,

Australian government will deliver a fund for the new Australian Institute for Nanoscience ( AIN) which will open in May 2015 to boost its research of nanotechnology, Minister for Innovation, Industry, Science and Research Kim Carr confirmed in a statement after breaking the ground for the new facility at the University of Sydney on Wednesday.

The AIN project is a major new building combining research laboratories with teaching facilities to drive cross-disciplinary collaboration to develop nanomaterials and devices.

The July 24, 2013 Australian government media release about the AIN sod-turning provides more details about the government’s investment in the institute and its backing of nanoscience/nanotechnology research,

Senator Kim Carr said the Australian Government’s $40 million contribution, through the Education Investment Fund, to assist in the facility’s construction backs in Labor’s commitment to giving our researchers the tools they need to pursue world-leading work.

“Nanotechnology is a transformative force for manufacturing and is predicted to be worth $US3 trillion globally by 2020. Australia needs to stake a claim to our slice of that pie now, by building well-researched prototypes for the market. AIN will help make that happen and keep Australian research internationally competitive.”

Senator Carr said AIN will increase our national research capability by bringing together world-class nanoscience researchers across three main areas:

  • New medical diagnostics and therapies combining quantum technology with imaging and drug delivery and solutions such as a fully implantable bionic eye;
  • Faster, more secure and more efficient communications based on photonics and quantum science technologies; and
  • Revolutionary optical instrumentation to explore the frontiers of our universe, along with faster data processing technologies for the SKA.

I’m not sure where Carr got the “… worth $US3 trillion globally by 2020” number for nanotechnology’s impact on the global economy. More interesting to me, are these comments from Carr’s speech (you can find the entire speech here),

It is a great pleasure to share in the progress of the Australian Institute for Nanoscience here at Sydney University.

Three years have passed since I announced the funding for this facility:

$40 million from the Federal Government;

backed by $71 million from the university;

and a further $20 million from other sources, including the New South Wales government, the Australian National Fabrication Facility; the ARC’s CUDOS; the Australian Astronomical Observatory and Bandwidth Foundry International.

It was one of the many projects made possible by the Education Investment Fund – which, over three rounds, secured a total of $3.5 billion in new research infrastructure for a federal contribution of $1.5 billion.

This is an impressive return on investment.

At that time, this was the sort of research guaranteed to bring out the anti-science crowd.

There were beat-ups in the press, demonstrations in universities, and scare campaigns run on worksites. [emphasis mine]

It was as if the Enlightenment had never happened. It was as if nanoscience was some kind of global conspiracy to kill us all with sunscreen. [emphasis mine]

But I saw this project differently. And I put my views on the record at the time this investment was announced.

As I said back then:

“I don’t begin by saying “this is too strange” or “this is too hard”. I don’t begin by saying “no”.

I begin by asking, “what’s in it for Australia?” – “what’s in it for the people we serve?” – and “how can we make this work?”

The speech continues with a very optimistic view of all the economic benefits to be derived from an investment in nanoscience/nanotechnology.

Given the extreme lack of interest in Canada and its very odd (or perhaps it’s a harbinger of the future?) almost unknown National Institute of Nanotechnology (NINT), which exists on a NINT University of Alberta website and on a NINT National Research Council website, the “beat-ups in the press, etc.” provide a fascinating and contrasting socio-cultural perspective. The difference is perhaps due to a very active, both in Australia and internationally, Friends of the Earth group.

Friends of the Earth Australia campaigned long (years) and hard against nanosunscreens in a leadup to some rather disturbing survey findings in 2012 (my Feb. 9, 2012 posting) where some 13% of Australians, first reported as 17%,  didn’t use any sunscreens whatsoever, due to their fear of ‘nanosunscreens’.

Kim Carr has been mentioned here before in an Aug. 26, 2011 posting which highlighted a study showing  Australians held positive (?) attitudes towards nanotechnology and those attitudes had gotten more positive over time. My guess, not having looked at the study, is that the study focussed on areas where people usually express positive attitudes (e. g. better health care with less invasive medical procedures) and not on environmental issues (e.g. nanosilver in your clothing washing off and ending up in the water supply).

I do love how elected officials, the world over, pick and choose their ‘facts’.