Category Archives: risk

Nanowaste or the end of the life cycle for nanoscale materials

A Jan. 27, 2015 Nanwerk spotlight article on nanowaste presents a comprehensive picture of possible issues (Note: Footnotes have been removed),

Based on their special chemical and physical properties, synthetically produced nanomaterials (engineered nanomaterials, ENMs) are currently being used in a wide range of products and applications. The Nanomaterial Databank of Nanowerk … currently lists nanomaterials composed of 28 different elements as well as of carbon (fullerenes, CNT, graphene), quantum dots consisting of several semi-conductor materials, a large number of simple nanoparticulate compounds (oxides, carbonates, nitrides) and those made up of complex compounds containing several components. On the one hand, the application of nanomaterials promises reduction potentials and sustainability effects for the environment, for example through resource and material savings ….

On the other hand, we know very little about the behavior of nanomaterials or about environmental and health risks when these products enter various waste streams at the end of their life cycles. A better understanding of the risks in the so-called End-of-Life-Phase (EOL) calls for considering the different disposal pathways and potential transformation processes that nanomaterials undergo in waste treatment plants. In the disposal phase no consideration is being given to either the special properties of nanomaterials or to potential recovery and re-use. …

There is no special legal framework in place for a separate treatment of nanomaterial containing wastes … or the monitoring of the processes. A prerequisite for such a framework would be exact knowledge about the nanomaterials being used, their form (species) and composition, potential transformation processes as well as about amounts and concentrations. Such information, however, is not available, and virtually no studies have been conducted on the EOL phase of products containing nanomaterials. Very little is known about how nanomaterial-containing wastes behave in thermal, biological or mechanical-biological waste treatment plants or in landfills. …

The spotlight article appears to be a reprint of an ITA (Institute of Technology Assessment) NanoTrust Dossier [“Nanowaste” – Nanomaterial-containing products at the end of their life cycle (NanoTrust Dossier No. 040en – August 2014)] by Sabine Greßler, Florian Part, and André Gazsó,

Abstract:
Based on their special chemical and physical properties, synthetically produced nanomaterials are currently being used in a wide range of products and applications. At the end of their product life cycle, nanomaterials can enter waste treatment plants and landfills via diverse waste streams. Little, however, is known about how nanomaterials behave in the disposal phase and whether potential environmental or health risks arise. There are no specific legal requirements for a separate treatment of nanomaterial-containing wastes. Virtually no information is available about the nanomaterials currently in use, their form and composition, or about their amounts and concentrations. The current assumption is that stable nanoparticles (e.g. metal oxides) are neither chemically nor physically altered in waste incineration plants and that they accumulate especially in the residues (e.g. slag). These residues are ultimately dumped. The disposal problem in the case of stable nanoparticles is therefore merely shifted to the subsequent steps in the waste treatment process. Carbon nanotubes (CNT) are almost completely combusted in incineration plants. Filter systems seem to be only partially efficient, and a release of nanoparticles into the environment cannot be excluded. Incinerating nanomaterials contained in products can also promote the development of organic pollutants as undesired by-products. Only few studies are available on the behavior of nanomaterials in landfills. Moreover, recycling such products could release nanomaterials, most likely when these are shredded and crushed.

This dossier offers a good review of the current state of affairs with regard to nanowaste. I haven’t read it exhaustively but it coincides with my understanding of the situation including the fact that there’s not much research on the topic.

BTW, NanoTrust is a project of the Austrian Academy of Sciences’ Institute of Technology Assessment (ITA). The nanowaste dossier is also available in German.

Government of Canada’s risk assessment for multi-walled carbon nanotubes

Lynn Bergeson’s Jan. 15, 2015 post on the Nanotechnology Now website mentions a newly issued Canadian risk assessment for multi-walled carbon nanotubes (MWCNTs),

Canada announced on January 9, 2015, that the New Substances Program has published six new risk assessment summaries for chemicals and polymers, including a summary for multi-wall carbon nanotubes.

… Environment Canada and Health Canada conduct risk assessments on new substances. These assessments include consideration of information on physical and chemical properties, hazards, uses, and exposure to determine whether a substance is or may become harmful to human health or environment as set out in Section 64 of the Canadian Environmental Protection Act, 1999 (CEPA 1999), and, if harm is suspected, to introduce any appropriate or required control measures. …

Here’s more information from the Summary of Risk Assessment Conducted Pursuant to subsection 83(1) of the Canadian Environmental Protection Act, 1999
Significant New Activity No. 17192: Multi-wall carbon nanotubes webpage,

Substance Identity

The substance is a short tangled multi-walled carbon nanotube that can be classified as a nanomaterial. [emphasis mine]

Notified Activities

The substance is proposed to be manufactured in or imported into Canada in quantities greater than 1000 kg/yr for use as an additive in plastics.

Environmental Fate and Behaviour

Based on its physical and chemical properties, if released to the environment, the substance will tend to partition to water, sediment, soil, and ambient air. The substance is expected to be persistent in these compartments because it is a stable inorganic chemical that will not degrade. Based on the limited understanding of uptake by organisms, more data is required to assess the bioaccumulation potential of this substance at the current schedule notification.

Ecological Assessment

Based on the available hazard information on the substance and surrogate data on structurally related nanomaterials, the substance has low to moderate (1-100 mg/L) acute toxicity in aquatic life (fish/daphnia/algae). The predicted no effect concentration was calculated to be less than 1 mg/L using the ErC50 from the most sensitive organism (P. subcapitata), which was used to estimate the environmental risk.

The notified and other potential activities in Canada were assessed to estimate the environmental exposure potential of the substance throughout its life cycle. Environmental exposure from the notified activities was determined through a conservative generic single point-source release blending scenario. The predicted environmental concentration for notified activities is estimated to be 2.1 µg/L.

Based on the current use profile in conjunction with low to moderate ecotoxicity endpoints, the substance is unlikely to cause ecological harm in Canada.

However, based on the current understanding of carbon nanotubes and nanomaterials in general, a change in the use profile of the substance (SNAc No. 17192) may significantly alter the exposure resulting in the substance becoming harmful to the environment.  Consequently, more information is necessary to better characterize potential environmental risks.

Human Health Assessment

Based on the available hazard information on the substance, the substance has a low potential for acute toxicity by the oral, dermal and inhalation routes of exposure (oral and dermal LD50 greater than 2000 mg/kg bw; inhalation LC50 greater than 1.3 mg/m3). It is a severe eye irritant (MAS score = 68), a mild skin irritant (PII = 1.08) and at most a weak sensitizer (because the positive control was tested at a concentration 10X higher than the test substance). It is not an in vitro mutagen (negative in a mammalian cell gene mutation test and in a mammalian chromosome aberration test).  Therefore the substance is unlikely to cause genetic damage.

Hazards related to substances used in the workplace should be classified accordingly under the Workplace Hazardous Materials Information System (WHMIS).

However, based on the available information on structurally related nanomaterials, the substance may cause respiratory toxicity, immunotoxicity, cardiovascular toxicity and carcinogenicity following oral and inhalation exposure.

When used as an additive in plastics, the substance is expected to be manufactured in or imported into Canada encapsulated in a solid polymer matrix. The potential site of exposure to the substance is expected to be within industrial facilities. Therefore, direct exposure of the general population is expected to be low. No significant environmental release is anticipated due to the specialized use under this notification and therefore indirect exposure of the general population from environmental media is also expected to be low. However, if the substance is produced in different forms (e.g. liquid polymer form), applied in different formulations or used in any other potential applications, an increased direct or indirect exposure potential may exist.

Based on the low potential for direct and indirect exposure of the general population under the industrial uses identified in this submission, the substance is not likely to pose a significant health risk to the general population, and is therefore unlikely to be harmful to human health.

However, based on the current understanding of carbon nanotubes and of nanomaterials in general, the risk arising from the use of the substance in consumer products is not known at this time.  The use of the substance in consumer products or in products intended for use by or for children may significantly alter the exposure of the general population resulting in the substance becoming harmful to human health.  Similarly, the import or manufacture of the substance in quantities greater than 10 000 kg/yr may significantly increase the exposure levels of the general population resulting in the substance becoming harmful to human health.  Consequently, more information is necessary to better characterize potential health risks.

I would like to see a definition for the word short as applied, in this risk assessment, to multi-walled carbon nanotubes. That said, this assessment is pretty much in line with current thinking about short, multi-walled carbon nanotubes. In short (wordplay noted), these carbon nanotubes are relatively safe (although some toxicological issues have been noted) as far as can be determined. However, the ‘relatively safe’ assessment may change as more of these carbon nanotubes enter the environment and as people are introduced to more products containing them.

One last comment, I find it surprising I can’t find any mention in the risk assessment of emergency situations such as fire, earthquake, explosions, etc. which could conceivably release short multi-walled carbon nanotubes into the air exposing emergency workers and people caught in a disaster. As well, those airborne materials might subsequently be found in greater quantity in the soil and water.

Silicon dioxide nanoparticles may affect the heart

This is an interesting piece of research although it’s difficult to draw conclusions since the testing was ‘in vitro’, which literally means ‘in glass’ and in practice means testing cells in a test tube, a petri dish or, possibly, on a slide. That said, this work centering on silicon dioxide nanoparticles, which are increasingly used in biomedical applications, suggests further investigation is warranted. From a Jan. 9, 2015 news item on Azonano,

Nanoparticles, extremely tiny particles measured in billionths of a meter, are increasingly everywhere, and especially in biomedical products. Their toxicity has been researched in general terms, but now a team of Israeli scientists has for the first time found that exposure nanoparticles (NPs) of silicon dioxide (SiO2) can play a major role in the development of cardiovascular diseases when the NP cross tissue and cellular barriers and also find their way into the circulatory system.

A Jan. 8, 2015American Technion Society news release by Kevin Hattori, which originated the news item, describes the research in more detail,

“Environmental exposure to nanoparticles is becoming unavoidable due to the rapid expansion of nanotechnology,” says the study’s lead author, Prof. Michael Aviram, of the Technion Faculty of Medicine, “This exposure may be especially chronic for those employed in research laboratories and in high tech industry where workers handle, manufacture, use and dispose of nanoparticles. Products that use silica-based nanoparticles for biomedical uses, such as various chips, drug or gene delivery and tracking, imaging, ultrasound therapy, and diagnostics, may also pose an increased cardiovascular risk for consumers as well.” [emphasis mine]

In this study, researchers exposed cultured laboratory mouse cells resembling the arterial wall cells to NPs of silicon dioxide and investigated the effects. SiO2 NPs are toxic to and have significant adverse effects on macrophages. a type of white blood cell that take up lipids, leading to atherosclerotic lesion development and its consequent cardiovascular events, such as heart attack or stroke. Macrophages accumulation in the arterial wall under atherogenic conditions such as high cholesterol, triglycerides, oxidative stress – are converted into lipids, or laden “foam cells” which, in turn, accelerate atherosclerosis development.

“Macrophage foam cells accumulation in the arterial wall are a key cell type in the development of atherosclerosis, which is an inflammatory disease” says co-author Dr. Lauren Petrick. “The aims of our study were to gain additional insight into the cardiovascular risk associated with silicon dioxide nanoparticle exposure and discover the mechanisms behind Si02’s induced atherogenic effects on macrophages. We also wanted to use nanoparticles as a model for ultrafine particle (UFP) exposure as cardiovascular disease risk factors.”

Both NPs and UFPs can be inhaled and induce negative biological effects. [emphasis mine] However, until this study, their effect on the development of atherosclerosis has been largely unknown. Here, researchers have discovered for the first time that the toxicity of silicon dioxide nanoparticles has a “significant and substantial effect on the accumulation of triglycerides in the macrophages,” at all exposure concentrations analyzed, and that they also “increase oxidative stress and toxicity.”

A recent update from the American Heart Association also suggested that “fine particles” in air pollution leads to elevated risk for cardiovascular diseases. However, more research was needed to examine the role of “ultrafine particles” (which are much smaller than “fine particles”) on atherosclerosis development and cardiovascular risk.

“The number of nano-based consumer products has risen a thousand fold in recent years, with an estimated world market of $3 trillion by the year 2020,” conclude the researchers. “This reality leads to increased human exposure and interaction of silica-based nanoparticles with biological systems. Because our research demonstrates a clear cardiovascular health risk associated with this trend, steps need to be taken to help ensure that potential health and environmental hazards are being addressed at the same time as the nanotechnology is being developed.

Unfortunately, there seems to be a little exaggeration at work in this news release. For example, I’m not sure how a consumer would go about inhaling a computer chip or more specifically the silicon dioxide nanoparticles embedded in the chip although I can see how someone involved in the manufacture of the chip might be exposed and inhale silicon dioxide nanoparticles. I’m not trying to negate the research but do want to point out that it has limitations.

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

Silicon dioxide nanoparticles increase macrophage atherogenicity: Stimulation of cellular cytotoxicity, oxidative stress, and triglycerides accumulation by Lauren Petrick, Mira Rosenblat, Nicole Paland, and Michael Aviram. Article first published online: 28 NOV 2014 DOI: 10.1002/tox.22084

Copyright © 2014 Wiley Periodicals, Inc.

This article is behind a paywall.

Quantum dots cycling through the food chain

Rice University (Texas, US) researchers have published a study which follows quantum dot nanoparticles as they enter the water supply and are taken up by plant roots and leaves and eaten by caterpillars. From a Dec. 16, 2014 news item on ScienceDaily,

In one of the most comprehensive laboratory studies of its kind, Rice University scientists traced the uptake and accumulation of quantum dot nanoparticles from water to plant roots, plant leaves and leaf-eating caterpillars.

The study, one of the first to examine how nanoparticles move through human-relevant food chains, found that nanoparticle accumulation in both plants and animals varied significantly depending upon the type of surface coating applied to the particles. The research is available online in the American Chemical Society’s journal Environmental Science & Technology.

A Dec. 16, 2014 Rice University news release (also on EurekAlert), which originated the news item, provides insight into some of the issues being addressed with this research (Note: Links have been removed),

“With industrial use of nanoparticles on the rise, there are increasing questions about how they move through the environment and whether they may accumulate in high levels in plants and animals that people eat,” said study co-author Janet Braam, professor and chair of the Department of BioSciences at Rice.

Braam and colleagues studied the uptake of fluorescent quantum dots by Arabidopsis thaliana, an oft-studied plant species that is a relative of mustard, broccoli and kale. In particular, the team looked at how various surface coatings affected how quantum dots moved from roots to leaves as well as how the particles accumulated in leaves. The team also studied how quantum dots behaved when caterpillars called cabbage loopers (Trichoplusia ni) fed upon plant leaves containing quantum dots.

“The impact of nanoparticle uptake on plants themselves and on the herbivores that feed upon them is an open question,” said study first author Yeonjong Koo, a postdoctoral research associate in Braam’s lab. “Very little work has been done in this area, especially in terrestrial plants, which are the cornerstone of human food webs.”

Some toxins, like mercury and DDT, tend to accumulate in higher concentrations as they move up the food chain from plants to animals. It is unknown whether nanoparticles may also be subject to this process, known as biomagnification.

While there are hundreds of types of nanoparticles in use, Koo chose to study quantum dots, submicroscopic bits of semiconductors that glow brightly under ultraviolet light. The fluorescent particles — which contained cadmium, selenium, zinc and sulfur — could easily be measured and imaged in the tests. In addition, the team treated the surface of the quantum dots with three different polymer coatings — one positively charged, one negatively charged and one neutral.

“In industrial applications, nanoparticles are often coated with a polymer to increase solubility, improve stability, enhance properties and for other reasons,” said study co-author Pedro Alvarez, professor and chair of Rice’s Department of Civil and Environmental Engineering. “We expect surface coatings to play a significant role in whether and how nanomaterials may accumulate in food webs.”

Previous lab studies had suggested that the neutral coatings might cause the nanoparticles to aggregate and form clumps that were so large that they would not readily move from a plant’s roots to its leaves. The experiments bore this out. Of the three particle types, only those with charged coatings moved readily through the plants, and only the negatively charged particles avoided clumping altogether. The study also found that the type of coating impacted the plants’ ability to biodegrade, or break down, the quantum dots.

Koo and colleagues found caterpillars that fed on plants containing quantum dots gained less weight and grew more slowly than caterpillars that fed on untainted leaves. By examining the caterpillar’s excrement, the scientists were also able to estimate whether cadmium, selenium and intact quantum dots might be accumulating in the animals. Again, the coating played an important role.

“Our tests were not specifically designed to measure bioaccumulation in caterpillars, but the data we collected suggest that particles with positively charged coatings may accumulate in cells and pose a risk of bioaccumulation,” Koo said. “Based on our findings, more tests should be conducted to determine the extent of this risk under a broader set of ecological conditions.”

The researchers have a couple of images illustrating their work,

The buildup of fluorescent quantum dots in the leaves of Arabidopsis plants is apparent in this photograph of the plants under ultraviolet light. Credit: Y. Koo/Rice University

The buildup of fluorescent quantum dots in the leaves of Arabidopsis plants is apparent in this photograph of the plants under ultraviolet light. Credit: Y. Koo/Rice University

And, there’s a caterpillar,

Cabbage looper

Cabbage looper

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

Fluorescence Reports Intact Quantum Dot Uptake into Roots and Translocation to Leaves of Arabidopsis thaliana and Subsequent Ingestion by Insect Herbivores by Yeonjong Koo, Jing Wang, Qingbo Zhang, Huiguang Zhu, E. Wassim Chehab, Vicki L. Colvin, Pedro J. J. Alvarez, and Janet Braam. Environ. Sci. Technol., Just Accepted Manuscript DOI: 10.1021/es5050562 Publication Date (Web): December 1, 2014

Copyright © 2014 American Chemical Society

This paper is open access but you must be registered on the website.

One final thought about the research, it did take place in a laboratory environment and there doesn’t seem to have been any soil involved so the uptake can not be directly compared (as I understand matters) to the uptake characteristics where plant cultivation requires soil. This seems to have been a study involving hydroponic framing practices.

Singaporeans’ perceptions of nanotechnology and consumer attitudes towards nanotechnologies in food production

This is the first time I’ve seen a study about nanotechnology perception and awareness from Asia. (As I’m sure this is not the first or the only such study, I lament my language skills once more. Since my primary search is for English language materials with my second language, French, as a very distant second, I am limited to translated materials.)

This piece of research comes from Singapore. From a Dec. 11, 2014 news item on the Asian Scientist magazine website,

A survey published in the Journal of Nanoparticle Research shows that while the Singaporean population is more familiar with nanotechnology than their Western counterparts in the US and Europe, they are also more wary of the risks involved.

Asia is expected to dominate the use and release of nanomaterials into the environment, largely due to the size of the population. Furthermore, the region in general—and Singapore in particular—has invested heavily in nanotechnology research, rapidly translating their findings into industrial and consumer products. However, there has been a lack of studies documenting public attitudes and acceptance of new technologies such as nanotechnology.

To address this gap of information, a team of researchers led by first author Dr. Saji George from the Nanyang Polytechnic (NYP) Center for Sustainable Nanotechnology conducted a survey of 1,080 Singaporeans above the age of 15. Their results revealed that approximately 80 percent had some understanding of nanotechnology.

A June 20, 2014 Nanyang Polytechnic media release provides additional details about the research,

In a recent public perception study conducted in Singapore with 1,000 respondents, researchers from Nanyang Polytechnic’s (NYP) Centre for Sustainable Nanotechnology (CSN) found that 80% of respondents were aware of nanotechnology, while only 40% of them were positive about its benefits. This was shared at the official launch of the CSN today. The event was graced by Mr Derek Ho, Director-General, Environmental Public Health Division, National Environment Agency (NEA).

The Centre is the first-of-its-kind among institutes of higher learning (IHLs) in Singapore. It is dedicated to studying the potential impact of novel engineered nanomaterials, and developing ways to ensure that nanotechnology applications are adopted in a sustainable manner for individuals and the environment. This makes the $1 million facility a key training facility for NYP’s students from the Schools of Chemical & Life Sciences, Engineering, and Health Sciences.

Perceptions influenced by exposure to prior information

The perception study conducted in collaboration with the United Kingdom’s Newcastle University, is part of a worldwide study. [emphasis mine] About 1,000 respondents were surveyed in Singapore. Among them, 80% had some level of familiarity with nanotechnology,  while only 40% of them were positive about its benefits. One of the strong determinants that influenced the perception of the public was their prior exposure to news on adverse effects of nanotechnology. This could be due to negative information on nanotechnology carried in the media. Often these are over interpretations of laboratory studies that tend to dampen public confidence in nanotechnology.

“Nanotechnology may be a double-edged sword in some applications. A large proportion of the population is already aware of it, and interestingly, 60% have actually come across negative information on nanotechnology. This points to the need for the Centre for Sustainable Nanotechnology to conduct its work robustly and effectively, to sharpen the benefits, and blunt the risks associated with nanotechnology. This will enable industries to better apply the relevant solutions, and for people to use products containing nanotechnology more confidently. Another impetus for the Centre is that through such studies, companies will learn what consumers are concerned about in specific types of products and how these concerns can be addressed during product design and manufacturing stages,” said Dr Joel Lee, Director of NYP’s School of Chemical & Life Sciences where the Centre is located.

The study also found variations in perception among different socio-demographic groups, and among applications of nanotechnology across different product ranges, for example food, baby products, medicine, clothing, cosmetics, water filters and electronics.

While this is a segue, there’s a very interesting tidbit about silver nanoparticles in this media release,

Smarter Antibacterial Nanotechnology

Since the CSN started operations in 2013, senior lecturers, Dr Saji George and Dr Hannah Gardner, from NYP’s Schools of Chemical & Life Sciences and Engineering, respectively, have studied the effectiveness of nano-silver in eliminating bacteria – which accounts for 30% of commercial nanotechnology – in applications currently available in the market. Nano-silver is largely used as an alternate anti-microbial solution in a range of industries, including clothing, baby products, personal care products and medicine.

Their research findings, now filed as a patent, uncovered that some drug resistant bacterial strains could also develop resistance to silver, contrary to the general notion that all bacterial strains will succumb to it. The duo then designed and developed a cost-effective method to generate cationic polymer coated silver nanoparticles. They observed that these nanoparticles could eliminate pathogenic bacteria regardless of their ability to resist antibiotics and silver.

Dr Lee added, “Nano-silver has captured the attention of industry and researchers. What we hope to achieve with the CSN is two-fold. We aim to be a resource for industries and even government regulatory agencies to tap on to better understand nanotechnology, its effects, and improve on its applications. These would also translate into real-world industry projects for our students and equip them to better serve the industry when they embark on their careers.”

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

Awareness on adverse effects of nanotechnology increases negative perception among public: survey study from Singapore by Saji George, Gulbanu Kaptan, Joel Lee, Lynn Frewer. Journal of Nanoparticle Research November 2014, 16:2751 Date: 22 Nov 2014

This paper is behind a paywall.

I did search for the “… worldwide study” regarding nanotechnology awareness and perceptions but found instead a recently published study on the topic of consumer attitudes towards nanotechnologies used in food production practices which features George and Frewer,

Consumer attitudes towards nanotechnologies applied to food production by L.J. Frewer, N. Gupta, S. George, A.R.H. Fischer, E.L. Giles, and D. Coles. Trends in Food Science & Technology, Volume 40, Issue 2, December 2014, Pages 211–225 (Special Issue: Nanotechnology in Foods: Science behind and future perspectives)

This article is behind a paywall.

rePOOPulate, silver nanoparticles, your gut, and Queen’s University (Canada)

A Nov. 19, 2014 Queen’s University (Ontario, Canada) news release by Anne Craig (also on EurekAlert), describes some research into nanosilver’s effects on the human (more or less) gut,

Queen’s University biologist Virginia Walker and Queen’s SARC Awarded Postdoctoral Fellow Pranab Das have shown nanosilver, which is often added to water purification units, can upset your gut. The discovery is important as people are being exposed to nanoparticles every day.

“We were surprised to see significant upset of the human gut community at the lowest concentration of nanosilver in this study,” says Dr. Das. “To our knowledge, this is the first time anyone has looked at this. It is important as we are more and more exposed to nanoparticles in our everyday lives through different routes such as inhalation, direct contact or ingestion.”

To conduct the research, Drs. Walker and Das utilized another Queen’s discovery, rePOOPulate, created by Elaine Petrof (Medicine). rePOOPulate is a synthetic stool substitute, which Dr. Petrof designed to treat C. difficile infections. In this instance, rather than being used as therapy, the synthetic stool was used to examine the impact of nanoparticles on the human gut.

The research showed that the addition of nanosilver reduced metabolic activity in the synthetic stool sample, perturbed fatty acids and significantly changed the population of bacteria. This information can help lead to an understanding of how nanoparticles could impact our “gut ecosystem.” [emphasis mine]

“There is no doubt that the nanosilver shifted the bacterial community, but the impact of nanosilver ingestion on our long-term health is currently unknown,” Dr. Walker says. “This is another area of research we need to explore.”

The findings by Drs. Das and Walker, Julie AK McDonald (Kingston General Hospital), Dr. Petrof (KGH)  and Emma Allen-Vercoe (University of Guelph) were published in the Journal of Nanomedicine and Nanotechnology.

It’s perturbing news. And, I notice the news release is carefully worded, “This information can help lead to an understanding of how nanoparticles could impact our ‘gut ecosystem.'”

The news release notes this about the ubiquity of nanosilver use,

Nanosilver is also used in biomedical applications, toys, sunscreen, cosmetics, clothing and other items.

I’m a little surprised by the reference to sunscreens; most of the material I’ve seen cites titanium dioxide and/or zinc oxide at the nanoscale.

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

Nanosilver-Mediated Change in Human Intestinal Microbiota by Pranab Das, Julie AK McDonald, Elaine O Petrof, Emma Allen-Vercoe, and Virginia K Walker. Nanomed Nanotechnol 5: 235. doi: 10.4172/2157-7439.1000235

The link takes you to a PDF version of the research paper,

Note: Queen’s University is located in Kingston, Ontario, Canada.

Nanosafety research: a quality control issue

Toxicologist Dr. Harald Krug has published a review of several thousand studies on nanomaterials safety exposing problematic research methodologies and conclusions. From an Oct. 29, 2014 news item on Nanowerk (Note: A link has been removed),

Empa [Swiss Federal Laboratories for Materials Science and Technology] toxicologist Harald Krug has lambasted his colleagues in the journal Angewandte Chemie (“Nanosafety Research—Are We on the Right Track?”). He evaluated several thousand studies on the risks associated with nanoparticles and discovered no end of shortcomings: poorly prepared experiments and results that don’t carry any clout. Instead of merely leveling criticism, however, Empa is also developing new standards for such experiments within an international network.

An Oct. 29, 2014 Empa press release (also on EurekAlert), which originated the news item, describes the new enthusiasm for research into nanomaterials and safety,

Researching the safety of nanoparticles is all the rage. Thousands of scientists worldwide are conducting research on the topic, examining the question of whether titanium dioxide nanoparticles from sun creams can get through the skin and into the body, whether carbon nanotubes from electronic products are as hazardous for the lungs as asbestos used to be or whether nanoparticles in food can get into the blood via the intestinal flora, for instance. Public interest is great, research funds are flowing – and the number of scientific projects is skyrocketing: between 1980 and 2010, a total of 5,000 projects were published, followed by another 5,000 in just the last three years. However, the amount of new knowledge has only increased marginally. After all, according to Krug the majority of the projects are poorly executed and all but useless for risk assessments.

The press release goes on to describe various pathways into the body and problems with research methodologies,

How do nanoparticles get into the body?

Artificial nanoparticles measuring between one and 100 nanometers in size can theoretically enter the body in three ways: through the skin, via the lungs and via the digestive tract. Almost every study concludes that healthy, undamaged skin is an effective protective barrier against nanoparticles. When it comes to the route through the stomach and gut, however, the research community is at odds. But upon closer inspection the value of many alarmist reports is dubious – such as when nanoparticles made of soluble substances like zinc oxide or silver are being studied. Although the particles disintegrate and the ions drifting into the body are cytotoxic, this effect has nothing to do with the topic of nanoparticles but is merely linked to the toxicity of the (dissolved) substance and the ingested dose.

Laboratory animals die in vain – drastic overdoses and other errors

Krug also discovered that some researchers maltreat their laboratory animals with absurdly high amounts of nanoparticles. Chinese scientists, for instance, fed mice five grams of titanium oxide per kilogram of body weight, without detecting any effects. By way of comparison: half the amount of kitchen salt would already have killed the animals. A sloppy job is also being made of things in the study of lung exposure to nanoparticles: inhalation experiments are expensive and complex because a defined number of particles has to be swirled around in the air. Although it is easier to place the particles directly in the animal’s windpipe (“instillation”), some researchers overdo it to such an extent that the animals suffocate on the sheer mass of nanoparticles.

While others might well make do without animal testing and conduct in vitro experiments on cells, here, too, cell cultures are covered by layers of nanoparticles that are 500 nanometers thick, causing them to die from a lack of nutrients and oxygen alone – not from a real nano-effect. And even the most meticulous experiment is worthless if the particles used have not been characterized rigorously beforehand. Some researchers simply skip this preparatory work and use the particles “straight out of the box”. Such experiments are irreproducible, warns Krug.

As noted in the news item, the scientists at Empa have devised a solution to some to of the problems (from the press release),

The solution: inter-laboratory tests with standard materials
Empa is thus collaborating with research groups like EPFL’s Powder Technology Laboratory, with industrial partners and with Switzerland’s Federal Office of Public Health (FOPH) to find a solution to the problem: on 9 October the “NanoScreen” programme, one of the “CCMX Materials Challenges”, got underway, which is expected to yield a set of pre-validated methods for lab experiments over the next few years. It involves using test materials that have a closely defined particle size distribution, possess well-documented biological and chemical properties and can be altered in certain parameters – such as surface charge. “Thanks to these methods and test substances, international labs will be able to compare, verify and, if need be, improve their experiments,” explains Peter Wick, Head of Empa’s laboratory for Materials-Biology Interactions.

Instead of the all-too-familiar “fumbling around in the dark”, this would provide an opportunity for internationally coordinated research strategies to not only clarify the potential risks of new nanoparticles in retrospect but even be able to predict them. The Swiss scientists therefore coordinate their research activities with the National Institute of Standards and Technology (NIST) in the US, the European Commission’s Joint Research Center (JRC) and the Korean Institute of Standards and Science (KRISS).

Bravo! and thank you Dr. Krug and Empa for confirming something I’ve suspected due to hints from more informed commentators. Unfortunately my ignorance. about research protocols has not permitted me to undertake a better analysis of the research. ,

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

Nanosafety Research—Are We on the Right Track? by Prof. Dr. Harald F. Krug. Angewandte Chemie International Edition DOI: 10.1002/anie.201403367 Article first published online: 10 OCT 2014

This is an open access paper.

Lung injury, carbon nanotubes, and aluminum oxide

It’s pretty much undisputed that long, multi-walled carbon nanotubes (MWCNTs) are likely to present a serious health hazard given their resemblance to asbestos fibres. It’s a matter of some concern that has resulted in a US National Institute of Occupational Safety and Health (NIOSH) recommendation for workplace exposure to all carbon nanotubes that is stringent. (My April 26, 2013 posting features the recommendation.)

Some recent research from North Carolina State University (NCSU) suggests that there may be a way to make long, multi-walled carbon nanotubes safer. From an Oct. 3, 2014 news item on Nanowerk,

A new study from North Carolina State University and the National Institute of Environmental Health Sciences (NIEHS) finds that coating multiwalled carbon nanotubes (CNTs) with aluminum oxide reduces the risk of lung scarring, or pulmonary fibrosis, in mice.

“This could be an important finding in the larger field of work that aims to predict and prevent future diseases associated with engineered nanomaterials,” says James Bonner, a professor of environmental and molecular toxicology at NC State …

An Oct. 3, 2014 NCSU news release, which originated the news item, describes the research in a little more detail,

Multiwalled CNTs have a wide array of applications, ranging from sporting goods to electronic devices. And while these materials have not been associated with adverse health effects in humans, research has found that multi-walled CNTs can cause pulmonary fibrosis and lung inflammation in animal models.

“Because multiwalled CNTs are increasingly used in a wide variety of products, it seems likely that humans will be exposed to them at some point,” Bonner says. “That means it’s important for us to understand these materials and the potential risk they pose to human health. The more we know, the better we’ll be able to engineer safer materials.”

For this study, the researchers used atomic layer deposition to coat multiwalled CNTs with a thin film of aluminum oxide and exposed mice to a single dose of the CNTs, via inhalation.

The researchers found that CNTs coated with aluminum oxide were significantly less likely to cause pulmonary fibrosis in mice. However, the coating of aluminum oxide did not prevent lung inflammation.

“The aluminum oxide coating doesn’t eliminate health risks related to multi-walled CNTs,” Bonner says, “but it does lower them.”

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

Atomic Layer Deposition Coating of Carbon Nanotubes with Aluminum Oxide Alters Pro-Fibrogenic Cytokine Expression by Human Mononuclear Phagocytes In Vitro and Reduces Lung Fibrosis in Mice In Vivo by Alexia J. Taylor, Christina D. McClure, Kelly A. Shipkowski, Elizabeth A. Thompson, Salik Hussain, Stavros Garantziotis, Gregory N. Parsons, and James C. Bonner. Published: September 12, 2014 DOI: 10.1371/journal.pone.0106870

This is an open access article.

The researchers offered this conclusion (part of the paper’s abstract),

These findings indicate that ALD [atomic layer deposition] thin film coating of MWCNTs with Al2O3 reduces fibrosis in mice and that in vitro phagocyte expression of IL-6, TNF-α, and OPN, but not IL-1β, predict MWCNT-induced fibrosis in the lungs of mice in vivo.

However, what I found most striking was this from the paper’s Discussion (section),

While the Al2O3 coating on MWCNTs appears to be the major factor that alters cytokine production in THP-1 and PBMCs in vitro, nanotube length is still likely an important determinant of the inflammatory and fibroproliferative effects of MWCNTs in the lung in vivo. In general, long asbestos fibers or rigid MWCNTs (i.e., >20 µm) remain in the lung and are much more persistent than shorter fibers or nanotubes [20]. Therefore, the nanotube fragments resulting from breakage of A-MWCNTs coated with 50 or 100 ALD cycles of Al2O3 would likely be cleared from the lungs more rapidly than uncoated long MWCNTs or those coated with only 10 ALD cycles of Al2O3. We observed that the fracturing of A-MWCNTs occurred only after sonication prior to administration to cells in vitro or mice in vivo. However, unsonicated A-MWCNTs could be more likely to fracture over time in tissues as compared to U-MWCNTs [uncoated]. We did not address the issue of A-MWCNT clearance before or after fracturing in the present study, but future work should focus the relative clearance rates from the lungs of mice exposed to A-MWCNTs in comparison to U-MWCNTs. Another potentially important consideration is whether or not ALD coating with Al2O3 alters the formation of a protein corona around MWCNTs. It is possible that differences in cytokine levels in the supernatants from cells treated with U- or A-MWCNTs could be due to differences in protein corona formation around functionalized MWCNTs that could modify the adsorptive capacity of the nanomaterial. Characterization of the protein corona and the adsorptive capacity for cytokines after ALD modification of MWCNTs should be another important focus for future work. [emphases mine]

In other words, researchers think coating long, MWCNTs with a certain type of aluminum might be safer due to its effect on various proteins and because coated MWCNTs are likely to fracture into smaller pieces and we know that short MWCNTs don’t seem to present a problem when inhaled.

Of course, there’s the research from Duke University (my Oct. 3, 2014 post) which suggests CNTs could present a different set of problems over time as they accumulate in the environment.

Carbon nanotube accumulation in Duke University’s (US) mesocosm

This Oct. 1, 2014 news item on ScienceDaily about carbon nanotubes accumulating in the wetlands is carefully worded,

A Duke University team has found that nanoparticles called single-walled carbon nanotubes accumulate quickly in the bottom sediments of an experimental wetland setting, an action they say could indirectly damage the aquatic food chain. [emphasis mine]

The results indicate little risk to humans ingesting the particles through drinking water, say scientists at Duke’s Center for the Environmental Implications of Nanotechnology (CEINT). But the researchers warn that, based on their previous research, the tendency for the nanotubes to accumulate in sediment could indirectly damage the aquatic food chain in the long term if the nanoparticles provide “Trojan horse” piggyback rides to other harmful molecules. [emphases mine]

There’s a lot of hedging (could, if) in the way this research is being described. I imagine the researchers are indicating they have concerns but have no wish to stimulate panic and worry.

An Oct. 1, 2014 Duke University news release (also on EurekAlert), which originated the news item, goes on to explain the interest in carbon nanotubes specifically,

Carbon nanotubes are rapidly becoming more common because of their usefulness in nanoelectric devices, composite materials and biomedicine.

The Duke study was done using small-scale replications of a wetland environment, called “mesocosms,” that include soil, sediments, microbes, insects, plants and fish. These ecosystems-in-a-box are “semi-closed,” meaning they get fresh air and rainwater but don’t drain to their surroundings. While not perfect representations of a natural environment, mesocosms provide a reasonable compromise between the laboratory and the real world.

“The wetland mesocosms we used are a much closer approximation of the natural processes constantly churning in the environment,” said Lee Ferguson, associate professor of civil and environmental engineering at Duke. “Although it’s impossible to know if our results are fully accurate to natural ecosystems, it is clear that the processes we’ve seen should be considered by regulators and manufacturers.”

Ferguson and his colleagues dosed the mesocosms with single-walled carbon nanotubes and measured their concentrations in the water, soil and living organisms during the course of a year. They found that the vast majority of the nanoparticles quickly accumulated in the sediment on the “pond” floor. However, they found no sign of nanoparticle buildup in any plants, insects or fish living in the mesocosms.

That sounds marvelous and then the researchers provide a few facts about carbon nanotubes,

While this is good news for humans or other animals drinking water after a potential spill or other contamination event, the accumulation in sediment does pose concerns for both sediment-dwelling organisms and the animals that eat them. Previous research has shown that carbon nanotubes take a long time to degrade through natural processes — if they do at all — and any chemical that binds to them cannot easily be degraded either.

“These nanoparticles are really good at latching onto other molecules, including many known organic contaminants,” said Ferguson. “Coupled with their quick accumulation in sediment, this may allow problematic chemicals to linger instead of degrading. The nanoparticle-pollutant package could then be eaten by sediment-dwelling organisms in a sort of ‘Trojan horse’ effect, allowing the adsorbed contaminants to accumulate up the food chain.

“The big question is whether or not these pollutants can be stripped away from the carbon nanotubes by these animals’ digestive systems after being ingested,” continued Ferguson. “That’s a question we’re working to answer now.”

It’s good to see this research is being followed up so quickly. I will keep an eye out for it and, in the meantime, wonder how the followup research will be conducted and what animals will be used for the tests.

Here’s a link to and a citation for the researchers’ most recent paper on possible ‘Trojan’ carbon nanotubes,

Fate of single walled carbon nanotubes in wetland ecosystems by Ariette Schierz, Benjamin Espinasse, Mark R. Wiesner, Joseph H. Bisesi, Tara Sabo-Attwood, and P. Lee Ferguson. Environ. Sci.: Nano, 2014, Advance Article DOI: 10.1039/C4EN00063C First published online 03 Sep 2014

This is an open access paper.

I have written about Duke University and its nanoparticle research in mesocosms before. Most recently, there was a Feb. 28, 2013 posting about work on silver nanoparticles which mentions research in the ‘mesocosm’ (scroll down about 50% of the way). There’s also an Aug. 15, 2011 posting which describes the ‘mesocosm’ project at some length.

For anyone unfamiliar with the Trojan horse story (from its Wikipedia entry; Note: Links have been removed),

The Trojan Horse is a tale from the Trojan War about the subterfuge that the Greeks used to enter the city of Troy and win the war. In the canonical version, after a fruitless 10-year siege, the Greeks constructed a huge wooden horse, and hid a select force of men inside. The Greeks pretended to sail away, and the Trojans pulled the horse into their city as a victory trophy. That night the Greek force crept out of the horse and opened the gates for the rest of the Greek army, which had sailed back under cover of night. The Greeks entered and destroyed the city of Troy, decisively ending the war.

OECD’s (Organization for Economic Cooperation and Development) latest report on its regulating manufactured nanomaterials questionnaire

As I have commented on several occasions, most of my information about Canada’s activities with regard to risk and nanomaterials comes from outside the country, notably the OECD (Organization for Economic Cooperation and Development).

Thank’s to Lynn Bergeson and her Sept. 17, 2014 posting on Nanotechnology Now for information about the latest publication from the OECD’s Working Party on Manufactured Nanomaterials (Note: a link has been removed),

On September 16, 2014, the Organization for Economic Cooperation and Development (OECD) published a document entitled Report of the Questionnaire on Regulatory Regimes for Manufactured Nanomaterials 2010-2011. … The Report summarizes responses to the Working Party on Manufactured Nanomaterials (WPMN) Questionnaire on Regulated Nanomaterials: 2010-2011, which was issued July 12, 2012. The Questionnaire contained four sections related to the oversight of nanomaterials in various OECD jurisdictions: regulatory updates; definitions and/or legal approaches for nanomaterials by jurisdiction; regulatory challenges; and opportunities for collaboration.

You can find all of the reports from the OECD’s WPMN here, including this latest report, which is no. 42, Report of the questionnaire on regulatory regimes for manufactured nanomaterials 2010-201, ENV/JM/MONO(2014)28. This is the third time there’s been a questionnaire and subsequent report.

I have quickly skimmed through the report and found a few interesting items about Canada’s current activities and collaborations vis à vis manufactured nanomaterials and risk. From the REPORT OF THE QUESTIONNAIRE ON REGULATORY REGIMES FOR MANUFACTURED NANOMATERIALS 2010-2011 which appears to have been published Sept. 4, 2014. I have had an unusually difficult time including excerpts from the report along with page numbers, etc. On the first try, after almost an hour of cutting and pasting, I was unable to get an intelligible version into a preview. To all intents and purposes the text was in place but the preview attempt resulted in a bizarre column of text overwriting the sidebar to the right of the posts.

I tried again and found that extensive reformatting was necessary and that the original table format has been lost. Nonetheless. you will find there are two pieces of legislation being reported on, CEPA (1999), which I believe has something to do with Environment Canada, and F&DA, which seems to be associated with Health Canada. One or both pieces of legislation may be referenced as per the OECD report. Page numbers from the document are included after the excerpted table entries.

Table 12: Hazard identification …

CEPA (1999)

Extrapolation between nanomaterials (i.e., choosing the appropriate surrogate)

Validity of testing methods and analytical tools to detect, characterize and measure nanomaterials

Participating in international forums such as the WPMN [OECD Working Party on Manufactured Nanomaterials], Expert Meetings, and ISO [International Standards Organization] TC/229 to support the generation and synthesis of appropriate science.

Support domestic research to help minimize challenges in hazard identification.

F&DA

Nanomaterial-based products under the F&DA (i.e. nanomedicines) can be associated with a broad spectrum of toxicities that are dependent on the nanoparticle properties (e.g. size, surface charge and solubility). However, there is currently no specific guidance document available for nanomedicines. Nanoparticle properties can significantly impact the PK profile/biodistribution of nanomedicines resulting in safety concerns. The components of the nanomedicines can also interact with the immune system and may trigger unique immunogenicity/immunotoxicity profile. Animals are generally not predictive of immunological responses for biologics (however, it may not be the case if the nanomedicine is a chemical drug), it is likely that immunological studies for nanomedicines should be carried out in human clinical trials. Long term studies may be required for a nanomaterial that persist and accumulated in particular tissues for an extended period of time.  p. 45

Table 13: Health and safety …

F&DA Veterinary Drugs

Due to the lack of a comprehensive understanding of the effects of nanomaterials on human, animal and environmental health, the Veterinary Drugs Directorate has not yet established a comprehensive occupational health and safety policy. Moreover, occupational health and safety is a shared responsibility between the federal and provincial governments in Canada.

At this time, there is no conclusive evidence linking exposure of nanomaterials from veterinary drugs or food sources to negative impact on human health. Additional research is necessary before a definitive policy approach can be taken.

F&DA Veterinary Drugs
Veterinary drugs including those that contain nanomaterials are regulated by the Food and Drugs Act and the Food and Drug Regulations. These provide the Veterinary Drugs Directorate with the authority to regulate the human health and safety aspects of veterinary drug products. The Regulations cover the aspects of the manufacturing, human and animal safety and efficacy assessment, and post-market surveillance of veterinary drug products including those containing nanomaterials. The latter products are subject to the same rigorous assessments as non-nanomaterial-containing veterinary drug products. p. 47

Table 14: Risk Assessment Methodologies

CEPA (1999)

Our understanding of risk assessments of nanomaterials is still evolving. Nanomaterials regulated under the industrial chemicals program employ a precautionary approach (i.e., exposure is typically mitigated), and nano-relevant information is requested whenever appropriate to conduct more informed risk assessments.

Canada also continues to work in international projects, such as the international life sciences institute NanoRelease project aimed at developing methods to quantify releases of nanomaterials from solid matrices.

Canada is also part of the Regulatory Cooperation Council (RCC) Nanotechnology Initiative with the United States. Under this project, Canada and the US are developing a classification scheme for nanomaterials to inform on the utilization of analogue/read- across, developing frameworks and common assumptions to better
inform risk assessments, and mining public and confidential use information to increase marketplace knowledge of nanomaterials. p. 49

Table 15: Risk Management and Nanomaterials in Commerce …

CEPA (1999)

Knowledge of use profiles of industrial nanomaterials; lack of specificity in risk
management measures given the overall lack of information and nomenclature systems for nanomaterials

Under the RCC, Canada and the US are gathering information on the uses of industrial nanomaterials in the two countries.  p. 52

Table 16: Research … (to support regulatory decisions)

CEPA (1999)

– foster domestic and international capacity to generate research on risk assessment priorities and needs
– applying research findings to nanomaterial risk assessments
– using research on nanomaterials to extrapolate to other nanomaterials

– Canada is actively supporting domestic and international research projects to help inform risk assessments.

F&DA

Filling knowledge gaps

HC [Health Canada] is conducting laboratory research to study the effects of lipid nanoparticles on the thermal stability of various recombinant proteins with the aim of identifying determinants of susceptibility to unintended deleterious interactions.  p. 55

Table 17: Impact of Regulatory Actions and Innovations and Economic Growth

CEPA (1999)

How to obtain the necessary information on nanomaterials, and how to regulate them in a manner that does not prevent them from offering their many benefits to society.

Consult with industry on proposed approaches. Focus information requests and requirements.  pp. 56/7

Table 18: Labelling Communication of Nanomaterials …

CEPA (1999)

Labelling of nanomaterials has not been considered under CEPA 1999 to date. p. 58

Table 19: Collaboration with other countries …

CEPA (1999) & F&DA

New Substances Program is involved in various international activities, including:
1) International Organization for Standardization (ISO) Technical Committee (TC) 229 on Nanotechnologies
2) Organisation for Economic Co-operation and Development (OECD) Working Party on
Manufactured Nanomaterials (WPMN) and Working Party on Nanotechnology (WPN)
3) Canada-US Regulatory Cooperation Council (RCC)
4) International Cooperation on Cosmetic Regulation (ICCR) – 2 Reports have been published
a) Criteria and Methods of Detection for Nanomaterials in Cosmetics:

http://www.fda.gov/downloads/InternationalPrograms/HarmonizationInitiatives/UCM235485.pdf

b) Methods for Characterization of Nanomaterials in Cosmetics

http://ec.europa.eu/consumers/sectors/cosmetics/files/pdf/iccr5_char_nano_en.pdf

5) International Regulators Nanotechnology Working Group
6) International Life Sciences Institutes (ILSI) – NanoRelease Food Additive Project
7) NanoLyse

In addition, for veterinary drugs, Health Canada collaborates with other regulatory agencies in USA, Europe, Australia, etc in the regulation of non-nanomaterial products and substances and would do the same for substances that are, or products containing nanomaterials pp. 59/60

Table 19: Expert Workshop Sponsorship [table number repetition noted]

CEPA (1999)

The Workshop on the Human and Environmental Risk Assessment of Nanomaterials convened by Health Canada and Environment Canada (March 24-26, 2010) provided an open forum for detailed dialogue on nanomaterials among science evaluators, research scientists and regulators. The Workshop was attended by 25 experts from Australia, Canada, Europe, Korea and the United States of America. In addition, seven observers attended the Workshop.

Regulatory Cooperation Council with the United States

F&DA Foods

Health Canada will be hosting a Joint NanoLyse/NanoRelease Workshop to discuss methods and safety of nanomaterials and share information from the respective projects. NanoLyse is an EU research consortium to develop methods of analysis for engineered nano-materials in foods and NanoRelease is an International Life Sciences Institute lead initiative to develop of analytical methods, alimentary canal models for uptake of engineered nano-materials and review of regulatory issues. p. 61

In any event, good luck with the reading and you can find out more about NanoLyse here and more about Canadian participation in the NanoRelease Food Additive Steering Committee project here.