Category Archives: health and safety

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.

Live webcast about data journalism on July 30, 2014 and a webinar featuring the 2014 NNI (US National Nanotechnology Initiative) EHS (Environment, Health and Safety) Progress Review on July 31, 2014

The Woodrow Wilson International Center for Scholars is hosting a live webcast on data journalism scheduled for July 30, 2014. For those us who are a little fuzzy as to what the term ‘data journalism’ means, this is probably a good opportunity to find out as per the description in the Wilson Center’s July 23, 2014 email announcement,

What is data journalism? Why does it matter? How has the maturing field of data science changed the direction of journalism and global investigative reporting? Our speakers will discuss the implications for policymakers and institutional accountability, and how the balance of power in information gathering is shifting worldwide, with implications for decision-making and open government.

This event will be live webcast and you may follow it on twitter @STIPcommonslab and #DataJournalism

Wednesday, July 30th, 2014
10am – 12pm EST
5th Floor Conference Room
[Woodrow Wilson International Center for Scholars
Ronald Reagan Building and International Trade Center
One Woodrow Wilson Plaza - 1300 Pennsylvania Ave., NW, Washington, DC 20004-3027
T 1-202-691-4000]

Speakers:

Alexander B. Howard
Writer and Editor, TechRepublic and founder of the blog “E Pluribus Unum.” Previously, he was a fellow at the Tow Center for Digital Journalism at Columbia University, the Ash Center at Harvard University and the Washington Correspondent for O’Reilly Media.

Kalev H. Leetaru
Yahoo! Fellow at Georgetown University, a Council Member of the World Economic Forum’s Global Agenda Council on the Future of Government, and a Foreign Policy Magazine Top 100 Global Thinker of 2013. For nearly 20 years he has been studying the web and building systems to interact with and understand the way it is reshaping our global society.

Louise Lief (Moderator)
Public Policy Scholar at the Wilson Center. Her project, “Science and the Media” explores innovative ways to make environmental science more accessible and useful to all journalists. She is investigating how new technologies and civic innovation tools can benefit both the media and science.

I believe you need to RSVP if you are attending in person but it’s not necessary for the livestream.

The other announcement comes via a July 23, 2014 news item on Nanowerk,

The National Nanotechnology Coordination Office (NNCO) will hold a public webinar on Thursday, July 31, 2014, to provide a forum to answer questions related to the “Progress Review on the Coordinated Implementation of the National Nanotechnology Initiative (NNI) 2011 Environmental, Health, and Safety Research Strategy.”

The full notice can be found on the US nano.gov website,

When: The webinar will be live on Thursday, July 31, 2014 from 12:00 pm-1 pm.
Where: Click here to register for the online webcast

While it’s open to the public, I suspect this is an event designed largely for highly interested parties such as the agencies involved in EHS activities, nongovernmental organizations that act as watchdogs, and various government policy wonks. Here’s how they describe their proposed discussions (from the event notice page),

Discussion during the webinar will focus on the research activities undertaken by NNI agencies to advance the current state of the science as highlighted in the Progress Review. Representative research activities as provided in the Progress Review will be discussed in the context of the 2011 NNI EHS Research Strategy’s six core research areas: Nanomaterial Measurement Infrastructure, Human Exposure Assessment, Human Health, the Environment, Risk Assessment and Risk Management Methods, and Informatics and Modeling.

How: During the question-and-answer segment of the webinar, submitted questions will be considered in the order received. A moderator will identify relevant questions and pose them to the panel of NNI agency representatives. Due to time constraints, not all questions may be addressed.  The moderator reserves the right to group similar questions and to skip questions, as appropriate. The NNCO will begin accepting questions and comments via email ([email protected]) at 1 pm on Thursday, July 24th (EDT) until the close of the webinar at 1 pm (EDT) on July 31st.

The Panelists:  The panelists for the webinar are subject matter experts from the Federal Government.

Additional Information: A public copy of the “Progress Review on the Coordinated Implementation of the National Nanotechnology Initiative 2011 Environmental, Health, and Safety Research Strategy” can be accessed at www.nano.gov/2014EHSProgressReview. The 2011 NNI EHS Research Strategy can be accessed at www.nano.gov/node/681.
– See more at: http://www.nano.gov/node/1166#sthash.Ipr0bFeP.dpuf

Carbon nanotubes: OCSiAl’s deal in Korea and their effect on the body after one year

I have two news items related only by their focus on carbon nanotubes. First, there’s a July 3, 2014 news item on Azonano featuring OCSiAl’s deal with a Korean company announced at NANO KOREA 2014,

At NANO KOREA 2014 OCSiAl announced an unprecedentedly large-scale deal with Korean company Applied Carbon Nano Technology [ACN] Co., Ltd. – one of the key industry players.

OCSiAl, the dominating graphene tubes manufacturer, that successfully presented its products and technology in Europe and USA, now to enter Asian nanotech markets. At NANO KOREA 2014 the company introduced TUBALL, the universal nanomodifier of materials featuring >75% of single wall carbon nanotubes, and announced signing of supply agreement with Applied Carbon Nano Technology Co., Ltd. (hereinafter referred to as ACN), a recognized future-oriented innovative company.

A July 3, 2014 OCSiAl news release, which originated the news item, describes the memorandum of understanding (MOU) in greater detail,

Under this MoU ACN would buy 100 kg of TUBALL. The upcoming deal is the first of OCSiAl’s Korean contracts to be performed in 2015 and it turns up the largest throughout SWCNT market, which annual turnover recently hardly reached 500 kg. The agreement is exceptionally significant as it opens fundamental opportunities for manufacturing of new nanomaterial-based product with the unique properties that were not even possible before.

“OCSiAl’s entry to Korean market required thorough preparation. We invested time and efforts to prove that our company, our technology and our products worth credibility, – says Viktor Kim, OCSiAl Vice President, – we urged major playmakers to take TUBALL for testing to verify the quality and effectiveness. We believe that ACN is more than an appropriate partner to start – they are experts at the market and they understand its future perspectives very clearly. We believe that mutually beneficial partnership with ACN will path the way for future contracts, since it will become indicative to other companies in Asia and all over the world”.

“It comes as no surprise that OCSiAl’s products here in Korea will be in a great demand soon. The country strives to become world’s leader in advanced technology, and we do realize the benefits of nanomaterial’s exploitation. TUBALL is a truly versatile additive which may be used across many market sectors, where adoption of new materials with top-class performance is essential”, – says Mr. Dae-Yeol Lee, CEO of ACN.

OCSiAl’s entering to Korean market will undoubtedly have a high-reaching impact on the industry. The recent merger with American Zyvex Technologies made OCSiAl the not only the world’s largest nanomaterial producer but a first-rate developer of modifiers of different materials based on carbon nanotubes. To its Korean partners OCSiAl offers TUBALL, the raw ‘as produced’ SWCNT material and masterbatches, which can be either custom-made or ready-to-use mixtures for different applications, including li-ion batteries, car tires, transparent conductive coatings and many others. “Since Korea is increasingly dynamic, our success here will build on continuous development of our product, – adds Viktor Kim, – And we are constantly working on new applications of graphene tubes to meet sophisticated demands of nanotech-savvy Korean consumers”.

OCSiAl’s Zyvex acquisition was mentioned in a June 23, 2014 posting here.

My second tidbit concerns a July 4, 2014 news item on Nanowerk about carbon nanotubes and their effect on the body (Note: A link has been removed),

Having perfected an isotope labeling method allowing extremely sensitive detection of carbon nanotubes in living organisms, CEA and CNRS researchers have looked at what happens to nanotubes after one year inside an animal. Studies in mice revealed that a very small percentage (0.75%) of the initial quantity of nanotubes inhaled crossed the pulmonary epithelial barrier and translocated to the liver, spleen, and bone marrow. Although these results cannot be extrapolated to humans, this work highlights the importance of developing ultrasensitive methods for assessing the behavior of nanoparticles in animals. It has been published in the journal ACS Nano (“Carbon Nanotube Translocation to Distant Organs after Pulmonary Exposure: Insights from in Situ 14C-Radiolabeling and Tissue Radioimaging”).

A July 1, 2014 CNRS [France Centre national de la recherche scientifique] press release, which originated the news item, describes both applications for carbon nanotubes and the experiment in greater detail,

Carbon nanotubes are highly specific nanoparticles with outstanding mechanical and electronic properties that make them suitable for use in a wide range of applications, from structural materials to certain electronic components. Their many present and future uses explain why research teams around the world are now focusing on their impact on human health and the environment.

Researchers from CEA and the CNRS joined forces to study the distribution over time of these nanoparticles in mice, following contamination by inhalation. They combined radiolabeling with radio imaging tools for optimum detection sensitivity. When making the carbon nanotubes, stable carbon (12C) atoms were replaced directly by radioactive carbon (14C) atoms in the very structure of the tubes. This method allows the use of carbon nanotubes similar to those produced in industry, but labeled with 14C. Radio imaging tools make it possible to detect up to twenty or so carbon nanotubes on an animal tissue sample.

A single dose of 20 µg [micrograms] of labeled nanotubes was administered at the start of the protocol, then monitored for one year. The carbon nanotubes were observed to translocate from the lungs to other organs, especially the liver, spleen, and bone marrow. The study demonstrates that these nanoparticles are capable of crossing the pulmonary epithelial barrier, or air-blood barrier. It was also observed that the quantity of carbon nanotubes in these organs rose steadily over time, thus demonstrating that these particles are not eliminated on this timescale. Further studies will have to determine whether this observation remains true beyond a year.

The CEA [French Alternative Energies and Atomic Energy Commission {Commissariat à l'énergie atomique et aux énergies alternatives}] and CNRS teams have developed highly specific skills that enable them to study the health and environmental impact of nanoparticles from various angles. Nanotoxicology and nanoecotoxicology research such as this is both a priority for society and a scientific challenge, involving experimental approaches and still emerging concepts.

This work is conducted as part of CEA’s interdisciplinary Toxicology and Nanosciences programs. These are management, coordination and support structures set up to promote multidisciplinary approaches for studying the potential impact on living organisms of various components of industrial interest, including heavy metals, radionuclides, and new products.

At the CNRS, these concerns are reflected in particular in major initiatives such as the International Consortium for the Environmental Implications of Nano Technology (i-CEINT), a CNRS-led international initiative focusing on the ecotoxicology of nanoparticles. CNRS teams also have a long tradition of close involvement in matters relating to standards and regulations. Examples of this include the ANR NanoNORMA program, led by the CNRS, or ongoing work within the French C’Nano network.

For those who would either prefer or like to check out  the French language version of the July 1, 2014 CNRS press release (La biodistribution des nanotubes de carbone dans l’organisme), it can be found here.

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

Carbon Nanotube Translocation to Distant Organs after Pulmonary Exposure: Insights from in Situ 14C-Radiolabeling and Tissue Radioimaging by Bertrand Czarny, Dominique Georgin, Fannely Berthon, Gael Plastow, Mathieu Pinault, Gilles Patriarche, Aurélie Thuleau, Martine Mayne L’Hermite, Frédéric Taran, and Vincent Dive. ACS Nano, 2014, 8 (6), pp 5715–5724 DOI: 10.1021/nn500475u Publication Date (Web): May 22, 2014

Copyright © 2014 American Chemical Society

This paper is behind a paywall.

European NanoSafety Cluster issues 2014 compendium of projects

A June 16, 2014 news item on Nanowerk profiles a recently published compendium of projects from the European NanoSafety Cluster (Note:  A link has been removed),

The EU NanoSafety Cluster is an initiative to maximise the synergies between the existing FP6 and FP7 projects addressing all aspects of nanosafety including toxicology, ecotoxicology, exposure assessment, mechanisms of interaction, risk assessment and standardisation.

About fifty projects are either completed or running and represent a total RTD investment of €137M, from the NMP and other programmes, under FP6 (13 projects, €31M) and FP7 (34 projects, €106M). [FP 6 and FP 7 are the Sixth Framework Programme and /seventh Framework, respectively; European Union-wide science funding programmes,the Horizon 2020 funding project supersedes FP 7]

These projects together with a significant number of projects supported by government resources in the EU member states and the FP7 associated states, and other projects addressing safety as side objective, represent the valuable efforts of the scientific and industrial research community for progress.

Here’s a description of the compendium from p. 5 of the PDF version of the Compendium of Projects in the European NanoSafety Cluster 2014 Edition,

This is the fourth edition of the Nanosafety Cluster compendium. It documents the status of important EU-funded projects on nanomaterial toxicity and exposure monitoring, integrated risk management, research infrastructure and coordination and support activities as well as regulatory-focussed research on nanosafety.

The compendium is not intended to be a guidance document for human health and environmental safety management of nanotechnologies, as such guidance documents already exist and are widely available.

Neither is the compendium intended to be a medium for the publication of scientific data and research results, as this task is covered by scientific conferences and the peer reviewed press.

The compendium aims to showcase the exciting and important European-wide collaborative research being undertaken to ensure the safe implementation of nanotechnologies, and to act as a one-stop-shop for all stakeholders interested in acquiring an overview of current research activities.This years’ compendium contains information on 30 running (or very recently finished) projects, including new entries describing the projects resulting from the last call of FP7, including eNanoMapper, NanoDefine and FutureNanoNeeds. …

What a good idea! I wonder if there’s an equivalent for the international scene?

DNA damage from engineered nanoparticles (zinc oxide, silver, silicon dioxide, cerium oxide and iron oxide)

Before launching into this research, there are a few provisos. This work was done in a laboratory, a highly specialized environment that does not mimic real-life conditions, and performed on animal cells (a hamster’s). As well, naturally occurring nanoparticles were not included (my Nov. 24, 2011 post has some information about naturally occurring nanomaterials including nanosilver which we have been ingesting for centuries).

That said, the studies from the Massachusetts Institute of Techology (MIT) and the Harvard School of Public Health (HSPH; last mentioned here in an April 2, 2014 post) are concerning (from an April 9, 2014 news item on Azonano).

A new study from MIT and the Harvard School of Public Health (HSPH) suggests that certain nanoparticles can also harm DNA. This research was led by Bevin Engelward, a professor of biological engineering at MIT, and associate professor Philip Demokritou, director of HSPH’s Center for Nanotechnology and Nanotoxicology.

The researchers found that zinc oxide nanoparticles, often used in sunscreen to block ultraviolet rays, significantly damage DNA. Nanoscale silver, which has been added to toys, toothpaste, clothing, and other products for its antimicrobial properties, also produces substantial DNA damage, they found.

The findings, published in a recent issue of the journal ACS Nano, relied on a high-speed screening technology to analyze DNA damage. This approach makes it possible to study nanoparticles’ potential hazards at a much faster rate and larger scale than previously possible.

More details about current testing requirements and the specific nanoparticles studied can be found in the April 8, 2014 MIT news release, which originated the news item,

The Food and Drug Administration does not require manufacturers to test nanoscale additives for a given material if the bulk material has already been shown to be safe. However, there is evidence that the nanoparticle form of some of these materials may be unsafe: Due to their immensely small size, these materials may exhibit different physical, chemical, and biological properties, and penetrate cells more easily.

“The problem is that if a nanoparticle is made out of something that’s deemed a safe material, it’s typically considered safe. There are people out there who are concerned, but it’s a tough battle because once these things go into production, it’s very hard to undo,” Engelward says.

The researchers focused on five types of engineered nanoparticles — silver, zinc oxide, iron oxide, cerium oxide, and silicon dioxide (also known as amorphous silica) — that are used industrially. Some of these nanomaterials can produce free radicals called reactive oxygen species, which can alter DNA. Once these particles get into the body, they may accumulate in tissues, causing more damage.

“It’s essential to monitor and evaluate the toxicity or the hazards that these materials may possess. There are so many variations of these materials, in different sizes and shapes, and they’re being incorporated into so many products,” says Christa Watson, a postdoc at HSPH and the paper’s lead author. “This toxicological screening platform gives us a standardized method to assess the engineered nanomaterials that are being developed and used at present.”

The researchers hope that this screening technology could also be used to help design safer forms of nanoparticles; they are already working with partners in industry to engineer safer UV-blocking nanoparticles. Demokritou’s lab recently showed that coating zinc oxide particles with a nanothin layer of amorphous silica can reduce the particles’ ability to damage DNA.

Given that Demokritou was part of a team that recently announced a new testing platform (Volumetric Centrifugation Method [VCM]) for nanoparticles as mentioned in my April 2, 2014 post, I was a little curious about the  platform for this project ( the CometChip) and, as always, curious about the results for all the tested engineered nanoparticles (Note: A link has been removed), from the news release,

Until now, most studies of nanoparticle toxicity have focused on cell survival after exposure. Very few have examined genotoxicity, or the ability to damage DNA — a phenomenon that may not necessarily kill a cell, but one that can lead to cancerous mutations if the damage is not repaired.

A common way to study DNA damage in cells is the so-called “comet assay,” named for the comet-shaped smear that damaged DNA forms during the test. The procedure is based on gel electrophoresis, a test in which an electric field is applied to DNA placed in a matrix, forcing the DNA to move across the gel. During electrophoresis, damaged DNA travels farther than undamaged DNA, producing a comet-tail shape.

Measuring how far the DNA can travel reveals how much DNA damage has occurred. This procedure is very sensitive, but also very tedious.

In 2010, Engelward and MIT professor Sangeeta Bhatia developed a much more rapid version of the comet assay, known as the CometChip. Using microfabrication technology, single cells can be trapped in tiny microwells within the matrix. This approach makes it possible to process as many as 1,000 samples in the time that it used to take to process just 30 samples — allowing researchers to test dozens of experimental conditions at a time, which can be analyzed using imaging software.

Wolfgang Kreyling, an epidemiologist at the German Research Center for Environmental Health who was not involved in the study, says this technology should help toxicologists catch up to the rapid rate of deployment of engineered nanoparticles (ENPs).

“High-throughput screening platforms are desperately needed,” Kreyling says. “The proposed approach will be not only an important tool for nanotoxicologists developing high-throughput screening strategies for the assessment of possible adverse health effects associated with ENPs, but also of great importance for material scientists working on the development of novel ENPs and safer-by-design approaches.”

Using the CometChip, the MIT and HSPH researchers tested the nanoparticles’ effects on two types of cells that are commonly used for toxicity studies: a type of human blood cells called lymphoblastoids, and an immortalized line of Chinese hamster ovary cells.

Zinc oxide and silver produced the greatest DNA damage in both cell lines. At a concentration of 10 micrograms per milliliter — a dose not high enough to kill all of the cells — these generated a large number of single-stranded DNA breaks.

Silicon dioxide, which is commonly added during food and drug production, generated very low levels of DNA damage. Iron oxide and cerium oxide also showed low genotoxicity.

Happily the researchers are taking a pragmatic approach to the results (from the news release),

More studies are needed to determine how much exposure to metal oxide nanoparticles could be unsafe for humans, the researchers say.

“The biggest challenge we have as people concerned with exposure biology is deciding when is something dangerous and when is it not, based on the dose level. At low levels, probably these things are fine,” Engelward says. “The question is: At what level does it become problematic, and how long will it take for us to notice?”

One of the areas of greatest concern is occupational exposure to nanoparticles, the researchers say. Children and fetuses are also potentially at greater risk because their cells divide more often, making them more vulnerable to DNA damage.

The most common routes that engineered nanoparticles follow into the body are through the skin, lungs, and stomach, so the researchers are now investigating nanoparticle genotoxicity on those cell types. They are also studying the effects of other engineered nanoparticles, including metal oxides used in printer and photocopier toner, which can become airborne and enter the lungs.

Kudos to the writer for the clarity and care shown here (I think it’s Anne Trafton but MIT is not including bylines as it did previously, so I’m uncertain).

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

High-Throughput Screening Platform for Engineered Nanoparticle-Mediated Genotoxicity Using CometChip Technology by Christa Watson, Jing Ge, Joel Cohen, Georgios Pyrgiotakis, Bevin P. Engelward, and Philip Demokritou. ACS Nano, 2014, 8 (3), pp 2118–2133 DOI: 10.1021/nn404871p Publication Date (Web): March 11, 2014
Copyright © 2014 American Chemical Society

This article is behind a paywall.

New method for measuring risks and quantities of engineered nanomaterials delivered to cells

Despite all the talk about testing engineered nanoparticles and their possible effects on cells, there are problems with the testing process which researchers at the Harvard School of Public Health (HSPH) claim to have addressed (h/t Nanowerk, March 28, 2014).

A March 28, 2014 HSPH press release explains the interest in testing the effects of engineered nanomaterials/nanoparticles on health and describes some of the problems associated with testing their interaction with cells,

Thousands of consumer products containing engineered nanoparticles — microscopic particles found in everyday items from cosmetics and clothing to building materials — enter the market every year. Concerns about possible environmental health and safety issues of these nano-enabled products continue to grow with scientists struggling to come up with fast, cheap, and easy-to-use cellular screening systems to determine possible hazards of vast libraries of engineered nanomaterials. However, determining how much exposure to engineered nanoparticles could be unsafe for humans requires precise knowledge of the amount (dose) of nanomaterials interacting with cells and tissues such as lungs and skin.

With chemicals, this is easy to do but when it comes to nanoparticles suspended in physiological media, this is not trivial. Engineered nanoparticles in biological media interact with serum proteins and form larger agglomerates which alter both their so called effective density and active surface area and ultimately define their delivery to cell dose and bio-interactions. This behavior has tremendous implications not only in measuring the exact amount of nanomaterials interacting with cells and tissue but also in defining hazard rankings of various engineered nanomaterials (ENMs). As a result, thousands of published cellular screening assays are difficult to interpret and use for risk assessment purposes.

The press release goes on to describe the new technique (Note: Links have been removed),

Scientists at the Center for Nanotechnology and Nanotoxicology at Harvard School of Public Health (HSPH) have discovered a fast, simple, and inexpensive method to measure the effective density of engineered nanoparticles in physiological fluids, thereby making it possible to accurately determine the amount of nanomaterials that come into contact with cells and tissue in culture.

The method, referred to as the Volumetric Centrifugation Method (VCM), was published in the March 28, 2014 Nature Communications.

The new discovery will have a major impact on the hazard assessment of engineered nanoparticles, enabling risk assessors to perform accurate hazard rankings of nanomaterials using cellular systems. Furthermore, by measuring the composition of nanomaterial agglomerates in physiologic fluids, it will allow scientists to design more effective nano-based drug delivery systems for nanomedicine applications.

“The biggest challenge we have in assessing possible health effects associated with nano exposures is deciding when something is hazardous and when it is not, based on the dose level. At low levels, the risks are probably miniscule,” said senior author Philip Demokritou, associate professor of aerosol physics in the Department of Environmental Health at HSPH. “The question is: At what dose level does nano-exposure become problematic? The same question applies to nano-based drugs when we test their efficiency using cellular systems. How much of the administered nano-drug will come in contact with cells and tissue? This will determine the effective dose needed for a given cellular response,” Demokritou said.

Federal regulatory agencies do not require manufacturers to test engineered nanoparticles, if the original form of the bulk material has already been shown to be safe. However, there is evidence that some of these materials could be more harmful in the nanoscale — a scale at which materials may penetrate cells and bypass biological barriers more easily and exhibit unique physical, chemical, and biological properties compared to larger size particles. Nanotoxicologists are struggling to develop fast and cheap toxicological screening cellular assays to cope with the influx of vast forms of engineered nanomaterials and avoid laborious and expensive animal testing. However, this effort has been held back due to the lack of a simple-to-use, fast, method to measure the dose-response relationships and possible toxicological implications. While biological responses are fairly easy to measure, scientists are struggling to develop a fast method to assess the exact amount or dose of nanomaterials coming in contact with cells in biological media.

“Dosimetric considerations are too complicated to consider in nano-bio assessments, but too important to ignore,” Demokritou said. “Comparisons of biological responses to nano-exposures usually rely on guesstimates based on properties measured in the dry powder form (e.g., mass, surface area, and density), without taking into account particle-particle and particle-fluid interactions in biological media. When suspended in fluids, nanoparticles typically form agglomerates that include large amounts of the suspending fluid, and that therefore have effective densities much lower than that of dry material. This greatly influences the particle delivery to cells, and reduces the surface area available for interactions with cells,” said Glen DeLoid, research associate in the Department of Environmental Health, one of the two lead authors of the study. “The VCM method will help nanobiologists and regulators to resolve conflicting in vitro cellular toxicity data that have been reported in the literature for various nanomaterials. These disparities likely result from lack of or inaccurate dosimetric considerations in nano-bio interactions in a cellular screening system,” said Joel Cohen, doctoral student at HSPH and one of the two lead authors of the study.

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

Estimating the effective density of engineered nanomaterials for in vitro dosimetry by Glen DeLoid, Joel M. Cohen, Tom Darrah, Raymond Derk, Liying Rojanasakul, Georgios Pyrgiotakis, Wendel Wohlleben, & Philip Demokritou. Nature Communications 5, Article number: 3514 doi:10.1038/ncomms4514 Published 28 March 2014

This paper is behind a paywall but a free preview is available via ReadCube Access.

NANoReg invites you to April 11, 2014 workshop in Athens, Greece

For anyone interested in nanomaterials and/or attending an EHS-themed (environment, health, and safety) event in Athens, Greece, NANoREG is holding an April 2014 workshop at the Industrial Technologies 2014 conference (April 9 – 11, 2014). From a March 14, 2014 news item on Nanowerk (Some links have been removed),

NANoREG will identify EHS [environment, health, and safety] aspects that are most relevant from a regulatory point of view. It will provide tools for testing the EHS aspects and the assessment and management of the risks to the regulators and other stakeholders.

To assure that the final results of the project can be implemented in an efficient and effective way, Industry and Regulators are strongly involved in the project.
We kindly invite you to attend the NANoREG workshop and to give your opinion on the regulatory testing of nanomaterials, as a valuable contribution to future economic success of nanotechnology!

The workshop will take place on Friday, April 11, 2014 from 11:15 a.m. to 1:30 p.m. in Athens, Greece, as part of the Industrial Technologies 2014 event. For registration please use the offi cial registration portal: www.naturalway.gr/industrial_technologies

Here’s more about the workshop from the NANoREG workshop page on the Industrial Technologies 2014 website,

1. The NANoREG approach: Answers from Science to the questions/needs of Industry and the Regulation Authorities.
2. First entrypoints, the regulatory questions and needs, an overview, matching of needs
3. NANoREG results: Materials, SOPs and the advancement of Regulatory Risk Assessment and Testing.
4.Overview of the NANoREG projects.
5. Whe window for industry participation, keeping pace with innovation.
6. Modes of collaboartion [sic] for industry.
7. Outlook

A joint workshops of EU FP7 Projects SANOWORK, nanoMICEX and Scaffold funded under the topic NMP.2011.1.3-2 “Worker Protection and exposure risk management strategies for nanomaterials production, use and disposal”, will focus on the main achievements of the three Projects in the related area. All three projects are committed to support the needs of companies and aim to provide a practical overview of the results of current research in the field of management of exposure to nanomaterials.

Here are links to the other three projects collaborating on the NANoREG workshop  SANOWORKnanoMICEX, and Scaffold.

Surprising facts about silver nanoparticles from the University of Michigan

Dr. Andrew Maynard, Director of the University of Michigan’s Risk Science Center, has featured seven surprising facts about silver nanoparticles in his latest video in the Risk Bites series. Before getting to the video,here’s an introduction to the topic of silver nanoparticles from a Feb. 18, 2014 posting by Ishani Hewage on the University of Michigan’s Risk Sense blog (Note: A link has been removed),

Silver – known for its germ-killing capabilities – has been used for thousands of years. In recent times though, concerns have been raised over the potential health and environmental risks associated with one particular form of silver that has been used increasingly in a range of products: engineered silver nanoparticle. In this week’s Risk Bites, Andrew Maynard, director of the Risk Science Center, rounds-up seven aspects of silver nanoparticles that might help you weigh up their risks and benefits.

“Silver has long been used for its medicinal properties,” says Andrew. “People used to intentionally dose themselves with silver nanoparticles in the form a silver laced tonic as a cure-all.”

Nowadays, the use of silver nanoparticles is not just limited to the medical field. The military, athletes and manufactures are increasingly using them to develop smart new technologies that inhibit bacterial growth and enhance overall performance.  These microscopically small particles make it easier to get silver into products without compromising them …

Without more ado, here’s the video, ‘7 surprising facts about silver nanoparticles and health':

Both the blog posting and this link will lead you to more information about silver nanoparticles.

Food and nanotechnology (as per Popular Mechanics) and zinc oxide nanoparticles in soil (as per North Dakota State University)

I wouldn’t expect to find an article about food in a magazine titled Popular Mechanics but there it is, a Feb. 19,2014 article by Christina Ortiz (Note: A link has been removed),

For a little more than a decade, the food industry has been using nanotechnology to change the way we grow and maintain our food. The grocery chain Albertsons currently has a list of nanotech-touched foods in its home brand, ranging from cookies to cheese blends.

Nanotechnology use in food has real advantages: The technology gives producers the power to control how food looks, tastes, and even how long it lasts.

Looks Good and Good for You?

The most commonly used nanoparticle in foods is titanium dioxide. It’s used to make foods such as yogurt and coconut flakes look as white as possible, provide opacity to other food colorings, and prevent ingredients from caking up. Nanotech isn’t just about aesthetics, however. The biggest potential use for this method involves improving the nutritional value of foods.

Nano additives can enhance or prevent the absorption of certain nutrients. In an email interview with Popular Mechanics, Jonathan Brown, a research fellow at the University of Minnesota, says this method could be used to make mayonnaise less fattening by replacing fat molecules with water droplets.

I did check out US grocer, Albertson’s list of ‘nanofoods’, which they provide and discovered that it’s an undated listing on the Project of Emerging Nanotechnologies’ Consumer Products Inventory (CPI). The inventory has been revived recently after lying moribund for a few years (my Oct. 28, 2013 posting describes the fall and rise) and I believe that this 2013 CPI incarnation includes some oversight and analysis of the claims made, which the earlier version did not include. Given that the Albertson’s list is undated it’s difficult to assess the accuracy of the claims regarding the foodstuffs.

If you haven’t read about nanotechnology and food before, the Ortiz article provides a relatively even-handed primer although it does end on a cautionary note. In any event, it was interesting to get a bit of information about the process of ‘nanofood’ regulation in the US and other jurisdictions (from the Ortiz article),

Aside from requiring manufacturers to provide proof that nanotechnology foods are safe, the FDA has yet to implement specific testing of its own. But many countries are researching ways to balance innovation and regulation in this market. In 2012 the European Food Safety Authority (EFSA) released an annual risk assessment report outlining how the European Union is addressing the issue of nanotech in food. In Canada the Food Directorate “is taking a case-by-case approach to the safety assessment of food products containing or using nanomaterials.”

I featured the FDA’s efforts regarding regulation and ‘nanofood’ in an April 23, 2012 posting,

It looks to me like this [FDA's draft guidance for 'nanofoods'] is an attempt to develop a relationship where the industry players in the food industry to police their nanotechnology initiatives with the onus being on industry to communicate with the regulators in a continuous process, if not at the research stage certainly at the production stage.

At least one of the primary issues with any emerging technology revolves around the question of risk. Do we stop all manufacturing and development of nanotechnology-enabled food products until we’ve done the research? That question assumes that taking any risks is not worth the currently perceived benefits. The corresponding question, do we move forward and hope for the best? does get expressed perhaps not quite so baldly; I have seen material which suggests that research into risks needlessly hampers progress.

After reading on this topic for five or so years, my sense is that most people are prepared to combine the two approaches, i.e., move forward while researching possible risks. The actual conflicts seem to centre around these questions, how quickly do we move forward; how much research do we need; and what is an acceptable level of risk?

On the topic of researching the impact that nanoparticles might have on plants (food or otherwise), a January 24, 2013 North Dakota State University (NDSU) news release highlights a student researcher’s work on soil, plants, and zinc oxide nanoparticles,

NDSU senior Hannah Passolt is working on a project that is venturing into a very young field of research. The study about how crops’ roots absorb a microscopic nutrient might be described as being ahead of the cutting-edge.

In a laboratory of NDSU’s Wet Ecosystem Research Group, in collaboration with plant sciences, Passolt is exploring how two varieties of wheat take up extremely tiny pieces of zinc, called nanoparticles, from the soil.

As a point of reference, the particles Passolt is examining are measured at below 30 nanometers. A nanometer is 1 billionth of a meter.

“It’s the mystery of nanoparticles that is fascinating to me,” explained the zoology major from Fargo. “The behavior of nanoparticles in the environment is largely unknown as it is a very new, exciting science. This type of project has never been done before.”

In Passolt’s research project, plants supplied by NDSU wheat breeders are grown in a hydroponic solution, with different amounts of zinc oxide nanoparticles introduced into the solution.

Compared to naturally occurring zinc, engineered zinc nanoparticles can have very different properties. They can be highly reactive, meaning they can injure cells and tissues, and may cause genetic damage. The plants are carefully observed for any changes in growth rate and appearance. When the plants are harvested, researchers will analyze them for actual zinc content.

“Zinc is essential for a plant’s development. However, in excess, it can be harmful,” Passolt said. “In one of my experiments, we are using low and high levels of zinc, and the high concentrations are showing detrimental effects. However, we will have to analyze the plants for zinc concentrations to see if there have been any effects from the zinc nanoparticles.”

Passolt has conducted undergraduate research with the Wet Ecosystem Research Group for the past two years. She said working side-by-side with Donna Jacob, research assistant professor of biological sciences; Marinus Otte; professor of biological sciences; and Mohamed Mergoum, professor of plant sciences, has proven to be challenging, invigorating and rewarding.

“I’ve gained an incredible skill set – my research experience has built upon itself. I’ve gotten to the point where I have a pretty big role in an important study. To me, that is invaluable,” Passolt said. “To put effort into something that goes for the greater good of science is a very important lesson to learn.”

According to Jacob, Passolt volunteered two years ago, and she has since become an important member of the group. She has assisted graduate students and worked on her own small project, the results of which she presented at regional and international scientific conferences. “We offered her this large, complex experiment, and she’s really taken charge,” Jacob said, noting Passolt assisted with the project’s design, handled care of the plants and applied the treatments. When the project is completed, Passolt will publish a peer-reviewed scientific article.

“There is nothing like working on your own experiment to fully understand science,” Jacob said. “Since coming to NDSU in 2006, the Wet Ecosystem Research Group has worked with more than 50 undergraduates, possible only because of significant support from the North Dakota IDeA Networks of Biomedical Research Excellence program, known as INBRE, of the NIH National Center for Research Resources.”

Jacob said seven undergraduate students from the lab have worked on their own research projects and presented their work at conferences. Two articles, so far, have been published by undergraduate co-authors. “I believe the students gain valuable experience and an understanding of what scientists really do during fieldwork and in the laboratory,” Jacob said. “They see it is vastly different from book learning, and that scientists use creativity and ingenuity daily. I hope they come away from their experience with some excitement about research, in addition to a better resume.”

Passolt anticipates the results of her work could be used in a broader view of our ecosystem. She notes zinc nanoparticles are an often-used ingredient in such products as lotions, sunscreens and certain drug delivery systems. “Zinc nanoparticles are being introduced into the environment,” she said. “It gets to plants at some point, so we want to see if zinc nanoparticles have a positive or negative effect, or no effect at all.”

Researching nanoparticles the effects they might have on the environment and on health is a complex process as there are many types of nanoparticles some of which have been engineered and some of which occur naturally, silver nanoparticles being a prime example of both engineered and naturally occurring nanoparticles. (As well, the risks may lie more with interactions between nanomaterials.) For an example of research, which seems similar to the NDSU effort, there’s this open access research article,

Low Concentrations of Silver Nanoparticles in Biosolids Cause Adverse Ecosystem Responses under Realistic Field Scenario by Benjamin P. Colman, Christina L. Arnaout, Sarah Anciaux, Claudia K. Gunsch, Michael F. Hochella Jr, Bojeong Kim, Gregory V. Lowry,  Bonnie M. McGill, Brian C. Reinsch, Curtis J. Richardson, Jason M. Unrine, Justin P. Wright, Liyan Yin, and Emily S. Bernhardt. PLoS ONE 2013; 8 (2): e57189 DOI: 10.1371/journal.pone.0057189

One last comment, the Wet Ecosystem Research Group (WERG) mentioned in the news release about Passolt has an interesting history (from the homepage; Note: Links have been removed),

Marinus Otte and Donna Jacob brought WERG to the Department of Biological Sciences in the Fall of 2006.  Prior to that, the research group had been going strong at University College Dublin, Ireland, since 1992.

The aims for the research group are to train graduate and undergraduate students in scientific research, particularly wetlands, plants, biogeochemistry, watershed ecology and metals in the environment.  WERG research  covers a wide range of scales, from microscopic (e.g. biogeochemical processes in the rhizosphere of plants) to landscape (e.g. chemical and ecological connectivity between prairie potholes across North Dakota).  Regardless of the scale, the central theme is biogeochemistry and the interactions between multiple elements in wet environments.

The group works to collaborate with a variety of researchers, including soil scientists, geologists, environmental engineers, microbiologists, as well as with groups underpinning management of natural resources, such the Minnesota Department of Natural Resources, the Department of Natural Resources of Red Lake Indian Reservation, and the North Dakota Department of Health, Division of Water Quality.

Currently, WERG has several projects, mostly in North Dakota and Minnesota.  Otte and Jacob are also Co-directors of the North Dakota INBRE Metal Analysis Core, providing laboratory facilities and mentoring for researchers in undergraduate colleges throughout the state. Otte and Jacob are also members of the Upper Midwest Aerospace Consortium.