Tag Archives: lungs

Health Canada advisory: Face masks that contain graphene may pose health risks

Since COVID-19, we’ve been advised to wear face masks. It seems some of them may not be as safe as we assumed. First, the Health Canada advisory that was issued today, April 2, 2021 and then excerpts from an in-depth posting by Dr. Andrew Maynard (associate dean in the Arizona State University College of Global Futures) about the advisory and the use of graphene in masks.

From the Health Canada Recalls & alerts: Face masks that contain graphene may pose health risks webpage,


  • Product: Face masks labelled to contain graphene or biomass graphene.
  • Issue: There is a potential that wearers could inhale graphene particles from some masks, which may pose health risks.
  • What to do: Do not use these face masks. Report any health product adverse events or complaints to Health Canada.


Health Canada is advising Canadians not to use face masks that contain graphene because there is a potential that they could inhale graphene particles, which may pose health risks.

Graphene is a novel nanomaterial (materials made of tiny particles) reported to have antiviral and antibacterial properties. Health Canada conducted a preliminary scientific assessment after being made aware that masks containing graphene have been sold with COVID-19 claims and used by adults and children in schools and daycares. Health Canada believes they may also have been distributed for use in health care settings.

Health Canada’s preliminary assessment of available research identified that inhaled graphene particles had some potential to cause early lung toxicity in animals. However, the potential for people to inhale graphene particles from face masks and the related health risks are not yet known, and may vary based on mask design. The health risk to people of any age is not clear. Variables, such as the amount and duration of exposure, and the type and characteristics of the graphene material used, all affect the potential to inhale particles and the associated health risks. Health Canada has requested data from mask manufacturers to assess the potential health risks related to their masks that contain graphene.

Until the Department completes a thorough scientific assessment and has established the safety and effectiveness of graphene-containing face masks, it is taking the precautionary approach of removing them from the market while continuing to gather and assess information. Health Canada has directed all known distributors, importers and manufacturers to stop selling and to recall the affected products. Additionally, Health Canada has written to provinces and territories advising them to stop distribution and use of masks containing graphene. The Department will continue to take appropriate action to stop the import and sale of graphene face masks.

Products affected

Face masks labelled as containing graphene or biomass graphene.

What you should do

  • Do not use face masks labelled to contain graphene or biomass graphene.
  • Consult your health care provider if you have used graphene face masks and have health concerns, such as new or unexplained shortness of breath, discomfort or difficulty breathing.
  • Report any health product adverse events or complaints regarding graphene face masks to Health Canada.

Dr. Andrew Maynard’s Edge of Innovation series features a March 26, 2021 posting about the use of graphene in masks (Note: Links have been removed),

Face masks should protect you, not place you in greater danger. However, last Friday Radio Canada revealed that residents of Quebec and Ottawa were being advised not to use specific types of graphene-containing masks as they could potentially be harmful.

The offending material in the masks is graphene — a form of carbon that consists of nanoscopically thin flakes of hexagonally-arranged carbon atoms. It’s a material that has a number of potentially beneficial properties, including the ability to kill bacteria and viruses when they’re exposed to it.

Yet despite its many potential uses, the scientific jury is still out when it comes to how safe the material is.

As with all materials, the potential health risks associated with graphene depend on whether it can get into the body, where it goes if it can, what it does when it gets there, and how much of it is needed to cause enough damage to be of concern.

Unfortunately, even though these are pretty basic questions, there aren’t many answers forthcoming when it comes to the substance’s use in face masks.

Early concerns around graphene were sparked by previous research on another form of carbon — carbon nanotubes. It turns out that some forms of these fiber-like materials can cause serious harm if inhaled. And following on from research here, a natural next-question to ask is whether carbon nanotubes’ close cousin graphene comes with similar concerns.

Because graphene lacks many of the physical and chemical aspects of carbon nanotubes that make them harmful (such as being long, thin, and hard for the body to get rid of), the indications are that the material is safer than its nanotube cousins. But safer doesn’t mean safe. And current research indicates that this is not a material that should be used where it could potentially be inhaled, without a good amount of safety testing first.

[downloaded from https://medium.com/edge-of-innovation/how-safe-are-graphene-based-face-masks-b88740547e8c] Original source: Wikimedia

When it comes to inhaling graphene, the current state of the science indicates that if the material can get into the lower parts of the lungs (the respirable or alveolar region) it can lead to an inflammatory response at high enough concentrations.

There is some evidence that adverse responses are relatively short-lived, and that graphene particles can be broken down and disposed of by the lungs’ defenses.

This is good news as it means that there are less likely to be long-term health impacts from inhaling the material.

There’s also evidence that graphene, unlike some forms of thin, straight carbon nanotubes, does not migrate to the outside layers of the lungs where it could potentially do a lot more damage.

Again, this is encouraging as it suggests that graphene is unlikely to lead to serious long-term health impacts like mesothelioma.

However, research also shows that this is not a benign material. Despite being made of carbon — and it’s tempting to think of carbon as being safe, just because we’re familiar with it — there is some evidence that the jagged edges of some graphene particles can harm cells, leading to local damage as the body responds to any damage the material causes.

There are also concerns, although they are less well explored in the literature, that some forms of graphene may be carriers for nanometer-sized metal particles that can be quite destructive in the lungs. This is certainly the case with some carbon nanotubes, as the metallic catalyst particles used to manufacture them become embedded in the material, and contribute to its toxicity.

The long and short of this is that, while there are still plenty of gaps in our knowledge around how much graphene it’s safe to inhale, inhaling small graphene particles probably isn’t a great idea unless there’s been comprehensive testing to show otherwise.

And this brings us to graphene-containing face masks.


Here, it’s important to stress that we don’t yet know if graphene particles are being released and, if they are, whether they are being released in sufficient quantities to cause health effects. And there are indications that, if there are health risks, these may be relatively short-term — simply because graphene particles may be effectively degraded by the lungs’ defenses.

At the same time, it seems highly irresponsible to include a material with unknown inhalation risks in a product that is intimately associated with inhalation. Especially when there are a growing number of face masks available that claim to use graphene.

… There are millions of graphene face masks and respirators being sold and used around the world. And while the unfolding news focuses on Quebec and one particular type of face mask, this is casting uncertainty over the safety of any graphene-containing masks that are being sold.

And this uncertainty will persist until manufacturers and regulators provide data indicating that they have tested the products for the release and subsequent inhalation of fine graphene particles, and shown the risks to be negligible.

I strongly recommend reading, in its entirety , Dr. Maynard’s March 26, 2021 posting, Which he has updated twice since first posting the story.

In short. you may want to hold off before buying a mask with graphene until there’s more data about safety.

Human lung enzyme can degrade graphene

Caption: A human lung enzyme can biodegrade graphene. Credit: Fotolia Courtesy: Graphene Flagship

The big European Commission research programme, Grahene Flagship, has announced some new work with widespread implications if graphene is to be used in biomedical implants. From a August 23, 2018 news item on ScienceDaily,

Myeloperoxidase — an enzyme naturally found in our lungs — can biodegrade pristine graphene, according to the latest discovery of Graphene Flagship partners in CNRS, University of Strasbourg (France), Karolinska Institute (Sweden) and University of Castilla-La Mancha (Spain). Among other projects, the Graphene Flagship designs based like flexible biomedical electronic devices that will interfaced with the human body. Such applications require graphene to be biodegradable, so our body can be expelled from the body.

An August 23, 2018 Grapehene Flagship press release (mildly edited version on EurekAlert), which originated the news item, provides more detail,

To test how graphene behaves within the body, researchers analysed how it was broken down with the addition of a common human enzyme – myeloperoxidase or MPO. If a foreign body or bacteria is detected, neutrophils surround it and secrete MPO, thereby destroying the threat. Previous work by Graphene Flagship partners found that MPO could successfully biodegrade graphene oxide.

However, the structure of non-functionalized graphene was thought to be more resistant to degradation. To test this, the team looked at the effects of MPO ex vivo on two graphene forms; single- and few-layer.

Alberto Bianco, researcher at Graphene Flagship Partner CNRS, explains: “We used two forms of graphene, single- and few-layer, prepared by two different methods in water. They were then taken and put in contact with myeloperoxidase in the presence of hydrogen peroxide. This peroxidase was able to degrade and oxidise them. This was really unexpected, because we thought that non-functionalized graphene was more resistant than graphene oxide.”

Rajendra Kurapati, first author on the study and researcher at Graphene Flagship Partner CNRS, remarks how “the results emphasize that highly dispersible graphene could be degraded in the body by the action of neutrophils. This would open the new avenue for developing graphene-based materials.”

With successful ex-vivo testing, in-vivo testing is the next stage. Bengt Fadeel, professor at Graphene Flagship Partner Karolinska Institute believes that “understanding whether graphene is biodegradable or not is important for biomedical and other applications of this material. The fact that cells of the immune system are capable of handling graphene is very promising.”

Prof. Maurizio Prato, the Graphene Flagship leader for its Health and Environment Work Package said that “the enzymatic degradation of graphene is a very important topic, because in principle, graphene dispersed in the atmosphere could produce some harm. Instead, if there are microorganisms able to degrade graphene and related materials, the persistence of these materials in our environment will be strongly decreased. These types of studies are needed.” “What is also needed is to investigate the nature of degradation products,” adds Prato. “Once graphene is digested by enzymes, it could produce harmful derivatives. We need to know the structure of these derivatives and study their impact on health and environment,” he concludes.

Prof. Andrea C. Ferrari, Science and Technology Officer of the Graphene Flagship, and chair of its management panel added: “The report of a successful avenue for graphene biodegradation is a very important step forward to ensure the safe use of this material in applications. The Graphene Flagship has put the investigation of the health and environment effects of graphene at the centre of its programme since the start. These results strengthen our innovation and technology roadmap.”

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

Degradation of Single‐Layer and Few‐Layer Graphene by Neutrophil Myeloperoxidase by Dr. Rajendra Kurapati, Dr. Sourav P. Mukherjee, Dr. Cristina Martín, Dr. George Bepete, Prof. Ester Vázquez, Dr. Alain Pénicaud, Prof. Dr. Bengt Fadeel, Dr. Alberto Bianco. Angewandte Chemie https://doi.org/10.1002/anie.201806906 First published: 13 July 2018

This paper is behind a paywall.

Explaining the link between air pollution and heart disease?

An April 26, 2017 news item on Nanowerk announces research that may explain the link between heart disease and air pollution (Note: A link has been removed),

Tiny particles in air pollution have been associated with cardiovascular disease, which can lead to premature death. But how particles inhaled into the lungs can affect blood vessels and the heart has remained a mystery.

Now, scientists have found evidence in human and animal studies that inhaled nanoparticles can travel from the lungs into the bloodstream, potentially explaining the link between air pollution and cardiovascular disease. Their results appear in the journal ACS Nano (“Inhaled Nanoparticles Accumulate at Sites of Vascular Disease”).

An April 26, 2017 American Chemical Society news release on EurekAlert, which originated the news item,  expands on the theme,

The World Health Organization estimates that in 2012, about 72 percent of premature deaths related to outdoor air pollution were due to ischemic heart disease and strokes. Pulmonary disease, respiratory infections and lung cancer were linked to the other 28 percent. Many scientists have suspected that fine particles travel from the lungs into the bloodstream, but evidence supporting this assumption in humans has been challenging to collect. So Mark Miller and colleagues at the University of Edinburgh in the United Kingdom and the National Institute for Public Health and the Environment in the Netherlands used a selection of specialized techniques to track the fate of inhaled gold nanoparticles.

In the new study, 14 healthy volunteers, 12 surgical patients and several mouse models inhaled gold nanoparticles, which have been safely used in medical imaging and drug delivery. Soon after exposure, the nanoparticles were detected in blood and urine. Importantly, the nanoparticles appeared to preferentially accumulate at inflamed vascular sites, including carotid plaques in patients at risk of a stroke. The findings suggest that nanoparticles can travel from the lungs into the bloodstream and reach susceptible areas of the cardiovascular system where they could possibly increase the likelihood of a heart attack or stroke, the researchers say.

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

Inhaled Nanoparticles Accumulate at Sites of Vascular Disease by Mark R. Miller, Jennifer B. Raftis, Jeremy P. Langrish, Steven G. McLean, Pawitrabhorn Samutrtai, Shea P. Connell, Simon Wilson, Alex T. Vesey, Paul H. B. Fokkens, A. John F. Boere, Petra Krystek, Colin J. Campbell, Patrick W. F. Hadoke, Ken Donaldson, Flemming R. Cassee, David E. Newby, Rodger Duffin, and Nicholas L. Mills. ACS Nano, Article ASAP DOI: 10.1021/acsnano.6b08551 Publication Date (Web): April 26, 2017

Copyright © 2017 American Chemical Society

This paper is behind a paywall.

3D bioprinting: a conference about the latest trends (May 3 – 5, 2017 at the University of British Columbia, Vancouver)

The University of British Columbia’s (UBC) Peter Wall Institute for Advanced Studies (PWIAS) is hosting along with local biotech firm, Aspect Biosystems, a May 3 -5, 2017 international research roundtable known as ‘Printing the Future of Therapeutics in 3D‘.

A May 1, 2017 UBC news release (received via email) offers some insight into the field of bioprinting from one of the roundtable organizers,

This week, global experts will gather [4] at the University of British
Columbia to discuss the latest trends in 3D bioprinting—a technology
used to create living tissues and organs.

In this Q&A, UBC chemical and biological engineering professor
Vikramaditya Yadav [5], who is also with the Regenerative Medicine
Cluster Initiative in B.C., explains how bioprinting could potentially
transform healthcare and drug development, and highlights Canadian
innovations in this field.


Bioprinted tissues or organs could allow scientists to predict
beforehand how a drug will interact within the body. For every
life-saving therapeutic drug that makes its way into our medicine
cabinets, Health Canada blocks the entry of nine drugs because they are
proven unsafe or ineffective. Eliminating poor-quality drug candidates
to reduce development costs—and therefore the cost to consumers—has
never been more urgent.

In Canada alone, nearly 4,500 individuals are waiting to be matched with
organ donors. If and when bioprinters evolve to the point where they can
manufacture implantable organs, the concept of an organ transplant
waiting list would cease to exist. And bioprinted tissues and organs
from a patient’s own healthy cells could potentially reduce the risk
of transplant rejection and related challenges.


Skin, cartilage and bone, and blood vessels are some of the tissue types
that have been successfully constructed using bioprinting. Two of the
most active players are the Wake Forest Institute for Regenerative
Medicine in North Carolina, which reports that its bioprinters can make
enough replacement skin to cover a burn with 10 times less healthy
tissue than is usually needed, and California-based Organovo, which
makes its kidney and liver tissue commercially available to
pharmaceutical companies for drug testing.

Beyond medicine, bioprinting has already been commercialized to print
meat and artificial leather. It’s been estimated that the global
bioprinting market will hit $2 billion by 2021.


Canada is home to some of the most innovative research clusters and
start-up companies in the field. The UBC spin-off Aspect Biosystems [6]
has pioneered a bioprinting paradigm that rapidly prints on-demand
tissues. It has successfully generated tissues found in human lungs.

Many initiatives at Canadian universities are laying strong foundations
for the translation of bioprinting and tissue engineering into
mainstream medical technologies. These include the Regenerative Medicine
Cluster Initiative in B.C., which is headed by UBC, and the University
of Toronto’s Institute of Biomaterials and Biomedical Engineering.


There are concerns about the quality of the printed tissues. It’s
important to note that the U.S. Food and Drug Administration and Health
Canada are dedicating entire divisions to regulation of biomanufactured
products and biomedical devices, and the FDA also has a special division
that focuses on regulation of additive manufacturing – another name
for 3D printing.

These regulatory bodies have an impressive track record that should
assuage concerns about the marketing of substandard tissue. But cost and
pricing are arguably much more complex issues.

Some ethicists have also raised questions about whether society is not
too far away from creating Replicants, à la _Blade Runner_. The idea is
fascinating, scary and ethically grey. In theory, if one could replace
the extracellular matrix of bones and muscles with a stronger substitute
and use cells that are viable for longer, it is not too far-fetched to
create bones or muscles that are stronger and more durable than their
natural counterparts.


This is still some way off. Optimistically, patients could see the
technology in certain clinical environments within the next decade.
However, some technical challenges must be addressed in order for this
to occur, beginning with faithful replication of the correct 3D
architecture and vascularity of tissues and organs. The bioprinters
themselves need to be improved in order to increase cell viability after

These developments are happening as we speak. Regulation, though, will
be the biggest challenge for the field in the coming years.

There are some events open to the public (from the international research roundtable homepage),


You’re invited to attend the open events associated with Printing the Future of Therapeutics in 3D.

Café Scientifique

Thursday, May 4, 2017
Telus World of Science
5:30 – 8:00pm [all tickets have been claimed as of May 2, 2017 at 3:15 pm PT]

3D Bioprinting: Shaping the Future of Health

Imagine a world where drugs are developed without the use of animals, where doctors know how a patient will react to a drug before prescribing it and where patients can have a replacement organ 3D-printed using their own cells, without dealing with long donor waiting lists or organ rejection. 3D bioprinting could enable this world. Join us for lively discussion and dessert as experts in the field discuss the exciting potential of 3D bioprinting and the ethical issues raised when you can print human tissues on demand. This is also a rare opportunity to see a bioprinter live in action!

Open Session

Friday, May 5, 2017
Peter Wall Institute for Advanced Studies
2:00 – 7:00pm

A Scientific Discussion on the Promise of 3D Bioprinting

The medical industry is struggling to keep our ageing population healthy. Developing effective and safe drugs is too expensive and time-consuming to continue unchanged. We cannot meet the current demand for transplant organs, and people are dying on the donor waiting list every day.  We invite you to join an open session where four of the most influential academic and industry professionals in the field discuss how 3D bioprinting is being used to shape the future of health and what ethical challenges may be involved if you are able to print your own organs.


The University of British Columbia and the award-winning bioprinting company Aspect Biosystems, are proud to be co-organizing the first “Printing the Future of Therapeutics in 3D” International Research Roundtable. This event will congregate global leaders in tissue engineering research and pharmaceutical industry experts to discuss the rapidly emerging and potentially game-changing technology of 3D-printing living human tissues (bioprinting). The goals are to:

Highlight the state-of-the-art in 3D bioprinting research
Ideate on disruptive innovations that will transform bioprinting from a novel research tool to a broadly adopted systematic practice
Formulate an actionable strategy for industry engagement, clinical translation and societal impact
Present in a public forum, key messages to educate and stimulate discussion on the promises of bioprinting technology

The Roundtable will bring together a unique collection of industry experts and academic leaders to define a guiding vision to efficiently deploy bioprinting technology for the discovery and development of new therapeutics. As the novel technology of 3D bioprinting is more broadly adopted, we envision this Roundtable will become a key annual meeting to help guide the development of the technology both in Canada and globally.

We thank you for your involvement in this ground-breaking event and look forward to you all joining us in Vancouver for this unique research roundtable.

Kind Regards,
The Organizing Committee
Christian Naus, Professor, Cellular & Physiological Sciences, UBC
Vikram Yadav, Assistant Professor, Chemical & Biological Engineering, UBC
Tamer Mohamed, CEO, Aspect Biosystems
Sam Wadsworth, CSO, Aspect Biosystems
Natalie Korenic, Business Coordinator, Aspect Biosystems

I’m glad to see this event is taking place—and with public events too! (Wish I’d seen the Café Scientifique announcement earlier when I first checked for tickets  yesterday. I was hoping there’d been some cancellations today.) Finally, for the interested, you can find Aspect Biosystems here.

Nano-decoy for human influenza A virus

While the implications for this research are exciting, keep in mind that so far they’ve been testing immune-compromised mice. An Oct. 24, 2016 news item on Nanowerk announces the research,

To infect its victims, influenza A heads for the lungs, where it latches onto sialic acid on the surface of cells. So researchers created the perfect decoy: A carefully constructed spherical nanoparticle coated in sialic acid lures the influenza A virus to its doom. When misted into the lungs, the nanoparticle traps influenza A, holding it until the virus self-destructs.

An Oct. 24, 2015 Rensselaer Polytechnic Institute press release by Mary L. Martialay, which originated the news item, describes the research (Note: Links have been removed),

In a study on immune-compromised mice, the treatment reduced influenza A mortality from 100 percent to 25 percent over 14 days. The novel approach, which is radically different from existing influenza A vaccines, and treatments based on neuraminidase inhibitors, could be extended to a host of viruses that use a similar approach to infecting humans, such as Zika, HIV, and malaria. …

“Instead of blocking the virus, we mimicked its target – it’s a completely novel approach,” said Robert Linhardt, a glycoprotein expert and Rensselaer Polytechnic Institute professor who led the research. “It is effective with influenza and we have reason to believe it will function with many other viruses. This could be a therapeutic in cases where vaccine is not an option, such as exposure to an unanticipated strain, or with immune-compromised patients.”

The project is a collaboration between researchers within the Center for Biotechnology and Interdisciplinary Studies (CBIS) at Rensselaer and several institutions in South Korea including Kyungpook National University. Lead author Seok-Joon Kwon, a CBIS research scientist, coordinated the project across borders, enabling the South Korean institutions to test a drug designed and characterized at Rensselaer. …

To access the interior of a cell and replicate itself, influenza A must first bind to the cell surface, and then cut itself free. It binds with the protein hemagglutinin, and severs that tie with the enzyme neuraminidase. Influenza A produces numerous variations each of hemagglutinin and neuraminidase, all of which are antigens within the pathogen that provoke an immune system response. Strains of influenza A are characterized according to the variation of hemagglutinin and neuraminidase they carry, thus the origin of the familiar H1N1 or H3N2 designations.

Medications to counter the virus do exist, but all are vulnerable to the continual antigenic evolution of the virus. A yearly vaccine is effective only if it matches the strain of virus that infects the body. And the virus has shown an ability to develop resistance to a class of therapeutics based on neuraminidase inhibitors, which bind to and block neuraminidase.

The new solution targets an aspect of infection that does not change: all hemagglutinin varieties of influenza A must bind to human sialic acid. To trap the virus, the team designed a dendrimer, a spherical nanoparticle with treelike branches emanating from its core. On the outermost branches, they attached molecules, or “ligands,” of sialic acid.

The research found that the size of the dendrimer and the spacing between the ligands is integral to the function of the nanoparticle. Hemagglutinin occurs in clusters of three, or “trimers,” on the surface of the virus, and researchers found that a spacing of 3 nanometers between ligands resulted in the strongest binding to the trimers. Once bound to the densely packed dendrimer, viral neuraminidase is unable to sever the link. The coat of the virus contains millions of trimers, but the research revealed that only a few links provokes the virus to discharge its genetic cargo and ultimately self-destruct.

A different approach, using a less structured nanoparticle, had been previously tested in unrelated research, but the nanoparticle selected proved both toxic, and could be inactivated by neuraminidase. The new approach is far more promising.

“The major accomplishment was in designing an architecture that is optimized to bind so tightly to the hemagglutinin, the neuraminidase can’t squeeze in and free the virus,” said Linhardt. “It’s trapped.”

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

Nanostructured glycan architecture is important in the inhibition of influenza A virus infection by Seok-Joon Kwon, Dong Hee Na, Jong Hwan Kwak, Marc Douaisi, Fuming Zhang, Eun Ji Park, Jong-Hwan Park, Hana Youn, Chang-Seon Song, Ravi S. Kane, Jonathan S. Dordick, Kyung Bok Lee, & Robert J. Linhardt. Nature Nanotechnology (2016)  doi:10.1038/nnano.2016.181 Published online 24 October 2016

This paper is behind a paywall.

Study nanomaterial toxicity without testing animals

The process of moving on from testing on animals is laborious as new techniques are pioneered and, perhaps more arduously, people’s opinions and habits are changed. The People for the Ethical Treatment of Animals (PETA) organization focusing the research end of things has announced a means of predicting carbon nanotube toxicity in lungs according to an April 25, 2016 news item on Nanowerk (Note: A link has been removed),

A workshop organized last year [2015] by the PETA International Science Consortium Ltd has resulted in an article published today in the journal Particle and Fibre Toxicology (“Aerosol generation and characterization of multi-walled carbon nanotubes [MWCNTs] exposed to cells cultured at the air-liquid interface”). It describes aerosol generation and exposure tools that can be used to predict toxicity in human lungs following inhalation of nanomaterials.

An April 25, 2016 PETA press release on EurekAlert, which originated the news item, explains further without much more detail,

Nanomaterials are increasingly being used in consumer products such as paints, construction materials, and food packaging, making human exposure to these materials more likely. One of the common ways humans may be exposed to these substances is by inhalation, therefore, regulatory agencies often require the toxicity of these materials on the lungs to be tested. These tests usually involve confining rats to small tubes the size of their bodies and forcing them to breathe potentially toxic substances before they are killed. However, time, cost, scientific and ethical issues have led scientists to develop methods that do not use animals. The tools described in the new article are used to deposit nanomaterials (or other inhalable substances) onto human lung cells grown in a petri dish.

Co-authors of the Particle and Fibre Toxicology article are scientists from the PETA Science Consortium , The Dow Chemical Company, Baylor University, and the U.S. NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM).

“Promoting non-animal methods to assess nanotoxicity has been a focus of the PETA International Science Consortium”, said Dr. Monita Sharma, co-author of the publication and Nanotechnology Specialist at the Consortium, “we organized an international workshop last year on inhalation testing of nanomaterials and this review describes some of the tools that can be used to provide a better understanding of what happens in humans after inhaling these substances.” During the workshop, experts provided recommendations on the design of an in vitro test to assess the toxicity of nanomaterials (especially multi-walled carbon nanotubes) in the lung, including cell types, endpoints, exposure systems, and dosimetry considerations. Additional publications summarizing the outcomes of the workshop are forthcoming.

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

Aerosol generation and characterization of multi-walled carbon nanotubes exposed to cells cultured at the air-liquid interface by William W. Polk, Monita Sharma, Christie M. Sayes, Jon A. Hotchkiss, and Amy J. Clippinger. Particle and Fibre Toxicology201613:20 DOI: 10.1186/s12989-016-0131-y Published: 23 April 2016

This is an open access paper.

Inadvertent carbon nanotube production from your car

It’s disconcerting to find out that cars inadvertently produce carbon nanotubes which are then spilled into the air we breathe. Researchers at Rice University (US) and Paris-Saclay University (France) have examined matter from car exhausts and dust in various parts of Paris finding carbon nanotubes (CNTs). Further, they also studied the lungs of Parisian children who have asthma and found CNTs there too.

The scientists have carefully stated that CNTs have been observed in lung cells but they are not claiming causality (i.e., they don’t claim the children’s asthma was caused by CNTs).

An Oct. 20, 2015 news item on Nanotechnology Now introduces the research,

Cars appear to produce carbon nanotubes, and some of the evidence has been found in human lungs.

Rice University scientists working with colleagues in France have detected the presence of man-made carbon nanotubes in cells extracted from the airways of Parisian children under routine treatment for asthma. Further investigation found similar nanotubes in samples from the exhaust pipes of Paris vehicles and in dust gathered from various places around the city.

The researchers reported in the journal EBioMedicine this month that these samples align with what has been found elsewhere, including Rice’s home city of Houston, in spider webs in India and in ice cores.

An Oct. 19, 2015 Rice University news release (also on EurekAlert), which originated the news item, painstakingly describes the work and initial conclusions,

The research in no way ascribes the children’s conditions to the nanotubes, said Rice chemist Lon Wilson, a corresponding author of the new paper. But the nanotubes’ apparent ubiquity should be the focus of further investigation, he said.

“We know that carbon nanoparticles are found in nature,” Wilson said, noting that round fullerene molecules like those discovered at Rice are commonly produced by volcanoes, forest fires and other combustion of carbon materials. “All you need is a little catalysis to make carbon nanotubes instead of fullerenes.”

A car’s catalytic converter, which turns toxic carbon monoxide into safer emissions, bears at least a passing resemblance to the Rice-invented high-pressure carbon monoxide, or HiPco, process to make carbon nanotubes, he said. “So it is not a big surprise, when you think about it,” Wilson said.

The team led by Wilson, Fathi Moussa of Paris-Saclay University and lead author Jelena Kolosnjaj-Tabi, a graduate student at Paris-Saclay, analyzed particulate matter found in the alveolar macrophage cells (also known as dust cells) that help stop foreign materials like particles and bacteria from entering the lungs.

The researchers wrote that their results “suggest humans are routinely exposed” to carbon nanotubes. They also suggested previous studies that link the carbon content of airway macrophages and the decline of lung function should be reconsidered in light of the new findings. Moussa confirmed his lab will continue to study the impact of man-made nanotubes on health.

The cells were taken from 69 randomly selected asthma patients aged 2 to 17 who underwent routine fiber-optic bronchoscopies as part of their treatment. For ethical reasons, no cells from healthy patients were analyzed, but because nanotubes were found in all of the samples, the study led the researchers to conclude that carbon nanotubes are likely to be found in everybody.

The study notes but does not make definitive conclusions about the controversial proposition that carbon nanotube fibers may act like asbestos, a proven carcinogen. But the authors reminded that “long carbon nanotubes and large aggregates of short ones can induce a granulomatous (inflammation) reaction.”

The study partially answers the question of what makes up the black material inside alveolar macrophages, the original focus of the study. The researchers found single-walled and multiwalled carbon nanotubes and amorphous carbon among the cells, as well as in samples swabbed from the tailpipes of cars in Paris and dust from various buildings in and around the city.

The news release goes on to detail how the research was conducted,

“The concentrations of nanotubes are so low in these samples that it’s hard to believe they would cause asthma, but you never know,” Wilson said. “What surprised me the most was that carbon nanotubes were the major component of the carbonaceous pollution we found in the samples.”

The nanotube aggregates in the cells ranged in size from 10 to 60 nanometers in diameter and up to several hundred nanometers in length, small enough that optical microscopes would not have been able to identify them in samples from former patients. The new study used more sophisticated tools, including high-resolution transmission electron microscopy, X-ray spectroscopy, Raman spectroscopy and near-infrared fluorescence microscopy to definitively identify them in the cells and in the environmental samples.

“We collected samples from the exhaust pipes of cars in Paris as well as from busy and non-busy intersections there and found the same type of structures as in the human samples,” Wilson said.

“It’s kind of ironic. In our laboratory, working with carbon nanotubes, we wear facemasks to prevent exactly what we’re seeing in these samples, yet everyone walking around out there in the world probably has at least a small concentration of carbon nanotubes in their lungs,” he said.

The researchers also suggested that the large surface areas of nanotubes and their ability to adhere to substances may make them effective carriers for other pollutants.

The study followed one released by Rice and Baylor College of Medicine earlier this month with the similar goal of analyzing the black substance found in the lungs of smokers who died of emphysema. That study found carbon black nanoparticles that were the product of the incomplete combustion of such organic material as tobacco.

Here’s an image of a sample,

 Caption: Carbon nanotubes (the long rods) and nanoparticles (the black clumps) appear in vehicle exhaust taken from the tailpipes of cars in Paris. The image is part of a study by scientists in Paris and at Rice University to analyze carbonaceous material in the lungs of asthma patients. They found that cars are a likely source of nanotubes found in the patients. Credit: Courtesy of Fathi Moussa/Paris-Saclay University

Caption: Carbon nanotubes (the long rods) and nanoparticles (the black clumps) appear in vehicle exhaust taken from the tailpipes of cars in Paris. The image is part of a study by scientists in Paris and at Rice University to analyze carbonaceous material in the lungs of asthma patients. They found that cars are a likely source of nanotubes found in the patients.
Credit: Courtesy of Fathi Moussa/Paris-Saclay University

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

Anthropogenic Carbon Nanotubes Found in the Airways of Parisian Children by Jelena Kolosnjaj-Tabi, Jocelyne Just, Keith B. Hartman, Yacine Laoudi, Sabah Boudjemaa, Damien Alloyeau, Henri Szwarc, Lon J. Wilson, & Fathi Moussa. EBioMedicine doi:10.1016/j.ebiom.2015.10.012 Available online 9 October 2015

This paper is open access.

ETA Oct. 26, 2015: Dexter Johnson, along with Dr. Andrew Maynard, provides an object lesson on how to read science research in an Oct. 23, 2015 posting on his Nanoclast blog (on the IEEE [Institute of Electrical and Electronics Engineers]),

“From past studies, the conditions in combustion engines seem to favor the production of at least some CNTs (especially where there are trace metals in lubricants that can act as catalysts for CNT growth),” explained Andrew Maynard Director, Risk Innovation Lab and Professor, School for the Future of Innovation in Society at Arizona State University, in an e-mail interview. Says Maynard:

What, to my knowledge, is still not known, is the relative concentrations of CNT in ambient air that may be inhaled, the precise nature of these CNT in terms of physical and chemical structure, and the range of sources that may lead to ambient CNT. This is important, as the potential for fibrous particles to cause lung damage depends on characteristics such as their length—and many of the fibers shown in the paper appear too short to raise substantial concerns.”

Nonetheless, Maynard praises the research for establishing that these carbon nanotube-like fibers are part of the urban aerosol and therefore end up in the lungs of anyone who breathes it in. However, he cautions that the findings don’t provide information on the potential health risks associated with these exposures.

It’s a good read not only for the information but the mild snarkiness (assuming you find that kind of thing amusing) that spices up the piece.

Ferroelectric switching in the lung, heart, and arteries

A June 23, 2014 University of Washington (state) news release (also on EurekAlert) describes how the human body (and other biological tissue) is capable of generating ferroelectricity,

University of Washington researchers have shown that a favorable electrical property is present in a type of protein found in organs that repeatedly stretch and retract, such as the lungs, heart and arteries. These findings are the first that clearly track this phenomenon, called ferroelectricity, occurring at the molecular level in biological tissues.

The news release gives a brief description of ferroelectricity and describes the research team’s latest work with biological tissues,

Ferroelectricity is a response to an electric field in which a molecule switches from having a positive to a negative charge. This switching process in synthetic materials serves as a way to power computer memory chips, display screens and sensors. This property only recently has been discovered in animal tissues and researchers think it may help build and support healthy connective tissues in mammals.

A research team led by Li first discovered ferroelectric properties in biological tissues in 2012, then in 2013 found that glucose can suppress this property in the body’s connective tissues, wherever the protein elastin is present. But while ferroelectricity is a proven entity in synthetic materials and has long been thought to be important in biological functions, its actual existence in biology hasn’t been firmly established.

This study proves that ferroelectric switching happens in the biological protein elastin. When the researchers looked at the base structures within the protein, they saw similar behavior to the unit cells of solid-state materials, where ferroelectricity is well understood.

“When we looked at the smallest structural unit of the biological tissue and how it was organized into a larger protein fiber, we then were able to see similarities to the classic ferroelectric model found in solids,” Li said.

The researchers wanted to establish a more concrete, precise way of verifying ferroelectricity in biological tissues. They used small samples of elastin taken from a pig’s aorta and poled the tissues using an electric field at high temperatures. They then measured the current with the poling field removed and found that the current switched direction when the poling electric field was switched, a sign of ferroelectricity.

They did the same thing at room temperature using a laser as the heat source, and the current also switched directions.

Then, the researchers tested for this behavior on the smallest-possible unit of elastin, called tropoelastin, and again observed the phenomenon. They concluded that this switching property is “intrinsic” to the molecular make-up of elastin.

The next step is to understand the biological and physiological significance of this property, Li said. One hypothesis is that if ferroelectricity helps elastin stay flexible and functional in the body, a lack of it could directly affect the hardening of arteries.

“We may be able to use this as a very sensitive technique to detect the initiation of the hardening process at a very early stage when no other imaging technique will be able to see it,” Li said.

The team also is looking at whether this property plays a role in normal biological functions, perhaps in regulating the growth of tissue.

Co-authors are Pradeep Sharma at the University of Houston, Yanhang Zhang at Boston University, and collaborators at Nanjing University and the Chinese Academy of Sciences.

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

Ferroelectric switching of elastin by Yuanming Liu, Hong-Ling Cai, Matthew Zelisko, Yunjie Wang, Jinglan Sun, Fei Yan, Feiyue Ma, Peiqi Wang, Qian Nataly Chen, Hairong Zheng, Xiangjian Meng, Pradeep Sharma, Yanhang Zhang, and Jiangyu Li. Proceedings of the National Academy of Sciences (PNAS) doi: 10.1073/pnas.1402909111

This paper is behind a paywall.

I think this is a new practice. There is a paragraph on the significance of this work (follow the link to the paper),

Ferroelectricity has long been speculated to have important biological functions, although its very existence in biology has never been firmly established. Here, we present, to our knowledge, the first macroscopic observation of ferroelectric switching in a biological system, and we elucidate the origin and mechanism underpinning ferroelectric switching of elastin. It is discovered that the polarization in elastin is intrinsic at the monomer level, analogous to the unit cell level polarization in classical perovskite ferroelectrics. Our findings settle a long-standing question on ferroelectric switching in biology and establish ferroelectricity as an important biophysical property of proteins. We believe this is a critical first step toward resolving its physiological significance and pathological implications.

Nanoscale metal oxides and lung cells

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

ASHLEY HALL: So is it a significant amount?

BRIAN GULSON: No, no it’s really not.

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

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

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

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

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

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

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

This paper is behind a paywall.