Tag Archives: toxicity

Membrane stretching as a new transport mechanism for nanomaterials

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This work comes from Catalonia, Spain by way of a collaboration between Chinese, German, and, of course, Spanish scientists. From a December 12, 2018 Universitat Rovira i Virgili press release (also on EurekAlert),

Increasing awareness of bioeffects and toxicity of nanomaterials interacting with cells puts in focus the mechanisms by which nanomaterials can cross lipid membranes. Apart from well-discussed energy-dependent endocytosis for large objects and passive diffusion through membranes by solute molecules, there can exist other transport mechanisms based on physical principles. Based on this hypothesis, the team of theoretical physics at Universitat Rovira i Virgili in Tarragona, led by Dr. Vladimir Baulin, designed a research project to investigate the interaction between nanotube and lipid membranes. In computer simulations, the researchers studied what they call a “model bilayer”, composed only by one type of lipids. Based on their calculations, the team of Dr. Baulin observed that ultra -short nanotube (10nm length) can insert perpendicularly to the lipid bilayer core.

They observed that these nanotubes stay trapped in the cell membrane, as commonly accepted by the scientific community. But a surprise appears when they stretched their model cell membrane, then inserted nanotubes which were trapped in the bilayer, suddenly started to escape from the bilayer on both sides. This means that it is possible to control the transport of nanomaterial across a cell membrane by tuning the membrane tension.

This is where Dr. Baulin contacted Dr. Jean-Baptiste Fleury at the Saarland University (Germany) to confirm this mechanism and to study experimentally this tension-mediated transport phenomena. Dr. Fleury and his team, designed a microfluidic experiment with a well-controlled phospholipid bilayer, an experimental model for cell membranes and added ultra-small carbon nanotubes (10nm in length) in solution. The nanotubes had an adsorbed lipid monolayer that guarantees their stable dispersion and prevent their clustering. Using a combination of optical fluorescent microscopy and electrophysiological measurements, the team of Dr. Fleury could follow individual nanotube crossing a bilayer and unravel their pathway on a molecular level. And as predicted by the simulations, they observed that nanotubes inserted into the bilayer by dissolving their lipid coating into the artificial membrane. When a tension of 4mN/m was applied to the bilayer, nanotubes spontaneously escaped the bilayer just in few milliseconds, while at lower tensions nanotubes remain trapped inside the membrane.

This discovery of translocation of tiny nanotubes through barriers protecting cells, i.e. lipid bilayer, may raise concerns about safety of nanomaterials for public health and suggest new mechanical mechanisms to control the drug delivery.

Caption: Nanotubes trapped inside the membrane. Credit: © URV

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

Tension-Induced Translocation of an Ultrashort Carbon Nanotube through a Phospholipid Bilayer by Yachong Guo, Marco Werner, Ralf Seemann, Vladimir A. Baulin, and Jean-Baptiste Fleury. ACS Nano, Article ASAP DOI: 10.1021/acsnano.8b04657 Publication Date (Web): November 19, 2018

Copyright © 2018 American Chemical Society

This paper is behind a paywall.

Artificial intelligence (AI) brings together International Telecommunications Union (ITU) and World Health Organization (WHO) and AI outperforms animal testing

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Following on my May 11, 2018 posting about the International Telecommunications Union (ITU) and the 2018 AI for Good Global Summit in mid- May, there’s an announcement. My other bit of AI news concerns animal testing.

Leveraging the power of AI for health

A July 24, 2018 ITU press release (a shorter version was received via email) announces a joint initiative focused on improving health,

Two United Nations specialized agencies are joining forces to expand the use of artificial intelligence (AI) in the health sector to a global scale, and to leverage the power of AI to advance health for all worldwide. The International Telecommunication Union (ITU) and the World Health Organization (WHO) will work together through the newly established ITU Focus Group on AI for Health to develop an international “AI for health” standards framework and to identify use cases of AI in the health sector that can be scaled-up for global impact. The group is open to all interested parties.

“AI could help patients to assess their symptoms, enable medical professionals in underserved areas to focus on critical cases, and save great numbers of lives in emergencies by delivering medical diagnoses to hospitals before patients arrive to be treated,” said ITU Secretary-General Houlin Zhao. “ITU and WHO plan to ensure that such capabilities are available worldwide for the benefit of everyone, everywhere.”

The demand for such a platform was first identified by participants of the second AI for Good Global Summit held in Geneva, 15-17 May 2018. During the summit, AI and the health sector were recognized as a very promising combination, and it was announced that AI-powered technologies such as skin disease recognition and diagnostic applications based on symptom questions could be deployed on six billion smartphones by 2021.

The ITU Focus Group on AI for Health is coordinated through ITU’s Telecommunications Standardization Sector – which works with ITU’s 193 Member States and more than 800 industry and academic members to establish global standards for emerging ICT innovations. It will lead an intensive two-year analysis of international standardization opportunities towards delivery of a benchmarking framework of international standards and recommendations by ITU and WHO for the use of AI in the health sector.

“I believe the subject of AI for health is both important and useful for advancing health for all,” said WHO Director-General Tedros Adhanom Ghebreyesus.

The ITU Focus Group on AI for Health will also engage researchers, engineers, practitioners, entrepreneurs and policy makers to develop guidance documents for national administrations, to steer the creation of policies that ensure the safe, appropriate use of AI in the health sector.

“1.3 billion people have a mobile phone and we can use this technology to provide AI-powered health data analytics to people with limited or no access to medical care. AI can enhance health by improving medical diagnostics and associated health intervention decisions on a global scale,” said Thomas Wiegand, ITU Focus Group on AI for Health Chairman, and Executive Director of the Fraunhofer Heinrich Hertz Institute, as well as professor at TU Berlin.

He added, “The health sector is in many countries among the largest economic sectors or one of the fastest-growing, signalling a particularly timely need for international standardization of the convergence of AI and health.”

Data analytics are certain to form a large part of the ITU focus group’s work. AI systems are proving increasingly adept at interpreting laboratory results and medical imagery and extracting diagnostically relevant information from text or complex sensor streams.

As part of this, the ITU Focus Group for AI for Health will also produce an assessment framework to standardize the evaluation and validation of AI algorithms — including the identification of structured and normalized data to train AI algorithms. It will develop open benchmarks with the aim of these becoming international standards.

The ITU Focus Group for AI for Health will report to the ITU standardization expert group for multimedia, Study Group 16.

I got curious about Study Group 16 (from the Study Group 16 at a glance webpage),

Study Group 16 leads ITU’s standardization work on multimedia coding, systems and applications, including the coordination of related studies across the various ITU-T SGs. It is also the lead study group on ubiquitous and Internet of Things (IoT) applications; telecommunication/ICT accessibility for persons with disabilities; intelligent transport system (ITS) communications; e-health; and Internet Protocol television (IPTV).

Multimedia is at the core of the most recent advances in information and communication technologies (ICTs) – especially when we consider that most innovation today is agnostic of the transport and network layers, focusing rather on the higher OSI model layers.

SG16 is active in all aspects of multimedia standardization, including terminals, architecture, protocols, security, mobility, interworking and quality of service (QoS). It focuses its studies on telepresence and conferencing systems; IPTV; digital signage; speech, audio and visual coding; network signal processing; PSTN modems and interfaces; facsimile terminals; and ICT accessibility.

…

I wonder which group deals with artificial intelligence and, possibly, robots.

Chemical testing without animals

Thomas Hartung, professor of environmental health and engineering at Johns Hopkins University (US), describes in his July 25, 2018 essay (written for The Conversation) on phys.org the situation where chemical testing is concerned,

Most consumers would be dismayed with how little we know about the majority of chemicals. Only 3 percent of industrial chemicals – mostly drugs and pesticides – are comprehensively tested. Most of the 80,000 to 140,000 chemicals in consumer products have not been tested at all or just examined superficially to see what harm they may do locally, at the site of contact and at extremely high doses.

I am a physician and former head of the European Center for the Validation of Alternative Methods of the European Commission (2002-2008), and I am dedicated to finding faster, cheaper and more accurate methods of testing the safety of chemicals. To that end, I now lead a new program at Johns Hopkins University to revamp the safety sciences.

As part of this effort, we have now developed a computer method of testing chemicals that could save more than a US$1 billion annually and more than 2 million animals. Especially in times where the government is rolling back regulations on the chemical industry, new methods to identify dangerous substances are critical for human and environmental health.

Having written on the topic of alternatives to animal testing on a number of occasions (my December 26, 2014 posting provides an overview of sorts), I was particularly interested to see this in Hartung’s July 25, 2018 essay on The Conversation (Note: Links have been removed),

Following the vision of Toxicology for the 21st Century, a movement led by U.S. agencies to revamp safety testing, important work was carried out by my Ph.D. student Tom Luechtefeld at the Johns Hopkins Center for Alternatives to Animal Testing. Teaming up with Underwriters Laboratories, we have now leveraged an expanded database and machine learning to predict toxic properties. As we report in the journal Toxicological Sciences, we developed a novel algorithm and database for analyzing chemicals and determining their toxicity – what we call read-across structure activity relationship, RASAR.

This graphic reveals a small part of the chemical universe. Each dot represents a different chemical. Chemicals that are close together have similar structures and often properties. Thomas Hartung, CC BY-SA

To do this, we first created an enormous database with 10 million chemical structures by adding more public databases filled with chemical data, which, if you crunch the numbers, represent 50 trillion pairs of chemicals. A supercomputer then created a map of the chemical universe, in which chemicals are positioned close together if they share many structures in common and far where they don’t. Most of the time, any molecule close to a toxic molecule is also dangerous. Even more likely if many toxic substances are close, harmless substances are far. Any substance can now be analyzed by placing it into this map.

If this sounds simple, it’s not. It requires half a billion mathematical calculations per chemical to see where it fits. The chemical neighborhood focuses on 74 characteristics which are used to predict the properties of a substance. Using the properties of the neighboring chemicals, we can predict whether an untested chemical is hazardous. For example, for predicting whether a chemical will cause eye irritation, our computer program not only uses information from similar chemicals, which were tested on rabbit eyes, but also information for skin irritation. This is because what typically irritates the skin also harms the eye.

How well does the computer identify toxic chemicals?

This method will be used for new untested substances. However, if you do this for chemicals for which you actually have data, and compare prediction with reality, you can test how well this prediction works. We did this for 48,000 chemicals that were well characterized for at least one aspect of toxicity, and we found the toxic substances in 89 percent of cases.

This is clearly more accurate that the corresponding animal tests which only yield the correct answer 70 percent of the time. The RASAR shall now be formally validated by an interagency committee of 16 U.S. agencies, including the EPA [Environmental Protection Agency] and FDA [Food and Drug Administration], that will challenge our computer program with chemicals for which the outcome is unknown. This is a prerequisite for acceptance and use in many countries and industries.

The potential is enormous: The RASAR approach is in essence based on chemical data that was registered for the 2010 and 2013 REACH [Registration, Evaluation, Authorizations and Restriction of Chemicals] deadlines [in Europe]. If our estimates are correct and chemical producers would have not registered chemicals after 2013, and instead used our RASAR program, we would have saved 2.8 million animals and $490 million in testing costs – and received more reliable data. We have to admit that this is a very theoretical calculation, but it shows how valuable this approach could be for other regulatory programs and safety assessments.

In the future, a chemist could check RASAR before even synthesizing their next chemical to check whether the new structure will have problems. Or a product developer can pick alternatives to toxic substances to use in their products. This is a powerful technology, which is only starting to show all its potential.

It’s been my experience that these claims having led a movement (Toxicology for the 21st Century) are often contested with many others competing for the title of ‘leader’ or ‘first’. That said, this RASAR approach seems very exciting, especially in light of the skepticism about limiting and/or making animal testing unnecessary noted in my December 26, 2014 posting.it was from someone I thought knew better.

Here’s a link to and a citation for the paper mentioned in Hartung’s essay,

Machine learning of toxicological big data enables read-across structure activity relationships (RASAR) outperforming animal test reproducibility by Thomas Luechtefeld, Dan Marsh, Craig Rowlands, Thomas Hartung. Toxicological Sciences, kfy152, https://doi.org/10.1093/toxsci/kfy152 Published: 11 July 2018

This paper is open access.

Australian scientists say that sunscreens with zinc oxide nanoparticles aren’t toxic to you

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The Australians have had quite the struggle over whether or not to use nanotechnology-enabled sunscreens (see my Feb. 9, 2012 posting about an Australian nanosunscreen debacle and I believe the reverberations continue even ’til today). This latest research will hopefully help calm the waters. From a Dec. 4, 2018 news item on ScienceDaily,

Zinc oxide (ZnO) has long been recognized as an effective sunscreen agent. However, there have been calls for sunscreens containing ZnO nanoparticles to be banned because of potential toxicity and the need for caution in the absence of safety data in humans. An important new study provides the first direct evidence that intact ZnO nanoparticles neither penetrate the human skin barrier nor cause cellular toxicity after repeated application to human volunteers under in-use conditions. This confirms that the known benefits of using ZnO nanoparticles in sunscreens clearly outweigh the perceived risks, reports the Journal of Investigative Dermatology.

A December 4, 2018 Elsevier (Publishing) press release (also on EurekAlert), which originated the news item, provides international context for the safety discussion while providing more details about this latest research,

The safety of nanoparticles used in sunscreens has been a highly controversial international issue in recent years, as previous animal exposure studies found much higher skin absorption of zinc from application of ZnO sunscreens to the skin than in human studies. Some public advocacy groups have voiced concern that penetration of the upper layer of the skin by sunscreens containing ZnO nanoparticles could gain access to the living cells in the viable epidermis with toxic consequences, including DNA damage. A potential danger, therefore, is that this concern may also result in an undesirable downturn in sunscreen use. A 2017 National Sun Protection Survey by the Cancer Council Australia found only 55 percent of Australians believed it was safe to use sunscreen every day, down from 61 per cent in 2014.

Investigators in Australia studied the safety of repeated application of agglomerated ZnO nanoparticles applied to five human volunteers (aged 20 to 30 years) over five days. This mimics normal product use by consumers. They applied ZnO nanoparticles suspended in a commercial sunscreen base to the skin of volunteers hourly for six hours and daily for five days. Using multiphoton tomography with fluorescence lifetime imaging microscopy, they showed that the nanoparticles remained within the superficial layers of the stratum corneum and in the skin furrows. The fate of ZnO nanoparticles was also characterized in excised human skin in vitro. They did not penetrate the viable epidermis and no cellular toxicity was seen, even after repeated hourly or daily applications typically used for sunscreens.

“The terrible consequences of skin cancer and photoaging are much greater than any toxicity risk posed by approved sunscreens,” stated lead investigator Michael S. Roberts, PhD, of the Therapeutics Research Centre, The University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, and School of Pharmacy and Medical Sciences, University of South Australia, Sansom Institute, Adelaide, QLD, Australia.

“This study has shown that sunscreens containing nano ZnO can be repeatedly applied to the skin with minimal risk of any toxicity. We hope that these findings will help improve consumer confidence in these products, and in turn lead to better sun protection and reduction in ultraviolet-induced skin aging and cancer cases,” he concluded.

“This study reinforces the important public health message that the known benefits of using ZnO nano sunscreens clearly outweigh the perceived risks of using nano sunscreens that are not supported by the scientific evidence,” commented Paul F.A. Wright, PhD, School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC, Australia, in an accompanying editorial. “Of great significance is the investigators’ finding that the slight increase in zinc ion concentrations in viable epidermis was not associated with cellular toxicity under conditions of realistic ZnO nano sunscreen use.

A November 21, 2018 University of South Australia press release (also on EurekAlert) provides some additional insight into the Australian situation,, Note: Links have been removed,

It’s safe to slap on the sunscreen this summer – in repeated doses – despite what you have read about the potential toxicity of sunscreens.

A new study led by the University of Queensland (UQ) and University of South Australia (UniSA) provides the first direct evidence that zinc oxide nanoparticles used in sunscreen neither penetrate the skin nor cause cellular toxicity after repeated applications.

The research, published this week in the Journal of Investigative Dermatology, refutes widespread claims among some public advocacy groups – and a growing belief among consumers – about the safety of nanoparticulate-based sunscreens.

UQ and UniSA lead investigator, Professor Michael Roberts, says the myth about sunscreen toxicity took hold after previous animal studies found much higher skin absorption of zinc-containing sunscreens than in human studies.

“There were concerns that these zinc oxide nanoparticles could be absorbed into the epidermis, with toxic consequences, including DNA damage,” Professor Roberts says.

The toxicity link was picked up by consumers, sparking fears that Australians could reduce their sunscreen use, echoed by a Cancer Council 2017 National Sun Protection Survey showing a drop in the number of people who believed it was safe to use sunscreens every day.

Professor Roberts and his co-researchers in Brisbane, Adelaide, Perth and Germany studied the safety of repeated applications of zinc oxide nanoparticles applied to five volunteers aged 20-30 years.

Volunteers applied the ZnO nanoparticles every hour for six hours on five consecutive days.

“Using superior imaging methods, we established that the nanoparticles remained within the superficial layers of the skin and did not cause any cellular damage,” Professor Roberts says.

“We hope that these findings help improve consumer confidence in these products and in turn lead to better sun protection. The terrible consequences of skin cancer and skin damage caused by prolonged sun exposure are much greater than any toxicity posed by approved sunscreens.”

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

Support for the Safe Use of Zinc Oxide Nanoparticle Sunscreens: Lack of Skin Penetration or Cellular Toxicity after Repeated Application in Volunteers by Yousuf H. Mohammed, Amy Holmes, Isha N. Haridass, Washington Y. Sanchez, Hauke Studier, Jeffrey E. Grice, Heather A.E. Benson, Michael S. Roberts. Jurnal of Investigative Dermatology. DOI: https://doi.org/10.1016/j.jid.2018.08.024 Article in Press Published online (Dec. 4, 2018?)

As of Dec. 11, 2018, this article is open access.

The Swiss come to a better understanding of nanomaterials

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Just to keep things interesting, after the report suggesting most of the information that the OECD (Organization for Economic Cooperation and Development) has on nanomaterials is of little value for determining risk (see my April 5, 2017 posting for more) the Swiss government has released a report where they claim an improved understanding of nanomaterials than they previously had due to further research into the matter. From an April 6, 2017 news item on Nanowerk,

In the past six years, the [Swiss] National Research Programme “Opportunities and Risks of Nanomaterials” (NRP 64) intensively studied the development, use, behaviour and degradation of engineered nanomaterials, including their impact on humans and on the environment.

Twenty-three research projects on biomedicine, the environment, energy, construction materials and food demonstrated the enormous potential of engineered nanoparticles for numerous applications in industry and medicine. Thanks to these projects we now know a great deal more about the risks associated with nanomaterials and are therefore able to more accurately determine where and how they can be safely used.

An April 6, 2017 Swiss National Science Foundation press release, which originated the news item, expands on the theme,

“One of the specified criteria in the programme was that every project had to examine both the opportunities and the risks, and in some cases this was a major challenge for the researchers,” explains Peter Gehr, President of the NRP 64 Steering Committee.

One development that is nearing industrial application concerns a building material strengthened with nanocellulose that can be used to produce a strong but lightweight insulation material. Successful research was also carried out in the area of energy, where the aim was to find a way to make lithium-ion batteries safer and more efficient.

Promising outlook for nanomedicine

A great deal of potential is predicted for the field of nanomedicine. Nine of the 23 projects in NRP 64 focused on biomedical applications of nanoparticles. These include their use for drug delivery, for example in the fight against viruses, or as immune modulators in a vaccine against asthma. Another promising application concerns the use of nanomagnets for filtering out harmful metallic substances from the blood. One of the projects demonstrated that certain nanoparticles can penetrate the placenta barrier, which points to potential new therapy options. The potential of cartilage and bone substitute materials based on nanocellulose or nanofibres was also studied.

The examination of potential health risks was the focus of NRP 64. A number of projects examined what happens when nanoparticles are inhaled, while two focused on ingestion. One of these investigated whether the human gut is able to absorb iron more efficiently if it is administered in the form of iron nanoparticles in a food additive, while the other studied silicon nanoparticles as they occur in powdered condiments. It was ascertained that further studies will be required in order to determine the doses that can be used without risking an inflammatory reaction in the gut.

What happens to engineered nanomaterials in the environment?

The aim of the seven projects focusing on environmental impact was to gain a better understanding of the toxicity of nanomaterials and their degradability, stability and accumulation in the environment and in biological systems. Here, the research teams monitored how engineered nanoparticles disseminate along their lifecycle, and where they end up or how they can be discarded.

One of the projects established that 95 per cent of silver nanoparticles that are washed out of textiles are collected in sewage treatment plants, while the remaining particles end up in sewage sludge, which in Switzerland is incinerated. In another project a measurement device was developed to determine how aquatic microorganisms react when they come into contact with nanoparticles.

Applying results and making them available to industry

“The findings of the NRP 64 projects form the basis for a safe application of nanomaterials,” says Christoph Studer from the Federal Office of Public Health. “It has become apparent that regulatory instruments such as testing guidelines will have to be adapted at both national and international level.” Studer has been closely monitoring the research programme in his capacity as the Swiss government’s representative in NRP 64. In this context, the precautionary matrix developed by the government is an important instrument by means of which companies can systematically assess the risks associated with the use of nanomaterials in their production processes.

The importance of standardised characterisation and evaluation of engineered nanomaterials was highlighted by the close cooperation among researchers in the programme. “The research network that was built up in the framework of NRP 64 is functioning smoothly and needs to be further nurtured,” says Professor Bernd Nowack from Empa, who headed one of the 23 projects.

The results of NRP 64 show that new key technologies such as the use of nanomaterials need to be closely monitored through basic research due to the lack of data on its long-term effects. As Peter Gehr points out, “We now know a lot more about the risks of nanomaterials and how to keep them under control. However, we need to conduct additional research to learn what happens when humans and the environment are exposed to engineered nanoparticles over longer periods, or what happens a long time after a one-off exposure.”

You can find out more about the Opportunities and Risks of Nanomaterials; National Research Programme (NRP 64) here.

The volatile lithium-ion battery

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On the heels of Samsung’s Galaxy Note 7 recall due to fires (see Alex Fitzpatrick’s Sept. 9, 2016 article for Time magazine for a good description of lithium-ion batteries and why they catch fire; see my May 29, 2013 posting on lithium-ion batteries, fires [including the airplane fires], and nanotechnology risk assessments), there’s new research on lithium-ion batteries and fires from China. From an Oct. 21, 2016 news item on Nanotechnology Now,

Dozens of dangerous gases are produced by the batteries found in billions of consumer devices, like smartphones and tablets, according to a new study. The research, published in Nano Energy, identified more than 100 toxic gases released by lithium batteries, including carbon monoxide.

An Oct. 20, 2016 Elsevier Publishing press release (also on EurekAlert), which originated the news item, expands on the theme,

The gases are potentially fatal, they can cause strong irritations to the skin, eyes and nasal passages, and harm the wider environment. The researchers behind the study, from the Institute of NBC Defence and Tsinghua University in China, say many people may be unaware of the dangers of overheating, damaging or using a disreputable charger for their rechargeable devices.

In the new study, the researchers investigated a type of rechargeable battery, known as a “lithium-ion” battery, which is placed in two billion consumer devices every year.

“Nowadays, lithium-ion batteries are being actively promoted by many governments all over the world as a viable energy solution to power everything from electric vehicles to mobile devices. The lithium-ion battery is used by millions of families, so it is imperative that the general public understand the risks behind this energy source,” explained Dr. Jie Sun, lead author and professor at the Institute of NBC Defence.

The dangers of exploding batteries have led manufacturers to recall millions of devices: Dell recalled four million laptops in 2006 and millions of Samsung Galaxy Note 7 devices were recalled this month after reports of battery fires. But the threats posed by toxic gas emissions and the source of these emissions are not well understood.

Dr. Sun and her colleagues identified several factors that can cause an increase in the concentration of the toxic gases emitted. A fully charged battery will release more toxic gases than a battery with 50 percent charge, for example. The chemicals contained in the batteries and their capacity to release charge also affected the concentrations and types of toxic gases released.

Identifying the gases produced and the reasons for their emission gives manufacturers a better understanding of how to reduce toxic emissions and protect the wider public, as lithium-ion batteries are used in a wide range of environments.

“Such dangerous substances, in particular carbon monoxide, have the potential to cause serious harm within a short period of time if they leak inside a small, sealed environment, such as the interior of a car or an airplane compartment,” Dr. Sun said.

Almost 20,000 lithium-ion batteries were heated to the point of combustion in the study, causing most devices to explode and all to emit a range of toxic gases. Batteries can be exposed to such temperature extremes in the real world, for example, if the battery overheats or is damaged in some way.

The researchers now plan to develop this detection technique to improve the safety of lithium-ion batteries so they can be used to power the electric vehicles of the future safely.

“We hope this research will allow the lithium-ion battery industry and electric vehicle sector to continue to expand and develop with a greater understanding of the potential hazards and ways to combat these issues,” Sun concluded.

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

Toxicity, a serious concern of thermal runaway from commercial Li-ion battery by Jie Sun, Jigang Li, Tian Zhou, Kai Yang, Shouping Wei, Na Tang, Nannan Dang, Hong Li, Xinping Qiu, Liquan Chend. Nano Energy Volume 27, September 2016, Pages 313–319  http://dx.doi.org/10.1016/j.nanoen.2016.06.031

This paper appears to be open access.

Study nanomaterial toxicity without testing animals

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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.

Research into nanosilver’s antibiotic properties and nanogold’s detection skills

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There is a puzzling and exciting announcement from the Canadian Light Source in a May 27, 2015 news item on Nanowerk,

Precious metals like silver and gold have biomedical properties that have been used for centuries, but how do these materials effectively combat the likes of cancer and bacteria without contaminating the patient and the environment?

These are the questions that researchers from Dalhousie University and the Canadian Light Source are trying to find out.

Perhaps I’m misreading the announcement but the statement that nanosilver and nanogold don’t contaminate the patient or the environment is a bit exuberant. There are published studies examining questions about whether or not nanosilver may affect the environment and health and the answer is that no one is certain yet. You can read more about two studies highlighted in my February 28, 2013 posting titled:  Silver nanoparticles, water, the environment, and toxicity. As for nanosilver and nanogold not contaminating patients, that too is a problematic statement. For example, I have this paper which cites several studies on nanogold and possible toxicity. The paper itself is a plea to standardize testing and protocols so researchers can do a better job of establishing toxicity issues with nanogold.

GoldNP_ToxicityMar2015

Reservations aside, it’s good to learn of some Canadian research in this area. From a May 26, 2015 Canadian Light Source news release, which originated the news item, provides more details about the research and its current focus on nanosilver,

“Gold and silver are both exciting materials,” said Peng Zhang, Associate Professor of Chemistry at Dalhousie. “We can use gold to either detect or kill cancer cells. Silver is also excited and a very promising material as an antibacterial agents.”

Zhang said that if you compare silver to current antibiotics, silver does not show drug-resistant behaviour. “But with silver, so far, we are not finding that,” he added.

Finding out why silver is such a great antibacterial agent is the focus of Zhang’s research, recently published in the journal Langmuir.

“We want to understand the relationship between the atomic structure and bioactivity of nanosilver as to why it is so efficient at inhibiting bacterial activity. It’s a big puzzle.”

Zhang said it is very hard to understand what is happening at the atomic level. Using small nanosilver particles is the most effective way, because when you make silver small, you can expect higher activity because of the increased surface area.

This poses another problem however, as the nanosilver needs to be stabilized with a coating or the silver particles will bond together forming large pieces of silver that do not efficiently interact with the bacteria.

Zhang’s group used two different coatings to compare the effectiveness of the silver as an antibacterial agent. The first was a small amino acid coating and the other was a larger polymer coating. And after testing the interactions between the nanosilver and the bacteria, and looking at the atomic structure of nanosilver using the CLS and the Advanced Photon Source, the researchers were surprised to find that the thicker, larger polymer coating actually created a better delivery method for sliver to inhibit the bacteria.

“We proposed that the small amino acid coating would bind so tightly to the silver surface that it would be difficult for  the silver atoms to interact with the bacteria, whereas the polymers are actually very good at staying in place and still releasing sufficient amount of silver with the bacteria.”

Zhang said the next steps will be to find out if the nanosilver is actually attacking good cells in living systems before they can make any further progress on determining whether nanosilver is an effective and efficient antibactieral agent that could be used to cure human and animal diseases.

Here’s an illustration provided by the researchers,

The atomic structure of nanosilver, revealed by synchrotron X-ray spectroscopy, is proving to be a determinant of silver’s antibacterial activity. Padmos, J. Daniel, et al. "Impact of Protecting Ligands on Surface Structure and Antibacterial Activity of Silver Nanoparticles." Langmuir 31.12 (2015): 3745-3752.

The atomic structure of nanosilver, revealed by synchrotron X-ray spectroscopy, is proving to be a determinant of silver’s antibacterial activity.
Padmos, J. Daniel, et al. “Impact of Protecting Ligands on Surface Structure and Antibacterial Activity of Silver Nanoparticles.” Langmuir 31.12 (2015): 3745-3752.

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

Impact of Protecting Ligands on Surface Structure and Antibacterial Activity of Silver Nanoparticles by J. Daniel Padmos, Robert T. M. Boudreau, Donald F. Weaver, and Peng Zhang. Langmuir, 2015, 31 (12), pp 3745–3752
DOI: 10.1021/acs.langmuir.5b00049 Publication Date (Web): March 15, 2015

Copyright © 2015 American Chemical Society

This paper is behind a paywall.

Copper nanoparticles, toxicity research, colons, zebrafish, and septic tanks

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Alicia Taylor, a graduate student at UC Riverside, surrounded by buckets of effluent from the septic tank system she used for her research. Courtesy: University of California at Riverside

Alicia Taylor, a graduate student at UC Riverside, surrounded by buckets of effluent from the septic tank system she used for her research. Courtesy: University of California at Riverside

Those buckets of efflluent are strangely compelling. I think it’s the abundance of orange. More seriously, a March 2, 2015 news item on Nanowerk poses a question about copper nanoparticles,

What do a human colon, septic tank, copper nanoparticles and zebrafish have in common?

They were the key components used by researchers at the University of California, Riverside and UCLA [University of California at Los Angeles] to study the impact copper nanoparticles, which are found in everything from paint to cosmetics, have on organisms inadvertently exposed to them.

The researchers found that the copper nanoparticles, when studied outside the septic tank, impacted zebrafish embryo hatching rates at concentrations as low as 0.5 parts per million. However, when the copper nanoparticles were released into the replica septic tank, which included liquids that simulated human digested food and household wastewater, they were not bioavailable and didn’t impact hatching rates.

A March 2, 2015 University of California at Riverside (UCR) news release (also on EurekAlert), which originated the news item, provides more detail about the research,

“The results are encouraging because they show with a properly functioning septic tank we can eliminate the toxicity of these nanoparticles,” said Alicia Taylor, a graduate student working in the lab of Sharon Walker, a professor of chemical and environmental engineering at the University of California, Riverside’s Bourns College of Engineering.

…

The research comes at a time when products with nanoparticles are increasingly entering the marketplace. While the safety of workers and consumers exposed to nanoparticles has been studied, much less is known about the environmental implications of nanoparticles. The Environmental Protection Agency is currently accessing the possible effects of nanomaterials, including those made of copper, have on human health and ecosystem health.

The UC Riverside and UCLA [University of California at Los Angeles] researchers dosed the septic tank with micro copper and nano copper, which are elemental forms of copper but encompass different sizes and uses in products, and CuPRO, a nano copper-based material used as an antifungal agent to spray agricultural crops and lawns.

While these copper-based materials have beneficial purposes, inadvertent exposure to organisms such as fish or fish embryos has not received sufficient attention because it is difficult to model complicated exposure environments.

The UC Riverside researchers solved that problem by creating a unique experimental system that consists of the replica human colon and a replica two-compartment septic tank, which was originally an acyclic septic tank. The model colon is made of a custom-built 20-inch-long glass tube with a 2-inch diameter with a rubber stopper at both ends and a tube-shaped membrane typically used for dialysis treatments within the glass tube.

To simulate human feeding, 100 milliliters of a 20-ingredient mixture that replicated digested food was pumped into the dialysis tube at 9 a.m., 3 p.m. and 9 p.m. for five-day-long experiments over nine months.

The septic tank was filled with waste from the colon along with synthetic greywater, which is meant to simulate wastewater from sources such as sinks and bathtubs, and the copper nanoparticles. The researchers built a septic tank because 20 to 30 percent of American households rely on them for sewage treatment. Moreover, research has shown up to 40 percent of septic tanks don’t function properly. This is a concern if the copper materials are disrupting the function of the septic system, which would lead to untreated waste entering the soil and groundwater.

Once the primary chamber of the septic system was full, liquid began to enter the second chamber. Once a week, the effluent was drained from the secondary chamber and it was placed into sealed five-gallon containers. The effluent was then used in combination with zebrafish embryos in a high content screening process using multiwall plates to access hatching rates.

The remaining effluent has been saved and sits in 30 five-gallon buckets in a closet at UC Riverside because some collaborators have requested samples of the liquid for their experiments.

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

Understanding the Transformation, Speciation, and Hazard Potential of Copper Particles in a Model Septic Tank System Using Zebrafish to Monitor the Effluent* by Sijie Lin, Alicia A. Taylor, Zhaoxia Ji, Chong Hyun Chang, Nichola M. Kinsinger, William Ueng, Sharon L. Walker, and André E. Nel. ACS Nano, 2015, 9 (2), pp 2038–2048 DOI: 10.1021/nn507216f
Publication Date (Web): January 27, 2015

Copyright © 2015 American Chemical Society

This paper is behind a paywall.

* Link added March 10, 2015.

Glove sensors and toxic substances

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Gloves that change colour as a signal you’re handling toxic substances have been developed by a research team at  the Fraunhofer Institute according to a May 2, 2013 Fraunhofer Research Institution for Modular Solid State Technologies EMFT news release (also on EurekAlert as a re-issued June 7, 2013 news release),

Employees in chemical production, the semiconductor industry or in laboratories are frequently exposed to harmful substances. The problem: Many of these aggressive substances are imperceptible to human senses, which makes handling them so risky. That’s why there is a broad range of solutions that employers can use to protect their staff from hazardous substances – from highly sensitive measuring equipment to heat imaging cameras. Soon, this spectrum will be enhanced by one more clever solution that is easy to handle, and that dispenses with a power supply. Researchers at the Fraunhofer Research Institution for Modular Solid State Technologies EMFT in Regensburg have engineered a glove that recognizes if toxic substances are present in the surrounding air.

Here’s an image of the glove,

The sensor glove turns blue in the presence of hazardous substances. (© Fraunhofer EMFT)

The sensor glove turns blue in the presence of hazardous substances. (© Fraunhofer EMFT)

The news release provides more details,

The protective glove is equipped with custom-made sensor materials and indicates the presence of toxic substances by changing colors. In this regard, the scientists adapted the materials to the corresponding analytes, and thus, the application. The color change – from colorless (no toxic substance) to blue (toxic substance detected), for example – warns the employee immediately. …

….

The warning signal is triggered by an indicator dye integrated into the glove that reacts to the presence of analytes, in this case, the toxic substances. The experts at EMFT used a variety of techniques in order to furnish textiles with sensor-activated dyes. The sensor-activated dyes are applied to the clothing with the customary dye and print process, for example, by affixing them in an immersion bath. Previously, the researchers used targeted chemical modification to adapt the color molecules to the fiber properties of the respective textile. Alternatively, the textiles can also be coated with sensor particles that are furnished with sensor dyes. For this purpose, the scientists integrated the dye molecules either into commercial pigments or they built them up on an entirely synthetic basis. The pigments are then manufactured according to the customary textile finishing process, for instance, the sensor particles are also suitable for silkscreening. “Which version we opt for depends on the requirements of the planned application,” says Trupp [Dr. Sabine Trupp, head of the Fraunhofer EMFT Sensor Materials group].

The challenge lies foremost in the tailored development of sensor dyes. “The dye molecule must detect a specific analyte in a targeted manner – only then will a chemical reaction occur. Moreover, the dye must adhere securely; it cannot disappear due to washing. We aim for the customer’s preferences in the color selection as well. All of these aspects must be kept in mind when developing the molecule and pigment properties,” explains Trupp.

The technology could be extended to do more and could be adapted for other applications (from the news release),

The expert already has new ideas about how the solution could be developed further. For example, a miniaturized sensor module, integrated into textiles, could record toxic substances, store the measurement data and even transmit them to a main unit. This way, you could document how frequently an individual within a hazardous environment was exposed to poisonous concentrations over a longer period of time.

The researchers also envision other potential applications in the foodstuffs industry: In the future, color indicator systems integrated into foils or bottle closures are intended to make the quality status of the packaged foods visible. Because the sell-by date does not represent a guarantee of any kind. Foodstuffs may often spoil prematurely – unnoticed by the consumer – due to a packaging error, or in the warehousing, or due to disruptions in the refrigeration chain. Oil-based and fat-containing products are specifically prone to this, as are meats, fish and ready meals.

The notion that food packaging could be designed to include sensors that alert consumers and retailers about product spoilage is not new and was mentioned recently and briefly in my Mar. 25, 2013 posting which featured excerpts from an interview with biotechnologist Christoph Meili about nanotechnology-enabled food packaging.

NanoSustain published four case studies: zinc oxide, titanium dioxide, carbon nanotubes, and nanocellulose

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A May 17, 2013 news item on Nanowerk highlight a European Commission-funded project, NanoSustain and its publication of a fact sheet and four case studies,,

NanoSustain, a €2.5 million NMP small collaborative project (2010-2013) funded by the European Union under FP7, has published a fact sheet and four case studies addressing these issues.

How do nanotechnology-based products impact human health and the environment?
Can they be recycled?
Can they be safely disposed of?
How can you find out?

The March 20, 2013 NanoSustain news release, which originated the news item, goes on to explain,

… the EC-funded NanoSustain project has been developing new sustainable solutions through an investigation of the life-cycle of nanotechnology-based products, in particular the physical and chemical characteristics of materials, hazard and exposure aspects, and end-of-life disposal or recycling to determine the fate and impact of nanomaterials.

A summary of the different materials and products tested within NanoSustain:

• Case Study #1: Titanium dioxide for paints
• Case Study #2: Zinc oxide for glazing products
• Case Study #3: Carbon nanotubes epoxy resins for plastics
– for structural or electrical/antistatic applications
• Case Study #4: Nanocellulose for advanced paper applications

Information about the individual experimental approaches

Descriptions of the different techniques developed

How these techniques have been successfully applied in physical-chemical characterisation; life-cycle analysis; final disposal; recycling.

Getting access to the case case studies and the fact sheet requires filling out a form but once you’ve done that you get instant access to the materials.

Here’s some information from EuroSustain’s fact sheet,

Factsheets

Analytical Techniques

Development of sustainable solutions for nanotechnology-based products based on hazard characterization and LCA1 The primary goal of the NanoSustain project is to develop new technical solutions for the sustainable design and use, recycling and final treatment of selected nanotechnology-based products.

To achieve this the project has the following objectives: 1) to assess the hazard of selected nanomaterials based on a comprehensive data survey and generation concerning their physicochemical (PC) and toxicological properties, exposure probabilities, etc., and the adaptation, evaluation, validation and use of existing analytical, testing and life-cycle assessment (LCA) methods; 2) to assess the impact of selected products during their life cycle in relation to material and energy flows (LCA); 3) to assess possible exposure routes and risks associated with the handling of these materials, their transformation and final fate; and 4) to explore the feasibility and sustainability of new technical solutions for end-of=life processes, such as reuse/recycling, final treatment or disposal.

…

Within NanoSustain an assessment has been made of the PC properties, exposure and toxicity, energy and material inputs and outputs at relevant stages of a material or product’s life-cycle. This means: material production, processing, manufacturing, use, transportation, and end-of-life (recycling/disposal). At each stage potential risks to human health and the environment have also been assessed, through a number of experimental models and test systems using materials that would be expected to be released from products containing nanomaterials.

Four nanomaterials were investigated that either already feature in commercial products or are expected to be commercialized on a large scale: titanium dioxide (TiO2) in paint, zinc oxide (ZnO) as a coating for glass, multi-walled carbon nanotubes (MWCNT) in epoxy resins, and nanocellulose in paper.

Detailed information on the nanomaterials have been summarized in internal project material datasheets (MDS), and will be made available as part of peer-reviewed publications on release studies and toxicological investigations. [emphases mine]

Having looked at the four case studies, each of which is two pages, I would describe them as teasers. There’s not a lot of information in them as to the results of the testing which makes sense when you see that they will be publishing in various publications.

I find the inclusion of titanium dioxide, zinc oxide and carbon nanotubes for life-cycle assessments easily understandable as they  have been integrated into many consumer products. However, it’s my understanding that nanocellulose has not reached that level of product integration. Still, given the number of times I’ve been told this is a ‘safe’ product, it’s interesting to see what NanoSustain has to say about its toxicity (from the NanoSustain’s nanocellulose case study),

Work in NanoSustain has provided new data and information on the physicochemical properties, potential human and environmental hazard and risk associated with relevant stages of the life-cycle of nanocellulose based products as well as on the overall energy and material input/output that may happen during manufacturing, use and disposal. Initial results indicate that the nanocellulose degrades efficiently under standard composting conditions, but does not in aquatic environments. Furthermore nanocellulose does not demonstrate any ecotoxicity. Unfortunately nanocellulose forms a gel when suspended in media for inhalation studies, and so no toxicology experiments could be performed (as for the other engineered nanomaterials studied in NanoSustain). Final results will be made available once published in peer-reviewed journals.

I have written many times about nanocellulose, a topic featuring some interesting and confusing nomenclature and taking this opportunity to highlight a couple of responses from folks who took the time to clarify things for me (from my Aug. 2, 2012 posting),

KarenS says:

Hi Maryse!

From my understanding, nanocrystaline cellulose (NCC), cellulose nanocrystals (CNC), cellulose whiskers (CW) and cellulose nanowhiskers (CNW) are all the same stuff: cylindrical rods of crystalline cellulose (diameter: 5-10 nm; length: 20-1000 nm). Cellulose nanofibers or nanofibrils (CNF), on the contrary, are less crystalline and are in the form of long fibers (diameter: 20-50 nm; length: up to several micrometers).

There is still a lot of confusion on the nomenclature of cellulose nanoparticles, but nice explanations (and pictures!) are given here (and also in other papers from the same conference):

http://www.tappi.org/Downloads/Conference-Papers/2012/12NANO/12NANO49.aspx

and there’s this from my Sept. 26, 2012 posting,

Gary Chinga Carrasco says:

The definition of cellulose nanofibrils as “diameter: 20-50 nm; length: up to several micrometers)” is somewhat simplified. For terminology on MFC terms you may want to take a look at: http://www.nanoscalereslett.com/content/6/1/417

Bringing this piece back to where I started, I look forward to seeing the NanoSustain case studies published with more details in the future.

Note: Since the folks at NanoSustain are likely using their form to collect data, I’m not linking back to the factsheet or nanocellulose case study as I would usually. So, if you want to look at the material, you do need to register via the form.