Tag Archives: nanotoxicology

nanoIndEx publishes guidance document on assessing exposure to airborne nanomaterials

Lynn Bergeson’s June 21, 2016 posting on Nanotechnology Now announced a newly published guidance document from the European Union’s nanoIndEx,

… The guidance document summarizes the key findings of the project, and is intended to present the state of the art in personal exposure assessment for nanomaterials. The conclusions section states: “Unfortunately, many nanotoxicological studies have used excessive, unrealistically high doses of [manufactured nanomaterials] and it is therefore debatable what their findings mean for the lower real-world exposures of humans. Moreover, it is not clear how to establish realistic exposure dose testing in toxicological studies, as available data on occupational exposure levels are still sparse.” According to the guidance document, future studies should focus on the potentially adverse effects of low-level and realistic exposure to manufactured nanomaterials, especially through the use of exposure doses similar to those identified in environmental sampling.

You can find the 49pp PDF here or here. To whet your appetite, here’s a bit from the introduction to the “Exposure to Airborne Nanomaterials; A Guidance Document,”

… While human exposure to MNMs may in principle occur during any stage of the material’s lifecycle, it is most likely in workplaces, where these materials are produced or handled in large quantities or over long periods of time. Inhalation is considered as the most critical uptake route, because the small particles are able to penetrate deep into the lung and deposit in the gas exchange region. Inhalation exposure to airborne nanomaterials therefore needs to be assessed in view of worker protection.

Exposure to airborne particles can generally best be assessed by measuring the individual exposure in the personal breathing zone (PBZ) of an individual. The PBZ is defined as a 30 cm hemisphere around mouth and nose [2]. Measurements in the PBZ require instruments that are small and light-weight. The individual exposure specifically to MNMs [manufactured nanomaterials, sometimes also known as engineered nanomaterials or nanoparticles] has not been assessable in the past due to the lack of suitable personal samplers and/or monitors. Instead, most studies related to exposure to MNMs have been carried out using either bulky static measurement equipment or not nanospecific personal samplers. In recent years, novel samplers and monitors have been introduced that allow for an assessment of the more nanospecific personal exposure to airborne MNMs. In the terminology used in nanoIndEx, samplers are devices that collect particles on a substrate, e.g. a filter
of flat surface, for subsequent analysis, whereas monitors are real-time instruments that deliver
information on the airborne concentrations with high time resolution. Scientifically sound investigations on the accuracy, comparability and field applicability of these novel samplers and monitors had been lacking. … (p. 4 print; p. 6 PDF)

There’s also a brief description of the nanoindEX project in the Introduction,

The three-year project started on June 1st, 2013, and has been funded under the frame of SIINN, the ERA-NET [European Research Area Network] for a Safe Implementation of Innovative Nanoscience and Nanotechnology [SINN]. The aim of the project was to scrutinise the instrumentation available for personal exposure assessment concerning their field readiness and usability in order to use this information to generate reliable data on personal exposure in real workplaces and to eventually widely distribute the findings among the interested public. This Guidance Document you are holding in your hands summarises the key findings of the project. (p. 5 print; p. 7 PDF)

As I understand it, the area of most concern where nanotoxicology is concerned would be inhalation of nanoparticles into the lungs as the body has fewer protections in the respiratory tract than it has elsewhere, e.g. skin or digestive system.

New model to track flow of nanomaterials through our air, earth, and water

Just how many tons of nanoparticles are making their way through the environment? Scientists at the Swiss Federal Laboratories for Materials Science and Technology (Empa) have devised a new model which could help answer that question. From a May 12, 2016 news item on phys.org,

Carbon nanotubes remain attached to materials for years while titanium dioxide and nanozinc are rapidly washed out of cosmetics and accumulate in the ground. Within the National Research Program “Opportunities and Risks of Nanomaterials” (NRP 64) a team led by Empa scientist Bernd Nowack has developed a new model to track the flow of the most important nanomaterials in the environment.

A May 12, 2016 Empa press release by Michael Hagmann, which also originated the news item, provides more detail such as an estimated tonnage for titanium dioxide nanoparticles produced annually in Europe,

How many man-made nanoparticles make their way into the air, earth or water? In order to assess these amounts, a group of researchers led by Bernd Nowack from Empa, the Swiss Federal Laboratories for Materials Science and Technology, has developed a computer model as part of the National Research Program “Opportunities and Risks of Nanomaterials” (NRP 64). “Our estimates offer the best available data at present about the environmental accumulation of nanosilver, nanozinc, nano-tinanium dioxide and carbon nanotubes”, says Nowack.

In contrast to the static calculations hitherto in use, their new, dynamic model does not just take into account the significant growth in the production and use of nanomaterials, but also makes provision for the fact that different nanomaterials are used in different applications. For example, nanozinc and nano-titanium dioxide are found primarily in cosmetics. Roughly half of these nanoparticles find their way into our waste water within the space of a year, and from there they enter into sewage sludge. Carbon nanotubes, however, are integrated into composite materials and are bound in products such as which are immobilized and are thus found for example in tennis racquets and bicycle frames. It can take over ten years before they are released, when these products end up in waste incineration or are recycled.

39,000 metric tons of nanoparticles

The researchers involved in this study come from Empa, ETH Zurich and the University of Zurich. They use an estimated annual production of nano-titanium dioxide across Europe of 39,000 metric tons – considerably more than the total for all other nanomaterials. Their model calculates how much of this enters the atmosphere, surface waters, sediments and the earth, and accumulates there. In the EU, the use of sewage sludge as fertilizer (a practice forbidden in Switzerland) means that nano-titanium dioxide today reaches an average concentration of 61 micrograms per kilo in affected soils.

Knowing the degree of accumulation in the environment is only the first step in the risk assessment of nanomaterials, however. Now this data has to be compared with results of eco-toxicological tests and the statutory thresholds, says Nowack. A risk assessment has not been carried out with his new model so far. Earlier work with data from a static model showed, however, that the concentrations determined for all four nanomaterials investigated are not expected to have any impact on the environment.

But in the case of nanozinc at least, its concentration in the environment is approaching the critical level. This is why this particular nanomaterial has to be given priority in future eco-toxicological studies – even though nanozinc is produced in smaller quantities than nano-titanium dioxide. Furthermore, eco-toxicological tests have until now been carried out primarily with freshwater organisms. The researchers conclude that additional investigations using soil-dwelling organisms are a priority.

Here are links to and citations for papers featuring the work,

Dynamic Probabilistic Modeling of Environmental Emissions of Engineered Nanomaterials by Tian Yin Sun†, Nikolaus A. Bornhöft, Konrad Hungerbühler, and Bernd Nowack. Environ. Sci. Technol., 2016, 50 (9), pp 4701–4711 DOI: 10.1021/acs.est.5b05828 Publication Date (Web): April 04, 2016

Copyright © 2016 American Chemical Society

Probabilistic environmental risk assessment of five nanomaterials (nano-TiO2, nano-Ag, nano-ZnO, CNT, and fullerenes) by Claudia Coll, Dominic Notter, Fadri Gottschalk, Tianyin Sun, Claudia Som, & Bernd Nowack. Nanotoxicology Volume 10, Issue 4, 2016 pages 436-444 DOI: 10.3109/17435390.2015.1073812 Published online: 10 Nov 2015

The first paper, which is listed in Environmental Science & Technology, appears to be open access while the second paper is behind a paywall.

Identifying minute amounts of nanomaterial in environmental samples

It’s been a while since I’ve had a story from one of Germany’s Franhaufer Institutes. Their stories are usually focused on research that’s about to commercialized but that’s not the case this time according to an April 28, 2016 news item on Nanowerk,

It is still unclear what the impact is on humans, animals and plants of synthetic nanomaterials released into the environment or used in products. It’s very difficult to detect these nanomaterials in the environment since the concentrations are so low and the particles so small. Now the partners in the NanoUmwelt project have developed a method that is capable of identifying even minute amounts of nanomaterials in environmental samples.

An April 28, 2016 Fraunhofer Institute press release, which originated the news item, provides more detail about the technology and about the NanoUmwelt project along with a touch of whimsy,

Tiny dwarves keep our mattresses clean, repair damage to our teeth, stop eggs sticking to our pans, and extend the shelf life of our food. We are talking about nanomaterials – “nano” comes from the Greek word for “dwarf”. These particles are just a few billionths of a meter small, and they are used in a wide range of consumer products. However, up to now the impact of these materials on the environment has been largely unknown, and information is lacking on the concentrations and forms in which they are present there. “It’s true that many laboratory studies have examined the effect of nanomaterials on human and animal cells. To date, though, it hasn’t been possible to detect very small amounts in environmental samples,” says Dr. Yvonne Kohl from the Fraunhofer Institute for Biomedical Engineering IBMT in Sulzbach.

A millionth of a milligram per liter 

That is precisely the objective of the NanoUmwelt project. The interdisciplinary project team is made up of eco- and human toxicologists, physicists, chemists and biologists, and they have just managed to take their first major step forward in achieving their goal: they have developed a method for testing a variety of environmental samples such as river water, animal tissue, or human urine and blood that can detect nanomaterials at a concentration level of nanogram per liter (ppb – parts per billion). That is equivalent to half a sugar cube in the volume of water contained in 1,000 competition swimming pools. Using the new method, it is now possible to detect not just large amounts of nanomaterials in clear fluids, as was previously the case, but also very few particles in complex substance mixtures such as human blood or soil samples. The approach is based on field-flow fractionation (FFF), which can be used to separate complex heterogeneous mixtures of fluids and particles into their component parts – while simultaneously sorting the key components by size. This is achieved by the combination of a controlled flow of fluid and a physical separation field, which acts perpendicularly on the flowing suspension.

For the detection process to work, environmental samples have to be appropriately processed. The team from Fraunhofer IBMT’s Bioprocessing & Bioanalytics Department prepared river water, human urine, and fish tissue to be fit for the FFF device. “We prepare the samples with special enzymes. In this process, we have to make sure that the nanomaterials are not destroyed or changed. This allows us to detect the real amounts and forms of the nanomaterials in the environment,” explains Kohl. The scientists have special expertise when it comes to providing, processing and storing human tissue samples. Fraunhofer IBMT has been running the “German Environmental Specimen Bank (ESB) – Human Samples”since January 2012 on behalf of Germany’s Environment Agency (UBA). Each year the research institute collects blood and urine samples from 120 volunteers in four cities in Germany. Individual samples are a valuable tool for mapping the trends over time of human exposure to pollutants. ”In addition, blood and urine samples have been donated for the NanoUmwelt project and put into cryostorage at Fraunhofer IBMT. We used these samples to develop our new detection method,” says Dr. Dominik Lermen, manager of the working group on Biomonitoring & Cryobanks at Fraunhofer IBMT. After approval by the UBA, some of the human samples in the ESB archive may also be examined using the new method.

Developing new cell culture models

Nanomaterials end up in the environment via different pathways, inter alia the sewage system. Human beings and animals presumably absorb them through biological barriers such as the lung or intestine. The project team is simulating these processes in petri dishes in order to understand how nanomaterials are transported across these barriers. “It’s a very complex process involving an extremely wide range of cells and layers of tissue,” explains Kohl. The researchers replicate the processes in a way as realistic as possible. They do this by, for instance, measuring the electrical flows within the barriers to determine the functionality of these barriers – or by simulating lung-air interaction using clouds of artificial fog. In the first phase of the NanoUmwelt project, the IBMT team succeeded in developing several cell culture models for the transport of nanomaterials across biological barriers. IBMT worked together with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME, which used pluripotent stem cells to develop a model for investigating cardiotoxicity. Empa, the Swiss partner in the project, delivered a placental barrier model for studying the transport of nanomaterials between mother and child.

Next, the partners want to use their method to measure the concentrations of nanoparticles in a wide variety of environmental samples. They will then analyze the results obtained so as to be in a better position to assess the behavior of nanomaterials in the environment and their potential danger for humans, animals, and the environment. “Our next goal is to detect particles in even smaller quantities,” says Kohl. To achieve this, the scientists are planning to use special filters to remove distracting elements from the environmental samples, and they are looking forward to develop new processing techniques.
NanoUmwelt – the objective

The NanoUmwelt research project was launched in October 2014 and will last for 36 months. Its objective is to develop methods for detecting minute amounts of nanomaterials in environmental samples. Using this information, the project partners will assess the effect of nanomaterials on humans, animals, and the environment. They are focusing on commercially significant, slowly degradable, metallic (silver, titanium dioxide), carbonic (carbon nanotubes) and polymer-based (polystyrene) nanomaterials.

http://www.nanopartikel.info/projekte/laufende-projekte/nanoumwelt

NanoUmwelt – the partners

The German Federal Ministry for Education and Research (BMBF) is providing the NanoUmwelt project with 1.8 million euros of funding as part of its NanoCare program. Led by Postnova Analytics GmbH, ten further partners are collaborating together on the project. Besides the Fraunhofer Institutes for Biomedical Engineering IBMT and for Molecular Biology and Applied Ecology IME, these partners include Germany’s Environment Agency, Empa (the Swiss Federal Laboratories for Materials Science and Technology), PlasmaChem GmbH, Senova GmbH (biological sciences and engineering), fzmb GmbH (Research Centre of Medical Technology and Biotechnology), the universities of Trier and Frankfurt, and the Rhine Water Control Station in Worms.

http://www.nanopartikel.info/projekte/laufende-projekte/nanoumwelt

How small is nano?

A nanometer (nm) is a billionth of a meter. To put this into context: the size of a single nanoparticle relative to a football is the same as that of a football relative to the earth. In the main, nanoscopic particles are not new materials. It’s simply that the increased overall surface area of these tiny particles gives them new functionalities as against larger particles of the same material.


The German Environmental Specimen Bank  

The German Environmental Specimen Bank (ESB) provides the country’s Federal Ministry for the Environment, Nature Conservation, Building and Nuclear Safety (BMUB) with a scientific basis both for adopting appropriate measures concerning environment and nature conservation and for monitoring the success of those measures. The human samples collected by the Fraunhofer Institute for Biomedical Engineering IBMT on behalf of Germany’s Environment Agency (UBA) give an overview of human exposure to environmental pollutants.

https://www.umweltprobenbank.de/de

Assuming I’ve understood this correctly, the NanoUmwelt project will be ending in 2017 (36 months in total) and the researchers have expended 1/2 of the time (18 months) allotted to developing a technique for measuring nanomaterials of heretofore unheard of quantities in environmental samples. With that done, researchers are now going to use the technique with human samples over the next 18 months.

What is the effect of nanoscale plastic on marine life?

A Nov.27, 2015 news item on Nanowerk announces a new UK (United Kingdom) research project designed to answer the question: what impact could nanoscale plastic particles  have on the marine environment?,

As England brings in pricing on plastic carrier bags, and Scotland reveals that similar changes a little over a year ago have reduced the use of such bags by 80%, new research led by Heriot-Watt University in conjunction with Plymouth University will look at the effect which even the most microscopic plastic particles can have on the marine environment.

While images of large ‘islands’ of plastic rubbish or of large marine animals killed or injured by the effects of such discards have brought home some of the obvious negative effects of plastics in the marine environment, it is known that there is more discarded plastic out there than we can account for, and much of it will have degraded into small or even microscopic particles.

It is the effect of these latter, known as nano-plastics, which will be studied under a £1.1m research project, largely funded by NERC [UK Natural Environment Research Council] and run by Heriot-Watt and Plymouth Universities.

A Nov. 25, 2015 Herriot-Watt University press release, which originated the news item, provides more details,

The project, RealRiskNano, will look at the risks these tiny plastic particles pose to the food web including filter-feeding organisms like mussels, clams and sediment dwelling organisms. It will focus on providing information to improve environmental risk assessment for nanoplastics, based on real-world exposure scenarios replicated in the laboratory.

Team leader Dr Theodore Henry, Associate Professor of Toxicology at Heriot-Watt’s School of Life Sciences, said that the study will build on previous research on nano-material toxicology, but will provide information which the earlier studies did not include.

“Pieces of plastic of all sizes have been found in even the most remote marine environments. It’s relatively easy to see some of the results: turtles killed by easting plastic bags which they take for jelly fish, or large marine mammals drowned when caught in discarded ropes and netting.

“But when plastics fragment into microscopic particles, what then? It’s easy to imagine that they simply disappear, but we know that nano-particles pose their own distinct threats purely because of their size. They’re small enough to be transported throughout the environment with unknown effects on organisms including toxicity and interference with processes of the digestive system.

An important component of the project, to be investigated by Dr Tony Gutierrez at Heriot-Watt, will be the study of interactions between microorganisms and the nanoplastics to reveal how these interactions affect their fate and toxicology.

The aim, said Dr Henry, is to provide the information which is needed to effect real change.“We simply don’t know what effects these nano-plastic particles may pose to the marine environment, to filter-feeders and on to fish, and through the RealRiskNano project we aim to provide this urgently needed information to the people whose job it is to assess risk to the marine ecosystem and decide what steps need to be taken to mitigate it.”

You can find the RealRiskNano website here.

Brown University (US) gets big bucks to study effect on nanomaterials on human health

In over seven years of blogging about nanotechnology, this is the most active funding period for health and environmental effects impacts I’ve seen yet. A Sept. 26, 2015 news item on Azonano features another such grant,

With a new federal grant of nearly $10.8 million over the next five years, Brown University researchers and students in the Superfund Research Program (SRP) will be able to advance their work studying how toxicant exposures affect health, how such exposures occur, how nanotechnologies could contain contamination, and how to make sure those technologies are safe.

A Sept. 24, 2015 Brown University news release, which originated the news item, describes of Brown’s SRP work already underway and how this new grant will support it,

“There is more research to be performed,” said Kim Boekelheide, program director, professor of pathology and laboratory medicine, and fellow of the Institute at Brown for Environment and Society (IBES). “Our scientific theme is integrated biomedical and engineering solutions to regulatory uncertainty, using interdisciplinary approaches to attack the really difficult contamination problems that matter.”

The program is pursuing four integrated projects. In one led by Boekelheide, a team is looking at the physiological effects of exposure to toxicants like trichloroethylene on the male reproductive system. In particular he hopes to find the subtle differences in biomolecular markers in sperm that could allow for very early detection of exposure. Meanwhile in another line of research, Eric Suuberg, professor of engineering, is studying how vapors from toxic material releases can re-emerge from the soil entering into buildings built at or near the polluted sites — and why it is hard to predict the level of exposure that inhabitants of these buildings may suffer.

In another project, Robert Hurt, an IBES fellow, SRP co-primary investigator and professor of engineering, is studying how graphene, an atomically thin carbon material, can be used to block the release and transport of toxicants to prevent human exposures. Hurt is also collaborating with Agnes Kane, an IBES fellow and chair and professor of pathology and laboratory medicine, who is leading a study of nanomaterial effects on human health, so they can be designed and used safely in environmental and other applications.

The program will also continue the program’s community outreach efforts in which they work and share information with communities near the state’s Superfund-designated and Brownfield contaminated sites. Scott Frickel, an IBES fellow and associate professor of sociology, is the new leader of community engagement. The program also includes a research translation core in which researchers share their findings and expertise with the U.S. Environmental Protection Agency, state agencies, and professionals involved in contamination management and cleanup. A training core provides opportunities for interdisciplinary research, field work, and industry “externships” for graduate students in engineering, pathobiology, and social sciences at Brown.

It’s good to see they are integrating social sciences into this project although I hope they aren’t attempting this move as a means to coopt and/or stifle genuine dissent and disagreement by giving a superficial nod to the social sciences and public engagement  while wending on their merry way.

Two-organ tests (body-on-a-chip) show liver damage possible from nanoparticles

This is the first time I’ve seen testing of two organs for possible adverse effects from nanoparticles. In this case, the researchers were especially interested in the liver. From an Aug. 12, 2014 news item on Azonano,

Nanoparticles in food, sunscreen and other everyday products have many benefits. But Cornell [University] biomedical scientists are finding that at certain doses, the particles might cause human organ damage.

A recently published study in Lab on a Chip by the Royal Society of Chemistry and led by senior research associate Mandy Esch shows that nanoparticles injure liver cells when they are in microfluidic devices designed to mimic organs of the human body. The injury was worse when tested in two-organ systems, as opposed to single organs – potentially raising concerns for humans and animals.

Anne Ju’s Aug. 11, 2014 article for Cornell University’s Chronicle describes the motivation for this work and the research itself in more detail,

“We are looking at the effects of what are considered to be harmless nanoparticles in humans,” Esch said. “These particles are not necessarily lethal, but … are there other consequences? We’re looking at the non-lethal consequences.”

She used 50-nanometer carboxylated polystyrene nanoparticles, found in some animal food sources and considered model inert particles. Shuler’s lab specializes in “body-on-a-chip” microfluidics, which are engineered chips with carved compartments that contain cell cultures to represent the chemistry of individual organs.

In Esch’s experiment, she made a human intestinal compartment, a liver compartment and a compartment to represent surrounding tissues in the body. She then observed the effects of fluorescently labeled nanoparticles as they traveled through the system.

Esch found that both single nanoparticles as well as small clusters crossed the gastrointestinal barrier and reached liver cells, and the liver cells released an enzyme called aspartate transaminase, known to be released during cell death or damage.

It’s unclear exactly what damage is occurring or why, but the results indicate that the nanoparticles must be undergoing changes as they cross the gastrointestinal barrier, and that these alterations may change their toxic potential, Esch said. Long-term consequences for organs in proximity could be a concern, she said.

“The motivation behind this study was twofold: one, to show that multi-organ, in vitro systems give us more information when testing for the interaction of a substance with the human body, and two … to look at nanoparticles because they have a huge potential for medicine, yet adverse effects have not been studied in detail yet,” Esch said.

Mary Macleod’s July 3, 2014 article for Chemistry World features a diagram of the two-organ system and more technical details about the research,

Schematic of the two-organ system [downloaded from http://www.rsc.org/chemistryworld/2014/07/nanoparticle-liver-gastrointestinal-tract-microfluidic-chip]

Schematic of the two-organ system [downloaded from http://www.rsc.org/chemistryworld/2014/07/nanoparticle-liver-gastrointestinal-tract-microfluidic-chip]

HepG2/C3A cells were used to represent the liver, with the intestinal cell co-culture consisting of enterocytes (Caco-2) and mucin-producing (HT29-MTX) cells. Carboxylated polystyrene nanoparticles were fluorescently labelled so their movement between the chambers could be tracked. Levels of aspartate transaminase, a cytosolic enzyme released into the culture medium upon cell death, were measured to give an indication of liver damage.

The study saw that single nanoparticles and smaller nanoparticle aggregates were able to cross the GI barrier and reach the liver cells. The increased zeta potentials of these nanoparticles suggest that crossing the barrier may raise their toxic potential. However, larger nanoparticles, which interact with cell membranes and aggregate into clusters, were stopped much more effectively by the GI tract barrier.

The gastrointestinal tract is an important barrier preventing ingested substances crossing into systemic circulation. Initial results indicate that soluble mediators released upon low-level injury to liver cells may enhance the initial injury by damaging the cells which form the GI tract. These adverse effects were not seen in conventional single-organ tests.

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

Body-on-a-chip simulation with gastrointestinal tract and liver tissues suggests that ingested nanoparticles have the potential to cause liver injury by Mandy B. Esch, Gretchen J. Mahler, Tracy Stokol, and Michael L. Shuler. Lab Chip, 2014,14, 3081-3092 DOI: 10.1039/C4LC00371C First published online 27 Jun 2014

This paper is open access until Aug. 12, 2014.

While this research is deeply concerning, it should be noted the researchers are being very careful in their conclusions as per Ju’s article, “It’s unclear exactly what damage is occurring or why, but the results indicate that the nanoparticles must be undergoing changes as they cross the gastrointestinal barrier, and that these alterations may change their toxic potential … Long-term consequences for organs in proximity could be a concern … .”

Deadline extension (travel grants and poster abstracts) for alternate testing strategies (ATS) of nanomaterials workshop

It seems there have been a couple of deadline extensions (to August 1, 2014) for the September 15-16, 2014 ‘Workshop to Explore How a Multiple Models Approach can Advance Risk Analysis of Nanoscale Materials’ in Washington, DC (first mentioned in my July 10, 2014 posting featuring a description of the workshop). You can go here to submit a poster abstract (from any country) and you can go here if you’re a student or young professional (from any country) in search of a $500 travel award.

I managed to speak to one of the organizers, Lorraine Sheremeta, (Assistant Director, Ingenuity Lab, University of Alberta and co-author a July 9, 2014 Nanowerk Spotlight article about the workshop). Lorraine (Lori) kindly spoke to me about the upcoming workshop, which she described as an academic conference,.

As I understand what she told me, the hosts for the September 15-16, 2014 Workshop to Explore How a Multiple Models Approach can Advance Risk Analysis of Nanoscale Materials in Washington, DC want to attract a multidisciplinary group of people to grapple with a few questions. First, they want to establish a framework for establishing which are the best test methods for nanomaterials. Second, they are trying to move away from animal testing and want to establish which methods are equal to or better than animal testing. Thirdly, they want to discuss what they are going to do with the toxicological data  that we have  been collecting on nanomaterials for years now.

Or, as she and her colleague from the Society of Risk Analysis (Jo Anne Shatkin) have put in it in their Nanowerk Spotlight article:

… develop a report on the State of the Science for ATS for nanomaterials, catalogue of existing and emerging ATS [alternate testing strategies] methods in a database; and develop a case study to inform workshop deliberations and expert recommendations

The collaborative team behind this event includes, the University of Alberta’s Ingenuity Lab, the Society for Risk Analysis, Environment Canada, Health Canada, and the Organization for Economic Co-operation and Development (OECD) Working Party on Manufactured Nanomaterials (WPMN) .

The speaker lineup isn’t settled at this time although they have confirmed Vicki Stone of Heriot-Watt University in Scotland (from her university bio page),

Vicki Stone, Professor of Toxicology, studies the effects of nanomaterials on humans and environmentally relevant species.  Current research projects investigate the mechanism of toxicity of a range of nanomaterials in cells of the immune system (macrophages and neutrophils), liver (hepatocytes) , gastrointestinal tract, blood vessels (endothelium) and lung.  She is interested in interactions between nanomaterials, proteins and lipids, and how this influences subsequent toxicity.  Current projects also develop in vitro alternatives using microfluidics as well as high resolution imaging of individual nanomaterials in 3D and over time.  In addition Vicki collaborates with ecotoxicologists to investigate the impacts of nanomaterials on aquatic organisms. Vicki coordinated a European project to identify the research priorities to develop an intelligent testing strategy for nanomaterials (www.its-nano.eu).

Vicki is Director of the Nano Safety Research Group at Heriot-Watt University, Edinburgh, and Director of Toxicology for SAFENANO (www.safenano.org). She has acted as the Editor-in-chief of the journal Nanotoxicology (http://informahealthcare.com/nan) for 6 years (2006-2011). Vicki has also published over 130 publications pertaining to particle toxicology over the last 16 years and has provided evidence for the government commissioned reports published by the Royal Society (2003) and the on Environmental Pollution (2008).  Vicki was previously a member of the UK Government Committee on the Medical Effects of Air Pollution (COMEAP) and an advisory board member for the Center for the Environmental Implications of NanoTechnology (CEINT; funded by the US Environmental Protection Agency)).

A representative from PETA (People for the Ethical Treatment of Animals) will also be speaking. I believe that will be Amy Clippinger (from the PETA website’s Regulatory Testing webpage; scroll down about 70% of the way),

Science adviser Amy Clippinger has a Ph.D. in cellular and molecular biology and genetics and several years of research experience at the University of Pennsylvania.

PETA representatives have been to at least one other conference on the topic of nano, toxicology, and animal testing as per my April 24, 2014 posting about NANOTOX 2014 in Turkey,

Writing about nanotechnology can lead you in many different directions such as the news about PETA (People for the Ethical Treatment of Animals) and its poster presentation at the NanoTox 2014 conference being held in Antalya, Turkey from April 23 – 26, 2014. From the April 22, 2014 PETA news release on EurekAlert,

PETA International Science Consortium Ltd.’s nanotechnology expert will present a poster titled “A tiered-testing strategy for nanomaterial hazard assessment” at the 7th International Nanotoxicology Congress [NanoTox 2014] to be held April 23-26, 2014, in Antalya, Turkey.

Dr. Monita Sharma will outline a strategy consistent with the 2007 report from the US National Academy of Sciences, “Toxicity Testing in the 21st Century: A Vision and a Strategy,” which recommends use of non-animal methods involving human cells and cell lines for mechanistic pathway–based toxicity studies.

There is a lot of interest internationally in improving how we test for toxicity of nanomaterials. As well, the drive to eliminate or minimize as much as possible the use of animals in testing seems to be gaining momentum.

Good luck to everyone submitting a poster abstract and/or an application for a travel grant!

In case you don’t want to scroll up, the SRA nano workshop website is here.

An upcoming alternate testing strategies (ATS) for nanomaterials workshop and the quest to reduce animal testing

It’s too late to announce a call for poster abstracts or travel awards but that still leaves the possibility of attending a September 15-16, 2014 Workshop to Explore How a Multiple Models Approach can Advance Risk Analysis of Nanoscale Materials in Washington, DC. In a July 9, 2014 Nanowerk Spotlight article,, Jo Anne Shatkin (President, Vireo Advisors) and Lorraine Sheremeta (Assistant Director, Ingenuity Lab, University of Alberta) tout the workshop in the context of describing new approaches to nanotoxicology research (Note: A link has been removed),

Engineered nanoscale materials (ENM or ‘nanomaterials’) offer the potential to create safer and more effective products through the use of smaller quantities of improved performance materials. Currently nanomaterials are used to improve the performance of life-saving drugs and medical technologies, to make renewable energy more efficient, to make value added products from industrial waste streams, to improve food, packaging, to lightweight materials used in transportation systems, and to improve many of the personal care products that we use every day. Nanomaterial manufacture and use is expected to increase over the coming years and despite the widespread use of nanomaterials in a variety of consumer products, we are only beginning to understand the impacts of these emerging materials on our health and the environment. To this end, the University of Alberta’s Ingenuity Lab is collaborating with the Society for Risk Analysis to evaluate the potential to use alternative test strategies (ATS) to improve our ability to assess nanomaterial toxicity and environmental impact.

Shatkin and Sheremeta describe toxicology tests and explain the importance of refining and improving these tests (from the article),

Standard in vivo toxicology test methods that depend heavily on the use of animals have long been used to assess chemical safety. [emphasis mine*] Existing and novel in vitro and in silico test methods provide important alternatives to in vivo animal testing for chemicals and potentially for ENM. Genotoxicity tests, for example, are used to assess the mutagenic potential of chemicals or nanomaterials in the replication of DNA in cells. Driven in part by increasing market and regulatory requirements for safer and more sustainable products, large international infrastructure has developed for creating, testing and validating in vitro test methods, and its use is expanding to chemical and nanomaterial assessment (NSF, 2007). The goals of reducing, refining and replacing animal testing (the commonly cited ‘three Rs’) – resonate with key and diverse stakeholders including animal rights groups, the bioethics community, the pharmaceutical industry, regulatory agencies and the broader public. [emphasis mine*]

Despite nearly a decade of effort in the conduct toxicology and exposure research to inform the assessment of health and environmental risks of nanomaterials, major gaps remain in the ability to understand and quantify risks. While there is now a large body of published data on carbon nanotubes and metal oxide nanoparticles, concern has been raised that speculation about nanomaterial risk has hardened into an assumption that there are ‘as-yet-to-be-discovered risks’ that we must identify and manage (Maynard, 2014) that demands extensive testing.

The authors describe ATS (alternative test strategies) in greater detail,

ATS approaches are regarded by many to have the potential for rapid screening of large numbers and types of materials. They can include a breadth of techniques including high throughput screening methods (HTS), high content screening, computational approaches, toxicogenomics, cell-based methods, in vitro assays and non-mammalian whole animal models. The emergence of ATS raises questions about how the results of these methods may be used for assessing the potential risks of ENM. For instance, ATS could be used in combination in a multiple models approach to evaluate new ENM in a number of rapid assays and compare with well-studied substances using in vivo testing; thereby identifying ENM for additional testing in a more strategic fashion than is possible through conventional testing approaches.

They also describe the current state of affairs with ATS,

In the United States, the U.S. ToxCast program has, as part of their 21st century toxicity screening program (NRC, 2007), tested 29 NMs with 62 in vitro test methods (Wang et al. 2013). Many researchers, including several from the University of Alberta, have proposed and developed ATS to include a variety of methods, some which are standardized for chemicals, and others which take advantage of developments including advanced biological mechanistic understanding, genomics, metabolomics, automation and informatics. However, these existing as well as emerging ATS have a short history with nanomaterials, and have not yet proven to be reliable for quantitative estimation of ENM risk. Still, several international efforts have developed ATS that have potential to be used for screening purposes, and to guide further testing priorities for regulatory decision making. The goal of the September [2014] workshop by the Society for Risk Analysis is to explore ways in which distinct ATS may be used for screening and prioritizing the need for more extensive testing of novel ENM.

The parties (including the authors of the article) involved in developing this risk workshop are listed, also mentioned are members of the international testing scene,

Lori Sheremeta, the Assistant Director of Ingenuity Lab in Edmonton Alberta and past Chair of the Society for Risk Analysis (SRA) Emerging Nanoscale Materials Specialty Group (ENMSG), is collaborating with U.S.-based nanomaterials risk expert Jo Anne Shatkin (an SRA Councilor and co-founder of the SRA ENMSG), Environment Canada, Health Canada, the SRA ENMSG and others on a Pilot Project with the Organization for Economic Co-operation and Development (OECD) Working Party on Manufactured Nanomaterials (WPMN) to develop a report on the State of the Science for ATS for nanomaterials, catalogue of existing and emerging ATS methods in a database; and develop a case study to inform workshop deliberations and expert recommendations.

There are many international efforts to develop, as well as to validate and standardize, these methods for chemicals, including organizations such as the US National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods (ICCVAM), the European Union Reference Laboratory European Centre for the Validation of Alternative Methods (EURL ECVAM), the Japanese Center for the Validation of Alternative Methods (JacVAM), the Korean Centre for the Validation of Alternative Methods (KoCVAM) and the OECD. There is wide recognition that the diversity of NMs renders it impractical to use traditional animal testing to evaluate safety, hence there is significant interest in assessing the performance of both existing and emerging alternative testing strategies for NMs. Further, the EU directive REACH (Directive 2006/121/EC) requires replacing in vivo testing, and there is widespread popular agreement about the desire to limit animal testing. Finally, there is a need for more biologically informative toxicology methods (Hartung, 2010; Silbergeld et al, 2011; Landsiedel et al, 2009).

A list of the workshop objectives is offered  in the article,

The main objectives of the workshop are to:

assess the state of the science on HTS and ATS from a ‘multiple models’ perspective to identify areas of common findings from differing approaches, areas of greatest uncertainty, and priorities for follow up in applied research toward risk assessment of ENM;
evaluate the ability to use data from ATS/HTS methods for screening purposes – combining suites of assays and comparing well-studied substances to novel ones;

assess the ability to use a suite of ATS methods to amplify the Weight of Evidence;

characterize uncertainty associated with predictive relationships and propose strategies to address uncertainties;

elicit the perspectives of diverse stakeholders about the use of HTS/ATS for screening purposes in risk analysis of ENM; and

develop a set of recommendations for these alternative approaches to become more widely adopted for environmental, health and safety decision making about ENM across the product life cycle. The output of the workshop holds potential for transformation through risk screening approaches that promote safer and more sustainable material and technology development.

You can find more about the September 15-16, 2014 Workshop to Explore How a Multiple Models Approach can Advance Risk Analysis of Nanoscale Materials in Washington, DC here.

The text in the article is a bit rough. Some of the ideas and topics don’t follow each other logically. So, be prepared to spend a little time reading, Happily, there are references included with the article.

I last mentioned Jo Anne Shatkin here in the context of a 2013 paper on alternative test strategies (ATS) in an Aug. 22, 2013 posting. I think the most recent mention of Lorraine Sheremeta here is in a Jan. 11, 2010 posting about Canada, nanotechnology, and food.

Final note, I am hoping to get some more information about the workshop and ATS scene from Lorraine Sheremeta to be published in a subsequent posting.

* I added the emphases at 0830 hours PDT July 10, 2014.

Reducing animal testing for nanotoxicity—PETA (People for the Ethical Treatment of Animals) presentation at NanoTox 2014

Writing about nanotechnology can lead you in many different directions such as the news about PETA (People for the Ethical Treatment of Animals) and its poster presentation at the NanoTox 2014 conference being held in Antalya, Turkey from April 23 – 26, 2014. From the April 22, 2014 PETA news release on EurekAlert,

PETA International Science Consortium Ltd.’s nanotechnology expert will present a poster titled “A tiered-testing strategy for nanomaterial hazard assessment” at the 7th International Nanotoxicology Congress [NanoTox 2014] to be held April 23-26, 2014, in Antalya, Turkey.

Dr. Monita Sharma will outline a strategy consistent with the 2007 report from the US National Academy of Sciences, “Toxicity Testing in the 21st Century: A Vision and a Strategy,” which recommends use of non-animal methods involving human cells and cell lines for mechanistic pathway–based toxicity studies.

Based on the current literature, the proposed strategy includes thorough characterization of nanomaterials as manufactured, as intended for use, and as present in the final biological system; assessment using multiple in silico and in vitro model systems, including high-throughput screening (HTS) assays and 3D systems; and data sharing among researchers from government, academia, and industry through web-based tools, such as the Nanomaterial Registry and NanoHUB

Implementation of the proposed strategy will generate meaningful information on nanomaterial properties and their interaction with biological systems. It is cost-effective, reduces animal use, and can be applied for assessing risk and making intelligent regulatory decisions regarding the use and disposal of nanomaterials.

PETA’s International Science Consortium has recently launched a nanotechnology webpage which provides a good overview of the basics and, as one would expect from PETA, a discussion of relevant strategies that eliminate the use of animals in nanotoxicity assessment,

What is nano?

The concept of fabricating materials at an atomic scale was introduced in 1959 by physicist Richard Feynman in his talk entitled “There’s Plenty of Room at the Bottom.” The term “nano” originates from the Greek word for “dwarf,” which represents the very essence of nanomaterials. In the International System of Units, the prefix “nano” means one-billionth, or 10-9; therefore, one nanometer is one-billionth of a meter, which is smaller than the thickness of a sheet of paper or a strand of hair.  …

Are there different kinds of nano?

The possibility of controling biological processes using custom-synthesized materials at the nanoscale has intrigued researchers from different scientific fields. With the ever increasing sophistication of nanomaterial synthesis, there has been an exponential increase in the number and type of nanomaterials available or that can be custom synthesized. Table 1 lists some of the nanomaterials that are currently available.

….

Oddly, given the question ‘Are there different kinds of nano?’, there’s no mention of nanobots.  Still it’s understandable that they’d focus on nanomaterials which are, as far as I know, the only ‘nano’ anything tested for toxicity. On that note, PETA’s Nanotechnology page offers this revelatory listing (scroll down about 3/4 of the way),

The following are some of the web-based tools being used by nanotoxicologists and material scientists:

Getting back to the NanoTox conference being held now in Antalya, I noticed a couple of familiar names on the list of keynote speakers (scroll down about 15% of the way), Kostas Kostarelos (last mentioned in a Feb. 28, 2014 posting about scientific publishing and impact factors’ scroll down about 1/2 way) and Mark Wiesner (last mentioned in a Nov. 13, 2013 posting about a major grant for one of his projects).