Tag Archives: nanotoxicology

Nano- and neuro- together for nanoneuroscience

This is not the first time I’ve posted about nanotechnology and neuroscience (see this April 2, 2013 piece about then new brain science initiative in the US and Michael Berger’s  Nanowerk Spotlight article/review of an earlier paper covering the topic of nanotechnology and neuroscience).

Interestingly, the European Union (EU) had announced its two  $1B Euro research initiatives, the Human Brain Project and the Graphene Flagship (see my Jan. 28, 2013 posting about it),  months prior to the US brain research push. For those unfamiliar with the nanotechnology effort, graphene is a nanomaterial and there is high interest in its potential use in biomedical technology, thus partially connecting both EU projects.

In any event, Berger is highlighting a nanotechnology and neuroscience connection again in his Oct. 18, 2017 Nanowerk Spotlight article, or overview of, a new paper, which updates our understanding of the potential connections between the two fields (Note: A link has been removed),

Over the past several years, nanoscale analysis tools and in the design and synthesis of nanomaterials have generated optical, electrical, and chemical methods that can readily be adapted for use in neuroscience and brain activity mapping.

A review paper in Advanced Functional Materials (“Nanotechnology for Neuroscience: Promising Approaches for Diagnostics, Therapeutics and Brain Activity Mapping”) summarizes the basic concepts associated with neuroscience and the current journey of nanotechnology towards the study of neuron function by addressing various concerns on the significant role of nanomaterials in neuroscience and by describing the future applications of this emerging technology.

The collaboration between nanotechnology and neuroscience, though still at the early stages, utilizes broad concepts, such as drug delivery, cell protection, cell regeneration and differentiation, imaging and surgery, to give birth to novel clinical methods in neuroscience.

Ultimately, the clinical translation of nanoneuroscience implicates that central nervous system (CNS) diseases, including neurodevelopmental, neurodegenerative and psychiatric diseases, have the potential to be cured, while the industrial translation of nanoneuroscience indicates the need for advancement of brain-computer interface technologies.

Future Developing Arenas in Nanoneuroscience

The Brain Activity Map (BAM) Project aims to map the neural activity of every neuron across all neural circuits with the ultimate aim of curing diseases associated with the nervous system. The announcement of this collaborative, public-private research initiative in 2013 by President Obama has driven the surge in developing methods to elucidate neural circuitry. Three current developing arenas in the context of nanoneuroscience applications that will push such initiative forward are 1) optogenetics, 2) molecular/ion sensing and monitoring and 3) piezoelectric effects.

In their review, the authors discuss these aspects in detail.

Neurotoxicity of Nanomaterials

By engineering particles on the scale of molecular-level entities – proteins, lipid bilayers and nucleic acids – we can stereotactically interface with many of the components of cell systems, and at the cutting edge of this technology, we can begin to devise ways in which we can manipulate these components to our own ends. However, interfering with the internal environment of cells, especially neurons, is by no means simple.

“If we are to continue to make great strides in nanoneuroscience, functional investigations of nanomaterials must be complemented with robust toxicology studies,” the authors point out. “A database on the toxicity of materials that fully incorporates these findings for use in future schema must be developed. These databases should include information and data on 1) the chemical nature of the nanomaterials in complex aqueous environments; 2) the biological interactions of nanomaterials with chemical specificity; 3) the effects of various nanomaterial properties on living systems; and 4) a model for the simulation and computation of possible effects of nanomaterials in living systems across varying time and space. If we can establish such methods, it may be possible to design nanopharmaceuticals for improved research as well as quality of life.”

“However, challenges in nanoneuroscience are present in many forms, such as neurotoxicity; the inability to cross the blood-brain barrier [emphasis mine]; the need for greater specificity, bioavailability and short half-lives; and monitoring of disease treatment,” the authors conclude their review. “The nanoneurotoxicity surrounding these nanomaterials is a barrier that must be overcome for the translation of these applications from bench-to-bedside. While the challenges associated with nanoneuroscience seem unending, they represent opportunities for future work.”

I have a March 26, 2015 posting about Canadian researchers breaching the blood-brain barrier and an April 13, 2016 posting about US researchers at Cornell University also breaching the blood-brain barrier. Perhaps the “inability” mentioned in this Spotlight article means that it can’t be done consistently or that it hasn’t been achieved on humans.

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

Nanotechnology for Neuroscience: Promising Approaches for Diagnostics, Therapeutics and Brain Activity Mapping by Anil Kumar, Aaron Tan, Joanna Wong, Jonathan Clayton Spagnoli, James Lam, Brianna Diane Blevins, Natasha G, Lewis Thorne, Keyoumars Ashkan, Jin Xie, and Hong Liu. Advanced Functional Materials Volume 27, Issue 39, October 19, 2017 DOI: 10.1002/adfm.201700489 Version of Record online: 14 AUG 2017

© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

I took a look at the authors’ information and found that most of these researchers are based in  China and in the UK, with a sole researcher based in the US.

Harvard University announced new Center on Nano-safety Research

The nano safety center at Harvard University (Massachusetts, US) is a joint center with the US National Institute of Environmental Health  Sciences according to an Aug. 29, 2016 news item on Nanowerk,

Engineered nanomaterials (ENMs)—which are less than 100 nanometers (one millionth of a millimeter) in diameter—can make the colors in digital printer inks pop and help sunscreens better protect against radiation, among many other applications in industry and science. They may even help prevent infectious diseases. But as the technology becomes more widespread, questions remain about the potential risks that ENMs may pose to health and the environment.

Researchers at the new Harvard-NIEHS [US National Institute of Environmental Health Sciences] Nanosafety Research Center at Harvard T.H. Chan School of Public Health are working to understand the unique properties of ENMs—both beneficial and harmful—and to ultimately establish safety standards for the field.

An Aug. 16, 2016 Harvard University press release, which originated the news item, provides more detail (Note: Links have been removed),

“We want to help nanotechnology develop as a scientific and economic force while maintaining safeguards for public health,” said Center Director Philip Demokritou, associate professor of aerosol physics at Harvard Chan School. “If you understand the rules of nanobiology, you can design safer nanomaterials.”

ENMs can enter the body through inhalation, ingestion, and skin contact, and toxicological studies have shown that some can penetrate cells and tissues and potentially cause biochemical damage. Because the field of nanoparticle science is relatively new, no standards currently exist for assessing the health risks of exposure to ENMs—or even for how studies of nano-biological interactions should be conducted.

Much of the work of the new Center will focus on building a fundamental understanding of why some ENMs are potentially more harmful than others. The team will also establish a “reference library” of ENMs, each with slightly varied properties, which will be utilized in nanotoxicology research across the country to assess safety. This will allow researchers to pinpoint exactly what aspect of an ENM’s properties may impact health. The researchers will also work to develop standardized methods for nanotoxicology studies evaluating the safety of nanomaterials.

The Center was established with a $4 million dollar grant from the National Institute of Environmental Health Science (NIEHS) last month, and is the only nanosafety research center to receive NIEHS funding for the next five years. It will also play a coordinating role with existing and future NIEHS nanotoxicology research projects nantionwide. Scientists from the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS), MIT, University of Maine, and University of Florida will collaborate on the new effort.

The Center builds on the existing Center for Nanotechnology and Nanotoxicology at Harvard Chan School, established by Demokritou and Joseph Brain, Cecil K. and Philip Drinker Professor of Environmental Physiology, in the School’s Department of Environmental Health in 2010.

A July 5, 2016 Harvard University press release announcing the $4M grant provides more information about which ENMs are to be studied,

The main focus of the new HSPH-NIEHS Center is to bring together  scientists from across disciplines- material science, chemistry, exposure assessment, risk assessment, nanotoxicology and nanobiology- to assess the potential  environmental Health and safety (EHS) implications of engineered nanomaterials (ENMs).

The $4 million dollar HSPH based Center  which is the only Nanosafety Research  Center to be funded by NIEHS this funding cycle, … The new HSPH-NIEHS Nanosafety Center builds upon the nano-related infrastructure in [the] collaborating Universities, developed over the past 10 years, which includes an inter-disciplinary research group of faculty, research staff and students, as well as state-of-the-art platforms for high throughput synthesis of ENMs, including metal and metal oxides, cutting edge 2D/3D ENMs such as CNTs [carbon nanotubes] and graphene, nanocellulose, and advanced nanocomposites, [emphasis mine] coupled with innovative tools to assess the fate and transport of ENMs in biological systems, statistical and exposure assessment tools, and novel in vitro and in vivo platforms for nanotoxicology research.

“Our mission is to integrate material/exposure/chemical sciences and nanotoxicology-nanobiology   to facilitate assessment of potential risks from emerging nanomaterials.  In doing so, we are bringing together the material synthesis/applications and nanotoxicology communities and other stakeholders including industry,   policy makers and the general public to maximize innovation and growth and minimize environmental and public health risks from nanotechnology”, quoted by  Dr Philip Demokritou, …

This effort certainly falls in line with the current emphasis on interdisciplinary research and creating standards and protocols for researching the toxicology of engineered nanomaterials.

Faster predictive toxicology of nanomaterials

As more nanotechnology-enabled products make their way to the market and concerns rise regarding safety, scientists work to find better ways of assessing and predicting the safety of these materials, from an Aug. 13, 2016 news item on Nanowerk,

UCLA [University of California at Los Angeles] researchers have designed a laboratory test that uses microchip technology to predict how potentially hazardous nanomaterials could be.

According to UCLA professor Huan Meng, certain engineered nanomaterials, such as non-purified carbon nanotubes that are used to strengthen commercial products, could have the potential to injure the lungs if inhaled during the manufacturing process. The new test he helped develop could be used to analyze the extent of the potential hazard.

An Aug. 12, 2016 UCLA news release, which originated the news item, expands on the theme,

The same test could also be used to identify biological biomarkers that can help scientists and doctors detect cancer and infectious diseases. Currently, scientists identify those biomarkers using other tests; one of the most common is called enzyme-linked immunosorbent assay, or ELISA. But the new platform, which is called semiconductor electronic label-free assay, or SELFA, costs less and is faster and more accurate, according to research published in the journal Scientific Reports.

The study was led by Meng, a UCLA assistant adjunct professor of medicine, and Chi On Chui, a UCLA associate professor of electrical engineering and bioengineering.

ELISA has been used by scientists for decades to analyze biological samples — for example, to detect whether epithelial cells in the lungs that have been exposed to nanomaterials are inflamed. But ELISA must be performed in a laboratory setting by skilled technicians, and a single test can cost roughly $700 and take five to seven days to process.

In contrast, SELFA uses microchip technology to analyze samples. The test can take between 30 minutes and two hours and, according to the UCLA researchers, could cost just a few dollars per sample when high-volume production begins.

The SELFA chip contains a T-shaped nanowire that acts as an integrated sensor and amplifier. To analyze a sample, scientists place it on a sensor on the chip. The vertical part of the T-shaped nanowire converts the current from the molecule being analyzed, and the horizontal portion amplifies that signal to distinguish the molecule from others.

The use of the T-shaped nanowires created in Chui’s lab is a new application of a UCLA patented invention that was developed by Chui and his colleagues. The device is the first time that “lab-on-a-chip” analysis has been tested in a scenario that mimics a real-life situation.

The UCLA scientists exposed cultured lung cells to different nanomaterials and then compared their results using SELFA with results in a database of previous studies that used other testing methods.

“By measuring biomarker concentrations in the cell culture, we showed that SELFA was 100 times more sensitive than ELISA,” Meng said. “This means that not only can SELFA analyze much smaller sample sizes, but also that it can minimize false-positive test results.”

Chui said, “The results are significant because SELFA measurement allows us to predict the inflammatory potential of a range of nanomaterials inside cells and validate the prediction with cellular imaging and experiments in animals’ lungs.”

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

Semiconductor Electronic Label-Free Assay for Predictive Toxicology by Yufei Mao, Kyeong-Sik Shin, Xiang Wang, Zhaoxia Ji, Huan Meng, & Chi On Chui. Scientific Reports 6, Article number: 24982 (2016) doi:10.1038/srep24982 Published online: 27 April 2016

This paper is open access.

Two nano workshops precede OpenTox Euro conference

The main conference OpenTox Euro is focused on novel materials and it’s being preceded by two nano workshops. All of of these events will be taking place in Germany in Oct. 2016. From an Aug. 11, 2016 posting by Lynn L. Bergeson on Nanotechnology Now,

The OpenTox Euro Conference, “Integrating Scientific Evidence Supporting Risk Assessment and Safer Design of Novel Substances,” will be held October 26-28, 2016. … The current topics for the Conference include: (1) computational modeling of mechanisms at the nanoscale; (2) translational bioinformatics applied to safety assessment; (3) advances in cheminformatics; (4) interoperability in action; (5) development and application of adverse outcome pathways; (6) open science applications showcase; (7) toxicokinetics and extrapolation; and (8) risk assessment.

On Oct. 24, 2016, two days before OpenTox Euro, the EU-US Nano EHS [Environmental Health and Safety] 2016 workshop will be held in Germany. The theme is: ‘Enabling a Sustainable Harmonised Knowledge Infrastructure supporting Nano Environmental and Health Safety Assessment’ and the objectives are,

The objective of the workshop is to facilitate networking, knowledge sharing and idea development on the requirements and implementation of a sustainable knowledge infrastructure for Nano Environmental and Health Safety Assessment and Communications. The infrastructure should support the needs required by different stakeholders including scientific researchers, industry, regulators, workers and consumers.

The workshop will also identify funding opportunities and financial models within and beyond current international and national programs. Specifically, the workshop will facilitate active discussions but also identify potential partners for future EU-US cooperation on the development of knowledge infrastructure in the NanoEHS field. Advances in the Nano Safety harmonisation process, including developing an ongoing working consensus on data management and ontology, will be discussed:

– Information needs of stakeholders and applications
– Data collection and management in the area of NanoEHS
– Developments in ontologies supporting NanoEHS goals
– Harmonisation efforts between EU and US programs
– Identify practice and infrastructure gaps and possible solutions
– Identify needs and solutions for different stakeholders
– Propose an overarching sustainable solution for the market and society

The presentations will be focused on the current efforts and concrete achievements within EU and US initiatives and their potential elaboration and extension.

The second workshop is being held by the eNanoMapper (ENM) project on Oct. 25, 2016 and concerns Nano Modelling. The objectives and workshop sessions are:

1. Give the opportunity to research groups working on computational nanotoxicology to disseminate their modelling tools based on hands-on examples and exercises
2. Present a collection of modelling tools that can span the entire lifecycle of nanotox research, starting from the design of experiments until use of models for risk assessment in biological and environmental systems.
3. Engage the workshop participants in using different modelling tools and motivate them to contribute and share their knowledge.

Indicative workshop sessions

• Preparation of datasets to be used for modelling and risk assessment
• Ontologies and databases
• Computation of theoretical descriptors
• NanoQSAR Modelling
• Ab-initio modelling
• Mechanistic modelling
• Modelling based on Omics data
• Filling data gaps-Read Across
• Risk assessment
• Experimental design

We would encourage research teams that have developed tools in the areas of computational nanotoxicology and risk assessment to demonstrate their tools in this workshop.

That’s going to be a very full week in Germany.

You can register for OpenTox Euro and more here.

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 … .”