Tag Archives: nanotoxicity

Ecotoxicology and environmental fate of manufactured nanomaterials—testing guidelines from Organization for Economic Cooperation and Development (OECD)

The Organization for Economic Cooperation and Development (OECD) has released guidelines for testing manufactured nanomaterials according to a March 11, 2014 news item on Nanowerk,

As part of its Programme on the Safety of Manufactured Nanomaterials, and in particular work on the testing and assessment of manufactured nanomaterials, OECD initiated a series of expert meetings to improve the applicability of the OECD Test Guidelines to nanomaterials. With this in mind, the Working Party on Manufactured Nanomaterials agreed to address the ecotoxicology and environmental fate of manufactured nanomaterials.

The OECD Expert Meeting on Ecotoxicology and Environmental Fate took place on 29th-31st January 2013 in Berlin, Federal Press Office. The event was hosted by the German delegation and funded by the German Federal Ministry of the Environment, Nature Conservation and Nuclear Safety (BMU) as well as the United States Environment Protection Agency (US EPA).

Three documents were published one of which being a preview,

The OECD expert meeting on ecotoxicology and environmental fate — Towards the development of improved OECD guidelines for the testing of nanomaterials by Dana Kühnel and Carmen Nickel. Science of The Total Environment Volume 472, 15 February 2014, Pages 347–353 http://dx.doi.org/10.1016/j.scitotenv.2013.11.055

This document is open access.

The report itself,

OECD. ENVIRONMENT DIRECTORATE.
JOINT MEETING OF THE CHEMICALS COMMITTEE AND
THE WORKING PARTY ON CHEMICALS, PESTICIDES AND BIOTECHNOLOGY. Environment, Health and Safety Publications
Series on the Safety of Manufactured Nanomaterials. ENV/JM/MONO(2014)1

ECOTOXICOLOGY AND ENVIRONMENTAL FATE OF MANUFACTURED NANOMATERIALS:
TEST GUIDELINES Expert Meeting Report
Series on the Safety of Manufactured Nanomaterials No. 40

Ecotoxicology and Environmental Fate of Manufactured Nanomaterials: Test Guidelines

There’s an addendum which includes the presentations made at the meeting (you can find both the report, proper, and the addendum on this page scroll to report no. 40),

OECD. ENVIRONMENT DIRECTORATE JOINT MEETING OF THE CHEMICALS COMMITTEE AND
THE WORKING PARTY ON CHEMICALS, PESTICIDES AND BIOTECHNOLOGY. Environment, Health and Safety Publications. ENV/JM/MONO(2014)1/ADD

ADDENDUM TO EXOTOXICOLOGY AND ENVIRONMENTAL FATE OF MANUFACTURED
NANOMATERIALS: TEST GUIDELINES

Series on the Safety of Manufactured Nanomaterials No. 40
Ecotoxicology and Environmental Fate of Manufactured Nanomaterials:
Test Guidelines.

As it can get a little tricky accessing OECD documents, I’ve tried to give a couple different links and as much identifying information as possible. Good luck!

Danish scientists provide insights into celllular response to silver nanoparticles

The conclusions are concerning but the scientists at the University of Southern Denmark are careful to note that this research on silver nanopartices was performed in a laboratory setting which does not necessarily predict what might happen under real life conditions.

As for the research itself, a Feb. 28, 2014 news item on Azonano has this to say,

Endocrine disrupters are not the only worrying chemicals that ordinary consumers are exposed to in everyday life. Also nanoparticles of silver, found in e.g. dietary supplements, cosmetics and food packaging, now worry scientists. A new study from the University of Southern Denmark shows that nano-silver can penetrate our cells and cause damage.

Silver has an antibacterial effect and therefore the food and cosmetic industry often coat their products with silver nanoparticles. Nano-silver can be found in e.g. drinking bottles, cosmetics, band aids, toothbrushes, running socks, refrigerators, washing machines and food packagings.

“Silver as a metal does not pose any danger, but when you break it down to nano-sizes, the particles become small enough to penetrate a cell wall. If nano-silver enters a human cell, it can cause changes in the cell”, explain Associate Professor Frank Kjeldsen and PhD Thiago Verano-Braga, Department of Biochemistry and Molecular Biology at the University of Southern Denmark.

A Feb. 27, 2014 University of Southern Denmark news release, which originated the news item, provides more detail about the research,

The researchers examined human intestinal cells, as they consider these to be most likely to come into contact with nano-silver, ingested with food.

“We can confirm that nano-silver leads to the formation of harmful, so called free radicals in cells. We can also see that there are changes in the form and amount of proteins. This worries us”, say Frank Kjeldsen and Thiago Verano-Braga.

A large number of serious diseases are characterized by the fact that there is an overproduction of free radicals in cells. This applies to cancer and neurological diseases such as Alzheimer’s and Parkinson’s.

Kjeldsen and Verano-Braga emphasizes that their research is conducted on human cells in a laboratory, not based on living people. They also point out that they do not know how large a dose of nano-silver, a person must be exposed to for the emergence of cellular changes.

“We don’t know how much is needed, so we cannot conclude that nano-silver can make you sick. But we can say that we must be very cautious and worried when we see an overproduction of free radicals in human cells”, they say.

Nano-silver is also sold as a dietary supplement, promising to have an antibacterial, anti-flu and cancer-inhibatory effect. The nano-silver should also help against low blood counts and bad skin. In the EU, the marketing of dietary supplements and foods with claims to have medical effects is not allowed. But the nano-silver is easy to find and buy online.

In the wake of the SDU-research, the Danish Veterinary and Food Administration now warns against taking dietary supplements with nano-silver.

“The recent research strongly suggests that it can be dangerous”, says Søren Langkilde from the Danish Veterinary and Food Administration to the Danish Broadcasting Corporation (DR).

The researchers supplied this image to illustrate the abstract for their paper (link and citation to follow),

Courtesy University of Southern Denmark

Courtesy University of Southern Denmark

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

Insights into the Cellular Response Triggered by Silver Nanoparticles Using Quantitative Proteomics by Thiago Verano-Braga, Rona Miethling-Graff, Katarzyna Wojdyla, Adelina Rogowska-Wrzesinska, Jonathan R. Brewer, Helmut Erdmann, and Frank Kjeldsen. ACS Nano, Article ASAP DOI: 10.1021/nn4050744 Publication Date (Web): February 10, 2014
Copyright © 2014 American Chemical Society

This paper is behind a paywall.

Silver ions in the environment

Earlier this week (Feb. 24, 2014), I published a post featuring Dr. Andrew Maynard, Director of the University of Michigan’s Risk Science Center in an introductory video describing seven surprising facts about silver nanoparticles. For those who want to delve more deeply, there’s a Feb. 25, 2014 news item on Nanowerk describing some Swiss research into silver nanoparticles and ions in aquatic environments,

It has long been known that, in the form of free ions, silver particles can be highly toxic to aquatic organisms. Yet to this day, there is a lack of detailed knowledge about the doses required to trigger a response and how the organisms deal with this kind of stress. To learn more about the cellular processes that occur in the cells, scientists from the Aquatic Research Institute, Eawag [Swiss Federal Institute of Aquatic Science and Technology], subjected algae to a range of silver concentrations.

In the past, silver mostly found its way into the environment in the vicinity of silver mines or via wastewater [emphasis mine] emanating from the photo industry. More recently, silver nanoparticles have become commonplace in many applications – as ingredients in cosmetics, food packaging, disinfectants, and functional clothing. Though a recent study conducted by the Swiss National Science Foundation revealed that the bulk of silver nanoparticles is retained in wastewater treatment plants, only little is known about the persistence and the impact of the residual nano-silver in the environment.

The Feb. 25, 2014 Eawag media release, which originated the news item, describes the research in further detail,

Smitha Pillai from the Eawag Department of Environmental Toxicology and her colleagues from EPF Lausanne and ETH Zürich studied the impact of various concentrations of waterborne silver ions on the cells of the green algae Chlamydomonas reinhardtii. Silver is chemically very similar to copper, an essential metal due to its importance in several enzymes. Because of that, silver can exploit the cells’ copper transport mechanisms and sneak into them undercover. This explains why, already after a short time, concentrations of silver in the intracellular fluid can reach up to one thousand times those in the surrounding environment.

A prompt response

Because silver damages key enzymes involved in energy metabolism, even low concentrations can cut photosynthesis and growth rates by a half in just 15 minutes. Over the same time period, the researchers also detected changes in the activity of about 1000 other genes and proteins, which they interpreted as a response to the stressor – an attempt to repair silver-induced damage. At low concentrations, the cells’ photosynthesis apparatus recovered within five hours, and recovery mechanisms were sufficient to deal with all but the highest concentrations tested.

A number of unanswered questions

At first glance, the results are reassuring because the silver concentrations that the algae are subject to in the environment are rarely as high as those applied in the lab, which allows them to recover quickly – at least externally. But the experiments also showed that even low silver concentrations have a significant effect on intracellular processes and that the algae divert their energy to repairing damage incurred. This can pose a problem when other stressors act in parallel, such as increased UV-radiation or other chemical compounds. Moreover, it remains unknown to this day whether the cells have an active mechanism to shuttle out the silver. Lacking such a mechanism, the silver could have adverse effects on higher organisms, given that algae are at the bottom of the food chain.

You can find the researchers’ paper here,

Linking toxicity and adaptive responses across the transcriptome, proteome, and phenotype of Chlamydomonas reinhardtii exposed to silver by Smitha Pillai, Renata Behra, Holger Nestler, Marc J.-F. Suter, Laura Sigg, and Kristin Schirmer. Proceedings of the National Academy of Sciences (PNAS) – early edition 18.February 2014, www.pnas.org/cgi/doi/10.1073/pnas.1319388111

The paper is available through the PNAS open access option.

I have published a number of pieces about aquatic enviornments and wastewater and nanotechnology-enabled products as useful for remediation efforts and as a source of pollution. Here’s a Feb. 28, 2013 posting where I contrasted two pieces of research on silver nanoparticles. The first was research in an aquatic environment and the other concerned wastewater.

Human immune system and nanotoxicology in Québec (Canada)

At this point it’s starting to seem like there are thousands and thousands of nanotoxicology studies so the announcement of a new study based in Québec (Canada) didn’t immediately cause excitement  until I caught sight of the word ‘inflammation” which casts a newish light on the topic. From the Dec. 4, 2013 news item on Azonano,

… Professor Girard [Professor Denis Girard INRS–Institut Armand-Frappier Research Centre] will focus on the effects of NPs [nanoparticles] on human immune system cells (eosinophils) that play a key role in inflammation.

“Several studies on NPs have examined how tissues react in contact with these tiny foreign bodies,” said Girard. “Researchers have found that eosinophils flock to the contact site, but they have not examined the phenomenon in greater detail.” To further investigate why eosinophils come into contact with NPs and the role they play, protocols require expertise in both nanotoxicology and immunology, which is rare.

The Nov. 28, 2013 INRS [Institut national de la recherche scientifique] Université news release by Stéphanie Thibault, which originated the news item, delves into the issue of inflammatory responses,

According to Professor Girard, understanding the inflammatory response is currently a priority in the field of nanotoxicology. For a number of years, researchers have been observing links between exposure to NPs and asthmatic symptoms in some animals. Does the human body undergo similar inflammation upon contact with NPs? In the absence of any standards for workers, it’s best to take a closer look, insists Girard. “At this time, nanoparticles have not been properly identified and are often handled without protection. If they enter the body through the skin, respiratory tract, or even ingestion, we have no idea what happens next.” In his lab, a variety of approaches will help further understanding of how nanoparticles of different types and sizes interact. Cellular processes will be examined in detail.

 

At the rate at which NPs are being developed, Girard could be conducting systematic nanotoxicology studies for many years to come. “I will of course need the support of a strong team,” said Girard. “I already have one I am very proud of, and it will be expanded for the new project.” …

I gather there are going to be some jobs generated from this grant,

His research is being funded by Institut de recherche Robert-Sauvé en santé et en sécurité du travail (IRSST), which will award him a renewable $300,000 grant for the next three years.

… The IRSST grant will be used to hire staff and student researchers.

While I have heard of the IRSST before,, the INRS is new to me. Here’s more from the INRS English language homepage,

INRS (Institut national de la recherche scientifique) is one of Canada’s top universities in terms of research intensity (funding per faculty member). It brings together 150 professors, over 700 graduate and postgraduate students, and a hundred postdoctoral researchers at four centers in Montreal, Québec City, Laval, and Varennes. Conducting applied and fundamental research essential to the advancement of science in Quebec and around the world, our research teams plays a critical role in finding solutions to problems facing our society. Founded in 1969, INRS is one of the nine establishments that make up the Université du Québec network.

 

“The Institute is dedicated to fundamental and applied research, graduate studies, and the training of researchers. In keeping with its mission and objectives as a research university, the Institute specifically gears its activities towards Quebec’s economic, social, and cultural development, as well as the transfer of knowledge and technology stemming from all its fields of study.” INRS letters patent, 1999

There you have it.

2014 Internatonal NanoSafety Congress in Iran extends deadline for submissions to Dec. 15, 2013

A Nov. 11, 2013 news item on Nanowerk highlights the 2014 Iran International NanoSafety Congress and the deadline extension,

The deadline for paper submission to Iran International Nanosafety Congress was extended to 15 December 2013.
Iran Nanosafety Congress will be held in Tehran University of Medical Sciences in association with Iran Nanosafety Network (INSN) of Iran Nanotechnology Initiative Council on 19-20 February [2014] to guarantee the safe and continuous development of nanotechnology, give correct information about nanosafety, identify active bodies in the field of nanosaftey and develop cooperation with other countries.
The scope of the congress is as follows:
– Exposure assessment
– Methodology: characterization, detection, and monitoring
– Occupational and environmental interactions
– Toxicology
– Ecotoxicology and life cycle analysis
– Standardization and regulations

The homepage for the Iran International NanoSafety Congress provides more information,

Dear Colleagues,
On behalf of the scientific and executive committees, it is our great pleasure to cordially invite you to attend the Iran NanoSafety Congress 2014 (INSC 2014) which will be held at the Ghods Auditorium in Tehran University of Medical Sciences, on 19-20 February 2014.

This Congress is jointly organized by the Iran Nanosafety Network (INSN) of Iran Nanotechnology Initiative Council (INIC) and Tehran University of Medical Sciences (TUMS), supported by Iran Nanohealth Committee of Food & Drug Organization (INC), Iranian Environmental Mutagen Society (IrEMS) and Iranian Society of Nanomedicine (ISNM).  The “Iran NanoSafety Congress 2014″ aims to cover all safety aspects of nanomaterials in human and environment. This Congress is focused on novel approaches and technologies being used to properly assess the safety, toxicity, and risk of nanomaterial for occupational and environmental health. The scientific program will consist of keynote/distinguished lectures, symposia, workshops, discussion panels and poster sessions. This congress will provide attendees good opportunities to meet scientists from all over the world to exchange the ideas and to launch national and international collaborations in different aspects of  Nanosafety. The organizing committee is also planning a variety of unique social programs to provide the chance for participants to enjoy from fascinating Iranian culture and warm spirit of friendship.

We look forward to welcoming you and your active participation in the INSC 2014 in Tehran, I.R. Iran.

Good luck with getting your submission in on time.

Toxicity, nanoparticles, soil, and Europe’s NANO-ECOTOXICITY Project

I have featured pieces on nanoparticles, toxicity, and soil in the past (this Aug. 15, 2011 posting about Duke University’s mesocosm project is probably the most relevant) but this study is the first one I’ve seen focusing on earthworms. From the Sept. 23, 2013 news item on Nanowerk (Note: A link has been removed),

From the clothes and make-up we wear to the electronic devices we use every day, nanotechnology is becoming ubiquitous. But while industry has mastered the production of such materials, little is known about their fate once their service life comes to an end. The NANO-ECOTOXICITY project looked into their impact on soil organisms.

The Sept. 23, 2013 CORDIS (European Commission Community Research and Development Information Service) news release, which originated the new item, offers a Q&A (Question and Answer) with the project research leader,

Dr Maria Diez-Ortiz, research leader of the NANO-ECOTOXICITY project, tells us about her research findings and how she expects them to help increase knowledge and shape tools allowing for standard environmental hazard and risk-assessment methodologies.

What is the background of the NANO-ECOTOXICITY project?

Nanotechnology is based on the idea that, by engineering the size and shape of materials at the scale of atoms, i.e. nanometres (nm), distinct optical, electronic, or magnetic properties can be tuned to produce novel properties of commercial value. However, there is an obvious concern that such novel properties may also lead to novel behaviour when interacting with biological organisms, and thus to potentially novel toxic effects.

Since nanoparticles (NPs) are similar in size to viruses, their uptake by and transport through tissues are based on mechanisms distinct from those of molecular uptake and transport. Therefore, there is concern that standard toxicological tests may not be applicable or reliable in relation to NPs, hence compromising current risk-assessment procedures.

The majority of research on nano-safety in the environment has so far focused on the aquatic environment. Current research on environmental fate, however, indicates that soils will become the biggest environmental sink for nanoparticles. Following their entry into liquid waste streams, nanoparticles will pass through wastewater-treatment. processes, ending up in waste sludge which may accumulate in the agricultural land where this sludge is often applied.

What are the main objectives of the project?

This project deals with the toxicokinetics – that is, the rate at which a chemical enters a body and affects it – of metal nanoparticles coming into contact with soil-dwelling organisms. The aim is to determine NPs’ fate and effects in terrestrial ecosystems by means of case studies with zinc oxide and silver NPs, which represent different fate kinetics.

The project’s main objectives are to assess the toxicity of metal nanoparticles in soils in the short and long term; the main route of exposure for earthworms and whether it differs from those of ionic metals; and, finally, the influence of the exposure media on metal nanoparticle toxicity.

What is new or innovative about the project and the way it is addressing these issues?

We have been running a long-term study where soils with AgNP [silver nanoparticles] were stored and left to age for up to a year; their toxicity was tested at the start and after three, seven and 12 months of ageing. The results showed that silver toxicity increased over time, meaning that short-term standard toxicity tests may underestimate the environmental risk of silver nanoparticles.

In parallel, we found that organisms exposed to silver nanoparticles in short-term studies accumulated higher silver concentrations than organisms that were exposed to the same mass concentration of ionic silver. However, these NP exposed organisms actually suffered lower toxic effects. This observation contradicts the prevailing assumption in toxicology that the internalised concentration is directly related to chemical concentration at the target site and hence to its toxicity. This observation creates a new paradigm for nano-ecotoxicology.

What is not yet known is whether the accumulated NP metal may in the longer-term ultimately become toxic (e.g. through dissolution and ion release) in cells and tissues where AgNPs may be stored. Should this occur, the high concentrations accumulated may ultimately result in greater long-term toxicity for NPs than for ionic forms. This may reveal these accumulated NPs as internalised ‘time bombs’ relevant to long-term effects and toxicity.

However, it has to be borne in mind that the redicted environmental concentrations resulting from current use of nanoparticles (e.g. results from EU projects like NANOFATE2) are many times smaller than those used in these studies, meaning that such accumulations of nanoparticle-related silver are unlikely to occur in the environment or, ultimately, in humans.

What difficulties did you encounter and how did you solve them?

The main problems encountered relate to the tracking of nanoparticles inside the tissues and soils, as both are complex matrices. The analysis of the particles is a challenge in itself, even when in water, but to get information about their state in these matrices often requires unrealistic exposure concentrations (due to low detection limits of the highly specialised techniques used for analysis) or extraction of the particles from the matrices, which could potentially change the state of the particles.

In this project, I travelled to University of Kentucky to work with Jason Unrine and used gentle water-based extractions of soil samples immediately before analysing them using ‘Field-flow fractionation’ and ‘Inductively coupled plasma mass spectrometry’ to identify the state of nanoparticles in my aged soils.

To look at what form (speciation) of silver and zinc from the nanoparticle exposures could be found inside worms I collaborated with NANOFATE researchers at Cardiff University who fixed and thinly sectioned the worm tissues. I was lucky to be given the time to use specialist facilities like the UK’s Diamond Light Source synchrotron to investigate where and in what form the metals and potential nanoparticles could be found in these tissues.

The main challenge is that as soon as you take nanoparticles out of the manufacturers’ bottle they start changing, particularly when put into environments likes natural soils and waters, or even organisms. Therefore a lot of characterisation is needed during exposure to establish the state of the nanoparticles the organisms have been exposed to and how fast they are changing from pristine particles to dissolved ions, or particles with completely different surfaces.

Technical solutions to characterisation have been found during this short project, but this will remain a logistical challenge for many years to come as the analysis equipment is still very specialised and expensive and therefore not generally available.

What are the concrete results from the research so far?

The project has helped us draw various conclusions regarding the impact of NPs on the environment and how to assess them. First, we now know that soil acidity, or pH, influences the dissolution and toxicity of ZnO nanoparticles [zinc oxide].

Then, we found that toxicity of silver nanoparticles’ increases over time and that the particles’ coating affects their toxicity to soil invertebrates.

As previously mentioned, earthworms exposed to silver nanoparticles for 28 days accumulated higher silver concentrations than earthworms exposed to silver ions, without the excess silver from the nanoparticles having a toxic effect. [emphasis mine] Moreover, soil ingestion was identified as the main route of exposure to AgNP and ZnONP in earthworms.

How can industry and decision-makers ensure that nanomaterials do not impact our environment?

We hope that this project, and the larger EU project NANOFATE to which it is linked, will provide knowledge and tools enabling standard environmental-hazard and risk-assessment methodologies to be applied to engineered nanoparticles (ENPs) with just a few judicious modifications. The current systems and protocols for chemical risk assessment have been developed over decades, and where no novel toxic mechanisms exist, our results tend to say that nano fits in as long as we measure the right things and characterise realistic exposures properly.

Our research aims to determine the minimum methodological tweaks needed. So far everything indicates that the potential benefits from nanotechnology can be realised and managed safely alongside other chemicals. While we are fairly confident at this stage that ENPs impose no greater acute effects on important biological parameters – like reproduction – than their ionic forms, the NANO-ECOTOXICITY results demonstrate that we have some way to go before we can state loud and clear that we do not believe there is any novel low-level or long-term effect.

As for all chemicals, proving such a negative is impossible using short-term tests. We think the final conclusions by industry and regulators on safe use of nanoparticles should and will have to be made according to a ‘weight of evidence’ approach – proving there is a gap between predicted likely exposure levels and those levels seen to cause any effects or accumulations within ecosystem species.

What are the next topics for your research?

This project has finished but the next step for any other funding opportunity would be to address increasingly environmentally relevant exposure scenarios by analysing how nanoparticles modify in the environment and interact with living tissues and organisms at different trophic levels. I would like to investigate nanoparticle transformation and interactions in living tissues. To date, the studies that have identified this ‘excess’ accumulation of non-toxic metal loads in nanoparticleexposed organisms have only been short term.

Apart from the obviously increased food-chain transfer potential, is also not known whether, over the longer term, the accumulated NP-derived metal ultimately becomes toxic when present in tissues and cells. Such transformation and release of metal ions within tissues may ultimately result in greater longterm toxicity for NPs than for ionic forms.

Furthermore, I want to test exposures in a functioning model ecosystem including interspecific interactions and trophic transfer. Since interactions between biota and nanoparticles are relevant in natural soil systems, caution is needed when attempting to predict the ecological consequences of nanoparticles based on laboratory assays conducted with only a single species. In the presence of the full complement of biological components of soil systems, complex NPs may follow a range of pathways in which coatings may be removed and replaced with exudate materials. Studies to quantify the nature of these interactions are therefore needed to identify the fate, bioavailability and toxicity of realistic ‘non-pristine’ forms of NPs present in real soil environments.

New to me was the material about ageing silver nanoparticles and their increased toxicity over time. While this is an interesting piece of information it’s not necessarily all that useful. It seems even with their increased uptake compared to silver ions, silver nanoparticles (Diez-Ortiz doesn’t indicate whether or not * they tested variously aged silver nanoparticles) did not have toxic effects on the earthworms tested.

The NANO-ECOTOXICITY website doesn’t appear to exist anymore but you can find the NANOFATE (Nanoparticle Fate Assessment and Toxicity in the Environment) website here.

* ‘not’ removed to clarify meaning, Oct. 9, 2013. (Note: I had on Oct. 8, 2013 removed ‘not’ in a second place from the sentence in an attempt t o clarify the meaning and ended up not making any sense at all.) Please read Maria Diez-Ortiz in the Comments, as she clarifies matters in a way I could never hope to.

Reliable method for detecting silver nanoparticle in fresh food and produce

The tone of an Aug. 22, 2013 news item on ScienceDaily about detecting silver naooparticles seems a bit alarmist,

Over the last few years, the use of nanomaterials for water treatment, food packaging, pesticides, cosmetics and other industries has increased. For example, farmers have used silver nanoparticles as a pesticide because of their capability to suppress the growth of harmful organisms. However, a growing concern is that these particles could pose a potential health risk to humans and the environment. In a new study, researchers at the University of Missouri have developed a reliable method for detecting silver nanoparticles in fresh produce and other food products. [emphasis mine]

“More than 1,000 products on the market are nanotechnology-based products,” said Mengshi Lin, associate professor of food science in the MU College of Agriculture, Food and Natural Resources. “This is a concern because we do not know the toxicity of the nanoparticles. [emphasis mine] Our goal is to detect, identify and quantify these nanoparticles in food and food products and study their toxicity as soon as possible.” [emphasis mine]

We leap from “could pose a potential health risk” to “we do not know the toxicity” to “study their toxicity as soon as possible” within the space of a few sentences. It’s a bit dizzying for those of us who prefer a more measured approach. The Aug. 22, 2013 University of Missouri news release on EurekAlert, which originated the news item, continues in this vein,

Lin and his colleagues, including MU scientists Azlin Mustapha and Bongkosh Vardhanabhuti, studied the residue and penetration of silver nanoparticles on pear skin. First, the scientists immersed the pears in a silver nanoparticle solution similar to pesticide application. The pears were then washed and rinsed repeatedly. Results showed that four days after the treatment and rinsing, silver nanoparticles were still attached to the skin, and the smaller particles were able to penetrate the skin and reach the pear pulp.

“The penetration of silver nanoparticles is dangerous to consumers because they have the ability to relocate in the human body after digestion,” Lin said. “Therefore, smaller nanoparticles may be more harmful to consumers than larger counterparts.”

When ingested, nanoparticles pass into the blood and lymph system, circulate through the body and reach potentially sensitive sites such as the spleen, brain, liver and heart.

The growing trend to use other types of nanoparticles has revolutionized the food industry by enhancing flavors, improving supplement delivery, keeping food fresh longer and brightening the colors of food. However, researchers worry that the use of silver nanoparticles could harm the human body.

Before I point out one of the other problems I have with this news release, here’s an image that seemingly shows how the silver nanoparticles were applied to the pears,

Caption: Graduate student Zhong Zhang applies silver nanoparticles to a piece of fruit. In a recent study, University of Missouri researchers found that these particles could pose a potential health risk to humans and the environment. Credit: University of Missouri

Caption: Graduate student Zhong Zhang applies silver nanoparticles to a piece of fruit. In a recent study, University of Missouri researchers found that these particles could pose a potential health risk to humans and the environment.
Credit: University of Missouri

Using a syringe to apply silver nanoparticles to a portion of a pear is not the same thing as applying a pesticide in an orchard.  I think it’s problematic to draw conclusions from a testing procedure that does not begin to emulate real life conditions where wind, rain, soil conditions and biological processes come into play.

I have written elsewhere about the difficulties of deciding if silver nanoparticles are good or bad notably in my April 16, 2013 posting, Silver nanoparticles: we love you/we hate you, which features links to various research pieces arguing both pro and con. The Duke University mesocosm project is mentioned in the April 16 posting and is featured in the Feb. 28, 2013 posting, Silver nanoparticles, water, the environment, and toxicity, because it that testing emulated real life conditions.

Reservations about the tone of the news release aside, here’s a link to and a citation for the published paper from the University of Missouri researchers,

Detection of Engineered Silver Nanoparticle Contamination in Pears by Zhong Zhang, Fanbin Kong, Bongkosh Vardhanabhuti, Azlin Mustapha, and Mengshi Lin. J. Agric. Food Chem., 2012, 60 (43), pp 10762–10767 DOI: 10.1021/jf303423q Publication Date (Web): October 19, 2012
Copyright © 2012 American Chemical Society

This article is behind a paywall.

Gloves, Québec’s (Canada) Institut de recherche Robert-Sauvé en santé et en sécurité du travail, and a workplace nanotoxicity methodology report

A new report on a workplace health and safety issue in regard to nanoparticles (Development of a Method of Measuring Nanoparticle Penetration through Protective Glove Materials under Conditions Simulating Workplace Use)  was released in June 2013 by Québec’s Institut de recherche Robert-Sauvé en santé et en sécurité du travail (IRSST). Little research has been done on exposure through skin (cutaneous exposure), most research has focused on exposure by inhalation according to the report (en français version here),

In the workplace, the main pathway to NP exposure is inhalation (Ostiguy et al., 2008a). Exposure by the cutaneous route has not been studied much, partly because of the widely held belief that skin offers an impermeable barrier to NPs (Truchon et al., 2008). Yet a growing number of studies have pointed to the possible percutaneous absorption of NPs, such as in the case of skin damaged by abrasion (Zhang et al., 2008), repeated flexion (Rouse et al., 2007) or even through intact skin (Ryman-Rasmussen et al., 2006). Pores, hair follicles and sweat glands may also play a role in facilitating absorption of NPs through the skin (Hervé-Bazin, 2007). The nanoparticles are then carried throughout the body by the lymphatic circulatory system (Papp et al., 2008). Induced direct toxic effects have also been reported for epidermal keratinocyte cells exposed to carbon nanotubes and other types of NPs (Shvedova, 2003). [p. 17 PDF version; p. 1 print version; Note: See report bibliography for citations]

The researchers examined gloves made of four different types of material: nitrile, latex, neoprene, and butyl rubber under a number of different conditions. One type of nanoparticle was used for the study, titanium dioxide in powder and liquid forms. The report summary provides a bit more detail about the decision to develop a methodology and the testing methods,

With the exponential growth in industrial applications of nanotechnologies and the increased risk of occupational exposure to nanomaterials, the precautionary principle has been recommended. To apply this principle, and even though personal protective equipment against nanoparticles must be considered only as a last resort in the risk control strategy, this equipment must be available. To respond to the current lack of tools and knowledge in this area, a method was developed for measuring the penetration of nanoparticles through protective glove materials under conditions simulating workplace use.

This method consists of an experimental device for exposing glove samples to nanoparticles in powder form or in colloidal solution, while at the same time subjecting them to static or dynamic mechanical stresses and conditions simulating the microclimate in the gloves. This device is connected to a data control and acquisition system. To complete the method, a sampling protocol was developed and a series of nanoparticle detection techniques was selected.

Preliminary tests were performed using this method to measure the resistance of four models of protective gloves of different thicknesses made of nitrile, latex, neoprene and butyl to the passage of commercial TiO2 nanoparticles in powder form or colloidal solution. The results seem to indicate possible penetration of the nanoparticles in some types of gloves, particularly when subjected to repeated mechanical deformation and when the nanoparticles are in the form of colloidal solutions. Additional work is necessary to confirm these results, and consideration should be given to the selection of the configurations and values of the parameters that best simulate the different possible workplace situations. Nevertheless, a recommendation can already be issued regarding the need for regular replacement of gloves that have been worn, particularly with the thinnest gloves and when there has been exposure to nanoparticles in colloidal solution.

For interested parties, here’s a citation for and a link to the report (PDF),

Development of a Method of Measuring Nanoparticle Penetration through Protective Glove Materials under Conditions Simulating Workplace Use by Dolez, Patricia; Vinches, Ludwig; Perron, Gérald; Vu-Khanh, Toan; Plamondon, Philippe; L’Espérance, Gilles; Wilkinson, Kevin; Cloutier, Yves; Dion, Chantal; Truchon, Ginette
Studies and Research Projects / Report  R-785, Montréal, IRSST, 2013, 124 pages.

I last wrote about gloves and toxicity in a June 11, 2013 posting about gloves with sensors (they turned blue when exposed to toxic levels of chemicals). It would be interesting if they could find a way to create gloves with sensors that warn you when you are reaching dangerous levels of exposure through your gloves. Of course, first they’d have to determine what constitute a dangerous level of exposure. The US National Institute of Occupational Health and Safety (NIOSH) recently released its recommendations for exposure to carbon nanofibers and carbon nanotubes (my April 26, 2013 posting). In layperson’s terms, the recommended exposure is close to zero exposure. Presumably, the decision was based on the principle of being ‘safe rather than sorry’.

One final comment about exposure to engineered nanoparticles through skin, to date there has been no proof that there has been any significant exposure via skin. In fact, the first significant breach of the skin barrier was achieved for medical research, Chad Mirkin and his team at Northwestern University trumpeted their research breakthrough (pun intended) last year, from my July 4, 2012 posting,

Researchers at Northwestern University (Illinois, US) have found a way to deliver gene regulation technology using skin moisturizers. From the July 3, 2012 news item on Science Blog,

A team led by a physician-scientist and a chemist — from the fields of dermatology and nanotechnology — is the first to demonstrate the use of commercial moisturizers to deliver gene regulation technology that has great potential for life-saving therapies for skin cancers.

The topical delivery of gene regulation technology to cells deep in the skin is extremely difficult because of the formidable defenses skin provides for the body. The Northwestern approach takes advantage of drugs consisting of novel spherical arrangements of nucleic acids. These structures, each about 1,000 times smaller than the diameter of a human hair, have the unique ability to recruit and bind to natural proteins that allow them to traverse the skin and enter cells.

This goes a long way to explaining why primary occupational health and safety research has focused on exposure via inhalation rather than skin.  That said, I think ensuring safety means minimizing exposure by all routes until more is known about the hazards.

You probably can’t poison yourself by eating too many nanoparticles

Researchers, Ingrid Bergin in the Unit for Laboratory Animal Medicine, at the University of Michigan in Ann Arbor and Frank Witzmann in the Department of Cellular and Integrative Physiology, at Indiana University School of Medicine, in Indianapolis, have stated that ingesting food and beverage (translated by me from the more scientific description) with nanoparticles (at today’s current levels) is unlikely to prove toxic. A June 26, 2013 Inderscience news release on EurekAlert describes the researchers’ research and their conclusions,

Writing in a forthcoming issue of the International Journal of Biomedical Nanoscience and Nanotechnology, researchers have compared existing laboratory and experimental animal studies pertaining to the toxicity of nanoparticles most likely to be intentionally or accidentally ingested. Based on their review, the researchers determined ingestion of nanoparticles at likely exposure levels is unlikely to cause health problems, at least with respect to acute toxicity. Furthermore, in vitro laboratory testing, which often shows toxicity at a cellular level, does not correspond well with in vivo testing, which tends to show less adverse effects.

Ingrid Bergin in the Unit for Laboratory Animal Medicine, at the University of Michigan in Ann Arbor and Frank Witzmann in the Department of Cellular and Integrative Physiology, at Indiana University School of Medicine, in Indianapolis, explain that the use of particles that are in the nano size range (from 1 billionth to 100 billionths of a meter in diameter, 1-100 nm, other thereabouts) are finding applications in consumer products and medicine. These include particles such as nano-silver, which is increasingly used in consumer products and dietary supplements for its purported antimicrobial properties. Nanoparticles can have some intriguing and useful properties because they do not necessarily behave in the same chemical and physical ways as non-nanoparticle versions of the same material.

Nanoparticles are now used as natural flavor enhancers in the form of liposomes and related materials, food pigments and in some so-called “health supplements”. They are also used in antibacterial toothbrushes coated with silver nanoparticles, for instance in food and drink containers and in hygienic infant feeding equipment. They are also used to carry pharmaceuticals to specific disease sites in the body to reduce side effects. Nanoparticles actually encompass a very wide range of materials from pure metals and alloys, to metal oxide nanoparticles, and carbon-based and plastic nanoparticles. Because of their increasing utilization in consumer products, there has been concern over whether these small scale materials could have unique toxicity effects when compared to more traditional versions of the same materials.

Difficulties in assessing the health risks of nanoparticles include the fact that particles of differing materials and shapes can have different properties. Furthermore, the route of exposure (e.g. ingestion vs. inhalation) affects the likelihood of toxicity. The U.S. researchers evaluated the current literature specifically with respect to toxicity of ingested nanoparticles. They point out that, in addition to intentional ingestion as with dietary supplements, unintentional ingestion can occur due to nanoparticle presence in water or as a breakdown product from coated consumer goods. Inhaled nanoparticles also represent an ingestion hazard since they are coughed up, swallowed, and eliminated through the intestinal tract.

Based on their review, the team concludes that, “Ingested nanoparticles appear unlikely to have acute or severe toxic effects at typical levels of exposure.” Nevertheless, they add that the current literature is inadequate to assess whether nanoparticles can accumulate in tissues and have long-term effects or whether they might cause subtle alterations in gut microbial populations. The researchers stress that better methods are needed for correlating particle concentrations used for cell-based assessment of toxicity with the actual likely exposure levels to body cells. Such methods may lead to better predictive value for laboratory in vitro testing, which currently over-predicts toxicity of ingested nanoparticles as compared to in vivo testing.

The researchers focused specifically on ingestion via the gastrointestinal tract which I take to mean that they focused largely on nanoparticles in food (eaten) and liquid (swallowed).

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

Nanoparticle toxicity by the gastrointestinal route: evidence and knowledge gaps by Ingrid L. Bergin; Frank A. Witzmann.  Int. J. of Biomedical Nanoscience and Nanotechnology, 2013 Vol.3, No.1/2, pp.163 – 210.  DOI: 10.1504/IJBNN.2013.054515

I think the abstract further helps to understand the research focus,

The increasing interest in nanoparticles for advanced technologies, consumer products, and biomedical applications has led to great excitement about potential benefits but also concern over the potential for adverse human health effects. The gastrointestinal tract represents a likely route of entry for many nanomaterials, both directly through intentional ingestion or indirectly via nanoparticle dissolution from food containers or by secondary ingestion of inhaled particles. Additionally, increased utilisation of nanoparticles may lead to increased environmental contamination and unintentional ingestion via water, food animals, or fish. The gastrointestinal tract is a site of complex, symbiotic interactions between host cells and the resident microbiome. Accordingly, evaluation of nanoparticles must take into consideration not only absorption and extraintestinal organ accumulation but also the potential for altered gut microbes and the effects of this perturbation on the host. The existing literature was evaluated for evidence of toxicity based on these considerations. Focus was placed on three categories of nanomaterials: nanometals and metal oxides, carbon-based nanoparticles, and polymer/dendrimers with emphasis on those particles of greatest relevance to gastrointestinal exposures.

The article is behind a paywall.

I last mentioned Frank Witzmann here in a May 8, 2013 posting titled, US multicenter (Nano GO Consortium) study of engineered nanomaterial toxicology.

‘Nano fest’ at the 245th meeting of the American Chemical Society

The American Chemical Society’s (ACS) 245th meeting (April 7 – 11, 2013) features a few items about nanotechnology: the funding of it and the toxicological testing of it, in two separate news items which bear a ‘political’ link.

An April 9, 2013 news item on Azonano tells of concerns regarding recent funding cuts resulting from the US budget sequestration,

Speaking at the 245th National Meeting & Exposition of the American Chemical Society, the world’s largest scientific society, A. Paul Alivisatos, Ph.D., expressed concern that the cuts come when nanotechnology is poised to deliver on those promises. He told the meeting, which continues through Thursday, that ill-conceived cuts could set back America’s progress in nanotechnology by decades.

“The National Science Foundation announced that they will issue a thousand fewer new grants this year because of sequestration,” said Alivisatos, referring to the across-the-board mandatory federal budget cuts that took effect on March 1. “What it means in practice is that an entire generation of early career scientists, some of our brightest and most promising scientists, will not have the funding to launch their careers and begin research properly, in the pathway that has established the United States as leader in nanotechnology research. It will be a setback, perhaps quite serious, for our international competitiveness in this key field.”

Alivisatos described applications of nanotechnology that can help reduce fossil fuel consumption and the accompanying emissions of carbon dioxide, the main greenhouse gas. He is professor of chemistry and materials science and the Larry and Diane Bock Professor of Nanotechnology at the University of California at Berkeley, director of the Lawrence Berkeley National Laboratory and co-editor of the ACS journal Nano Letters. …

Alivisatos expressed concern, however, that cuts in federal funding will take a heavy toll on the still-emerging field. He explained that the reductions stand to affect scientists at almost every stage of making contributions to society. Young scientists, for instance, will find it more difficult to launch research programs in new and promising fields.[emphases mine]  Established scientists will have to trim research programs, and may not have the money to explore promising new leads.

“We haven’t been able to communicate adequately with the public and policymakers, and explain the impact of what may sound like small and unimportant cuts in funding.” Alivisatos said. “A 5 percent reduction in funding — well, to the public, it seems like nothing. In reality, these cuts will be applied in ways that do maximal damage to our ability to be globally competitive in the future.”

Coincidentally or not,  the ACS had placed an Apr. 8, 2013 news release on EurekAlert highlighting some work in the field of nanotoxicology led by a ‘young’ scientist (I imagine she received her funding prior to sequestration) doing some exciting work,

Earlier efforts to determine the health and environmental effects of the nanoparticles that are finding use in hundreds of consumer products may have produced misleading results by embracing traditional toxicology tests that do not take into account the unique properties of bits of material so small that 100,000 could fit in the period at the end of this sentence.

That was among the observations presented here today at the 245th National Meeting & Exposition of the American Chemical Society (ACS), the world’s largest scientific society, by one of the emerging leaders in nanoscience research. The talk by Christy Haynes, Ph.D., was among almost 12,000 presentations at the gathering, which organizers expect to attract more than 14,000 scientists and others.

Haynes delivered the inaugural Kavli Foundation Emerging Leader in Chemistry Lecture at the meeting, … Sponsored by the Kavli Foundation, the Emerging Leaders Lectures recognize the work of outstanding young chemical scientists. [emphasis mine] …

“Christy Haynes is the perfect scientist to launch this prestigious lecture series,” said Marinda Li Wu, Ph.D., president of the ACS. “Haynes’ research is making an impact in the scientific community in efforts to use nanoparticles and nanotechnology in medicine and other fields. And that research has sparked the popular imagination, as well. Haynes was included in Popular Science‘s ‘Brilliant 10′ list, a group of ‘geniuses shaking up science today.’ [emphasis mine] We are delighted to collaborate with the Kavli Foundation in highlighting the contributions of such individuals.”

Moving on from politics to science, the EurekAlert Apr. 8, 2013 news release offers a standard discussion regarding gold and nanoparticle gold before highlighting the aspect that marks Haynes’ fresh approach to toxicity at the nanoscale,

A 1-ounce nugget of pure gold, for instance, has the same chemical and physical properties as a 2-ounce nugget or a 27-pound gold bar. For nanoparticles, however, size often dictates the physical and chemical properties, and those properties change as the size decreases.

Haynes said that some of the earlier nanotoxicology tests did not fully take those and other factors into account when evaluating the effects of nanoparticles. In some cases, for instance, the bottom line in those tests was whether cells growing in laboratory cultures lived or died after exposure to a nanoparticle.

“While these results can be useful, there are two important limitations,” Haynes explained. “A cell can be alive but unable to function properly, and it would not be apparent in those tests. In addition, the nature of nanoparticles — they’re more highly reactive — can cause ‘false positives’ in these assays.”

Haynes described a new approach used in her team’s work in evaluating the toxicity of nanoparticles. It focuses on monitoring how exposure to nanoparticles affects a cell’s ability to function normally, rather than just its ability to survive the exposure. In addition, they have implemented measures to reduce “false-positive” test results, which overestimate nanoparticle toxicity. One of the team’s safety tests, for instance, determines whether key cells in the immune system can still work normally after exposure to nanoparticles. In another, the scientists determine whether bacteria exposed to nanoparticles can still communicate with each other, engaging in the critical biochemical chatter that enables bacteria to form biofilms, communities essential for them to multiply in ways that lead to infections.

“So far, we have found that nanoparticles made of silver or titanium may be the most problematic, though I would say that neither is as bad as some of the alarmist media speculations, especially when they are stabilized appropriately,” said Haynes. “I think that it will be possible to create safe, stable coatings on nanoparticles that will make them stable and allow them to leave the body appropriately. We need more research, of course, in order to make informed decisions.”

Hopefully, you find this mixture of science and politics as interesting as I do.

ETA Apr. 10, 2013: Dexter Johnson has commented on and provided some contextual information about nanotechnology research funding in the US in response to the Alivisatos talk about sequestration and its possible impact on nanotechnology research in Apr. 9, 2013 posting (Note: A link has been removed),

There is always room for the argument that reassessing and reallocating resources can help make nanotechnology more efficient and productive, something observers have pointed out in NASA taking on less of its own nanotechnology research and outsourcing it to other government organizations. But it’s not always easy to tell which fundamental research projects will turn out to have been the most productive, and worse, the timing of these cuts could be extremely painful as they occur at a critical moment for U.S. nanotechnology.

Dexter’s piece is well worth reading.