Category Archives: risk

Nanosafety research: a quality control issue

Toxicologist Dr. Harald Krug has published a review of several thousand studies on nanomaterials safety exposing problematic research methodologies and conclusions. From an Oct. 29, 2014 news item on Nanowerk (Note: A link has been removed),

Empa [Swiss Federal Laboratories for Materials Science and Technology] toxicologist Harald Krug has lambasted his colleagues in the journal Angewandte Chemie (“Nanosafety Research—Are We on the Right Track?”). He evaluated several thousand studies on the risks associated with nanoparticles and discovered no end of shortcomings: poorly prepared experiments and results that don’t carry any clout. Instead of merely leveling criticism, however, Empa is also developing new standards for such experiments within an international network.

An Oct. 29, 2014 Empa press release (also on EurekAlert), which originated the news item, describes the new enthusiasm for research into nanomaterials and safety,

Researching the safety of nanoparticles is all the rage. Thousands of scientists worldwide are conducting research on the topic, examining the question of whether titanium dioxide nanoparticles from sun creams can get through the skin and into the body, whether carbon nanotubes from electronic products are as hazardous for the lungs as asbestos used to be or whether nanoparticles in food can get into the blood via the intestinal flora, for instance. Public interest is great, research funds are flowing – and the number of scientific projects is skyrocketing: between 1980 and 2010, a total of 5,000 projects were published, followed by another 5,000 in just the last three years. However, the amount of new knowledge has only increased marginally. After all, according to Krug the majority of the projects are poorly executed and all but useless for risk assessments.

The press release goes on to describe various pathways into the body and problems with research methodologies,

How do nanoparticles get into the body?

Artificial nanoparticles measuring between one and 100 nanometers in size can theoretically enter the body in three ways: through the skin, via the lungs and via the digestive tract. Almost every study concludes that healthy, undamaged skin is an effective protective barrier against nanoparticles. When it comes to the route through the stomach and gut, however, the research community is at odds. But upon closer inspection the value of many alarmist reports is dubious – such as when nanoparticles made of soluble substances like zinc oxide or silver are being studied. Although the particles disintegrate and the ions drifting into the body are cytotoxic, this effect has nothing to do with the topic of nanoparticles but is merely linked to the toxicity of the (dissolved) substance and the ingested dose.

Laboratory animals die in vain – drastic overdoses and other errors

Krug also discovered that some researchers maltreat their laboratory animals with absurdly high amounts of nanoparticles. Chinese scientists, for instance, fed mice five grams of titanium oxide per kilogram of body weight, without detecting any effects. By way of comparison: half the amount of kitchen salt would already have killed the animals. A sloppy job is also being made of things in the study of lung exposure to nanoparticles: inhalation experiments are expensive and complex because a defined number of particles has to be swirled around in the air. Although it is easier to place the particles directly in the animal’s windpipe (“instillation”), some researchers overdo it to such an extent that the animals suffocate on the sheer mass of nanoparticles.

While others might well make do without animal testing and conduct in vitro experiments on cells, here, too, cell cultures are covered by layers of nanoparticles that are 500 nanometers thick, causing them to die from a lack of nutrients and oxygen alone – not from a real nano-effect. And even the most meticulous experiment is worthless if the particles used have not been characterized rigorously beforehand. Some researchers simply skip this preparatory work and use the particles “straight out of the box”. Such experiments are irreproducible, warns Krug.

As noted in the news item, the scientists at Empa have devised a solution to some to of the problems (from the press release),

The solution: inter-laboratory tests with standard materials
Empa is thus collaborating with research groups like EPFL’s Powder Technology Laboratory, with industrial partners and with Switzerland’s Federal Office of Public Health (FOPH) to find a solution to the problem: on 9 October the “NanoScreen” programme, one of the “CCMX Materials Challenges”, got underway, which is expected to yield a set of pre-validated methods for lab experiments over the next few years. It involves using test materials that have a closely defined particle size distribution, possess well-documented biological and chemical properties and can be altered in certain parameters – such as surface charge. “Thanks to these methods and test substances, international labs will be able to compare, verify and, if need be, improve their experiments,” explains Peter Wick, Head of Empa’s laboratory for Materials-Biology Interactions.

Instead of the all-too-familiar “fumbling around in the dark”, this would provide an opportunity for internationally coordinated research strategies to not only clarify the potential risks of new nanoparticles in retrospect but even be able to predict them. The Swiss scientists therefore coordinate their research activities with the National Institute of Standards and Technology (NIST) in the US, the European Commission’s Joint Research Center (JRC) and the Korean Institute of Standards and Science (KRISS).

Bravo! and thank you Dr. Krug and Empa for confirming something I’ve suspected due to hints from more informed commentators. Unfortunately my ignorance. about research protocols has not permitted me to undertake a better analysis of the research. ,

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

Nanosafety Research—Are We on the Right Track? by Prof. Dr. Harald F. Krug. Angewandte Chemie International Edition DOI: 10.1002/anie.201403367 Article first published online: 10 OCT 2014

This is an open access paper.

Lung injury, carbon nanotubes, and aluminum oxide

It’s pretty much undisputed that long, multi-walled carbon nanotubes (MWCNTs) are likely to present a serious health hazard given their resemblance to asbestos fibres. It’s a matter of some concern that has resulted in a US National Institute of Occupational Safety and Health (NIOSH) recommendation for workplace exposure to all carbon nanotubes that is stringent. (My April 26, 2013 posting features the recommendation.)

Some recent research from North Carolina State University (NCSU) suggests that there may be a way to make long, multi-walled carbon nanotubes safer. From an Oct. 3, 2014 news item on Nanowerk,

A new study from North Carolina State University and the National Institute of Environmental Health Sciences (NIEHS) finds that coating multiwalled carbon nanotubes (CNTs) with aluminum oxide reduces the risk of lung scarring, or pulmonary fibrosis, in mice.

“This could be an important finding in the larger field of work that aims to predict and prevent future diseases associated with engineered nanomaterials,” says James Bonner, a professor of environmental and molecular toxicology at NC State …

An Oct. 3, 2014 NCSU news release, which originated the news item, describes the research in a little more detail,

Multiwalled CNTs have a wide array of applications, ranging from sporting goods to electronic devices. And while these materials have not been associated with adverse health effects in humans, research has found that multi-walled CNTs can cause pulmonary fibrosis and lung inflammation in animal models.

“Because multiwalled CNTs are increasingly used in a wide variety of products, it seems likely that humans will be exposed to them at some point,” Bonner says. “That means it’s important for us to understand these materials and the potential risk they pose to human health. The more we know, the better we’ll be able to engineer safer materials.”

For this study, the researchers used atomic layer deposition to coat multiwalled CNTs with a thin film of aluminum oxide and exposed mice to a single dose of the CNTs, via inhalation.

The researchers found that CNTs coated with aluminum oxide were significantly less likely to cause pulmonary fibrosis in mice. However, the coating of aluminum oxide did not prevent lung inflammation.

“The aluminum oxide coating doesn’t eliminate health risks related to multi-walled CNTs,” Bonner says, “but it does lower them.”

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

Atomic Layer Deposition Coating of Carbon Nanotubes with Aluminum Oxide Alters Pro-Fibrogenic Cytokine Expression by Human Mononuclear Phagocytes In Vitro and Reduces Lung Fibrosis in Mice In Vivo by Alexia J. Taylor, Christina D. McClure, Kelly A. Shipkowski, Elizabeth A. Thompson, Salik Hussain, Stavros Garantziotis, Gregory N. Parsons, and James C. Bonner. Published: September 12, 2014 DOI: 10.1371/journal.pone.0106870

This is an open access article.

The researchers offered this conclusion (part of the paper’s abstract),

These findings indicate that ALD [atomic layer deposition] thin film coating of MWCNTs with Al2O3 reduces fibrosis in mice and that in vitro phagocyte expression of IL-6, TNF-α, and OPN, but not IL-1β, predict MWCNT-induced fibrosis in the lungs of mice in vivo.

However, what I found most striking was this from the paper’s Discussion (section),

While the Al2O3 coating on MWCNTs appears to be the major factor that alters cytokine production in THP-1 and PBMCs in vitro, nanotube length is still likely an important determinant of the inflammatory and fibroproliferative effects of MWCNTs in the lung in vivo. In general, long asbestos fibers or rigid MWCNTs (i.e., >20 µm) remain in the lung and are much more persistent than shorter fibers or nanotubes [20]. Therefore, the nanotube fragments resulting from breakage of A-MWCNTs coated with 50 or 100 ALD cycles of Al2O3 would likely be cleared from the lungs more rapidly than uncoated long MWCNTs or those coated with only 10 ALD cycles of Al2O3. We observed that the fracturing of A-MWCNTs occurred only after sonication prior to administration to cells in vitro or mice in vivo. However, unsonicated A-MWCNTs could be more likely to fracture over time in tissues as compared to U-MWCNTs [uncoated]. We did not address the issue of A-MWCNT clearance before or after fracturing in the present study, but future work should focus the relative clearance rates from the lungs of mice exposed to A-MWCNTs in comparison to U-MWCNTs. Another potentially important consideration is whether or not ALD coating with Al2O3 alters the formation of a protein corona around MWCNTs. It is possible that differences in cytokine levels in the supernatants from cells treated with U- or A-MWCNTs could be due to differences in protein corona formation around functionalized MWCNTs that could modify the adsorptive capacity of the nanomaterial. Characterization of the protein corona and the adsorptive capacity for cytokines after ALD modification of MWCNTs should be another important focus for future work. [emphases mine]

In other words, researchers think coating long, MWCNTs with a certain type of aluminum might be safer due to its effect on various proteins and because coated MWCNTs are likely to fracture into smaller pieces and we know that short MWCNTs don’t seem to present a problem when inhaled.

Of course, there’s the research from Duke University (my Oct. 3, 2014 post) which suggests CNTs could present a different set of problems over time as they accumulate in the environment.

Carbon nanotube accumulation in Duke University’s (US) mesocosm

This Oct. 1, 2014 news item on ScienceDaily about carbon nanotubes accumulating in the wetlands is carefully worded,

A Duke University team has found that nanoparticles called single-walled carbon nanotubes accumulate quickly in the bottom sediments of an experimental wetland setting, an action they say could indirectly damage the aquatic food chain. [emphasis mine]

The results indicate little risk to humans ingesting the particles through drinking water, say scientists at Duke’s Center for the Environmental Implications of Nanotechnology (CEINT). But the researchers warn that, based on their previous research, the tendency for the nanotubes to accumulate in sediment could indirectly damage the aquatic food chain in the long term if the nanoparticles provide “Trojan horse” piggyback rides to other harmful molecules. [emphases mine]

There’s a lot of hedging (could, if) in the way this research is being described. I imagine the researchers are indicating they have concerns but have no wish to stimulate panic and worry.

An Oct. 1, 2014 Duke University news release (also on EurekAlert), which originated the news item, goes on to explain the interest in carbon nanotubes specifically,

Carbon nanotubes are rapidly becoming more common because of their usefulness in nanoelectric devices, composite materials and biomedicine.

The Duke study was done using small-scale replications of a wetland environment, called “mesocosms,” that include soil, sediments, microbes, insects, plants and fish. These ecosystems-in-a-box are “semi-closed,” meaning they get fresh air and rainwater but don’t drain to their surroundings. While not perfect representations of a natural environment, mesocosms provide a reasonable compromise between the laboratory and the real world.

“The wetland mesocosms we used are a much closer approximation of the natural processes constantly churning in the environment,” said Lee Ferguson, associate professor of civil and environmental engineering at Duke. “Although it’s impossible to know if our results are fully accurate to natural ecosystems, it is clear that the processes we’ve seen should be considered by regulators and manufacturers.”

Ferguson and his colleagues dosed the mesocosms with single-walled carbon nanotubes and measured their concentrations in the water, soil and living organisms during the course of a year. They found that the vast majority of the nanoparticles quickly accumulated in the sediment on the “pond” floor. However, they found no sign of nanoparticle buildup in any plants, insects or fish living in the mesocosms.

That sounds marvelous and then the researchers provide a few facts about carbon nanotubes,

While this is good news for humans or other animals drinking water after a potential spill or other contamination event, the accumulation in sediment does pose concerns for both sediment-dwelling organisms and the animals that eat them. Previous research has shown that carbon nanotubes take a long time to degrade through natural processes — if they do at all — and any chemical that binds to them cannot easily be degraded either.

“These nanoparticles are really good at latching onto other molecules, including many known organic contaminants,” said Ferguson. “Coupled with their quick accumulation in sediment, this may allow problematic chemicals to linger instead of degrading. The nanoparticle-pollutant package could then be eaten by sediment-dwelling organisms in a sort of ‘Trojan horse’ effect, allowing the adsorbed contaminants to accumulate up the food chain.

“The big question is whether or not these pollutants can be stripped away from the carbon nanotubes by these animals’ digestive systems after being ingested,” continued Ferguson. “That’s a question we’re working to answer now.”

It’s good to see this research is being followed up so quickly. I will keep an eye out for it and, in the meantime, wonder how the followup research will be conducted and what animals will be used for the tests.

Here’s a link to and a citation for the researchers’ most recent paper on possible ‘Trojan’ carbon nanotubes,

Fate of single walled carbon nanotubes in wetland ecosystems by Ariette Schierz, Benjamin Espinasse, Mark R. Wiesner, Joseph H. Bisesi, Tara Sabo-Attwood, and P. Lee Ferguson. Environ. Sci.: Nano, 2014, Advance Article DOI: 10.1039/C4EN00063C First published online 03 Sep 2014

This is an open access paper.

I have written about Duke University and its nanoparticle research in mesocosms before. Most recently, there was a Feb. 28, 2013 posting about work on silver nanoparticles which mentions research in the ‘mesocosm’ (scroll down about 50% of the way). There’s also an Aug. 15, 2011 posting which describes the ‘mesocosm’ project at some length.

For anyone unfamiliar with the Trojan horse story (from its Wikipedia entry; Note: Links have been removed),

The Trojan Horse is a tale from the Trojan War about the subterfuge that the Greeks used to enter the city of Troy and win the war. In the canonical version, after a fruitless 10-year siege, the Greeks constructed a huge wooden horse, and hid a select force of men inside. The Greeks pretended to sail away, and the Trojans pulled the horse into their city as a victory trophy. That night the Greek force crept out of the horse and opened the gates for the rest of the Greek army, which had sailed back under cover of night. The Greeks entered and destroyed the city of Troy, decisively ending the war.

OECD’s (Organization for Economic Cooperation and Development) latest report on its regulating manufactured nanomaterials questionnaire

As I have commented on several occasions, most of my information about Canada’s activities with regard to risk and nanomaterials comes from outside the country, notably the OECD (Organization for Economic Cooperation and Development).

Thank’s to Lynn Bergeson and her Sept. 17, 2014 posting on Nanotechnology Now for information about the latest publication from the OECD’s Working Party on Manufactured Nanomaterials (Note: a link has been removed),

On September 16, 2014, the Organization for Economic Cooperation and Development (OECD) published a document entitled Report of the Questionnaire on Regulatory Regimes for Manufactured Nanomaterials 2010-2011. … The Report summarizes responses to the Working Party on Manufactured Nanomaterials (WPMN) Questionnaire on Regulated Nanomaterials: 2010-2011, which was issued July 12, 2012. The Questionnaire contained four sections related to the oversight of nanomaterials in various OECD jurisdictions: regulatory updates; definitions and/or legal approaches for nanomaterials by jurisdiction; regulatory challenges; and opportunities for collaboration.

You can find all of the reports from the OECD’s WPMN here, including this latest report, which is no. 42, Report of the questionnaire on regulatory regimes for manufactured nanomaterials 2010-201, ENV/JM/MONO(2014)28. This is the third time there’s been a questionnaire and subsequent report.

I have quickly skimmed through the report and found a few interesting items about Canada’s current activities and collaborations vis à vis manufactured nanomaterials and risk. From the REPORT OF THE QUESTIONNAIRE ON REGULATORY REGIMES FOR MANUFACTURED NANOMATERIALS 2010-2011 which appears to have been published Sept. 4, 2014. I have had an unusually difficult time including excerpts from the report along with page numbers, etc. On the first try, after almost an hour of cutting and pasting, I was unable to get an intelligible version into a preview. To all intents and purposes the text was in place but the preview attempt resulted in a bizarre column of text overwriting the sidebar to the right of the posts.

I tried again and found that extensive reformatting was necessary and that the original table format has been lost. Nonetheless. you will find there are two pieces of legislation being reported on, CEPA (1999), which I believe has something to do with Environment Canada, and F&DA, which seems to be associated with Health Canada. One or both pieces of legislation may be referenced as per the OECD report. Page numbers from the document are included after the excerpted table entries.

Table 12: Hazard identification …

CEPA (1999)

Extrapolation between nanomaterials (i.e., choosing the appropriate surrogate)

Validity of testing methods and analytical tools to detect, characterize and measure nanomaterials

Participating in international forums such as the WPMN [OECD Working Party on Manufactured Nanomaterials], Expert Meetings, and ISO [International Standards Organization] TC/229 to support the generation and synthesis of appropriate science.

Support domestic research to help minimize challenges in hazard identification.

F&DA

Nanomaterial-based products under the F&DA (i.e. nanomedicines) can be associated with a broad spectrum of toxicities that are dependent on the nanoparticle properties (e.g. size, surface charge and solubility). However, there is currently no specific guidance document available for nanomedicines. Nanoparticle properties can significantly impact the PK profile/biodistribution of nanomedicines resulting in safety concerns. The components of the nanomedicines can also interact with the immune system and may trigger unique immunogenicity/immunotoxicity profile. Animals are generally not predictive of immunological responses for biologics (however, it may not be the case if the nanomedicine is a chemical drug), it is likely that immunological studies for nanomedicines should be carried out in human clinical trials. Long term studies may be required for a nanomaterial that persist and accumulated in particular tissues for an extended period of time.  p. 45

Table 13: Health and safety …

F&DA Veterinary Drugs

Due to the lack of a comprehensive understanding of the effects of nanomaterials on human, animal and environmental health, the Veterinary Drugs Directorate has not yet established a comprehensive occupational health and safety policy. Moreover, occupational health and safety is a shared responsibility between the federal and provincial governments in Canada.

At this time, there is no conclusive evidence linking exposure of nanomaterials from veterinary drugs or food sources to negative impact on human health. Additional research is necessary before a definitive policy approach can be taken.

F&DA Veterinary Drugs
Veterinary drugs including those that contain nanomaterials are regulated by the Food and Drugs Act and the Food and Drug Regulations. These provide the Veterinary Drugs Directorate with the authority to regulate the human health and safety aspects of veterinary drug products. The Regulations cover the aspects of the manufacturing, human and animal safety and efficacy assessment, and post-market surveillance of veterinary drug products including those containing nanomaterials. The latter products are subject to the same rigorous assessments as non-nanomaterial-containing veterinary drug products. p. 47

Table 14: Risk Assessment Methodologies

CEPA (1999)

Our understanding of risk assessments of nanomaterials is still evolving. Nanomaterials regulated under the industrial chemicals program employ a precautionary approach (i.e., exposure is typically mitigated), and nano-relevant information is requested whenever appropriate to conduct more informed risk assessments.

Canada also continues to work in international projects, such as the international life sciences institute NanoRelease project aimed at developing methods to quantify releases of nanomaterials from solid matrices.

Canada is also part of the Regulatory Cooperation Council (RCC) Nanotechnology Initiative with the United States. Under this project, Canada and the US are developing a classification scheme for nanomaterials to inform on the utilization of analogue/read- across, developing frameworks and common assumptions to better
inform risk assessments, and mining public and confidential use information to increase marketplace knowledge of nanomaterials. p. 49

Table 15: Risk Management and Nanomaterials in Commerce …

CEPA (1999)

Knowledge of use profiles of industrial nanomaterials; lack of specificity in risk
management measures given the overall lack of information and nomenclature systems for nanomaterials

Under the RCC, Canada and the US are gathering information on the uses of industrial nanomaterials in the two countries.  p. 52

Table 16: Research … (to support regulatory decisions)

CEPA (1999)

– foster domestic and international capacity to generate research on risk assessment priorities and needs
– applying research findings to nanomaterial risk assessments
– using research on nanomaterials to extrapolate to other nanomaterials

– Canada is actively supporting domestic and international research projects to help inform risk assessments.

F&DA

Filling knowledge gaps

HC [Health Canada] is conducting laboratory research to study the effects of lipid nanoparticles on the thermal stability of various recombinant proteins with the aim of identifying determinants of susceptibility to unintended deleterious interactions.  p. 55

Table 17: Impact of Regulatory Actions and Innovations and Economic Growth

CEPA (1999)

How to obtain the necessary information on nanomaterials, and how to regulate them in a manner that does not prevent them from offering their many benefits to society.

Consult with industry on proposed approaches. Focus information requests and requirements.  pp. 56/7

Table 18: Labelling Communication of Nanomaterials …

CEPA (1999)

Labelling of nanomaterials has not been considered under CEPA 1999 to date. p. 58

Table 19: Collaboration with other countries …

CEPA (1999) & F&DA

New Substances Program is involved in various international activities, including:
1) International Organization for Standardization (ISO) Technical Committee (TC) 229 on Nanotechnologies
2) Organisation for Economic Co-operation and Development (OECD) Working Party on
Manufactured Nanomaterials (WPMN) and Working Party on Nanotechnology (WPN)
3) Canada-US Regulatory Cooperation Council (RCC)
4) International Cooperation on Cosmetic Regulation (ICCR) – 2 Reports have been published
a) Criteria and Methods of Detection for Nanomaterials in Cosmetics:

http://www.fda.gov/downloads/InternationalPrograms/HarmonizationInitiatives/UCM235485.pdf

b) Methods for Characterization of Nanomaterials in Cosmetics

http://ec.europa.eu/consumers/sectors/cosmetics/files/pdf/iccr5_char_nano_en.pdf

5) International Regulators Nanotechnology Working Group
6) International Life Sciences Institutes (ILSI) – NanoRelease Food Additive Project
7) NanoLyse

In addition, for veterinary drugs, Health Canada collaborates with other regulatory agencies in USA, Europe, Australia, etc in the regulation of non-nanomaterial products and substances and would do the same for substances that are, or products containing nanomaterials pp. 59/60

Table 19: Expert Workshop Sponsorship [table number repetition noted]

CEPA (1999)

The Workshop on the Human and Environmental Risk Assessment of Nanomaterials convened by Health Canada and Environment Canada (March 24-26, 2010) provided an open forum for detailed dialogue on nanomaterials among science evaluators, research scientists and regulators. The Workshop was attended by 25 experts from Australia, Canada, Europe, Korea and the United States of America. In addition, seven observers attended the Workshop.

Regulatory Cooperation Council with the United States

F&DA Foods

Health Canada will be hosting a Joint NanoLyse/NanoRelease Workshop to discuss methods and safety of nanomaterials and share information from the respective projects. NanoLyse is an EU research consortium to develop methods of analysis for engineered nano-materials in foods and NanoRelease is an International Life Sciences Institute lead initiative to develop of analytical methods, alimentary canal models for uptake of engineered nano-materials and review of regulatory issues. p. 61

In any event, good luck with the reading and you can find out more about NanoLyse here and more about Canadian participation in the NanoRelease Food Additive Steering Committee project here.

FOE, nano, and food: part three of three (final guidance)

The first part of this food and nano ‘debate’ started off with the May 22, 2014 news item on Nanowerk announcing the Friends of the Earth (FOE) report ‘Way too little: Our Government’s failure to regulate nanomaterials in food and agriculture‘. Adding energy to FOE’s volley was a Mother Jones article written by Tom Philpott which had Dr. Andrew Maynard (Director of the University of Michigan’s Risk Science Center) replying decisively in an article published both on Nanowerk and on the Conversation.

The second part of this series focused largely on a couple of  research efforts (a June 11, 2014 news item on Nanowerk highlights a Franco-German research project, SolNanoTox) and in the US (a  June 19, 2014 news item on Azonano about research from the University of Arizona focusing on nanoscale additives for dietary supplement drinks) and noted another activist group’s (As You Sow) initiative with Dunkin’ Donuts (a July 11, 2014 article by Sarah Shemkus in a sponsored section in the UK’s Guardian newspaper0).

This final part in the series highlights the US Food and Drug Administration’s (FDA) final guidance document on nanomaterials and food issued some five weeks after the FOE’s report and an essay by a Canadian academic on the topic of nano and food.

A July 9, 2014 news item on Bloomberg BNA sums up the FDA situation,

The Food and Drug Administration June 24 [2014] announced new guidance to provide greater regulatory clarity for industry on the use of nanotechnology in FDA-regulated products, including drugs, devices, cosmetics and food.

In this final guidance, the agency said that nanotechnology “can be used in a broad array of FDA-regulated products, including medical products (e.g., to increase bioavailability of a drug), foods (e.g., to improve food packaging) and cosmetics (e.g., to affect the look and feel of cosmetics).”

Also on the agency website, the FDA said it “does not make a categorical judgment that nanotechnology is inherently safe or harmful. We intend our regulatory approach to be adaptive and flexible and to take into consideration the specific characteristics and the effects of nanomaterials in the particular biological context of each product and its intended use.”

This July 18, 2014 posting by Jeannie Perron, Miriam Guggenheimm and Allan J. Topol of Covington & Burling LLP on the National Law Review blog provides a better summary and additional insight,

On June 24, 2014, the Food and Drug Administration (FDA) released three final guidance documents addressing the agency’s general approach to nanotechnology and its use by the food and cosmetics industries, as well as a draft guidance on the use of nanomaterials in food for animals.

These guidance documents reflect FDA’s understanding of nanomaterials as an emerging technology of major importance with the potential to be used in novel ways across the entire spectrum of FDA- regulated products.

The documents suggest that FDA plans to approach nanotechnology-related issues cautiously, through an evolving regulatory structure that adapts to manufacturers’ changing uses of this technology. FDA has not established regulatory definitions of “nanotechnology,” “nanomaterial,” “nanoscale,” or other related terms. …

The notion of an “evolving regulatory structure” is very appealing in situations with emerging technologies with high levels of uncertainty. It’s surprising that more of the activist groups don’t see an opportunity with this approach. An organization that hasn’t devised a rigid regulatory structure has no investment in defending it. Activist groups can make the same arguments, albeit from a different perspective, about an emerging technology as the companies do and, theoretically, the FDA has become a neutral party with the power to require a company to prove its products’ safety.

You can find the FDA final guidance and other relevant documents here.

Finally, Sylvain Charlebois, associate dean at the College of Business and Economics at the University of Guelph, offers a rather provocative (and not from the perspective you might expect given his credentials) opinion on the topic of ‘nano and food’  in a July 18, 2014 article for TheRecord.com,

Nanotechnology and nanoparticles have been around for quite some time. In fact, consumers have been eating nanoparticles for years without being aware they are in their food.

Some varieties of Dentyne gum and Jell-O, M&M’s, Betty Crocker whipped cream frosting, Kool-Aid, Pop-Tarts, you name it, contain them. Even food packaging, such as plastic containers and beer bottles, have nanoparticles.

While consumers and interest groups alike are registering their concerns about genetically modified organisms, the growing role of nanotechnology in food and agriculture is impressive. When considering the socio-economic and ethical implications of nanotechnology, comparisons to the genetic modification debate are unavoidable.

The big picture is this. For years, capitalism has demonstrated its ability to create wealth while relying on consumers’ willingness to intrinsically trust what is being offered to them. With trans fats, genetically modified organisms and now nanoparticles, our food industry is literally playing with fire. [emphasis mine]

Most consumers may not have the knowledge to fully comprehend the essence of what nanotechnology is or what it can do. However, in an era where data access in almost constant real-time is king, the industry should at least give public education a shot.

In the end and despite their tactics, the activist groups do have a point. The food and agricultural industries need to be more frank about what they’re doing with our food. As Charlebois notes, they might want to invest in some public education, perhaps taking a leaf out of the Irish Food Board’s book and presenting the public with information both flattering and nonflattering about their efforts with our food.

Part one (an FOE report is published)

Part two (the problem with research)

ETA Aug. 22, 2014: Coincidentally, Michael Berger has written an Aug. 22, 2014 Nanowerk Spotlight article titled: How to identify nanomaterials in food.

ETA Sept. 1, 2014: Even more coincidentally, Michael Berger has written a 2nd Nanowerk Spotlight (dated Aug. 25, 2014) on the food and nano topic titled, ‘Nanotechnology in Agriculture’ based on the European Union’s Joint Research Centre’s ‘Workshop on Nanotechnology for the agricultural sector: from research to the field”, held on November 21-22 2013′.

FOE, nano, and food: part two of three (the problem with research)

The first part of this roughly six week food and nano ‘debate’ started off with the May 22, 2014 news item on Nanowerk announcing the Friends of the Earth (FOE) report ‘Way too little: Our Government’s failure to regulate nanomaterials in food and agriculture‘. Adding energy to FOE’s volley was a Mother Jones article written by Tom Philpott which had Dr. Andrew Maynard (Director of the University of Michigan’s Risk Science Center) replying decisively in an article published both on Nanowerk and on the Conversation.

Coincidentally or not, there were a couple of news items about ‘nano and food’ research efforts during the ‘debate’. A June 11, 2014 news item on Nanowerk highlights a Franco-German research project into the effects that nanomaterials have on the liver and the intestines while noting the scope of the task researchers face,

What mode of action do nanomaterials ingested via food have in liver and intestine? Which factors determine their toxicity? Due to the large number of different nanomaterials, it is hardly possible to test every one for its toxic properties. [emphasis mine] For this reason, specific properties for the classification of nanomaterials are to be examined within the scope of the Franco-German research project “SolNanoTox”, which began on 1 March 2014. The [German] Federal Institute for Risk Assessment (BfR) requires data on bioavailability for its assessment work, in particular on whether the solubility of nanomaterials has an influence on uptake and accumulation in certain organs, such as liver and intestine. “We want to find out in our tests whether the criterion ‘soluble or insoluble’ is a determining factor for uptake and toxicity of nanomaterials,” says BfR President Professor Dr. Andreas Hensel.

A June 13, 2014 German Federal Institute for Risk Assessment (BfR) press release, which originated the news item, details the research and the participating agencies,

A risk assessment of nanomaterials is hardly possible at the moment and involves a very high degree of uncertainty, as important toxicological data on their behaviour in tissue and cells are still missing. [emphasis mine] The German-French SolNanoTox research project examines which role the solubility of nanomaterials plays with regard to their accumulation and potential toxic properties. The project is to run for three and a half years during which the BfR will work closely with its French sister organisation ANSES. Other partners are the Institut des Sciences Chimiques de Rennes and Universität Leipzig. The German Research Foundation and French Agence Nationale de la Recherche (ANR) are funding the project.

The tasks of the BfR include in vitro tests (e.g. the investigation of the influence of the human gastrointestinal system) and analysis of biological samples with regard to the possible accumulation of nanomaterials. In addition to this, the BfR uses modern methods of mass spectrometry imaging to find out whether nanoparticles alter the structure of biomolecules, e.g. the structure of the lipids of the cellular membrane. So far, these important tests, which are necessary for assessing possible changes in DNA or cellular structures caused by nanomaterials in food, have not been conducted.

Metallic nanoparticles are to be studied (from the press release),

In the project, two fundamentally different types of nanoparticles are examined as representatives for others of their type: titanium dioxide as representative of water insoluble nanoparticles and aluminium as an example of nanomaterials which show a certain degree of water solubility after oxidation. [emphases mine] It is examined whether the degree of solubility influences the distribution of the nanomaterials in the body and whether soluble materials may possibly accumulate more in other organs than insoluble ones. The object is to establish whether there is a direct toxic effect of insoluble nanomaterials in general after oral uptake due to their small size.

Different innovative analytical methods are combined in the project with the aim to elucidate the behaviour of nanomaterials in tissue and their uptake into the cell. The main focus is on effects which can trigger genotoxic damage and inflammation. At first, the effects of both materials are examined in human cultures of intestinal and liver cells in an artificial environment (in vitro). In the following, it has to be verified by animal experimentation whether the observed effects can also occur in humans. This modus operandi allows to draw conclusions on effects and mode of action of orally ingested nanomaterials with different properties. The goal is to group nanomaterials on the basis of specific properties and to allocate the corresponding toxicological properties to these groups. Motivation for the project is the enormous number of nanomaterials with large differences in physicochemical properties. Toxicological tests cannot be conducted for all materials.

In the meantime, a June 19, 2014 news item on Azonano (also on EurekAlert but dated June 18, 2014) features some research into metallic nanoparticles in dietary supplement drinks,

Robert Reed [University of Arizona] and colleagues note that food and drink manufacturers use nanoparticles in and on their products for many reasons. In packaging, they can provide strength, control how much air gets in and out, and keep unwanted microbes at bay. As additives to food and drinks, they can prevent caking, deliver nutrients and prevent bacterial growth. But as nanoparticles increase in use, so do concerns over their health and environmental effects. Consumers might absorb some of these materials through their skin, and inhale and ingest them. What doesn’t get digested is passed in urine and feces to the sewage system. A handful of initial studies on nanomaterials suggest that they could be harmful, but Reed’s team wanted to take a closer look.

They tested the effects of eight commercial drinks containing nano-size metal or metal-like particles on human intestinal cells in the lab. The drinks changed the normal organization and decreased the number of microvilli, finger-like projections on the cells that help digest food. In humans, if such an effect occurs as the drinks pass through the gastrointestinal tract, these materials could lead to poor digestion or diarrhea, they say. The researchers’ analysis of sewage waste containing these particles suggests that much of the nanomaterials from these products are likely making their way back into surface water, where they could potentially cause health problems for aquatic life.

This piece is interesting for two reasons. First, the researchers don’t claim that metallic nanoparticles cause digestion or diarrhea due to any action in the gastrointestinal tract. They studied the impact that metallic nanoparticles in supplementary drinks had on cells (in vitro testing) from the gastrointestinal tract. Based on what they observed in the laboratory, “… these materials could lead to poor digestion or diarrhea… .” The researchers also suggest a problem could occur as these materials enter surface water in increasing quantities.

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

Supplement Drinks and Assessment of Their Potential Interactions after Ingestion by Robert B. Reed, James J. Faust, Yu Yang, Kyle Doudrick, David G. Capco, Kiril Hristovski, and Paul Westerhoff. ACS Sustainable Chem. Eng., 2014, 2 (7), pp 1616–1624 DOI: 10.1021/sc500108m Publication Date (Web): June 2, 2014

Copyright © 2014 American Chemical Society

With Paul Westerhoff as one of the authors and the reference to metallic nanoparticles entering water supplies, I’m guessing that this research is associated with the LCnano (lifecycle nano) project headquartered at Arizona State university (April 8, 2014 posting).

Getting back to the Franco-German SolNanoTox project, scientists do not know what happens when the cells in your intestines, liver, etc. encounter metallic or other nanoparticles, some of which may be naturally occurring. It should also be noted that we have likely been ingesting metallic nanoparticles for quite some time. After all, anyone who has used silver cutlery has ingested some silver nanoparticles.

There are many, many questions to be asked and answered with regard to nanomaterials in our foods.  Here are a few of mine:

  • How many metallic and other nanoparticles did we ingest before the advent of ‘nanomaterials in food’?
  • What is the biopersistence of naturally occurring and engineered metallic and other nanoparticles in the body?
  • Is there an acceptable dose versus a fatal dose? (Note: There’s naturally occurring formaldehyde in pears as per my May 19, 2014 post about doses, poisons, and the Sense about Science group’s campaign/book, Making Sense of Chemical Stories.)
  • What happens as the metallic and other engineered nanoparticles are added to food and drink and eventually enter our water, air, and soil?

Returning to the ‘debate’, a July 11, 2014 article by Sarah Shemkus for a sponsored section in the UK’s Guardian newspaper highlights an initiative taken by an environmental organization, As You Sow, concerning titanium dioxide in Dunkin’ Donuts’ products (Note: A link has been removed),

The activists at environmental nonprofit As You Sow want you to take another look at your breakfast doughnut. The organization recently filed a shareholder resolution asking Dunkin’ Brands, the parent company of Dunkin’ Donuts, to identify products that may contain nanomaterials and to prepare a report assessing the risks of using these substances in foods.

Their resolution received a fair amount of support: at the company’s annual general meeting in May, 18.7% of shareholders, representing $547m in investment, voted for it. Danielle Fugere, As You Sow’s president, claims that it was the first such resolution to ever receive a vote. Though it did not pass, she says that she is encouraged by the support it received.

“That’s a substantial number of votes in favor, especially for a first-time resolution,” she says.

The measure was driven by recent testing sponsored by As You Sow, which found nanoparticles of titanium dioxide in the powdered sugar that coats some of the donut chain’s products. [emphasis mine] An additive widely used to boost whiteness in products from toothpaste to plastic, microscopic titanium dioxide has not been conclusively proven unsafe for human consumption. Then again, As You Sow contends, there also isn’t proof that it is harmless.

“Until a company can demonstrate the use of nanomaterials is safe, we’re asking companies either to not use them or to provide labels,” says Fugere. “It would make more sense to understand these materials before putting them in our food.”

As You Sow is currently having 16 more foods tested. The result should be available later this summer, Fugere says.

I wonder if As You Sow will address the question of whether the nanoscale titanium dioxide they find indicates that nanoscale particles are being deliberately added or whether the particles are the inadvertent consequence of the production process. That said, I find it hard to believe no one in the food industry is using engineered nanoscale additives as they claim  (the other strategy is to offer a nonanswer) in Shemkus’ article (Note: Links have been removed).,

In a statement, Dunkin’ Donuts argues that the titanium dioxide identified by As You Sow does not qualify as a nanomaterial according to European Union rules or draft US Food and Drug Administration regulations. The company also points out that there is no agreed-upon standard method for identifying nanoparticles in food.

In 2008, As You Sow filed nanomaterial labeling resolutions with McDonald’s and Kraft Foods. In response, McDonald’s released a statement declaring that it does not support the use of nanomaterials in its food, packaging or toys. Kraft responded that it would make sure to address health and safety concerns before ever using nanomaterials in its products.

While Shemkus’ article appears in the Guardian’s Food Hub which is sponsored by the Irish Food Board, this article manages to avoid the pitfalls found in Philpott’s nonsponsored article.

Coming next: the US Food and Drug Administration Guidance issued five weeks after the FOE kicks off the ‘nano and food’ debate in May 2014 with its ‘Way too little: Our Government’s failure to regulate nanomaterials in food and agriculture‘ report.

Part one (an FOE report is published)

Part three (final guidance)

FOE, nano, and food: part one of three (an FOE report is published)

It seems the food and nano debate of Spring/Summer 2014 has died down, for a while at least. The first volley (from my perspective) was the May 2014 release of ‘Way too little: Our Government’s failure to regulate nanomaterials in food and agriculture’ by the Friends of the Earth (FOE) Australia. Here’s how the report is described in a May 22, 2014 news item on Nanowerk,

Friends of the Earth’s new report, Way too little (pdf), looks at the now widespread presence of nanomaterials in our food chain and how little Food Standards Australia New Zealand (FSANZ) is doing to ensure our safety.

You can find the following passage on p. 6 of FOE’s report ‘Way too little: Our Government’s failure to regulate nanomaterials in food and agriculture‘,

This report will examine the changes since our 2008 report including the development of new food, food contact and agricultural products. It will review the current literature relating to the potential environmental, health and safety impacts associated with nanotechnology and summarise the Australian regulatory responses to date.

This updated report uncovers the:

•accelerating rate of commercialisation and rapidly increasing number of commercial products containing nanomaterials in the food and agricultural sectors;

•lack of information regarding which nanomaterials have been released and the likely exposure of humans and natural systems to these materials;

•lack of basic steps to allow us to track nanomaterials that have been released, such as
labelling and a register of products containing nanomaterials;

•growing gap between the pace of commercialisation and environmental, health and safety assessments;

•increasingly large body of peer reviewed evidence that certain nanomaterials may cause harm to human health or the environment;

•failure of regulators to respond to the growingevidence of risks;

•lack of basic knowledge that is critical in order to fully analyse the particular environmental, health and safety issues associated with nanotechnology.

Six years ago, inaction was based on a perceived lack of data. Inaction is still the norm but that is no longer an excuse our Government can use. Scientists and scientific bodies such as the US National Research Council have given us more than enough evidence to justify a pro-active regulatory regime and a properly funded R&D program that will effectively target those areas of greatest environmental and health concern.

Unfortunately, our Federal Government seems unwilling to provide the levels of funding required for such work or to adopt appropriate regulation. The notion of precaution has been replaced with an attitude that it is the obligation of industry to determine whether their products are safe and regulators will only act when harm is shown. While France, Belgium and Denmark are implementing a mandatory register for nanomaterials and the EU’s is in the process of implementing a nano food labelling regime, Australian consumers remain in the dark.

This needs to change.

One of the issues with increased regulation and labeling is whether the benefits outweigh disadvantages such as the increased difficulty of getting needed foodstuffs to the marketplace and, of course, cost.

Tom Philpott in a May 28, 2014 article for Mother Jones magazine titled ‘Big Dairy Is Putting Microscopic Pieces of Metal in Your Food’ is a strong proponent for FOE’s position, albeit his geographic focus is the US and he seems most concerned with metallic nanoparticles (Note: Links have been removed),

Examples include Silk Original Soy Milk, Rice Dream Rice Drink, Hershey’s Bliss Dark Chocolate, and Kraft’s iconic American Cheese Singles, all of which now contain nano-size titanium dioxide*. As recently as 2008, only eight US food products were known to contain nanoparticles, according to a recent analysis [May 2014 report] from Friends of the Earth—a more than tenfold increase in just six years.

Philpott goes on to mention the US Food and Drug Administration’s (FDA) 2012 draft guidance on nanomaterials and food,

Back in 2012, the FDA released a draft, pending public comment, of a proposed new framework for bringing nano materials into food. The document reveals plenty of reason for concern. For example: “so-called nano-engineered food substances can have significantly altered bioavailability and may, therefore, raise new safety issues that have not been seen in their traditionally manufactured counterparts.” The report went on to note that “particle size, surface area, aggregation/agglomeration, or shape may impact absorption, distribution, metabolism and excretion (ADME) and potentially the safety of the nano-engineered food substance.”

What FDA is saying here is obvious: If nanoparticles didn’t behave differently, the industry wouldn’t be using them in the first place.

So what’s the remedy? Rather than require rigorous safety studies before companies can lace food with nanoparticles, the FDA’s policy draft proposes “nonbinding recommendations” for such research. Even that rather porous safety net doesn’t yet exist—the agency still hasn’t implemented the draft proposal it released more than two years ago.[emphasis mine]

June 27, 2014, the FDA issued a final ‘food and nanotechnology’ guidance document (more on that later).

In the meantime, Dr. Andrew Maynard (Director of the University of Michigan’s Risk Science Center) strongly countered Philpott’s Mother Jones article with his own article published both on The Conversation (June 3, 2014) and on Nanowerk (June 4, 2014),

Recently the American publication Mother Jones published an article on the dangers of food laced with tiny metal oxide particles. The article, however, is laced with errors and misinformation.

The source material for the article came from a report by the environmental organisation Friends of the Earth, an online database of nanotechnology-based consumer products and a peer-reviewed paper published in 2012. However, the analysis of the information is flawed.

..

Bad journalism

The inventory Philpott cites is the Project on Emerging Nanotechnologies Consumer Products Inventory, which I helped establish in 2006 as a way better understand the increasing number of consumer products that were using engineered nanomaterials. It provides a useful but only qualitative sense of what was being used where, and relies on intermittent web searches and other sources of intelligence. The inventory was never meant to be comprehensive or authoritative.

Briefly, Andrew’s argument is that the FOE report (Way too little) which claims a tenfold increase since 2008 of food products with added nano titanium dioxide (and which Philpotts uses to build his case) is erroneous. In 2006, the inventory was voluntary and there was no oversight. At that time, eight food products had been added to the list. In 2013, the inventory was revived (Oct. 28, 2013 posting) and new information added from a 2012 academic paper. The products from the 2012 paper may have predated the 2006 inventory products, or not. There is no way to tell. Andrew notes this in his measured way,

As someone who works on the risks and benefits of nanotechnology, I can see how errors in translation crept into this story. The 2012 paper was addressing a legitimate concern that little is know about how much titanium dioxide is in the processed food chain. The Consumer Products Inventory provides important and unique insights into nanoparticles being used in products. Friends of the Earth have every right to ask what is known about the potential risks in what we’re eating. And reporters like Philpott have a professional obligation to highlight issues of concern and interest to their readers.

The problem with exaggerated and inflated claims is that FOE proves itself to be an unreliable source and Philpott’s failure to investigate adequately puts his own credibility into question. How can you trust either FOE’s materials or Philpott’s articles? The easiest way to begin rebuilding credibility is to admit one’s mistakes. To date, I have not seen any such attempts from FOE or Philpott.

Coming next: a research initiative into the health effects of nano and food and a research paper on nano in commercial drinks both of which help illustrate why there are concerns and why there is a reluctance to move too quickly.

Part two (the problem with research)

Part three (final guidance)

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 … .”

Corporate influence, nanotechnology regulation, and Friends of the Earth (FoE) Australia

The latest issue of the newsletter, Chain Reaction # 121, July 2014, published by Friends of the Earth (FoE) Australia features an article by Louise Sales ‘Corporate influence over nanotechnology regulation‘ that has given me pause. From the Sales article,

I recently attended an Organisation for Economic Co-operation and Development (OECD) seminar on the risk assessment and risk management of nanomaterials. This was an eye-opening experience that graphically illustrated the extent of corporate influence over nanotechnology regulation globally. Representatives of the chemical companies DuPont and Evonik; the Nanotechnology Industries Association; and the Business and Industry Advisory Committee to the OECD (BIAC) sat alongside representatives of countries such as Australia, the US and Canada and were given equal speaking time.

BIAC gave a presentation on their work with the Canadian and United States Governments to harmonise nanotechnology regulation between the two countries. [US-Canada Regulatory Cooperative Council] [emphasis mine] Repeated reference to the involvement of ‘stakeholders’ prompted me to ask if any NGOs [nongovernmental organizations] were involved in the process. Only in the earlier stages apparently − ‘stakeholders’ basically meant industry.

A representative of the Nanotechnology Industries Association told us about the European NANoREG project they are leading in collaboration with regulators, industry and scientists. This is intended to ‘develop … new testing strategies adapted to innovation requirements’ and to ‘establish a close collaboration among authorities, industry and science leading to efficient and practically applicable risk management approaches’. In other words industry will be helping write the rules.

Interestingly, when I raised concerns about this profound intertwining of government and industry with one of the other NGO representatives they seemed almost dismissive of my concerns. I got the impression that most of the parties concerned thought that this was just the ‘way things were’. As under-resourced regulators struggle with the regulatory challenges posed by nanotechnology − the offer of industry assistance is probably very appealing. And from the rhetoric at the meeting one could be forgiven for thinking that their objectives are very similar − to ensure that their products are safe. Right? Wrong.

I just published an update about the US-Canada Regulatory Cooperation Council (RCC; in  my July 14, 2014 posting) where I noted the RCC has completed its work and final reports are due later this summer. Nowhere in any of the notices is there mention of BIAC’s contribution (whatever it might have been) to this endeavour.

Interestingly. BIAC is not an OECD committee but a separate organization as per its About us page,

BIAC is an independent international business association devoted to advising government policymakers at OECD and related fora on the many diversified issues of globalisation and the world economy.

Officially recognised since its founding in 1962 as being representative of the OECD business community, BIAC promotes the interests of business by engaging, understanding and advising policy makers on a broad range of issues with the overarching objectives of:

  • Positively influencing the direction of OECD policy initiatives;

  • Ensuring business and industry needs are adequately addressed in OECD policy decision instruments (policy advocacy), which influence national legislation;

  • Providing members with timely information on OECD policies and their implications for business and industry.

Through its 38 policy groups, which cover the major aspects of OECD work most relevant to business, BIAC members participate in meetings, global forums and consultations with OECD leadership, government delegates, committees and working groups.

I don’t see any mention of safety either in the excerpt or elsewhere on their About us page.

As Sales notes in her article,

Ultimately corporations have one primary driver and that’s increasing their bottom line.

I do wonder why there doesn’t seem to have been any transparency regarding BIAC’s involvement with the RCC and why no NGOs (according to Sales) were included as stakeholders.

While I sometimes find FoE and its fellow civil society groups a bit shrill and over-vehement at times, It never does to get too complacent. For example, who would have thought that General Motors would ignore safety issues (there were car crashes and fatalities as a consequence) over the apparently miniscule cost of changing an ignition switch. From What is the timeline of the GM recall scandal? on Vox.com,

March 2005: A GM project engineering manager closed the investigation into the faulty switches, noting that they were too costly to fix. In his words: “lead time for all solutions is too long” and “the tooling cost and piece price are too high.” Later emails unearthed by Reuters suggested that the fix would have cost GM 90 cents per car. [emphasis mine]

March 2007: Safety regulators inform GM of the death of Amber Rose, who crashed her Chevrolet Cobalt in 2005 after the ignition switch shut down the car’s electrical system and air bags failed to deploy. Neither the company nor regulators open an investigation.

End of 2013: GM determines that the faulty ignition switch is to blame for at least 31 crashes and 13 deaths.

According to a July 17, 2014 news item on CBC (Canadian Broadcasting Corporation) news online, Mary Barra, CEO of General Motors, has testified on the mater before the US Senate for a 2nd time, this year,

A U.S. Senate panel posed questions to a new set of key players Thursday [July 17, 2014] as it delves deeper into General Motors’ delayed recall of millions of small cars.

An internal report found GM attorneys signed settlements with the families of crash victims but didn’t tell engineers or top executives about mounting problems with ignition switches. It also found that GM’s legal staff acted without urgency.

GM says faulty ignition switches were responsible for at least 13 deaths. It took the company 11 years to recall the cars.

Barra will certainly be asked about how she’s changing a corporate culture that allowed a defect with ignition switches to remain hidden from the car-buying public for 11 years. It will be Barra’s second time testifying before the panel.

H/T ICON (International Council on Nanotechnology) July 16, 2014 news item. Following on the topic of transparency, ICON based at Rice University in Texas (US) has a Sponsors webpage.

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

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

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

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

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

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

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

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

They also describe the current state of affairs with ATS,

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

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

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

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

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

The main objectives of the workshop are to:

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

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

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

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

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

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

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

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

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

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