Last reviewed 20 June 2012

Nanotechnology may seem like the stuff of science fiction, but with developments in this field continuing apace do we understand the toxicology of the nanoparticles and compounds we are creating? Dave Howell reports.

The development of nanoparticles has been nothing short of meteoric over the last few years. Every sector from engineering to the food supply chain has been hosts for new nanomaterials. However, due to the nature of the nanoparticles themselves, and the fact that little historical data exists about their reaction with other substances, or within living organisms, has lead to calls for more control and research into this area of material science.

Following a request from the European Commission, the Scientific Committee at the European Food Safety Authority (EFSA) looked closely at the risks associated with what it calls Engineered Nanomaterials (ENM) in foodstuffs. The EFSA concluded: “There are currently uncertainties related to the identification, characterisation and detection of ENM that are related to the lack of suitable and validated test methods to cover all possible applications, aspects and properties of ENM. Similarly, there are a number of uncertainties related to the applicability of current standard biological and toxicological testing methods to ENM. For these reasons, the proposed ENM Guidance will need to be updated based on experience and acquired knowledge. It is acknowledged that the field is under fast development, and consequently this guidance document will be revised as appropriate.”

The speed with which the nanotechnology sector is developing is a concern especially with so little information about the reactive properties of the nanoparticles that are being developed. Says Paul Morris, MD at Addmaster, the developers of the Biomaster range of silver based antimicrobial technologies: “I don’t think we do understand the toxicology of the nanoparticles we have and those we are developing at the moment. I do think that we can draw parallels with asbestos, and the health issues that this brings. I can remember in the early days of nanoparticle compounds I saw a test where these particles had moved through a breezeblock wall simply via the change in air pressure.”

Nanoparticles are being developed for a wide range of applications, but it’s within the food industry that the most concern is being aired. A recent piece of research by TNS that asked the public their views on nanotechnology found that in many cases there was a concern about nanoparticle additives to food, and the use of this technology in packaging. A clear benefit for the consumer seemed to be absent with those surveyed seeing nanotechnology as benefiting the food supplier and not the consumer. More testing at EU level and package label information was also seen as of paramount importance.

Nanotoxicology

The number of nano products is growing. The Project on Emerging Nanotechnologies (PEN) states that over 1300 manufacturer-identified, nanotechnology-enabled products have entered the commercial marketplace around the world.

“The use of nanotechnology in consumer products continues to grow on a rapid and consistent basis,” says PEN Director David Rejeski. “When we launched the inventory in March 2006 it contained 212 products. If the current trend continues, the number of products could reach 3400 by 2020.”

Health and fitness items continue to dominate the PEN inventory, representing 56% of products listed. More products are based on nanoscale silver — used for its antimicrobial properties — than any other nanomaterial; 313 products (24% of the inventory) use silver nanoparticles. The updated inventory represents products from over 30 countries, including the USA, China, Canada, Germany, and India. This update also identifies products that were previously available, but for which there is no current information.

One of the main issues that nanotechnology has presented is whether a universally accepted definition of what the nanoscale actually is. Many materials are claimed to be “nano”. However particles from 1–100nm are claimed to be nanoparticles, all of which can also have differing molecular characteristics.

Moreover, it’s now vital to appreciate that compounds on a nano scale can exhibit very different interactions than materials on larger scales. Andrew Maynard, at the University of Michigan’s Risk Science Centre quoting from this paper on nanotoxicology states: “There is a strong sense that emerging, novel and complex materials that have been engineered at the nanoscale may exhibit unusual or unanticipated toxicity from a conventional perspective, and that research is needed to understand and address how these designed-materials might cause harm in ways that are not readily understood at present. In this respect a differential approach to toxicology studies is required – one which helps identify where emerging materials and products deviate from established ones in their potential to cause harm, and focuses research on narrowing the resulting knowledge gap.”

Regulating the unknown

The potential risks associated with the use of nanoparticles are not disputed, but robust testing regimes and global regulatory frameworks are conspicuous by their absence. Some moves have already been made. In 2009 Norway and Canada became the first regions to introduce mandatory safety checks on all nanomaterials. However, these services have yet to become active and with others in the USA and the EU also in a nascent stage of development, the issue of potential toxic affects with nanoparticles remains a clear and present danger.

One of the main concerns with the potential toxicology of nanoparticles is whether the existing regulations can be applied to these materials. A good example is the Toxic Substances Control Act 1976 that the US Environmental Protection Agency has been using in relation to nanoparticles, but is realising that this piece of legislation may not be appropriate. The main concern is that in most cases the existing legislation considers the toxicology and physicochemical properties of materials in their bulk form, and not at the nano scale. Where toxicology is concerned a decision has to be made whether nanoparticles have the same molecular identity as their bulk counterparts. If not, they must be treated differently and their potential reaction with their host compounds, the organisms that consume them and the wider environment must be considered as a matter of urgency.

Writing in WIREs Nanomed Nanobiotechnol, Steffan F. Hansen, Department of Environmental Engineering, Technical University of Denmark commented: “Current regulation on nanomaterials in most countries is highly dependent on (eco)toxicological data and risk assessments to support and implement regulations. When risk assessment of nanomaterials is discussed, it is often in the context of previous experience with chemical risk assessment. Although there are some regional differences, chemical risk assessment consists of four parts — hazard identification, dose–response assessment, exposure assessment, and risk characterization. Although a lot of effort is being put into investigating the applicability of each of these four elements, each of them holds a number of limitations that are not easily overcome. Toxicity has been reported for multiple nanoparticles, but for most nanoparticles further confirmation is required, before one can say that a hazard has been identified.”

In its review, BIS (UK Department for Business, Innovation and Skills) concluded: “The general lack of information about the potential impacts of nanotechnologies can lead to uncertainties relating to the setting of appropriate exposure levels, and raises fundamental questions about fulfilling the manner in which obligations arising under regulations might be translated in practice. Regulatory queries have been raised in respect of the three main areas of protection: consumer protection, environmental protection and health and safety. As a result of incomplete information about the potential human and environmental implications of free, engineered nanomaterials, the ability of regulatory measures providing general exemption or prescribing specific substance thresholds to capture potential risks associated with nanotechnologies is unclear.” The FSA (Food Standards Agency) is currently funding research on the analytical methods for detection of nanoparticles in food, with the results due later this year.

When the toxicology of nanomaterials is considered, the Houston Chronicle back in 2007 perhaps said it best: “If nanotechnology is a racehorse, then industry is a jockey whipping it along to market at a breakneck pace. The regulatory community is a poor old trainer limping along in the backstretch, pleading to wrap the horse's legs for safety."

The Royal Society and The Royal Academy of Engineering in their Nanoscience and nanotechnologies: opportunities and uncertainties report concluded: “In many cases, decisions about how regulations should be modified to address particular risks of nanoparticles and nanotubes will require more information than is currently available about hazard to humans and the environment, and a better understanding of exposure pathways. The enforcement of regulations will require appropriate measurement techniques to monitor exposure. The research centre on toxicology and epidemiology of nanoparticles and nanotubes that we recommended will address these knowledge gaps, and one of its functions will be to advise regulators who will also have an opportunity to influence its research programme.”

With Andrew Maynard concluding: “We can now begin to appreciate the challenges presented by simple nanoscale materials such as TiO2, ZnO, Ag, carbon nanotubes and CeO2. But these simple materials are merely the vanguard of a new era of complex materials, where novel and dynamic functionality is engineered into multifaceted substances. If we are to meet the challenge of ensuring the safe use of this new generation of substances, it is time to move beyond “nano” toxicology and towards a new toxicology of sophisticated materials.”

As a new branch of chemical and molecular science, nanotechnology has the potential to deliver many new and beneficial materials in a wide range of sectors. However, the development of new novel nanomaterials — especially those used in active and intelligent packaging solutions — may have a number of unknown reactions that have yet to present themselves to developers.

Generally the regulatory community is divided between those that feel existing legislation can be flexible enough to encompass nanomaterials, and those that feel the existing regulatory framework is inadequate. However, more importantly, many in the scientific community do feel that the development of nanomaterials and their unknown potential toxicity should slow the commercial development of these materials until more research is carried out. Unfortunately with vast commercial interest in nanomaterial development it’s more likely that the development of even more complex nano-based materials will accelerate with scant regard for their potential toxicity.