Nanotechnology

What exactly are nanoscience and nanotechnology? Nanoscience is defined as the study of phenomena and the manipulation of materials at the atomic, molecular and macromolecular scales, where properties differ significantly from those at a larger scale. The recognition that the properties of materials change significantly at the nanoscale, due to quantum effects, is important and emphasises the need to consider size in the assessment of risk-benefits of the use of these materials in food and food-related products. Nanotechnology involves the design, production and application of structures, devices and systems, by controlling the shape and size at the nanometre scale.

The term ‘nano’ is derived from the Greek word for dwarf. To put things in perspective, a nanometre (nm) is one-billionth of a metre, or approximately one hundred thousandth of the width of a human hair. Nanoscience and nanotechnology are generally concerned with materials with dimensions in the range of 1 to 100 nm in size, in any one dimension. This definition is still a matter for debate, especially around structures made from nanoparticles that have been aggregated together to form larger particles. Thus, nanoscience and nanotechnology are about understanding and engineering materials at the molecular or atomic level. Richard Feynman, the Nobel prize winner for physics in 1965, was one of the first to recognise the potential for new properties at the ‘nano’ level and introduced the concept with his talk entitled ‘There is plenty of room at the bottom - an invitation to enter a new world of physics’.

The significance of this is that when the particle size is very small, it can lead to fundamental changes in properties of the material or element. Most people will be familiar with the opaque nature of the filler particles of titanium dioxide, generally used as an intense white pigment. However, nanoparticles of titanium dioxide are transparent, suggesting novel uses in transparent sunscreens, food packaging or plastic food containers. Silver nanoparticles can be incorporated into bandages and provide an antibacterial function, whereas larger silver particles are far less effective. Carbon is mainly a soft material but when organised in nanotubes, becomes extremely hard.

Why should this be the case? Surely the properties of materials are set by the properties of the atoms or molecules? We now know that this is not always the case. The nanoscale structures have very different properties. An example given is that a 1mm cube of sand would very slowly dissolve in water over the period of millions of years. On the other hand, a cube of 1nm would dissolve in about 1 second. One reason the properties are different, when particles are very small, is due to the surface area to volume ratio. In a cube of 1cm, approximately 1 in 10 million atoms are on the surface. In a cube of 1nm however, 80 in 100 are surface atoms. The surface properties dominate in the nanomaterial. Examples of the use of these special properties can be found in nature, with the formation of colour on some butterfly wings due to the arrangement of scales of chitin to form structures called gyroids. These are very narrowly spaced which causes the light to move through them in a complicated way producing colour.

Nanotechnology is here to stay, and already forms the basis of a number of commercially available non-food products. Examples of non-food applications using nanotechnology include pharmaceutical products, automobile paints, transparent sunscreens, stain- and water-repellent clothing, improved sports equipment, self-cleaning glass, paving slabs and concrete. Further details and examples can be found at: http://www.UnderstandingNano.com

With regard to packaging, there are many ways that nanotechnology can benefit the industry and the consumer, hence this is an area that has developed more than others. Packaging protects food from physical damage but also from chemical and microbial spoilage, as much as possible. ‘Use by’ and ‘Best before’ dates are selected based on real time shelf life studies where the growth of organisms is monitored, and the chemical changes leading to unwanted quality changes, such as rancidity, are also checked. These dates are chosen to ensure that the food product is safe, with a margin for error or variability due to the environmental conditions. Using smart packaging, the real in-product changes can be detected and, in some cases, slowed down.

Smart packaging includes active and intelligent packaging. Active packaging works to slow down oxidation or moisture changes in the product increasing shelf life. Examples of active packaging include plastic beer bottles or juice packaging with nanoclay incorporated into the plastic to slow down oxygen transfer, and nano-silver to prevent microbial growth.

Intelligent packaging tells the consumer or retailer when the product is no longer safe or useable, as well as potentially many other useful areas of information through interaction with the internet. Examples of intelligent packaging include labels that turn red when the product has started to spoil as well as QR codes that provide selected information to mobile phones.

Nanotechnology can provide benefits in growing crops and farming animals. These are reviewed by Fraceto et al (2016)[³] who describe four main areas that are potentially of benefit:

• Productivity increases by using nano-pesticides and fertilisers
• Soil improvement using nanoclays and gels
• Plant growth increases by using nanomaterials
• Environmental monitoring using smart sensors

Using these techniques is at an early stage but it is considered important that they are developed further to cope with the growth in population and increased food and water demands.

Making materials smaller, or building up materials atom by atom, can generate novel and useful properties as described above. However, there are some concerns about nanotechnology and the unknown properties of nanoparticles. In particular there are concerns that certain nanoparticles are potentially toxic to the environment or to human or animal health.

Examples of these concerns are the use of nano silver as an antibacterial coating in household goods such as washing machines, dishwashers, plastic food containers etc. Additionally, the potential for nano silica or nano titanium dioxide, allegedly present in the nano form in certain foods containing these ingredients, to be absorbed into the body through the calcium uptake mechanism has given rise to concerns and research into potentially harmful effects on human health. In a limited study on nano silver impregnated into plastic food containers no evidence of migration of the silver into the food was found, suggesting that it is safe to use these products.

Titanium dioxide is an approved food colour (E171) with a ‘non-specified’ Acceptable Daily Intake (ADI). TiO₂ is widely used as a white pigment primarily in surface coatings. In terms of food packaging, TiO₂ is used as a filler particle in paper and increasingly in plastics and building materials or sunscreens as nanoparticles of TiO₂ are transparent but retain their resistance to UV radiation. This has led to their use in coatings on glass and in sunscreens and lotions where they are of great benefit and no or little toxicity. The Scientific Committee on Cosmetics and Non-Food Products (SCCNFP) considered the use of TiO₂ as a UV filter and declared it safe at any size. The pigment is also used directly within foods, for example in confectionery products such as sugar coatings, where it is used to produce a pure white base onto which other colours can be added, thus enhancing the clarity of their colour, or as a clouding agent in dry beverage mixes. However, the limited toxicity data available on animals and humans suggest that such materials will not penetrate beneath the epidermis.

An interesting situation arises in materials such as SiO₂, which are present in certain vegetables but is also an allowed food additive (E551) used as an anti-caking agent. The preparations of SiO₂ are not monodisperse but polydisperse containing pENMs (persistent engineered nanomaterials) a fraction of particles that are nano-sized. Most suggested definitions of pENMs take into account this type of polydispersity and, in addition to defining a size range (usually 1–100nm), they suggest that if more than 1% of the number size distribution contains particles in this size range they need to be classified as pENMs. Irrespective of whether commercial SiO₂ preparations should be classified as pENMs, and hence could become subject to future re-testing and possible labelling as ENMs (engineered nanomaterials), it is suggested that their use will result in the ingestion of SiO₂ nanoparticles. The mode of uptake, distribution, possible accumulation and toxicity of these particles is unknown. Recent toxicology studies have not demonstrated any harmful effects (http://www.efsa.europa.eu/en/efsajournal/pub/5088).

To date, no firm evidence has been found for these harmful effects, but it is wise to be cautious where certain nanoparticles are concerned. In the general use of nanoparticles, it is important to assess how products of nanotechnology and their manufacture may eventually lead to the release of particulate nanomaterials into the environment, and to estimate the subsequent levels of exposure to these materials. The extent to which these materials can enter to the human body, the sites of penetration and possible accumulation of these materials will ultimately determine the possible risks of exposure, particularly for nanomaterials that cannot be metabolized within our bodies.

Globally, there is pressure to produce an  an enforceable definition of 'nano' that can be used to regulate the use, approval and possible labelling of nanotechnology products. A number of reviews and reports have suggested the concept of ‘engineered nanomaterials’ (ENMs) as the nanotechnology products that require definition and regulation. These definitions are intended to be generic and not designed specifically for food materials. The use of the term nanomaterials is important for the food industry because materials are, by definition, composed of structures formed from atoms or molecules: this definition would implicitly exclude natural food biopolymers such as carbohydrates, proteins and lipids. The term engineered is generally taken to mean processed or manufactured and thus, because many of these biomolecules are produced commercially, and have one dimension in the nanoscale range, they would be included in the broader term ‘engineered nanoparticles’.

The current proposed definitions of nanomaterials include, as a category, what might be termed persistent engineered nanomaterials. The exclusive use of the term pENMs would exclude the natural self-assembled nanostructures present in native food materials (e.g. plant cell wall material, fibres in meat and fish, or starch) and presumably the nanostructures induced in processed food systems.  There is still debate as to whether a definition of nanomaterials should include additional qualifications relating to the characterization of internal nanostructures, or measurements of surface to volume ratios designed to capture applications that use aggregates, agglomerates or composites containing particulate nanomaterials. A consequence of the inclusion of such terms would mean that the term nanomaterials would include most natural or processed food materials, for which the characterization of the internal nanostructures would be difficult if not impossible. This would then require specific exemptions for these food materials.

There is also an awareness of the need to distinguish between two types of pENMs, those that are metabolised within the body, and persistent pENMs, that are not broken down and may accumulate within the body. The latter group is suggested to be those that require special attention and would include silver, titanium dioxide and silicon dioxide.

Scientists and technologists have a responsibility to ensure the safety of the products that they develop. Consumers are entitled to expect any changes in food composition or packaging materials that involve nanotechnology to be necessary and safe, the appropriate toxicity testing to have been done and the results to be freely available in the public domain. The idea that size can alter toxicity is not unprecedented in the food industry. There has been published work that suggested that low molecular weight carrageenan may be harmful. This led to concerns about the presence of low molecular weight material in carrageenan used in the food industry.

The present position of the FDA on nanotechnology in food recognises the importance of particles size, and the need for collection of information on the properties and potential toxicity of ENMs. In 2007, the FDA published the results of a Task Force on nanotechnology. Following recommendations from this Task Force, the agency issued (June 2011) a draft guidance for industry, intended to enable industry to determine whether a FDA-regulated product involves the application of nanotechnology. A recent draft guideline (April 2012) contains information, which is intended to alert manufacturers to factors they should consider when determining whether a significant change in a manufacturing process, such as nanotechnology, for a food substance already in the market will:

•  affect the identity of the food substance
•  affect the safety of the use of the food substance
•  affect the regulatory status of the use of the food substance
•  require a new regulatory submission to FDA

Access to the current and evolving FDA guidelines on the regulation and use of nanotechnology and ENMs in food and food contact materials is available through the FDA homepage: http://www.fda.gov/ScienceResearch/SpecialTopics/Nanotechnology/ ^[5]

It is now recognised that size is important and that the properties of nanomaterials can differ considerably from those of the macroscopic form of the material. Hence the safety guidelines and evaluation procedures used for the macroscopic form may not be adequate for assessment of the equivalent nanomaterials. In the absence of a complete picture of the food safety and potential toxicological properties of individual types of nanomaterials, and at this early stage in the development of the technology, it seems to be appropriate to regard nanomaterials as a separate class of either “novel foods” or new additives for food and / or food packaging use, and to control them under one of the respective regulatory frameworks, accordingly.

Dependent on the nature and proposed use of the nanoparticles, it may be an appropriate condition of the authorisation to require a specific post-market monitoring scheme (again, on a case-by-case basis). Furthermore, should the initial assessment indicate that particular consumer groups may be subject to additional risk, specific advisory labelling may also be required (as is currently the case for phytosterols) in addition to the general requirements proposed below.

The Food and Agricultural Organisation (FAO) of the United Nations and the World Health Organisation (WHO) convened an expert meeting on the potential safety aspects of the application of nanotechnologies in the food and agricultural sectors in June 2009. The key findings, conclusions and recommendations of the meeting were published in 2010 http://www.fao.org/docrep/012/i1434e/i1434e00.pdf ^[8]. Following the expert meeting, the FAO/WHO commissioned a report summarising and analysing the information that has since become available, and determining the possible courses of action that should be followed by the FAO and WHO. The report entitled ‘State of the art on the initiatives and activities relevant to risk assessment and risk management of nanotechnologies in the food and agriculture sectors’ collected information on the actual and proposed uses of nanomaterials resulting in human exposure through food or food contact materials since 2009. It reviewed national and international activities on the risk analysis of nanomaterials in the food and agricultural sectors carried out since 2009 (https://doi.org/10.1016/j.foodres.2014.03.022).

Nanoparticles intended for direct food additive use, such as TiO2, should be considered under the framework of Directive 89/107 and be assessed either as novel additives or, in the case where the macro-material is already approved, through potential amendments of the appropriate purity criteria (Directive 96/77/EC). The definition of a nanomaterial could have implication for the use of materials such as SiO₂ or TiO₂, depending on the level of particles in the nanoscale range in the preparations, and thus the need for labelling or additional safety assessment of the nanoforms. An alternative would be to eliminate the fraction in the nanoscale range.

It seems clear that nanotechnology will have both direct and indirect impacts on the food industry. Most of the anticipated impacts are likely to enhance the choice and quality of foods and, in most of these applications, there would appear to be negligible safety concern.

Although nanotechnology will contribute to these enhancements, it is unlikely that its use will be advertised prominently or explicitly and, hence, it is unlikely to provoke direct interest or concern. However, if the impacts are associated in consumers’ minds with nanotechnology, then we do not, as yet, have sufficient evidence from social science-based studies to show whether they will be well received.

Nevertheless, as with any relatively new technology, there will be fears by some and problems, actual or speculative. It is, therefore, important to assess public understanding, reaction and potential concerns over the use of nanotechnology and, in the event that such concerns are identified, it will be important that any use of nanotechnology addresses them. There will be the need for risk assessments, and for appropriate regulatory controls to be introduced.

Most concern potentially centres around the possible ingestion of free persistent particulate engineered nanomaterials, where there is a lack of knowledge on whether the reduced size may, in some cases, lead to an increase in toxicity. This is partly because the small size of these particles may allow them to reach regions within cells or tissue that normal macroscopic particles of the same composition could not reach. Hence, the conventional toxicity tests may be inadequate and there may be special issues related to bio-accumulation of nanoparticles.

It is essential that the use of nanotechnology in the food industry should be, and should be seen to be, necessary and to enhance the safety and quality of foods.

The consumer should therefore be consulted about the use of nanotechnology in food and should be able to exercise choice when purchasing foods that have been produced and packaged with the use of this technology. Identifying the use of such particles, where they are used in foods, would facilitate consumer choice and when foods containing authorised, free persistent nanoparticles are placed on the market, the label should indicate that fact.

The detailed definition of engineered nanomaterials (ENMs) adopted by the EU and internationally will be important for the food industry. The best solution would be a focus on persistent engineered nanomaterials. If labelling is mandatory for all products falling within this definition, then the use of a tiered risk assessment processes may be useful into dividing products into low and potentially high-risk classes (effectively digestible and persistent nanomaterials). Such restricted labelling, associated with publicly available risk assessment data could help foster public confidence and allow consumer choice in the use of this technology.