Memorandum by Central Science Laboratory
This submission is meant to provide a brief
summary of findings of the studies carried out at Central Science
Laboratory (CSL) into the potential applications and implications
of nanotechnologies in food. More detailed findings are submitted
as two separate reports on the studies that the CSL team has recently
carried out for the Food Standards Agency.
A number of recent reports and reviews have
identified the current and short-term projected applications of
nanotechnologies for food and beverages (Bouwmeester et al., 2007;
Chaudhry et al., 2008; EFSA, 2008; Food Safety Authority of Ireland,
2008). Like other sectors, nanotechnologies are promising to revolutionise
the food sectorfrom production to processing, storage,
and development of innovative materials, products and applications.
Currently, such applications in the food sector are new emergent,
but their number and range is expected to increase in the coming
years. Virtually all current applications of nanotechnologies
in food are outside Europe, although some supplements and food
packaging materials are available in the EU. Also, the global
nature of food business means that more products and applications
are likely to be available in the EU in the coming years. This
also means that there will be a need for regulation of the risks,
and establishment of liabilities at the global level.
The current and short-term projected applications
of nanotechnologies include nano-sized or nanoencapsulated ingredients
and additives for food, beverage, and health-food applications.
A current niche for such applications is in the areas where there
is an overlap between the food, medicines, and cosmetics sectors.
For example, some food products are marketed as a means to enhance
nutrition for different lifestyles, or as an aid to beauty, health
and wellbeing. These hybrid sectors have been the first focus
of nanotechnology applications, which have only recently started
to appear in the mainstream food sector. Thus the vast majority
of the currently available nanotechnology products is in the areas
of supplements, healthfoods and nutraceuticals, with only a few
products in the food and beverage areas. The main tenet behind
the development of nano-sized food ingredients and additives appears
to be the enhanced uptake and bioavailability of nano-sized substances
in the body, although other benefits such as improvement in taste,
consistency, stability and texture etc have also been claimed
(Chaudhry et al., 2008).
A major application area for engineered nanoparticles
(ENPs) is for food packaging. Whilst most nanotechnology applications
for food and beverages are currently at R&D or near-market
stages, the applications for food packaging are rapidly becoming
a commercial reality. A contributing factor to such developments
seems to be the expectation that, due to the fixed or embedded
nature of ENPs in plastic polymers, they are not likely to pose
any significant risk to the consumer. Indeed, nanotechnology applications
for food contact materials (FCMs) already make up the largest
share of the current and short-term predicted nanofood market
The currently available information suggests
that nanomaterials used in (health)food applications include both
inorganic (metal, metal oxides) and organic materials. In addition
to the ENPs, there is a possibility that certain microscale materials
used in the food and feed area may contain a nanoscale fraction
due to natural size range variation (EFSA, 2008).
Based on the available information, the ENP
likely to be found in food fall into three categories: metal and
metal oxide (including alkaline earth metal and silicate), surface
functionalised, and organic ENPs. Examples of these include:
A number of meal/metal-oxide ENPs are known
to used in (health)food products and food packaging applications.
These include ENPs of transition metals such as silver and iron;
alkaline earth metals such as calcium and magnesium; and non metals
such as selenium and silicates. Others ENPs that can potentially
be used in food applications include titanium dioxide. Food packaging
is the major area of application of metal(oxide) ENPs. Example
applications include plastic polymers with nano-clay as gas barrier,
nano-silver and nano-zinc oxide for antimicrobial action, nano-titanium
dioxide for UV protection, nano-titanium nitride for mechanical
strength and as a processing aid, nano-silica for surface coating
etc. The use of insoluble metal(oxide) ENPs in food applications,
especially those that are unlikely to be assimilated in the Gl
tract, raises a number of concerns. The likelihood of translocation
of such ENPs with potentially large reactive surfaces to various
cells and tissues in the body may lead to certain risks to consumer
health; for example, potential cellular damage and inflammatory
reactions due to generation of reactive oxygen radical species
(Oberdörster, 2000; Li et al., 2003; Donaldson et al., 2004).
ENPs can also adsorb or bind different substances on their surfaces
(imon and Joner 2008), and thus may carry potentially harmful
chemicals and foreign substances into the blood and to various
tissues and organs in the body.
Certain metal(oxide) ENPs, such as that of silver,
magnesium oxide and zinc oxide, are known to have strong antimicrobial
activity. Especially, there is an increasing use of nanosilver
in a number of consumer products, including (health)food and food
packaging applications. Indeed, the use of nano-silver as an antimicrobial,
antiodorant, and a (proclaimed) health supplement, has already
surpassed all other ENPs currently in use in different sectors
(Woodrow Wilson, 2008). This has also led to concerns over its
safety to human health when ingested orally. Despite this, there
is no published research at present on how the intake of nanosilver
via food and drinks might affect the cellular function or the
gut natural microflora.
Nano-silica is known to be used in food contact
surfaces and food packaging applications, and some reports suggest
its use in clearing of beers and wines, and as a free flowing
agent in powdered soups. The conventional bulk form of silica
is a permitted food additive (Si02, E551), but concerns have been
raised over the safety of nano-silica because it is likely to
remain undigested in the Gl tract and thus may pose a risk due
to greater uptake and translocation in the body. In this regard,
a commercial product "Slim Shake Chocolate", available
in the USA, is understood to incorporate nano-sized silica particles
(between 4 to 6 nm in diameter) that are coated with
coco to enhance the chocolate flavour through the increase in
surface area that hits the taste buds.
Titanium dioxide, in conventional bulk form,
is an already approved additive for food use (Ti02 E171),
but there is a concern that the conventional form may also contain
a nano-sized fraction. Nano-titanium dioxide is used in a number
of consumer products (eg paints, coatings) and its use may extend
to foodstuffs. For example, a patent by Mars Inc. (US Patent US5741505)
describes nano-scale inorganic coatings applied directly on food
surface to provide moisture or oxygen barrier and thus improve
shelf life and/or the flavour impact of foods. The materials used
for the nano-coatings, applied in a continuous process as a thin
amorphous film of 50 nm or less, include titanium dioxide.
The main intended applications described in the patent include
2. Surface Functionalised Nanomaterials
Surface functionalised nanoparticles are the
second generation nanoparticles that add certain functionality
to the matrix, such as antimicrobial activity, or a preservative
action through absorption of oxygen. For food packaging materials,
functionalised ENPs are used to bind with the polymer matrix to
offer mechanical strength or a barrier against movement of gases,
volatile components (such as flavours) or moisture. Compared to
inert materials, the use of this category of ENPs in food applications
is likely to grow in the future. They are also more likely to
be react with different food components, or become bound to food
matrices. Examples include organically-modified nano-clays that
are currently used in food packaging to enhance gas-barrier properties.
The nanoclay mineral is mainly montmorillonite (also termed as
bentonite), which is a natural clay obtained from volcanic ash/rocks,
and has a natural nano-scaled layer structure.
3. Organic Nanomaterials
A number of organic nano-sized materials are
used (or have been developed for use) in food products. These
include vitamins, antioxidants, colours, flavours, and preservatives.
The main principle behind the development of nano-sized organic
substances is the greater uptake, absorption and bioavailability
in the body, compared to conventional bulk equivalents. However,
a greater uptake and bioavailability of certain compounds, such
as certain preservatives, can also be detrimental to consumer
health. Also developed for use in food products are nano-sized
carrier systems for nutrients and supplements. These are based
on nanoencapsulation of the substances both in liposomes and micelles
as well as protein based carriers. Such nano-carrier systems are
used for taste masking of ingredients and additives, and their
protection from degradation during processing. They are also claimed
for enhanced bioavailability of nutrients/supplements, antimicrobial
activity and other health benefits. There is a wide range of materials
available in this category, for example, food additives (eg benzoic
acid, citric acid, ascorbic acid), and supplements (eg vitamins
A and E, isoflavones, ß-carotene, lutein, omega-3 fatty
acids, coenzyme-Q10). The concept of nano-delivery systems has
essentially originated from research into targeted delivery of
drugs and therapeutics. The use of similar technology in foodstuffs
is interesting in the sense that whilst it can offer increased
absorption, uptake and bioavailability, it also has the potential
to alter tissue distribution of the substances in the body. For
example, certain water-soluble compounds (such as vitamin-C) have
been rendered fat dispersible through nano-carrier technology.
Vice versa, certain fat-dispersible compounds (eg vitamin-A) have
been rendered water dispersible. It is hoped that these nano-carriers
are completely broken down and their contents are released in
the GIT. As such, the encapsulated compounds will not be any different
from their conventional equivalents. However, if a nano-carrier
system is capable of delivering the encapsulated substance to
the bloodstream, its absorption, tissue distribution and bioavailabiiity
may be drastically different from the conventional forms. This
raises the concern that some nano-carriers may act as a "Trojan
Horse" and facilitate translocation of the encapsulated substances
or other foreign materials to unintended parts of the body.
It is also worth mentioning that there are many
other nanomaterials that are used for other applications but their
use in food/food packaging is uncertain or unlikely. Examples
include certain carbon-based materials (such as fullerenes, carbon
nanotubes). Although, recent studies have linked carbon nanotubes
with potential harmful effects in biological system, they are
not likely to be used in food applications. This is because functionalities
that carbon nanotubes offer mainly derive from their enhanced
tensile strength and electrical conductivity, which are of little
relevance to potential use in food, although there may be some
applications in the packaging area.
It is known that the conventional physicochemical
rules are not fully applicable at the nanometer scale, and that
there can be some fundamental shifts in physicochemical properties,
behaviour, and interactions of ENPs compared to their bulk equivalents.
For example, quantum effects may have a much greater influence
on the properties of ENPs, especially of those in the lower nanometer
size range, compared to their bulk equivalents. In some cases,
such changes in physicochemical properties may also lead to a
change in the effects and impacts on biological systems. Some
studies have suggested a deviating toxicity profile for some ENPs
compared to their conventional equivalents (Donaldson et al. 2001;
Nel et al. 2006. An important aspect to consider in relation to
potential harmful effects of ENP is their increased ability to
penetrate cellular barriers (Geiser et al., 2005; Oberdörster
et al., 2004). This adds a new dimension to particulate toxicology,
as ENPs can potentially reach new targets in the body where entry
of larger particulates is restricted (Jani et al. 1990; Carr et
al. 1996; Hillyer and Albrecht 2001; Hoet et al. 2004; Florence
2005; des Rieux et al. 2006; De Jong et al. 2008). ENPs are also
known to adsorb or bind different compounds and moieties on their
surfaces (imon and Joner 2008), and may act as a carrier
of potentially harmful chemicals and foreign substances into the
blood and different tissues and organs in the body.
Depending on the surface chemistry, systemically
introduced ENPs have been found to interact with various biological
entities, such as eg plasma proteins, platelets and cells (Nemmar
et al. 2002; imon and Joner 2008). Such interactions may
have a substantial effect on the distribution and excretion of
an ENP (Dobrovolskaia 2007). In this regard, there is emerging
evidence to suggest that ENPs become coated with certain biomolecules,
especially proteins, and these coatings can direct them to specific
locations in the body (Lynch and Dawson 2008). For example, coating
with apolipoprotein E has been associated with their transport
to the brain (Michaelis et al. 2006). The protein "corona"
is, however, also reported to be changeable in different surroundings
(Cedervall et al. 2007). This suggests that ENPs can undergo complex
and dynamic interactions in biological environments, and studies
carried out on "neat" ENPs under artificial conditions
may not represent their true behaviour and effects in real-life
Nanomaterials that are likely to dissolve/solubilise
either in the food matrix or in the Gl tract are not likely to
raise health concerns as, once digested or dissolved, they are
not likely to behave any differently from the conventional bulk
equivalents. One example is that of nano-selenium, which is being
marketed as an additive to a tea product in China for a number
of (proclaimed) health benefits. However, nano-selenium is likely
to solubilise in food or in the Gl tract. Another example is that
of a mayonnaise (currently under development) which is composed
of nano-micelles that contain nano-droplets of water inside. The
mayonnaise is being developed to offer taste and texture attributes
similar to the full fat equivalent, but with a significant reduction
in the amount of fat intake by the consumer.
It is also worth highlighting that currently
there are a number of major knowledge gaps in regard to the behaviour,
interactions, fate and toxicological effects of most ENPs in the
Gl tract. It is possible that the ENPs added (or migrated) to
food will not remain in a free form (and hence not available for
translocation) because of agglomeration, binding with food components,
reaction with stomach acid or digestive enzymes. Furthermore,
much of the available toxicological information relates to in
vitro studies, or to exposure through inhalation of ENPs, and
full extent of hazard, exposure, and risk from the ingestion of
ENPs via food and drinks are therefore largely unknown.
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