With the expected increase in the applications of nanotechnology, there is an urgent
need to identify by clear unequivocal descriptions what can be considered as a
nanomaterial and what should not be. This need to identify a nanomaterial comes from
the uncertainty regarding the safety evaluation and risk assessment of nanomaterials.
The SCENIHR was invited to provide advice on the essential elements of a science-based
overarching working definition of the term "nanomaterial". More specifically they were
asked to identify:
The types of physical and chemical properties particular to nanomaterials,
The threshold(s) at which nanomaterial-specific properties could be expected to
Potential methodology for nanomaterial characterisation
The scientific opinion concluded that:
Whereas physical and chemical properties of materials may change with size,
there is no scientific justification for a single upper and lower size limit
associated with these changes that can be applied to adequately define all
There is scientific evidence that no single methodology (or group of tests) can
be applied to all nanomaterials.
Size is universally applicable to define all nanomaterials and is the most suitable
measurand. Moreover, an understanding of the size distribution of a
nanomaterial is essential and the number size distribution is the most relevant
The scientific opinion recognised however that specific requirements regarding risk
assessment for regulatory purposes for certain areas and applications may require
modifications of any overarching definition.
The major question for both regulators and manufacturers is to identify when a material
or product can be considered a nanomaterial. This opinion has tried to address the
complexity and the uncertainties and provide advice on the essential scientific elements
for a working definition of the term "nanomaterial" for regulatory purposes using specific
examples that may be applicable to certain classes of nanomaterials.
It should be stressed that "nanomaterial" is a categorisation of a material by the size of
its constituent parts. It neither implies a specific risk nor does it necessarily mean that
this material actually has new hazard properties compared to its constituent parts.
However, size influences bio-distribution (and distribution kinetics) in an organism or in
an ecosystem which should be taken into consideration in the risk assessment of
There is sufficient evidence to indicate that there can be a change in some properties of
the material when it or its constituent parts are at the nanoscale which is, for instance,
due to the increased surface-to-volume ratio. These nano-specific properties raise
concerns over their potential to cause harm to humans and the environment. The
reaction rate of nanoparticles often relates to the available surface area. Consequently,
chemical reactivity per mass dose increases for smaller particles of the same type; this
effect may or may not be associated with an increase in biological activity or toxicity. It is
this possible change in reaction rate that warrants the careful evaluation of possible risks
associated with nanotechnology products. However, it is not currently possible to identify
a specific size at which a specific property would change or appear, or a specific property
that is introduced or changed with size.
Several international and national organisations have proposed definitions for the
nanoscale and for nanomaterials (summarised in Annex I). In most of the proposed
definitions, the size refers to one or more external dimensions or an internal structure
within a specified size range. An upper limit of 100 nm or approximately 100 nm is
commonly used. However, there is no scientific evidence to qualify the appropriateness
of this value or any other single upper limit. Some definitions also include a reference to
specific properties or nano-specific properties.
It should be noted that, in the metric system, the "nanoscale" is the range below 1
micrometre (?m) and above 999 picometre (pm). Criteria relevant for the discrimination
between nano and non-nano are discussed using a working definition for the nanoscale
being approximately 1 to 100 nm. Any material with one or more internal or external
dimensions in the nanoscale is then considered a nanomaterial. The feasibility of
including specific properties as elements of a definition was assessed.
When considering any definition for nanoscale and nanomaterial, size is the predominant
feature. This requires that adequate validated methodologies are available for carrying
out measurements at the nanoscale (i.e. below 1 ?m). Any nanomaterial should be
described by its size, and by its number size distribution, including the methodologies
used for the measurement.
Solely referring to size as "one or more external dimensions" will NOT capture aggregates
and agglomerates of primary particles or, importantly, more complex multi-component
nanomaterials that are used in medical and cosmetic applications as their external
dimension is likely to be larger than a specified upper size limit. The inclusion of a
reference to "internal structure" with the same specified range as the external
dimensions will include materials that consist of aggregates, agglomerates and multicomponent
assemblies within the scope of the definition. This would also include
nanoporous and nanocomposite materials. If possible, also for the constituents of multicomponent
nanomaterials the size and number size distribution should be provided.
To distinguish a nanostructured material from a non-nanostructured material, the volume
specific surface area (VSSA) can be a complementary criterion, based on its integral
material surface area per unit volume. For powders and/or dry solid materials, the VSSA
can be determined using a nitrogen absorption methodology called the BET method after
Brunauer, Emmett and Teller (Brunauer et al. 1938). A limitation of the BET-method is
that it is only applicable to powders and/or dry solid materials and not to nanomaterials
embedded in solids and suspensions. Other methods exist that can be used for the
analysis of both powders and particles dispersed in liquids but most still remain difficult
to use on a routine basis. More developments are needed in the area of analysing
powders and particles in liquids. Expressing the surface area related to the volume
instead of mass allows for an additional criterion independent of the density and size or
size distribution of the nanomaterial. A VSSA above 60m2/cm3 would indicate an average
size below 100 nm, thus indicating a high nanomaterial or nanostructure content.
Data on the size distribution should be taken into account when describing a
nanomaterial. When only a part of the material has a size within the size range of the
definition or description, it should be clear whether and when such a material will be
considered a nanomaterial. This may be by allowing a part (a certain percentage) of the
number size distribution to be below a certain threshold or by using the information on
the size distribution itself. Based on its geometric mean and geometric standard
deviation, a material might be considered a nanomaterial when >0.15% of the material,
as indicated by the number size distribution, has a size below the designated upper size
As size is a key element in any definition of the term "nanomaterial", there seems to be a
need for the development of validated standardised methods to determine size (including
that of its constituent parts where relevant) and its corresponding distribution to ensure
comparability of results.
There is a multitude of possibilities for the application of coatings and surface
modifications to nanomaterials. Purposely applied and environmentally acquired coatings
can have a major impact on nanomaterial interaction with biological systems. The coating
and core together control the properties of a given nanomaterial. As a result, it is not
useful to look at either the properties of the core or of the coating in isolation as they
may not be representative of how the nanomaterial will behave in a given environment.
The diversity in coatings of nanomaterials makes it impossible to include criteria based
on surface properties within a definition as these properties may vary with coatings
Several physico-chemical properties from the OECD Working Party on Manufactured
Nanomaterials (WPMN) list of characteristics were evaluated as possible discriminators
for the identification of a nanomaterial. They were crystalline phase, photocatalytic
activity, zeta potential, redox potential, radical formation potential, water solubility and
the octanol-water partition coefficient. It was concluded that while all of these properties
are very useful for risk assessment, none of them appear to be universally applicable as
a criterion within a definition for all nanomaterials.
Like any other material, nanomaterials can be degraded either mechanically, chemically
or by dissolution; in fluids, they can form agglomerates or stable dispersions depending
on solvent chemistry and surface coating. Features associated with solubility (and
degradability) of nanomaterials are very important for risk assessment in view of the
possibility for persistence and accumulation both in man and the environment. These
features include size and shape, water solubility, surface charge and surface reactivity.
However, these features cannot be translated into a definition as they are part of the
characterisation of a nanomaterial and can change for each individual nanomaterial
depending on chemical composition, surface modification and the immediate environment
of the nanomaterial.
Certain nanomaterials and composite materials may contain internal or external
structures at the nanoscale that were incorporated to confer nanospecific characteristics.
As the external dimensions of nanocomposites would be typically larger than 100 nm, a
definition based solely on external size would not consider most nanocomposites to be
nanomaterials. The internal structure with a size at the nanoscale would be an element
to include in a definition, as then nanocomposites will be included in the definition of a
nanomaterial. There are also nanocomposites where one phase is the solid bulk. Exclusion criteria would have to be developed to avoid considering macroscopic composite objects as nanomaterials.
In order to specifically designate purposely made nanomaterials within regulations, the
term "engineered" or "manufactured" may be used. When considering purposely made
nanomaterials, the meaning of "engineered" or "manufactured" needs to include the
processing (e.g. grinding or milling resulting in size reduction, or chemical processing) of
materials to obtain materials at the nanoscale.
In conclusion, size (and its distribution) is universally applicable to all nanomaterials and
is the most suitable measurand. A defined size range would facilitate a uniform
interpretation. For regulatory purposes the number size distribution should also be
considered using both the geometric mean size and its geometric standard deviation for
further refinement of the definition. Alternatively a specific fraction of the number size
distribution might be allowed to be within the specified size ranges of the definition. For
dry powders, the volume specific surface area (VSSA) may be added to the size as a
complementary discriminator to identify nanomaterials. In addition, the definition should
include both external and internal nanostructures.
A size of 1 nm is proposed as the lower limit for the definition of nanomaterials.
However, around 1 nm the distinction between molecules, nanoclusters and nanoparticles
is unclear. In general molecules should be excluded. However, exceptions can be made
to allow for inclusion of certain specific entities.
At the moment, no scientific data are available to indicate that a specific size associated
with special properties due to the nanoscale can be identified for nanomaterials in
general. There is no scientific evidence in favour of a single upper limit. Although an
upper limit of 100 nm is commonly used, there is no scientific evidence to qualify the
appropriateness of this value. Notably, the use of a single upper threshold value might be
too limiting for the classification of nanomaterials and a differentiated approach might be
more appropriate. This approach could be based on a relatively high upper threshold for
which it is assumed that the size distribution at the lower end will most likely be above
the lower, more critical threshold. The lower threshold would be the critical one for which
extensive nano-specific information would be needed in order to perform case-by-case
For specific areas and applications, modifications of any overarching definition may be
needed due to specific requirements regarding risk assessment for regulatory purposes.