What is a nanomaterial?

A nanomaterial is a material in which at least one external dimension is in the nanoscale range (1-100 nanometers). Nanomaterials exhibit unique properties that are different from their bulk counterparts due to their small size. These properties arise from the increased surface area, quantum confinement, and enhanced reactivity of nanomaterials.

Despite the many potential benefits of nanomaterials, there are also some concerns about their safety. Nanomaterials can be inhaled, swallowed, or absorbed through the skin, and they may pose a risk to human health. More research is needed to assess the potential risks and benefits of nanomaterials.

Nanomaterials in cosmetics

In the context of cosmetics, a nanomaterial is defined as an intentionally manufactured material with at least one external dimension or an internal structure in the nanoscale range (1-100 nanometers). This means that the material is so small that it can only be seen with an electron microscope.

Nanomaterials are being increasingly used in cosmetics due to their unique properties, such as their ability to:

• Improve the efficacy of cosmetic products: Nanoparticles can be used to deliver active ingredients deeper into the skin, making them more effective.
• Increase the stability of cosmetic products: Nanoparticles can help to stabilize active ingredients and protect them from degradation.
• Enhance the aesthetic properties of cosmetic products: Nanoparticles can be used to improve the texture, color, and fragrance of cosmetic products.

Definition of nanomaterials:

Regulation (EC) No 1223/2009 specifically covers the use of nanomaterials in cosmetic products. The Regulation provides a definition of nanomaterial, as well as a mechanism for notification, labelling, and safety evaluation of cosmetic products containing nanomaterials. Under Article 2 (1) (k), “nanomaterial” means an insoluble or bio persistent and intentionally manufactured material with one or more external dimensions, or an internal structure, on the scale from 1 to 100 nm”. In view of the EU Chemicals Strategy for Sustainability (Ares, 2021), it is likely that the definition for a nanomaterial in the Cosmetic Regulation will be aligned with the recently published 2022/C 229/01 Commission Recommendation of 10 June 2022 on the definition of nanomaterial. The Regulation therefore mainly covers those nanomaterials that are intentionally produced and are insoluble/poorly-soluble or bio persistent (e.g., metals, metal oxides, carbon materials, etc.), and not those that are either completely soluble or degraded and are not persistent in biological systems (e.g., liposomes, oil/water emulsions, etc.). When dealing with the question of solubility, as provided in the current definition, it is important to note that any nano-specific risk may change (even diminish) when a nanomaterial is dissolved. But it is the time period during which the dissolution happens that determines the considerations for risk assessment based on either particle risk or soluble substance risk. Partial dissolution over a long period of time may lead to the mistaken claim that the material is 'soluble', and therefore not a nanomaterial under the scope of the current definition provided in the Cosmetic Regulation (EC) No 1223/2009.

Potential safety issues of nanomaterials

The use of nanomaterials in cosmetics is subject to a high level of protection of human health under the EU Cosmetics Regulation. This is because nano forms of some substances may differ from their conventional (bulk) forms in terms of physicochemical properties, biokinetic behaviour, and/or biological effects. Any intended use of nanomaterials (other than colourants, preservatives and UV filters and not otherwise restricted by the EUCosmetics Regulation) in cosmetic products must be notified to the Commission by the RP through the Cosmetic Product Notification Portal (CPNP) at least six months prior to placing them on the market, except if they were already on the market before 11 January 2013.In case of a safety concern over a nanomaterial, the Commission shall request the SCCSfor a scientific Opinion on the safety of the nanomaterial for use in relevant categories of cosmetic products in consideration of the reasonably foreseeable consumer exposure.The SCCS was recently mandated by the Commission to provide scientific advice to facilitate the identification of any safety concerns relating to the nanomaterials intended for use in cosmetic products, so that they can be prioritised for safety assessment. The advice has recently been published (SCCS/1618/2020), which provides the key scientific aspects of a nanomaterial that should trigger consumer safety concerns, and therefore the need for further evidence-based safety assessment.Although there are currently no hard and fast rules for identifying the safety concerns for nanomaterials, as a general principle, each of the following attributes should add a further degree of safety concern. For example, where:

i. The nanomaterial has constituent particles that have sizes in the lower range of the nanoscale.

ii. The nanomaterial is insoluble, or only partially soluble.

iii. The chemical nature of the nanomaterial suggests the potential for a toxicological hazard.

iv. The nanomaterial has certain physical/morphological features (e.g. needle shape, rigidlong fibres) that are associated with a higher potential for harmful effects. The nanomaterial has surface reactivity in terms of catalytic (including photocatalytic)activity, potential for radical formation, or other surface properties (e.g. potential allergenicity due to proteinaceous surface).

v. The nanomaterial has a different bio kinetic behaviour than the conventional equivalent.For example, a surface modification/coating (e.g. hydrophobic coatings, encapsulation)has been applied to core nanoparticles to alter their ADME properties and as a result make them more accessible systemically, compared to the neat nanoparticles and/or their conventional chemical forms.

vi. The nanomaterial is used as vehicle to carry other substances that have not been assessed for safety as individual components, or together in the form of nano-scale entity.

vii. There is a likelihood of systemic exposure of the consumer to nanoparticles through the use of final products. The frequency of use, and/or the amounts of the relevant consumer product are relatively high.

viii.There is evidence for persistence/accumulation of nanoparticles in the body.

ix. Nanoparticles have other distinctive properties not present in conventional form of the same material, or have a new activity/function (e.g. a smart/functional nanomaterial).

x. The nanomaterial is so novel that it does not have a conventional comparator to allow assessment of changes in properties, behaviour or effects.

xi. The nanomaterial is used in a product that is inhalable (taken up by inhalation into respiratory tract and lung), and the particles are respirable (can reach respiratory epithelium i.e. alveoli).

xii. The assessment of genotoxicity is performed inadequately, e.g. in vitro studies are without information on stability of the test suspension, or evidence of cell exposure(internalisation).

While this section only provides a brief guidance on nanomaterials in cosmetics, the SCCS has published a more detailed specific Guidance on Risk Assessment of Nanomaterials( SCCS/1611/19, under revision), which is an update of a previous guidance published in2012 (SCCS/1484/12), a Memorandum on the Relevance, Adequacy and Quality of theData Expected in Safety Dossiers on Nanomaterials (SCCS/1524/13), and a checklist for the applicants submitting dossiers on nanomaterials as cosmetic ingredients(SCCS/1588/17). Safety assessors need to consult these documents to ensure that any testing to generate evidence on the safety of nanomaterials is carried out with special considerations of the nano-size related characteristics of the materials, and in compliance with the ban on animal testing of cosmetic ingredients. In this regard, it is important to note that, as indicated in the memorandum (SCCS/1524/13), the SCCS will only consider data that are relevant to the nanomaterial(s) under evaluation, are sufficiently complete, and are of appropriate quality to support the safety assessment. The SCCS has also published a number of scientific Opinions in the past few years on the nano-form of different materials. Each of the Opinions can be consulted via the EuropeanCommission website. SCCS Opinions can provide further information on the type o fscientific evidence needed in a safety dossier on nanomaterials intended for use as cosmetic ingredients.In general, a number of reviews have concluded that the existing risk assessment paradigm, in use for conventional chemicals, should in principle be also applicable to engineered nanomaterials. However, it has also been pointed out that the current testing methods may need certain adaptations to take account of the special features of nanomaterials (Rocks et al., 2008; SCENIHR, 2009; SCCS, 2012; EC, 2012; ECHA, 2017; EFSA, 2018;EFSA, 2021a, EFSA 2021b, EC 2022).

Special features of nanomaterials:

- Due to high surface energies, nanoparticles have a tendency to stick together to form agglomerates and aggregates, and/or bind with other moieties on the particle surface.This particle behaviour can change in the presence of certain stabilising/dispersing agents. Characterisation of nanomaterials, prior to and during a test, is therefore a key to ensuring that results obtained are valid.

- Most of the currently available test methods were developed for conventional substances that can be solubilised. In contrast, nanomaterials generally comprise insoluble or poorly soluble nanoparticles that are dispersed in a test medium in the form of a nano-suspension rather than a solution. The applied concentration of a nanomaterial may therefore drop during the test due to particle agglomeration, sedimentation, binding with other moieties in the medium, or sticking to the sides ofthe glass/plastic ware. This could lead to only a partial or no exposure of the test systems during the test. Nanomaterials are known to adsorb or bind different substances on their surfaces, including proteins (Šimon and Joner, 2008; Lynch andDawson, 2008; Monopoli et al., 2012; Moore et al., 2015). They may also bind other substances in the test medium and carry them into the exposed test systems, leading to artefacts in the results.

- The toxicological hazards of chemical substances are currently measured and expressed in terms of weight or volume units (such as mg/kg, or mg/l). These conventionalmetrics may not be fully adequate to account for nanomaterial toxicity. It is thereforeimportant that tests on nanomaterials are not only evaluated in terms of weight/volume concentration, but that results are also expressed in other dose-describing metrics, such as particle number concentration, surface area etc.

- Due to the insoluble particulate nature, and the nano-dimensions, nanomaterials may show an altered uptake and bio kinetic profile in a biological system compared to equivalent conventional forms, e.g. transport of insoluble particles across biological membrane barriers is not driven by concentration-gradient based diffusion partitioning, but by other mechanisms such as endocytosis and/or active (energy-driven) uptake and transport.

- Currently, there are uncertainties in regard to whether the endpoints identified by the current testing methods will be sufficient to identify and characterise all the hazards that may be associated with a nanomaterial.

Source: SCCS Notes of guidance for the testing of cosmetic ingredients and their safety evaluation

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