Regulatory Aspects of Nanomaterials in the EU^†

1 Nanomaterials in the Regulatory Framework of the EU

Nanotechnology is considered to be a key enabling technology (KET) by the European Commission (EC). It is an enabling technology, which is relevant for many sectors, such as chemicals, consumer products, health, energy, and the environment. As a consequence, the European Union's (EU) regulatory framework, which consists of several pieces of horizontal and sector-specific legislation ¹, ², covers nanomaterials (NMs) explicitly or implicitly. Thus, in principle, nanomaterials, and especially potential risks associated with them, are covered by existing legislation, even if nanomaterials are not explicitly mentioned. Examples of such legislation can be found in ³. Furthermore, recently updated product-specific EU legislation as well as newly proposed legislation explicitly address nanomaterials, including nanomaterial-specific information requirements, authorization of nanomaterials for specific uses, and a safety assessment that takes into account nano-specific characteristics. The second regulatory review on nanomaterials by the EC ¹ concluded that nanomaterials are similar to normal chemicals/substances in that some may be toxic and some may not. Possible risks are related to specific nanomaterials and specific uses. Risk assessment of nanomaterials should be performed on a case-by-case basis, using pertinent information. Current risk assessment methods are applicable, even if further research on particular aspects of risk assessment is still required.

The rules established by each piece of EU legislation apply only within its subject matter, purpose, and scope. For example, the cosmetic products regulation “establishes rules to be complied with by any cosmetic product made available on the market” ⁶ whereas the novel food regulation “lays down rules for the placing of novel foods on the market within the Union” ⁷. All other legislative provisions have corresponding definitions of their scope. A specific piece of legislation can cover nanomaterials only within its scope. Therefore, any regulatory definition of nanomaterial can be implemented in a legally binding way only within a defined regulatory context. Although the EC has adopted a recommendation for a definition of the term nanomaterial, this term is currently not defined in a unique, regulatory binding way, but its definition and implementation depends on the specific regulatory context. Definitions of nanomaterial within specific regulatory contexts are further discussed in Sect. 3.

An overview of selected EU regulations with relevance for nanomaterials is provided in Tab. 1. For example, engineered nanomaterials are considered a novel food (if they had not been used for human consumption to a significant degree within the EU before May 15, 1997), hence, they are covered by the novel food regulation ⁷ and specific provisions for their safety assessment and authorization as food apply from 2018 onwards. Engineered nanomaterials present in food must also be indicated in the list of ingredients ⁸. Nanomaterials used in food contact materials must be explicitly authorized ⁹ and specific risk assessment of nanomaterials is required ⁷, ⁹.

The regulation on cosmetic products ⁶ requires a premarket notification of cosmetic products that contain nanomaterials. In addition to the identification of the nanomaterial, the notification has to contain the specification of the nanomaterial including size of particles, physical and chemical properties, an estimate of the quantity of nanomaterial contained in cosmetic products intended to be placed on the market per year, the toxicological profile of the nanomaterial, relevant safety data of the nanomaterial, and the reasonably foreseeable exposure conditions. The EC should also publish and regularly update a catalog of all nanomaterials used in cosmetic products. The authorization of substances for cosmetic use (restricted substances, colorants, preservatives, UV filters) does not include the nanoform. The latter must be explicitly authorized for the use in cosmetic products. Furthermore, all ingredients of a cosmetic product present in the form of nanomaterials have to be indicated in the list of ingredients by adding the word nano to the ingredient name. The labeling is not intended to indicate any hazard or risk but rather should enable consumers to make informed choices in their selection of products.

Specific provisions for nanomaterials are also required for biocidal products under EU legislation ¹⁰. The biocidal products regulation (BPR) uses the same definitions for the terms substance and mixture as REACH and states that a biocidal product can be a substance or a mixture. The BPR requires approval of active substances and furthermore authorization of biocidal products ¹⁰. The approval of an active substance does not cover its nanoform except where explicitly mentioned, and for active substances that are nanomaterials, a separate dossier with all data requirements is necessary. For the authorization of a biocidal product containing nanomaterials, a dedicated risk assessment is needed assessing the nanomaterial's risk to human health, animal health, and the environment. Products containing nanomaterials are excluded from the simplified authorization procedure. If a biocidal product contains nanomaterials this has to be indicated on its label. Furthermore, when test methods are applied to nanomaterials for the purpose to obtain the approval of an active substance or authorization for a biocidal product, an explanation must be provided of their scientific appropriateness for nanomaterials, and where applicable, of the technical adaptations/adjustments that have been made in order to respond to the specific characteristics of these materials.

The proposal for a regulation for medical devices requires special care when devices contain or consist of nanomaterial that can be released into the patient's or user's body and an indication on the label of such devices that it incorporates or consists of nanomaterial ¹¹. The authorization of a non-nanoform of a substance or ingredient does not cover the authorization of the nanoform. Rather, a separate safety assessment upon which an authorization can be based is required for nanomaterials. The proposal also specifies that medical devices incorporating or consisting of a nanomaterial belong to class III, i.e., the highest risk class, unless the nanomaterial is encapsulated or bound in such a manner that it cannot be released into the patient's or user's body when the device is used within its intended purpose.

Certain legislative provisions cover nanomaterials implicitly. As an example, it is discussed in the following how nanomaterials are covered by the regulation concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) ⁴. REACH is the most comprehensive legislative provision for chemicals (substances) in the EU and applies to chemicals in whatever size, shape, or physical state. Nanomaterials are substances at the nanoscale covered by the REACH definition of substance as laid down in its article 3(1) ⁴ and the normal REACH provisions apply.

Most information requirements in REACH are triggered by the tonnage, i.e., the quantity of a substance produced or imported per year per manufacturer or importer. Substances that are marketed in the EU in volumes ≥ 1 t y⁻¹ have to be registered, and for ≥ 10 t y⁻¹ a chemical safety assessment is required.

Since a registration dossier should address all forms of a substance in terms of safety assessment, this applies to nanomaterials as well ¹², ¹³. According to the European Chemicals Agency's (ECHA) guidance on the registration, the term form refers to a parameter relevant for substance identification, but differences in this parameter between substances do not trigger different substance identities for registration ¹⁴. For substances that exist only in (the) nanoform(s), i.e., the substance meets the requirements of the EC recommendation for the definition of nanomaterial and has a specific shape and a specific surface chemistry as additional parameters ¹⁴, the registrant must submit a registration dossier for that/those nanomaterial(s) and the information requirements that need to be met in the dossier are triggered by the annual tonnage of the nanoform(s). For substances that exist in non-nanoform (sometimes called bulk form) as well as in nanoform(s), common practice allows two possibilities for registration. The registrant can either submit a separate dossier for the nanoform(s) and the information requirements will then be triggered by the tonnage of the nanoform alone. Alternatively, the registrant can explicitly cover the nanoform in the dossier of the non-nanoform and then the information requirements are triggered by the total tonnage of the substance. The tonnage-dependent information requirements are laid down in the REACH annexes VII – X which describe in detail and based on the tonnage of the substance which endpoints must be tested and how ⁴. The REACH annexes are under review in 2016. Among modifications planned is the introduction of specific requirements for nanomaterials and when (if) adopted nanomaterials will be addressed explicitly in REACH in the near future.

2 Expert Groups and International Organizations

Given that nanomaterials can have properties which are very different from those of the non-nanoform of the same material ¹⁵ they might also pose a risk to human health and the environment which is different to that of the non-nanoform. Safety data generated on the non-nanoform therefore are not necessarily adequate for the nanoform. Moreover, tests which were developed for the safety assessment of chemicals might not be (directly) applicable to nanomaterials or even completely new tests might be required that capture the peculiarities of nanomaterials. Guidelines for safety assessment of chemicals will have to be adapted to fully capture possible hazards and risks originating from the use of nanomaterials. In light of the uncertainties regarding the safety of nanomaterials, it is necessary to develop best practices, facilitate harmonization of assessment practices and methodologies, and to increase confidence and mutual understanding among stakeholders how to best approach the risk assessment of nanomaterials.

On a global scale, the Organisation for Economic Co-operation and Development (OECD), within its framework on chemicals safety, launched a strategic program in 2006 to provide a global forum for the discussion of manufactured nanomaterials, especially their safety evaluation and risk assessment, and to promote the responsible development of these technologies. OECD's Working Party on Manufactured Nanomaterials (WPMN) thus promotes international cooperation on human health and environmental safety aspects of manufactured nanomaterials and focusses on generating appropriate methods and strategies to ensure safe use of nanotechnology ¹⁶. Through the WPMN's program for the testing of manufactured nanomaterial, OECD WPMN members, together with non-OECD economies and industry, tested a selected list of manufactured nanomaterials for endpoints relevant to physicochemical properties, environmental fate and toxicology, mammalian toxicology, and material safety. The outcomes of this testing program are currently being analyzed and a number of material-specific dossiers with results from that program were already published ¹⁷. One objective of the testing program was to learn how far OECD test guidelines are applicable to nanomaterials ¹⁸. Data obtained following these guidelines are covered by the OECD agreement of Mutual Acceptance of Data (MAD) in the assessment of chemicals ¹⁹. MAD is an essential component for international harmonization of approaches to chemical safety through regulatory recognition of these test guidelines. Hence, data on nanomaterials obtained following OECD test guidelines that are applicable to nanomaterials are covered by MAD as well.

In REACH, challenges regarding the safety of nanomaterials are dealt with by the ECHA, the EU executive agency in charge of implementing REACH. Within the agency's Guidance on Information Requirements and Chemical Safety Assessment (IR & CSA) there are appendices with recommendations for registering nanomaterials. Those appendices are frequently updated, improved and extended to take into account new findings relevant for nanomaterials in the context of REACH.

Furthermore, the ECHA nanomaterials working group (NMWG), consisting of experts from EU member states, the European Commission, ECHA, and accredited stakeholders' organizations provides informal advice on scientific and technical issues regarding the implementation of REACH and Classification, Labelling and Packaging (CLP) legislation in relation to nanomaterials. Furthermore, ECHA organized a working group assessing already registered nanomaterials (GAARN) which worked on best practices for assessing and managing the safety of nanomaterials under the REACH regulation. ECHA considers the output of these expert groups when new or updated guidelines are being developed.

In other legislative sectors such as food, feed, and cosmetics there are also scientific committees and expert groups which address sector-specific risk assessment of nanomaterials. In the implementation of legislation for the food and feed sector, for which the European Food Safety Authority (EFSA) is in charge, the EFSA scientific committee has developed guidance on the risk assessment of the application of nanoscience and nanotechnologies in the food and feed chain ²⁰. It provides practical recommendations on how to assess applications from industry to use engineered nanomaterials (ENMs) in food additives, enzymes, flavorings, food contact materials, novel foods, food supplements, feed additives, and pesticides. In addition, EFSA reevaluates certain materials specifically taking into account the fact that some of these materials may be present in the nanoform.

In addition, with its network for risk assessment of nanotechnologies in food and feed, EFSA aims to facilitate harmonization of assessment practices and methodologies, to enhance exchange of information and data between EFSA and member states and to achieve synergies in risk assessment activities ²¹.

When preparing policy and proposals related to consumer safety, health, and the environment, the European Commission relies on independent scientific committees to provide it with scientific advice and draw its attention to new and emerging problems. As of 2016, the Scientific Committee on Consumer Safety (SCCS) and the Scientific Committee on Health, Environmental and Emerging Risks (SCHEER) provide opinions on questions concerning emerging or newly identified health and environmental risks, including new technologies such as nanotechnologies (SCHEER) and opinions on health and safety risks (chemical, biological, mechanical, and other physical risks) of nonfood consumer products (e.g., cosmetic products and their ingredients, toys, textiles, clothing, personal care, and household products) and services, including also the use of nanomaterials in such products (SCCS). The SCCS has already produced scientific opinions on the safety of a number of nanoforms of substances when used as ingredients in cosmetic products ²² following its guidance for this assessment ²³. These opinions are used by the EC in decisions whether such substances are authorized, restricted, or banned as cosmetics ingredients. In the past, the Scientific Committee for Emerging and Newly Identified Health Risks (SCENIHR) has provided an opinion on risk assessment of products of nanotechnologies ²⁴ and other advice related to the safety of nanomaterials.

The work of the scientific committees also feeds into the work of other EU bodies such as the EFSA, the European Medicines Agency (EMA), and the ECHA. All scientific opinions of the scientific committees are published on the internet.

3 Definition of Nanomaterial

Nanomaterials are explicitly and implicitly covered by EU legislation, and legal clarity on what is meant by the term nanomaterial is therefore necessary. In the European Union, the term nanomaterial has been defined in different documents with regulatory relevance, namely in an overarching nonbinding recommendation adopted by the EC in 2011 ²⁵ as well as in several sector-specific pieces of law. The latter either have implemented the overarching definition provided by the European Commission or use a dedicated and to some extent different definition of the term. An overview is given in ²⁶.

The recommendation by the EC on the definition of nanomaterial ²⁵ concerns natural, incidental, and manufactured particulate material, refers to constituent particles – elsewhere sometimes also called primary particles – and uses size as the most important defining parameter. The material is a nanomaterial if 50 % or more of the constituent particles (by number) have one or more external dimensions in the size range 1 – 100 nm. A material can also be considered as nanomaterial if its volume-specific surface area is larger than 60 m²cm⁻³. Fullerenes, graphene flakes, and single-wall carbon nanotubes with one or more external dimensions below 1 nm are explicitly included as nanomaterials in the definition. This definition should be used to determine whether a material should be considered as nanomaterial for legislative and policy purposes in the EU. It defines a class of materials that need to be addressed under legislation without any prejudgement of their potential hazards. The practical implementation of the EC's definition of nanomaterials relies on the possibility to verify by measurements whether a material meets that definition. The resulting requirements for particle size measurements and the capabilities of currently available measurements have been described by the Joint Research Centre (JRC) ²⁷. The analysis shows that the available methods cover the requirements to a varying degree, depending on the material properties, size range to be measured, the presence of aggregates, etc. Validated methods, reference materials, and, in general, practical guidance is still needed.

Several pieces of sector-specific legislation have already implemented the EC's recommendation or slightly different sector-specific variations thereof: its text is included as such in the regulation on biocidal products ¹⁰, in the EC's proposal for a regulation on medical devices ¹¹, and referred to in the appendixes to the ECHA guidance for implementation of REACH containing recommendations for nanomaterials ²⁸ where it is used as a working definition for the purposes of REACH.

Some regulations use a dedicated and to some extent different definition of the term. The regulation (EC) No 1223/2009 on cosmetic products ⁶, predating the recommendation, aims at ensuring a high level of protection of human health and specifies that cosmetic products should be safe under normal or reasonably foreseeable conditions of use. Nanomaterials are explicitly addressed in that regulation, which defines a nanomaterial as “an insoluble or biopersistant and intentionally manufactured material with one or more external dimensions, or an internal structure, on the scale from 1 to 100 nm”.

The purpose of the EU regulation 2015/2283 on novel foods ⁷ is to ensure the effective functioning of the internal market while providing a high level of protection of human health and consumers' interests. It explicates that novel foods should be safe and calls for clear criteria for the assessment of the safety risks arising from novel foods. Only novel foods authorized may be placed on the market in the EU. Nanomaterials are specifically addressed in that regulation and considered as novel food. For example, when test methods are applied to nanomaterials, an explanation should be provided of their scientific appropriateness for nanomaterials and, where applicable, of the technical adaptations and adjustments that have been made in order to respond to the specific characteristics of those materials. The novel food regulation includes a specific definition of engineered nanomaterial. According to that definition an engineered nanomaterial means any intentionally produced material that has one or more dimensions of the order of 100 nm or less or that is composed of discrete functional parts, either internally or at the surface, many of which have one or more dimensions of the order of 100 nm or less. It includes also structures, agglomerates, or aggregates, which may have a size above the order of 100 nm but retain properties that are characteristic of the nanoscale. There are no clear size boundaries referring to nanomaterials and it covers only engineered nanomaterials, i.e., nanomaterials that are manufactured to perform a specific function in the food. The definition also considers properties that are characteristic of the nanoscale, i.e., those related to the large specific surface area of the materials and/or specific physicochemical properties that are different from those of the non-nanoform of the same material. The nanomaterial definition as laid down in the novel food regulation is also valid for the EU Regulation on the Provision of Food Information to Consumers ⁸ with specific consequences for nanomaterials. For example, all ingredients that are present in food as nanomaterials must be indicated as such on the product label. An overview of all relevant regulatory aspects of nanomaterials in food and feed is found in ²⁹.

The EC intends to amend the sector-specific regulatory definitions of nanomaterials valid for cosmetic products and foodstuff by harmonizing it with the EC's recommendation ¹, while still taking into account sector-specific needs.

The EC's recommendation on a definition of nanomaterial ²⁵ is under review in 2016, with the goal to identify issues encountered since its adoption and a possible revision of the definition as a result of the review. JRC supports the EC in the review regarding scientific/technical matters and prepared three reports covering related scientific and technical issues. These reports contain a compilation of information concerning the experience with the definition ²⁶, the JRC's assessment of collected information concerning the experience with the definition ³⁰, and a scientific-technical evaluation of options to clarify the definition and to facilitate its implementation ³¹. Core findings from the reports address the scope of the definition with regard to the origin of the nanomaterials, size as the sole defining property of a nanoparticle as well as the range of 1 to 100 nm as definition of the nanoscale. It addresses also several issues which deserve clarification ³¹. It is, however, concluded that many of the issues identified in the reports can be clarified by developing new or improved guidance.

4 Information on Nanomaterials in Consumer Products

There are several ways to provide information on nanomaterials in consumer products to consumers. One possibility is to provide certain information on the packaging of the product, i.e., labeling ³². Another possibility is to accumulate structured information on nanomaterials in an IT-based system which is accessible by consumers. Such structured information can be called a register, inventory, or observatory, depending on the focus and details of the information it contains. Authorities and other organizations may also analyze and evaluate collected information and publish it as reports, (annotated) inventory lists, or dossiers. Some EU member states, namely France, Denmark, Belgium, and Sweden, already have their own registration schemes for nanomaterials and/or products containing nanomaterials, or they plan to install such schemes in the near future.

The biocides regulation ¹⁰, the cosmetic products regulation ⁶, the regulation on the provision of food information ⁸, and the proposal for the medical devices regulation ¹¹ provide information on the presence of nanomaterials in products within their scope by product labeling, see Sect. 1. In the cosmetics sector, publication of a catalog of all nanomaterials used in cosmetic products is also foreseen.

Public information on nanomaterials and their presence in products can also be found in a number of databases and web resources. The status of such resources in terms of completeness, coverage of specific sectors, quality, and up-to-date information varies and can also change quickly. A (not necessarily complete) catalog of such resources can be found in the JRC Web Platform on Nanomaterials ³³. It provides an overview of the information publicly available on nanomaterials within the EU and beyond, with sections on the regulatory framework, general information on nanomaterials, nanomaterials, products and registries, policy, research, ethics, and society. The EC currently prefers not to introduce a compulsory registry for nanomaterials and their properties and use but intends to establish a so-called nanoobservatory.

5 Research Needs and Project Examples

There are uncertainties on the knowledge relevant for adequate regulatory coverage of nanomaterials. This regards the type and amount of information required on nanomaterials as well as the relevance of study results for regulatory purposes. Despite the large number of research projects on nanomaterials in recent years (a compendium of such projects funded by the EC can be found in ³⁴), research specifically addressing regulatory needs is scarce. The reason for this may be partially due to an uncertainty about which questions actually should be addressed for regulatory purposes.

6 Conclusions

Nanomaterials are a specific group of chemicals and covered by the EU regulatory framework. Certain regulations have specific provisions for nanomaterials with consequences for the provision of information and the assessment of the safety of these materials. Regulatory definitions of the term nanomaterial are provided either by an overarching definition recommended by the EC or by sector-specific definitions in the regulatory texts. For transparency reasons, the presence of nanomaterials in certain products including cosmetics and food must be indicated on the label in the list of ingredients. Further information to consumers is provided in web resources and databases. In order to reduce uncertainties regarding the safety of nanomaterials, best practices, guidelines and assessment practices, and methods for the safety testing of nanomaterials are being developed. Still, more research with specific relevance for regulatory questions is needed, in particular regarding the implementation of the definition of nanomaterials, the enforcement of product labeling for the presence of nanomaterials, the development of methods for the safety testing of nanomaterials, and a better availability of quality data on nanomaterials for regulatory purposes.