A new Recommendation on the definition of nanomaterial (2022/C 229/01) was adopted by the European Commission in 2022 to serve different policy, legislative, and research purposes when addressing nanomaterials or issues concerning products of nanotechnologies. It is broadly applicable across a wide variety of fields. The present guidance supports the implementation of the nanomaterial definition adopted in the new Recommendation.
This guidance gives an overview of the key terms and concepts, provides a decision tree to identify nanomaterials, and addresses the identification of nanomaterials through measurements for the new Recommendation on the definition of nanomaterials. Furthermore, an Annex listing documentary standards relevant to a harmonised and coherent regulatory implementation of the definition of a nanomaterial at the European Union and national level was added.
Basic classification: exclusion based on material properties
Non-particulate materials, single molecules, materials consisting of non-solid particles, and nanostructured materials that are not agglomerates or aggregates, are not nanomaterials.
Selection of the analysis route: information on the material and method matching
The choice of an appropriate route largely depends on the state of the material and the availability of specific physicochemical data which may be crucial for the accurate analysis by the selected screening or confirmatory measurement method. For many dispersion methods, it is also important to know whether the particles have a nearly equiaxial or near-spherical shape since highly non-symmetrical particles can yield significantly biased equivalent sphere diameters. If required, the general shape of most particles can be determined qualitatively using electron microscopy analysis.
Screening
The flow chart distinguishes screening techniques/methods that can characterize material in a powder state or in dispersion. Depending on several criteria, such as the material’s dispersibility and physicochemical properties, the availability of suitable techniques, and regulatory requirements, the most suitable path is selected. For instance, a wrong dispersion procedure or inappropriate conditions may degrade or dissolve the particles. Great care should be taken when dispersing the material, and in general, the appropriateness of the dispersion route should be evaluated.
When selecting a screening method, it is important that the material properties and the applied method’s measurement capabilities match. The availability of information on material synthesis/production and provenance can be of great help when selecting a suitable screening method. It has also to be kept in mind that most screening methods require additional material information to allow a reliable calculation of the equivalent median particle size, x50. In this case, the material needs to be further analysed using a suitable confirmatory method.
Identification of nanomaterials through measurements
The identification of nanomaterials through measurements is based on measured data on the external dimensions of the constituent particles. Furthermore, the volume-specific surface area (VSSA) can be used to classify a material as a conventional material. The VSSA is equal to the sum of the surface areas of all particles divided by the sum of the volumes of all particles. The quantification step includes the actual generation of the experimental data by an applied method, as well as all related aspects that are necessary to guarantee the correct and accurate performance of the method. The following sections explain important aspects of sample preparation and give an overview of mainstream methods considered applicable for assessing the particle size distribution and the VSSA of solid particles.
From the methods listed in OECD TG 125, laboratories may select a screening or confirmatory method that is appropriate for a specific material taking into account the properties of the material and the measurement performance characteristics of the method. Although electron microscopy will in most cases be the preferred method for providing regulatory relevant information within the EU, the following questions may help to select a suitable method for a certain material.
This often means that for a given measurement, for instance, particles from 5 nm to 50 nm or from 50 nm to 500 nm can be measured, but not from 5 nm to 500 nm.
Counting methods such as electron microscopy or particle tracking analysis investigate particles individually and construct the Particle size distribution (PSD) from these particle-by-particle-based measurement results. Whereas the obtained PSDs are intrinsically number-based, the minimum number of particles that has to be measured in order to yield a PSD that is representative of the material can be an issue. For image analysis-based methods, ISO 13322-1 provides a specific procedure to estimate the minimum number of particles to be measured for a given level of accuracy. Other method-specific guidelines for determining the optimal number of particles are available in the OECD TG 125.
They harmonise the application of analytical instruments/techniques and methods and thus lead to better reliability and comparability of measurement results. These operations typically include aspects such as sampling, sample preparation, calibration, data acquisition, and analysis. For the analysis of collected data, documentary standards may advise using a counting rule that is not compatible with the EC NM definition, so this should be carefully checked.