Nanoforms of a substance may be distinguished from one another through differences in their physicochemical properties. When registering nanoforms of a substance for assessment under the EU REACH framework, five basic descriptors are required for their identification: composition, surface chemistry, size, specific surface area and shape. To make the risk assessment of similar nanoforms efficient, a number of grouping frameworks have been proposed, which often require assessment of similarity on individual physicochemical properties as part of the justification of similarity between NFs. Similarity assessment requires understanding of the achievable accuracy of the available methods. It must be demonstrated that measured differences between NFs are greater than the achievable accuracy of the method, to have confidence that the measured differences are indeed real. To estimate the achievable accuracy of a method, we assess the reproducibility of six analytical techniques routinely used to measure these five basic descriptors of nanoforms. These techniques were inductively coupled plasma mass spectrometry (ICP-MS), Thermogravimetric analysis (TGA), Electrophoretic light scattering, BET specific surface area and transmission and scanning electron microscopy (TEM and SEM). Assessment was performed on representative test materials to evaluate the reproducibility of methods on single NFs of substances. The achievable accuracy was defined as the relative standard deviation of reproducibility (RSDR) for each method. Well established routine methods such as inductively coupled plasma mass spectrometry for main constituent analysis (ICP-MS), BET (Brunauer–Emmett–Teller) measurements of specific surface area, transmission and scanning electron microscopy for size and shape and Electrophoretic Light Scattering for surface potential and isoelectric point, all performed well with low RSDR, generally between 5 and 20%, with maximal fold differences usually <1.5 fold between laboratories. Applications of technologies such as thermo-gravimetric analysis (TGA) for measuring water content and putative organic impurities, additives or surface treatments (through loss on ignition), which have a lower technology readiness level, demonstrated poorer reproducibility, but still within 5 fold differences. Expected reproducibility can be calculated as a function of the proportional content of an analyte in the material. ICPMS and TGA achievable accuracies are evaluated in the context of this relationship and the implications for rules for similarity assessment on composition are discussed.

CROSS Richard;  BOSSA Nathan;  STOLPE Bjorn;  LOOSLI Frederic;  MØNSTER SAHLGREN Nicklas;  CLAUSEN Per Axel;  DELPIVO Camilla;  MICHAEL Persson;  VALSESIA Andrea;  PONTI Jessica;  MĖHN Dóra;  AG SELECI Didem;  MUELLER Philipp;  VON DER KAMMER Frank;  RAUSCHER Hubert;  SPURGEON David;  SVENDSEN Claus;  WOHLLEBEN Wendel; 

2022-07-18

ELSEVIER

JRC126869

2452-0748 (online),   

https://www.sciencedirect.com/science/article/pii/S2452074822000325?via%3Dihub,    https://publications.jrc.ec.europa.eu/repository/handle/JRC126869,   

10.1016/j.impact.2022.100410 (online),