TY - JOUR
T1 - Reproducibility of methods required to identify and characterize nanoforms of substances
AU - Cross, Richard K
AU - Bossa, Nathan
AU - Stolpe, Björn
AU - Loosli, Frédéric
AU - Sahlgren, Nicklas Mønster
AU - Clausen, Per Axel
AU - Delpivo, Camilla
AU - Persson, Michael
AU - Valsesia, Andrea
AU - Ponti, Jessica
AU - Mehn, Dora
AU - Seleci, Didem Ag
AU - Müller, Philipp
AU - von der Kammer, Frank
AU - Rauscher, Hubert
AU - Spurgeon, Dave
AU - Svendsen, Claus
AU - Wohlleben, Wendel
N1 - Publisher Copyright:
© 2022
PY - 2022/7/1
Y1 - 2022/7/1
N2 - Nanoforms (NFs) 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 NFs efficient, a number of grouping frameworks have been proposed, which often require assessment of similarity on individual physicochemical properties as part of the group justification. Similarity assessment requires an 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: inductively coupled plasma mass spectrometry (ICP-MS), Thermogravimetric analysis (TGA), Electrophoretic light scattering (ELS), Brunauer-Emmett-Teller (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 methods such as ICP-MS quantification of metal impurities, BET measurements of specific surface area, TEM and SEM for size and shape and ELS 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 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. The expected achievable accuracy of ICP-MS may be estimated for untested analytes using established relationships between concentration and reproducibility, but this is not yet the case for TGA measurements of loss on ignition or water content. The results here demonstrate an approach to estimate the achievable accuracy of a method that should be employed when interpreting differences between NFs on individual physicochemical properties.
AB - Nanoforms (NFs) 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 NFs efficient, a number of grouping frameworks have been proposed, which often require assessment of similarity on individual physicochemical properties as part of the group justification. Similarity assessment requires an 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: inductively coupled plasma mass spectrometry (ICP-MS), Thermogravimetric analysis (TGA), Electrophoretic light scattering (ELS), Brunauer-Emmett-Teller (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 methods such as ICP-MS quantification of metal impurities, BET measurements of specific surface area, TEM and SEM for size and shape and ELS 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 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. The expected achievable accuracy of ICP-MS may be estimated for untested analytes using established relationships between concentration and reproducibility, but this is not yet the case for TGA measurements of loss on ignition or water content. The results here demonstrate an approach to estimate the achievable accuracy of a method that should be employed when interpreting differences between NFs on individual physicochemical properties.
KW - Metals
KW - Microscopy, Electron, Scanning
KW - Microscopy, Electron, Transmission
KW - Reproducibility of Results
KW - Water
KW - Nanoform
KW - Similarity
KW - Reproducibility
KW - Grouping
UR - http://www.scopus.com/inward/record.url?scp=85137135597&partnerID=8YFLogxK
U2 - 10.1016/j.impact.2022.100410
DO - 10.1016/j.impact.2022.100410
M3 - Article
C2 - 35787478
SN - 2452-0748
VL - 27
JO - NanoImpact
JF - NanoImpact
M1 - 100410
ER -