Risk assessment of chemical substances is always a challenging process. It can be supported by using the potential of the in silico methods such as the read-across approach. Several frameworks and... Show moreRisk assessment of chemical substances is always a challenging process. It can be supported by using the potential of the in silico methods such as the read-across approach. Several frameworks and methodologies can be found, e.g. the Read-across Assessment Framework (RAAF) developed by ECHA, which describes how the analysis is carried out using the read-across approach. However, they are focused on classical chemical substances, not nanomaterials. Thus, our goal was to evaluate publicly available read-across frameworks in the context of ENM. Especially, in view of the recent update of the REACH regulations (Annex VI), which introduced the concept of “nanoform” of the substance. We examined the possibilities as well as the challenges for nanomaterials when applying available frameworks by carrying out readacross case studies for selected nanoforms of nano-SiO2. Structural properties of five ENMs and data related to their ecotoxicity were extracted from the JRC Repository characterization dossier on nanoSiO2 amorphous materials and the corresponding NanoReg2 H2020 project deliverable. From all endpoints available, toxicity results towards the Carp leucocyte cell line were considered as the most appropriate. For the purposes of the case study, we decided to treat one of the nano-SiO2 as a target (NM200) and the four others (NM 201- 204) as source analogues. The analysis consisted of several steps: i) identification and characterization of all nanoforms; ii) development of grouping hypothesis; iii) assignment to groups; iv) data gathering; v) applicability assessment; vi) filling data gaps. After passing through all the stages we were able to estimate the toxicity of target ENM. The formulated hypothesis of the read-across approach for the assessment of ecotoxicity was as follows: SiO2 nanoforms can be separated into two distinct groups based on how the following properties influenced cytotoxicity in fish cells: i) surface area, ii) coating mass, iii) size distribution in stock and media solutions, iv) polydispersity in stock and media solutions. This leads to the follow-up hypothesis of novel SiO2 ENMs with similar physicochemical/structural parameters inducing similar toxicological activities in fish cells. Subsequently, we employed similarity analysis in the space of the mentioned properties. Based on the calculated Euclidean distances, the target nanoform (NM200), has been placed within the group of toxic source analogues (NM201 and 204). Therefore, according to the worst-case approach, one can assume that the target nanoform will be highly toxic to fish cells. The results and lessons learned from this exercise will be discussed further in the context of the work carried out in the PATROLS project. Show less
