Determining nanoform similarity via assessment of surface reactivity by abiotic and in vitro assays

Didem Ag Seleci, Georgia Tsiliki, Kai Werle, Derek A. Elam, Omena Okpowe, Karsten Seidel, Xiangyu Bi, Paul Westerhoff, Emma Innes, Matthew Boyles, Mark Miller, Anna Giusti, Vicki Stone, Fiona Murphy, Andrea Haase, Vicki Stone, Wendel Wohlleben

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Abstract

Grouping of substances is a method used to streamline hazard and risk assessment. Assessment of similarity provides the scientific evidence needed for formation of groups. This work reports on justification of grouping of nanoforms (NFs) via similarity of their surface reactivity. Four reactivity assays were used for concentration dependent detection of reactive oxygen species (ROS) generated by NFs: abiotic assays FRAS, EPR and DCFH2-DA, as well as the in vitro assay of NRF2/ARE responsive luciferase reporter activation in the HEK293 cell line. Representative materials (CuO, Mn 2O 3, BaSO 4, CeO 2 and ZnO) and three case studies of each several NFs of iron oxides, Diketopyrrolopyrroles (DPP)-based organic pigments and silicas were assessed. A novel similarity assessment algorithm was applied to quantify similarities between pairs of NFs, in a four-step workflow on concentration-response curves, individual concentration and response ranges, and finally the representative materials. We found this algorithm to be applicable to all abiotic and in vitro assays that were tested. Justification of grouping must include the increased potency of smaller particles via the scaling of effects with specific surface, and hence quantitative similarity analysis was performed on concentration-response in mass-metrics. CuO and BaSO 4 were the most and least reactive representative materials respectively, and all assays found BaSO 4/CuO not similar, as confirmed by their different NOAECs of in vivo studies. However, similarity outcomes from different reactivity assays were not always in agreement, highlighting the need to generate data by one assay for the representative materials and the candidate group of NFs. Despite low similarity scores in vitro some pairs of case study NFs can be accepted as sufficiently similar because the in vivo NOAECs are similar, highlighting the conservative assessment by the abiotic assays.

Original languageEnglish
Article number100390
JournalNanoImpact
Volume26
Early online date7 Feb 2022
DOIs
Publication statusPublished - Apr 2022

Keywords

  • Concentration-response
  • Grouping
  • Nanoforms
  • Similarity
  • Surface reactivity

ASJC Scopus subject areas

  • Materials Science (miscellaneous)
  • Safety, Risk, Reliability and Quality
  • Safety Research
  • Public Health, Environmental and Occupational Health

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