AUTHOR=Wiemann Martin , Vennemann Antje , Schuster Tobias B. , Nolde Jürgen , Krueger Nils TITLE=Surface Treatment With Hydrophobic Coating Reagents (Organosilanes) Strongly Reduces the Bioactivity of Synthetic Amorphous Silica in vitro JOURNAL=Frontiers in Public Health VOLUME=Volume 10 - 2022 YEAR=2022 URL=https://www.frontiersin.org/journals/public-health/articles/10.3389/fpubh.2022.902799 DOI=10.3389/fpubh.2022.902799 ISSN=2296-2565 ABSTRACT=Synthetic amorphous silica (SAS) are industrially relevant materials whose bioactivity in vitro is strongly diminished e.g. by protein binding to the particle surface. Here we investigated the in vitro bioactivity of fourteen SAS (pyrogenic, precipitated or colloidal), nine of which were surface treated with organosilanes, using alveolar macrophages as a highly sensitive test system. Dispersion of the hydrophobic SAS required pre-wetting with ethanol and extensive ultrasonic treatment in the presence of 0.05 % BSA (Protocol 1). Hydrophilic SAS were suspended by moderate ultrasonic treatment (Protocol 2) and also by Protocol 1. Suspensions were administered to NR8383 alveolar macrophages under serum-free conditions for 16 h and the release of LDH, GLU, H2O2 und TNFα was measured in cell culture supernatants. While seven surface treated hydrophobic SAS exhibited virtually no bioactivity, two materials (AEROSIL® R 504, AEROSIL® R 816) had minimal effects on NR8383 cells. In contrast, non-treated SAS elicited considerable increases of LDH, GLU, and TNFα, while the release of H2O2 was low except for CAB-O-SIL® S17D Fumed Silica. Dispersing hydrophilic SAS with Protocol 1 gradually reduced the bioactivity but did not abolish it. Results show that hydrophobic coating reagents, which bind covalently to the SAS surface, abrogate the bioactivity of SAS even under serum-free in vitro conditions. Results may have implications for the hazard assessment of hydrophobic surface treated SAS in the lung.