82 From silica to engineered stone particles: unveiling properties and mechanisms of surface-mediated toxicity

Abstract Engineered stone (ES) silicosis is an emerging global occupational health concern caused by inhalation of respirable particles generated during ES processing (Ramkissoon et al. 2025). ES composites are primarily composed of crystalline silica, fillers, pigments, and polymeric resins. This study investigates the molecular determinants of ES dust toxicity, focusing on nearly free silanols (NFS), a key trigger of crystalline silica pathogenicity (Pavan et al. 2020; 2024), and oxidative stress potentially mediated by metal species. ES dusts were obtained from controlled cutting of slabs and characterized for bulk and surface features using a suite of physico-chemical techniques. Surface functionalities were assessed by IR spectroscopy, and reactive oxygen species (ROS) by EPR spectroscopy, before and after incubation in simulated lung fluids. Membrane damage, an initiating event in silica-induced toxicity, was quantified by red blood cell lysis assay. As-cut ES dusts showed minimal membranolytic activity due to masking of surface silanols by the resin. Incubation in artificial lysosomal fluid promoted resin degradation, exposing NFS and releasing transition metal ions. These changes markedly increased both membrane damage and ROS generation. Overall, these results highlight NFS exposure and metal-driven oxidative stress as combined mechanisms in silica-based ES dust toxicity. By extending this framework to low-silica ES dusts, further insights could be gained into the interplay between material composition, surface chemistry, and biological responses.