The Combined Role of Silanols and Oxidative Stress in Determining Engineered Stone Dust Toxicity

Engineered stone (ES) silicosis is emerging as a global occupational health crisis, caused by exposure to respirable particles generated during the processing of ES composite materials. ES composites comprise crystalline silica (predominantly quartz), inorganic aggregates, polymeric resins, and pigments. The severity of lung disease in workers contrasts with the modest effects observed in short-term in vitro studies, exposing a critical gap in our mechanistic understanding of ES dust toxicity. In this work, we examined the surface chemistry and reactivity of ES dust obtained from a slab with high crystalline silica content, before and after incubation (up to two months) in simulated lung fluids: artificial lysosomal fluid (ALF, pH similar to 4.5) and lung lining fluid simulant (Gamble's solution, GS, pH similar to 7.4). Damage to model membranes (red blood cell, RBC), an initiating event in ES-induced toxicity, was quantified by membranolytic assay. Pristine ES dust was negligibly membranolytic. Incubation in ALF markedly increased ES membranolytic activity, correlating with partial degradation of the resin. A complete removal of the resin produced a dust with further enhanced activity, associated with the exposure of nearly free silanol (NFS) groups, a recognized molecular trigger of quartz toxicity. NFS were detected by infrared spectroscopy after H/D isotopic exchange. ALF incubation also led to substantial release of transition metal ions, which catalyzed the formation of hydroxyl and carboxyl radicals, detected by EPR spectroscopy. In contrast, GS exposure resulted in minimal membranolytic activity and low radical generation. Our findings suggest that prolonged residence of ES dust in lung cellular environments, particularly lysosomes, promotes resin degradation, exposes reactive silanols, and releases transition metal ions, thereby imparting both membranolytic and oxidative potential. This work provides new molecular insight into ES dust toxicity, emphasizes the urgency of safer occupational practices, and paves the way to safe-by-design strategies for future composite materials.