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

## TL;DR

This study explores how engineered stone dust becomes toxic in the lungs by revealing how it reacts in simulated lung environments, leading to membrane damage and oxidative stress.

## Contribution

The study identifies the combined role of silanols and oxidative stress in engineered stone dust toxicity, offering new molecular insights.

## Key findings

- Incubation in artificial lysosomal fluid increased membranolytic activity and exposed reactive silanol groups.
- Transition metal ion release in acidic conditions catalyzed radical formation, contributing to toxicity.
- Lung lining fluid simulant showed minimal membranolytic activity and low radical generation compared to lysosomal fluid.

## Abstract

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 ∼ 4.5) and lung lining
fluid simulant (Gamble’s solution, GS, pH ∼ 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.