Crystalline Silica and Silicosis

Abstract

Silicosis is a lung disease that results from inhalation of respiratory particles of some crystalline forms of the mineral silica. Silicosis can be of an acute or chronic form depending on the exposure dose rate. Acute silicosis is associated with an infiltration of inflammatory cells, alveolar proteinosis, and diffuse fibrosis. Chronic simple silicosis is associated with an inflammation and a nodular fibrosis (silicotic nodules). Either form of silicosis can continue to progress after exposure has been discontinued. There are eight different crystalline silica polymorphs that differ in their inherent toxicity and propensity to cause silicosis. Based on in vitro and in vivo studies, – tridymite, cristobalite, and quartz are polymorphs with high toxicity, while coesite and stishovite are crystalline silica polymorphs that are relatively much less toxic. The other silica polymorphs have not been studied in any detail. The mechanism by which crystalline silica causes silicosis appears to be multifactorial. Hydrogen bonding of silanol groups present on the surface of crystalline silica with constituents in cell membranes contributes to the cytotoxic effect and tissues injury produced of crystalline silica. In addition, the surface chemistry of crystalline silica can result in the production of reactive oxygen species and this is also believed to contribute to the toxic effects of this mineral. Importantly, the surface structure (crystalline vs. amorphous), composition (metals present in the silica, e.g., iron), or compounds that can be associated with crystalline silica (iron) can influence its bioactivity. In addition to a direct cytotoxic action, crystalline silica can activate cells to release proinflammatory and fibrosis-producing cytokines. This may occur through a direct activation of cell surface receptors (e.g., scavenger receptors) or from the ability of crystalline silica to evoke redox changes within inflammatory cells and epithelial cells activating intracellular signal pathways. Epidemiology studies have revealed an association between crystalline silica exposure and/or silicosis and increased lung cancer risk. While the mechanism underlying this association has not be elucidated, recent studies indicate that inflammation associated with fibrogenic exposure levels of crystalline silica may contribute to the carcinogenic response. Specifically, it has been proposed that inflammatory cell-derived oxidants cause mutations in epithelial cells that are induced to proliferate in response to growth factors also produced by inflammatory cells. The combination of chronic inflammation and cell proliferation is responsible for the association between lung cancer and crystalline silica exposure.