Pulmonary Toxicity of Silica Linked to Its Micro- or Nanometric Particle Size and Crystal Structure: A Review

Silicon dioxide (SiO(2)) is a mineral compound present in the Earth’s crust in two mineral forms: crystalline and amorphous. Based on epidemiological and/or biological evidence, the pulmonary effects of crystalline silica are considered well understood, with the development of silicosis, emphysema, chronic bronchitis, or chronic obstructive pulmonary disease. The structure and capacity to trigger oxidative stress are recognized as relevant determinants in crystalline silica’s toxicity. In contrast, natural amorphous silica was long considered nontoxic, and was often used as a negative control in experimental studies. However, as manufactured amorphous silica nanoparticles (or nanosilica or SiNP) are becoming widely used in industrial applications, these paradigms must now be reconsidered at the nanoscale (<100 nm). Indeed, recent experimental studies appear to point towards significant toxicity of manufactured amorphous silica nanoparticles similar to that of micrometric crystalline silica. In this article, we present an extensive review of the nontumoral pulmonary effects of silica based on in vitro and in vivo experimental studies. The findings of this review are presented both for micro- and nanoscale particles, but also based on the crystalline structure of the silica particles.