Alignment of in vitro and in vivo pulmonary inflammation models using crystalline quartz silica

Abstract Background Systematic in vitro–in vivo comparisons are increasingly used to assess the relevance and predictivity of in vitro lung models for inhalation toxicology and regulatory risk assessment. Here, we compared inflammatory endpoints across established in vitro and in vivo pulmonary models following exposure to crystalline quartz silica particles (DQ12). To better align exposure timelines, in vitro responses assessed at 24 h were extended to 7 days, matching the post-exposure period recommended in OECD inhalation testing guidelines for animal testing. To test its potential and limitations, we utilized a harmonized in vitro co-culture model consisting of the human bronchial cell line Calu-3 and human monocyte-derived macrophages, which were exposed to DQ12 particles. Results No increased cytotoxicity or impairment of barrier integrity, as assessed by transepithelial electrical resistance (TEER) and tight junction protein 1 (TJP1) gene expression, was observed 7 days after exposure in vitro, in contrast to clear tissue damage detected in vivo. However, we observed increased release of interleukin (IL)-6 and IL-8, measured at both protein and gene levels. Gene expressions of IL-1β, IL-6, and IL-8 showed positive correlations between the in vitro and in vivo models. Conclusions By extending exposure duration and aligning time points, this study identified inflammatory biomarkers that correlate between an in vitro lung model and in vivo data. These findings demonstrate the value of refined in vitro models for assessing particle-induced lung inflammation and support their relevance for hazard assessment.