Pulmonary inflammatory and fibrogenic responses in rats following intratracheal instillation of dusts from natural and engineered stones.

Engineered stone (ES) fabrication workers face risks from exposure to respirable crystalline silica (RCS), leading to accelerated silicosis. Toxicological data to elucidate pulmonary effects attributed to ES dusts, particularly those with varying compositions, are lacking. This study aimed to determine pulmonary effects following intratracheal instillation (IT) of ES dust in rats. Male Sprague-Dawley rats received a single 10 mg IT dose of dust from one of three ES types containing varying amounts of crystalline silica (CS) (ES A [high CS], ES B [mid CS], ES C [low CS]), or granite, MIN-U-SIL 5 (MS 5, positive control), or saline. Pulmonary inflammation and fibrosis were assessed via bronchoalveolar lavage fluid (BALF) analysis and lung histology at 1-, 21-, and 84-days post-exposure. Early BALF inflammation as evidenced by increased levels of neutrophils and lymphocytes, and cytotoxicity by elevated LDH activity was found in all exposure groups. Neutrophils primarily correlated with higher CS content (MS 5, ES A, ES B). Persistent inflammation comparable with pure silica was noted by increased levels of neutrophils and macrophages and cytotoxicity by elevated LDH activity at 21- and 84-days post-exposure was most pronounced in MS 5 and high-CS ES A groups. By 84-day post-exposure, granulomatous inflammation in lung, BALF and lymph node, was associated with alveolar lipoproteinosis, type II epithelial changes, lymph node and alveolar fibrosis. Toxicity appeared to be driven by complex interactions between silica and trace metal content of dust. These findings warrant further research to assess combined effects of particle characteristics and chemical co-exposures.