Sublethal pulmonary toxicity screening of silica nanoparticles in rats after direct intratracheal instillation.

The present aimed to characterize the toxicity of silica nanoparticles in Sprague Dawley rats and determine the dose levels for a repeated-dose toxicity study. Silica nanoparticles (SiO₂, 20 nm and 50 nm) were administered as a single intratracheal instillation of standardized SiO₂ 20 nm (low dose, 200 µg/mL; high dose, 400 µg/mL) and 50 nm (low dose, 200 µg/mL; high dose, 400 µg/mL). Each group consisted of five male rats. We documented the mortality rate, clinical signs, body weight, bronchoalveolar lavage fluid analysis, hematological values, serum chemistry values, organ weight, gross findings at necropsy, and histopathological assessments. Rats treated with 200 µg/mL and 400 µg/mL SiO₂ 50 nm exhibited a decreased mean corpuscular volume, while those treated with 400 µg/mL of SiO₂ 50 nm showed increases in absolute monocyte and absolute lymphocyte count as well as prothrombin time. In addition, rats treated with 400 µg/mL SiO₂ 20 nm and 50 nm presented reduced creatinine, alanine aminotransferase, and sodium levels. Therefore, a single intratracheal instillation of SiO₂ 20 nm and 50 nm elicited no toxicity up to a dose of 400 µg/mL, and the approximate lethal dose of this test substance exceeded 400 µg/mL in male Sprague Dawley rats under the present experimental conditions.