Silver nanoparticles (Ag NPs) are emerging as one of the fastest growing categories of manufactured materials in the nanotechnology industry, which may lead to an increased risk of worker exposure to this nanomaterial. The goal of these studies was to characterize pulmonary toxicity of Ag NPs using an in vivo model. Ag NPs were 20 nm in diameter with a polyvinylpovidone coating (PVP, 0.3% wt) (NanoAmor, Inc.). Specific surface area was measured to be 7.54 +/- 0.103 m2/g. Ag NPs were suspended in a dispersion medium (DM, phosphate-buffered saline + 0.6 mg/ml rat serum albumin + 0.01 mg/ml dipalmitoyl phosphocholine) and sonicated. Aggregate size was evaluated in DM using dynamic light scattering and average agglomerates were approximately 150 nm. On day 0, Sprague-Dawley rats were intratracheally-instilled with Ag NPs in DM at doses of 9.35, 37.6, 112, 224, or 449 ug, SiO2 at a dose of 449 ug (positive control), or DM alone (vehicle control). Rats were humanely sacrificed 1, 7, 14, and 28 days post-exposure, the right lung was lavaged, and lung-associated lymph nodes (LALN) were removed for analysis. Lavage fluid parameters (lactate dehydrogenase and albumin), cellular influx into the lung (macrophage, neutrophil, and lymphocytes), and LALN cell number and phenotype were evaluated to assess lung injury, inflammation, and immune response. Indices of lung injury and inflammation were significantly elevated in a dose-dependent manner at days 1 and 7, which exceeded the positive control at the highest dose. By day 14, only the rats exposed to 449 ug Ag NP dose had significantly elevated parameters similar to that of the positive control which persisted out to day 28. There was a dose-dependent increase in LALN cell number beginning at day 7 and continuing in the 3 highest doses out to day 28. There was also a dose-dependent increase in lymphocytes in the lavage fluid. Collectively, these data demonstrate the Ag NPs have the capacity to induce pulmonary injury and inflammation, as well as alter immune responses in the lung.
Biological-effects; Cell-biology; Cell-function; Cellular-reactions; Cytotoxic-effects; Epidemiology; Exposure-levels; Immune-reaction; Immunochemistry; Immunotoxins; Inhalation-studies; Laboratory-animals; Lung-cells; Lung-disorders; Lung-irritants; Microscopic-analysis; Microscopy; Molecular-biology; Molecular-structure; Nanotechnology; Physiological-effects; Pulmonary-disorders; Pulmonary-system; Pulmonary-system-disorders; Quantitative-analysis; Respiratory-hypersensitivity; Respiratory-irritants
The Toxicologist. Society of Toxicology 50th Annual Meeting and ToxExpo, March 6-10, 2011, Washington, DC