Pulmonary effects of silver nanoparticle size, coating, and dose over time upon intratracheal instillation

Silver nanoparticles (Ag NPs) can be found in myriad consumer products, medical equipment/supplies, and public spaces. However, questions remain regarding the risks associated with Ag NP exposure. As part of a consortium-based effort to better understand these nanomaterials, this study examined how Ag NPs with varying sizes and coatings affect pulmonary responses at different time-points. Four types of Ag NPs were tested: 20 nm (C20) and 110 nm (C110) citrate-stabilized NPs, and 20 nm (P20) and 110 nm (P110) PVP-stabilized NPs. Male, Sprague Dawley rats were intratracheally instilled with Ag NPs (0, 0.1, 0.5, or 1.0 mg/kg bodyweight [BW]), and bronchoalveolar lavage fluid (BALF) and lung tissues were obtained at 1, 7, and 21 days post-exposure for analysis of BAL cells and histopathology. All Ag NP types produced significantly elevated polymorphonuclear cells (PMNs) in BALF on Days 1, 7, and/or 21 at the 0.5 and/or 1.0 mg/kg BW dose(s). Histology of animals exposed to 1.0 mg/kg BW Ag NPs showed patchy, focal, centriacinar inflammation for all time-points; though neutrophils, macrophages, and/or monocytes were also found in the airway submucosa and perivascular regions at Days 1 and 7. Confocal microscopy of ethidium homodimer-stained lungs at Day 1 showed dead/dying cells at branch points along the main airway. By Day 21, only animals exposed to the high dose of C110 or P110 exhibited significant BALF neutrophilia and marked cellular debris in alveolar airspaces. Findings suggest that 110 nm Ag NPs may produce lasting effects past Day 21 post instillation.