Acute Pulmonary Toxicity and Microglial Activation following Inhalation of Aerosolized Engineered Nanomaterials in Rodents

AbstractEngineered nanomaterials (ENMs) are used in diverse consumer products including, but not limited to antibacterial agents, paints, food additives, cosmetics, rubber-curing agents, textile UV-absorbers, contrast elements for magnetic resonance imaging, heating agents for cancer thermotherapy, and carriers for drug and gene delivery. Nanomaterials possess a greater surface area to volume ratio yielding a greater reactive surface area and unique physiochemical properties, but potentially possessing greater biological activity and possible toxicity than their bulky counterparts. With more than 1800 ENM-based consumer products on the market, greater demands for nanomaterials may pose increased risk for consumer and occupational exposure, in particular for workers who manufacture, handle, and package ENMs and ENM-based products. Hence, there is a need to better understand and test the hazards of these nanomaterials and their effects on human health and the environment. The aim of this study was to assess the potential implications of silver silicate (Ag-SiO2), zinc oxide (ZnO) and reduced graphene oxide (rGO) to the respiratory tract, especially when inhaled. The focus of this study was on the upper respiratory tract composed of the nasal cavity and possible transport to the brain (via the olfactory bulb) and the lower respiratory tract formed by the bronchial tree and lung parenchyma. These two regions of the respiratory system were selected for study, based on unique patterns of particle deposition for each region and the potential implications for nanoparticles being retained in each of these regions following deposition. To address the aim of our study, an acute, single day nose-only inhalation exposure regimen to aerosols of each nanomaterial was conducted in Sprague Dawley rats. Aerosols were well-characterized before and during the study. Animals were necropsied immediately (day 0) and on days 1, 7, 21 or day 56 post-exposure to ENMs. Bronchoalveolar lavage fluid, lung tissues and the nasal cavity with the contiguous olfactory bulbs were collected for assessment. Experiments were conducted to evaluate the pulmonary toxicity via BALF analysis, histological examination, gene expresssion and immunohistochemical staining. For the nasal cavity and olfactory bulb, histological examination and studies of microglial activation were conducted