Minute Translocation of Inhaled Ultrafine Insoluble Iridium Particles from Lung Epithelium to Extrapulmonary Tissues

Abstract

Recently it was speculated that ultrafine particles (UPs) may translocate from deposition sites in the lungs to the systemic circulation. This translocation could lead to accumulation and potentially adverse reactions in critical organs such as liver, heart and even brain, and is consistent with the hypothesis that ultrafine insoluble particles may play a role in the onset of cardiovascular diseases, as growing evidence from epidemiological studies suggests. Aerosols of ultrafine 192Ir radiolabelled iridium particles (15 and 80 nm count median diameter) were produced with a spark generator and inhaled by young adult, healthy, male WKY rats, ventilated for 1 h via an endotracheal tube. After exposure, excreta were collected separately and quantitatively. At time points ranging from 6 h to 7 days, rats were killed, and a complete balance of 192Ir activity retained in various organs, tissues and the remaining carcass, and cleared by excretion, was determined by gamma spectroscopy. In additional studies the biokinetics of UPs and soluble 192Ir were studied after administration by either gavage, lung instillation or intravenous injection. Both batches of ultrafine iridium particles proved to be almost insoluble. Particles retained in the peripheral lungs were predominantly cleared via the mucociliary escalator into the gastrointestinal tract and faeces during the first week after particle inhalation. Additionally, minute particle translocation of <1% of the deposited particles into secondary organs such as liver, spleen, heart and brain was estimated after systemic uptake in the lungs. This study indicates that tiny fractions, at most, of UPs have access from the peripheral lungs to systemic circulation and extrapulmonary organs. Therefore, it is not consistent with the hypothesis that ultrafine insoluble particles may play a role in the onset of cardiovascular diseases. However, chemical particle composition and long-term biokinetics may be another important determinant.