EXPERIMENTAL AND MATHEMATICAL MODELING OF THE IRON OXIDE NANOPARTICLE PULMONARY RETENTION AT LONG-TERM LOW-LEVEL INHALATION EXPOSURE

Abstract

Airborne Fe2O3 nanoparticles (NPs) with the mean diameter of 14±4 nm produced at spark ablation from 99.99% pure iron rods were fed into a «nose-only» exposure tower for rats exposed for 4 h a day, 5 days a week during 3, 6 or 10 months at a mean concentration of 1.14±0.01 mg/m3. Nanoparticles filtered out of the air exhausted from the exposure tower proved insoluble in de-ionized water but gradually dissolved in the cell free fluid supernatant produced by broncho-alveolar lavage and in the sterile bovine blood serum. The Fe2O3 content in lungs was measured by the Electron Paramagnetic Resonance (EPR) spectroscopy. NP retention in lungs and in brain was visualized with the Transmission Electron Microscopy (TEM). It was found a relatively low but significant pulmonary accumulation of Fe2O3, gradually increasing with time but tending to attain an equilibrium level. Besides, TEM-images showed nanoparticles retention within alveolocytes and the myelin sheaths of brain fibers associated with their ultrastructural damage. A multi compartment system model was developed and identified which describes toxicokinetics of inhaled nanoparticles after their deposition in the lower airways as a process controlled by their (a) high ability to penetrate through the alveolar membrane; (b) active endocytosis; (c) in vivo dissolution. However, in this particular study, dissolution-depending mechanisms proved to be dominant due to the rather high solubility of the finest Fe2O3-NPs in biological milieux.