Silver nanoparticle uptake in the human lung assessed through in-vitro and in-silico methods

Silver nanoparticles (AgNP) are commonly used in medical, cosmetics, clothing, and industrial applications for their antibacterial and catalytic properties. As AgNP become more prevalent, the doses to which humans are exposed may increase and pose health risks, particularly through incidental inhalation. This exposure was evaluated through in-vitro methods simulating lung fluids and lung epithelium, and through computational fluid dynamics (CFD) methods of AgNP transport. A high-dose scenario simulated a short-term inhalation of 10 μg AgNP/m³, based on an exposure limit recommended by the National Institute of Occupational Safety and Health for the case of a health-care worker who handles AgNP-infused wound dressings, and regularly wears AgNP-imbedded clothing. Bioaccessibility tests were followed by a Parallel Artificial Membrane Permeability Assay (PAMPA) and supported by CFD models of the lung alveoli, membrane, pores, and blood capillaries. Results indicate that such exposure produces an average and maximum AgNP flux of approximately 4.7 × 10^-21 and 6.5 × 10^-19 mol m^-2·s^-1 through lung tissue, respectively, yielding a blood-silver accumulation of 0.46-64 mg per year, which may exceed the lowest adverse effect level of 25 mg for an adult male. Results from in-silico simulations were consistent with values estimated in vitro (within an order of magnitude), which suggest that CFD models may be used effectively to predict silver exposure from inhaled AgNP. Although the average short-term exposure concentrations are 3 orders of magnitude smaller than the reported threshold for mammalian cytotoxicity effects (observed at 5000 ppb), cumulative effects resulting from constant exposure to AgNP may pose risks to human health in the long-term, with predicted bioaccumulation reaching potential toxic effects after only five months of exposure, based on maximum flux.