Keywords: nanoparticles, health effects, dose response, avalanche scenario, colligative effects, particle overload, alveolar macrophage, cell surface, particle surface, inhalation toxicology, human health, risk assessment, polystyrene, nanoparticle numbers, surface area, obstruction, lungs, nanotechnology, nanotoxicity
Insights into the health effects of nanoparticles: why numbers matter
We find that nanoparticle numbers do matter when estimating risk. Previous reports by others establish that particle surface area is related to changes in biological function of exposed cells. Many of these reports describe the impact of particle surface area on the alveolar macrophage (the primary cell involved in the clearance of particles deposited in the gas exchange region of the lung). For these cells, the change in function is indicated by a decrease in the macrophage's ability to clear particles. However, when macrophages are exposed to nanoparticles, this change in function may not be strictly due to surface chemistry: Instead, the cumulative projected area of the particles may reflect the degree to which the inner or outer surface of the macrophage is shielded from other objects or molecules. We apply this alternative interpretation to in vitro measurements of macrophage uptake of 26 nm diameter fluorescent beads and to in vivo data presented for TiO2 nanoparticles. We show that the observed decrease in macrophage-mediated alveolar clearance of polystyrene test particles can be directly related to the potential for TiO2 particles to mask the surface of the macrophage. We further confirm this observation by a series of confocal laser scanning microscopy in vitro studies. Both nanoparticle number and surface area are relevant; they help predict the potential for obstruction of molecular mechanisms.