Respiratory exposure to nanomaterials with high aspect ratios may potentially induce greater toxicity than a low aspect ratio nanoparticle of similar composition. Production and use of silver nanomaterials is one of the fastest growing sectors in nanotechnology. The goal of this study was to characterize lung toxicity of silver nanowires (AgNWs) of varying lengths in vivo. Two AgNWs samples (nanoComposix, Inc.) approximately 50 nm in diameter, 4 microm and 20 microm long, were diluted in dispersion medium (DM; phosphate-buffered saline+0.6 mg/ml rat serum albumin+ 0.01 mg/ml dipalmitoyl phosphocholine). Male Sprague-Dawley rats were intratracheally-instilled with 10, 50, 125, or 500 microg of AgNWs, 500 microg alpha-quartz (positive control), or DM (vehicle control) on day 0. Rats were sacrificed 1, 3, and 10 days post-exposure, the right lungs were lavaged, and the left lungs were preserved for analysis of oxidative stress. Both wire samples caused a dose-dependent increase in lung injury (lactate dehydrogenase activity and albumin content in lavage fluid) and inflammation (increased lung neutrophils and phagocyte oxidant production). Both short and long wires at the 10 microg dose had no effect on lung toxicity. At the 50 and 125 microg doses, the long wires were slightly more potent than the short wires when comparing increases in lung injury. There was no difference in injury parameters comparing wires at the highest dose. However, at day 10 there was greater toxicity and less resolution of injury and inflammation in the rats exposed to 125 or 500 microg of short AgNWs compared with the equivalent doses of long AgNWs. In this study, although the longer wire caused slightly more lung injury immediately following exposure, the shorter wire induced greater toxicity over the time course; this finding may be due to greater wire number and surface area in the short wire sample when comparing samples on an equivalent mass basis.
The Toxicologist. Society of Toxicology 51st Annual Meeting and ToxExpo, March 11-15, 2012, San Francisco, California