Pulmonary toxicity following repeated intratracheal instillation of dispersed silver nanoparticles in rats.
Roberts-JR; Kenyon-A; Young-S; Schwegler-Berry-D; Hackley-VA; MacCuspie-RI; Stefaniak-AB; Kashon-ML; Chen-BT; Antonini-JM
Toxicologist 2012 Mar; 126(Suppl 1):141
Silver nanoparticles (Ag NPs) are one of the fastest growing categories of manufactured materials in the nanotechnology industry. Our previous studies showed a dose-dependent increase in lung injury and inflammation in rats after a single bolus intratracheal instillation (IT) of 20 nm Ag NPs, persisting for 1 month post-IT at the highest dose (449 microg/rat) with resolution by 3 months post-IT. The goal of this study was to characterize pulmonary toxicity of Ag NPs after repeated lower dose IT of Ag NPs. Primary Ag NPs were 20 nm in diameter with a 0.3% wt polyvinylpovidone coating (NanoAmor, Inc.). Specific surface area was measured to be 7.54 + / - 0.10 m2/g. Ag NPs were suspended in a dispersion medium (DM, phosphate-buffered saline + 0.6 mg/ml rat serum albumin + 0.01 mg/ml dipalmitoyl phosphocholine) and sonicated. Aggregate size in DM ranged from ~ 20 to 1000 nm with an average size of 180 nm. On day 0, Sprague-Dawley rats were exposed 1x/wk for 8 wk via IT with 9.35 microg Ag NP, 112 microg Ag NP, or DM alone. Rats were humanely sacrificed 7, 28, and 84 days following the last IT, the right lung was lavaged, and the left lung was preserved for pathology analysis. Indices of lung injury (albumin and lactate dehydrogenase) were increased up to 28 days post exposure, and proteins indicative of inflammation and immune response were altered in the lavage fluid from rats exposed to the high dose. Neutrophils and lymphocytes recovered by lavage were increased in rats exposed to the high dose at all time points after treatment, with resolution of the response evident over time. Although some proteins indicative of inflammation in the lavage fluid of rats exposed to the low dose were elevated at the early time points post-exposure, there were no significant increases in lung injury parameters or cellular influx into the lungs of rats in this group. These data indicate that Ag NPs induce acute pulmonary injury and inflammation that resolves over time, unlike other toxic nanomaterials.
Nanotechnology; Respiratory-system-disorders; Hazardous-materials; Toxic-materials; Toxic-effects; Pulmonary-system; Lung-function; In-vivo-study; Laboratory-testing; Laboratory-animals; Oxidative-processes; Dose-response; Lung-disorders; Toxic-dose; Surface-properties; Proteins; Immune-reaction; Immunotoxins; Cellular-reactions
The Toxicologist. Society of Toxicology 51st Annual Meeting and ToxExpo, March 11-15, 2012, San Francisco, California