Short versus long silver nanowires: a comparison of in vivo pulmonary effects post instillation

Abstract

BackgroundSilver nanowires (Ag NWs) are increasingly being used to produce touchscreens for smart phones and computers. When applied in a thin film over a plastic substrate, Ag NWs create a transparent, highly-conductive network of fibers enabling the touch interface between consumers and their electronics. Large-scale application methods utilize techniques whereby Ag NW suspensions are deposited onto substrates via droplets. Aerosolized droplets increase risk of occupational Ag NW exposure. Currently, there are few published studies on Ag NW exposure-related health effects. Concerns have risen about the potential for greater toxicity from exposure to high-aspect ratio nanomaterials compared to their non-fibrous counterparts. This study examines whether Ag NWs of varying lengths affect biological responses and silver distribution within the lungs at different time-points.MethodsTwo different sizes of Ag NWs (2 μm [S-Ag NWs] and 20 μm [L-Ag NWs]) were tested. Male, Sprague-Dawley rats were intratracheally instilled with Ag NWs (0, 0.1, 0.5, or 1.0 mg/kg). Broncho-alveolar lavage fluid (BALF) and lung tissues were obtained at 1, 7, and 21 days post exposure for analysis of BAL total cells, cell differentials, and total protein as well as tissue pathology and silver distribution.Results and conclusionsThe two highest doses produced significant increases in BAL endpoints. At Day 1, Ag NWs increased total cells, inflammatory polymorphonuclear cells (PMNs), and total protein. PMNs persisted for both Ag NW types at Day 7, though not significantly so, and by Day 21, PMNs appeared in line with sham control values. Striking histopathological features associated with Ag NWs included 1) a strong influx of eosinophils at Days 1 and 7; and 2) formation of Langhans and foreign body giant cells at Days 7 and 21. Epithelial sloughing in the terminal bronchioles (TB) and cellular exudate in alveolar regions were also common. By Day 21, Ag NWs were primarily enclosed in granulomas or surrounded by numerous macrophages in the TB-alveolar duct junction. These findings suggest short and long Ag NWs produce pulmonary toxicity; thus, further research into exposure-related health effects and possible exposure scenarios are necessary to ensure human safety as Ag NW demand increases.Electronic supplementary materialThe online version of this article (doi:10.1186/s12989-014-0052-6) contains supplementary material, which is available to authorized users.

Static and Dynamic Microscopy of the Chemical Stability and Aggregation State of Silver Nanowires in Components of Murine Pulmonary Surfactant

“…51 In the recent work by Silva et al , instillation of AgNWs in rats led to the deposition of AgNWs in the deep lungs. 9 Both AgNW lengths tested produced significant numbers of Ag-positive macrophages at Day 1. 9 Herein, sp-A/D induced agglomeration of the AgNW also within 24 hours, which could therefore be responsible for the high uptake of AgNWs by macrophages in the Silva study.…”

“…8 Recently, AgNWs were shown to produce dose-dependent inflammation in murine lungs and responses dependent on both AgNW length and dissolution rates. 9 The toxicity of AgNWs has not been thoroughly investigated and discrepancies still exist on the mechanism of biological action of AgNMs in general. 10, 11 The lack of consistency could be in part due to the fact that most studies have not considered the fate of AgNMs in biologically relevant environments and alterations to the physicochemical properties of as-synthesized NMs.…”

Macrophage and Multinucleated Giant Cell Classification

“…Inhalation of inorganic particles is also known to induce MGC formation. MGC have been observed in the lungs of rodents after exposure to silica [115,116], asbestos [115,117], sepiolite nanoclay [116], silver nanowires [118], or multiwalled carbon nanotubes [119]. Giant cell interstitial pneumonitis is a pathological pattern of hard metal lung disease that is characterized by the presence of MGC [120,121].…”

“…There is a growing body of studies that describe MGC formation in response to particle inhalation. MGC are frequently [129] Crohn's disease and ulcerative colitis [130] Langerhans cell histiocytosis [131] Rheumatoid disease [132] Sarcoidosis [71] Vasculitides such as giant cell arteritis [133] Endogenous materials Keratin [134] Lipids [74] and cholesterol crystals [135] Monosodium urate crystals [136] Exogenous materials Engineered nanomaterials such as silver nanowires [118] and carbon nanotubes [119] Medical implants [137] Metals such as Al [138], Be [122], Zr [139], and Co/WC alloys [140] Minerals such as asbestos [141], silica [141], and talc [142] Plant materials [143] such as cactus spines, corn starch used with medical gloves, and wood splinters Infectionbacteria Brucellosis [144] Cat-scratch disease [145] Mycobacteria infection such as leprosy [146] and tuberculosis [106] Syphilis [147] Infection -fungus African histoplasmosis [148] Aspergillosis [149] Cryptococcosis [150] Infectionparasite Filariasis such as dirofilariasis [151] and onchocerciasis [152] Leishmaniasis [153] Schistosomiasis [154] observed in response to inhalation of antigens that cause hypersensitivity pneumonitis [113,114] and inhalation of other organic materials such as mycobacteria and fungi (Table 1.2). Inhalation of inorganic particles is also known to induce MGC formation.…”

Silver Nanowires: Synthesis, Antibacterial Activity and Biomedical Applications

“…In vivo studies are even more limited that in vitro ones; an in vivo toxicity study carried out by Silva et al evaluated the effect of AgNWs length on rats after intratecal instillation of a bolus dose [73]. They could not find a specific effect linked to length only, but they observed that both short (2 µm) and long (20 µm) AgNWs induced a dose-dependent foreign-body response.…”