Abstract
The purpose of this study was to determine the acute pulmonary toxicity of metallic silver nanoparticles (MSNPs, 20.30 nm in diameter). Acute pulmonary toxicity and body distribution of inhaled MSNPs in mice were evaluated using a nose-only exposure chamber (NOEC) system. Bronchoalveolar lavage (BAL) fluid analysis, Western blotting, histopathological changes, and silver burdens in various organs were determined in mice. Mice were exposed to MSNPs for 6 hrs. The mean concentration, total surface area, volume and mass concentrations in the NOEC were maintained at 1.93 × 107 particles/cm3, 1.09 × 1010 nm2/cm3, 2.72 × 1011 nm3/cm3, and 2854.62 µg/m3, respectively. Inhalation of MSPNs caused mild pulmonary toxicity with distribution of silver in various organs but the silver burdens decreased rapidly at 24-hrs post-exposure in the lung. Furthermore, inhaled MSNPs induced activation of mitogen-activated protein kinase (MAPK) signaling in the lung. In summary, single inhaled MSNPs caused mild pulmonary toxicity, which was associated with activated MAPK signaling. Taken together, our results suggest that the inhalation toxicity of MSNPs should be carefully considered at the molecular level.
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References
American Conference of Governmental Industrial Hygienists. (2001). Threshold limit values for chemical substances and physical agents and biological exposure indices. Cincinatti, OH.
Bleehen, S.S., Gould, D.J., Harrington, C.I., Durrant, T.E., Slater, D.N. and Underwood, J.C. (1981). Occupational argyria; light and electron microscopic studies and X-ray microanalysis. Br. J. Dermatol., 104, 19–26.
Cano, E. and Mahadevan, L.C. (1995). Parallel signal processing among mammalian MAPKs. Trends. Biochem. Sci., 20, 117–122.
Davis, R.J. (1993). The mitogen-activated protein kinase signal transduction pathway. J. Biol. Chem., 268, 14553–14556.
DiVincenzo, G.D., Giordano, C.J. and Schriever, L.S. (1985). Biologic monitoring of workers exposed to silver. Int. Arch. Occup. Environ. Health. 56, 207–215.
Drake, P.L. and Hazelwood, K.J. (2005). Exposure-related health effects of silver and silver compounds: a review. Ann.Occup. Hyg., 49, 575–585.
Duffin, R., Tran, L., Brown, D., Stone, V. and Donaldson, K. (2007). Proinflammogenic effects of low-toxicity and metal nanoparticles in vivo and in vitro: highlighting the role of particle surface area and surface reactivity. Inhal. Toxicol., 19, 849–856.
Granqvist, C. and Buhrman, R. (1976). Ultrafine metal particles. J. Appl. Phys., 47, 2200–2219.
Jain, P. and Pradeep, T. (2005). Potential of silver nanoparticle-coated polyurethane foam as an antibacterial water filter. Biotechnol. Bioeng., 90, 59–63.
Ji, J.H., Jung, J.H., Kim, S.S., Yoon, J.U., Park, J.D., Choi, B.S., Chung, Y.H., Kwon, I.H., Jeong, J., Han, B.S., Shin, J.H., Sung, J.H., Song, K.S. and Yu, I.J. (2007). Twenty-eight-day inhalation toxicity study of silver nanoparticles in Sprague-Dawley rats. Inhal. Toxicol., 19, 857–871.
Jung, J.H., Oh, H.C., Noh, H.S., Ji, J.H. and Kim, S.S. (2006). Metal nanoparticle generation using a small ceramic heater with a local heating area. J. Aerosol Sci., 37, 1662–1670.
Kim, H.W., Park, I.K., Cho, C.S., Lee, K.H., Beck, G.R., Jr., Colburn, N.H. and Cho, M.H. (2004). Aerosol delivery of glucosylated polyethylenimine/phosphatase and tensin homologue deleted on chromosome 10 complex suppresses Akt downstream pathways in the lung of K-ras null mice. Cancer Res., 64, 7971–7976.
Kim, J.S., Kuk, E., Yu, K.N., Kim, J.H., Park, S.J., Lee, H.J., Kim, S.H., Park, Y.K., Park, Y.H., Hwang, C.Y., Kim, Y.K., Lee, Y.S., Jeong, D.H. and Cho, M.H. (2007). Antimicrobial effects of silver nanoparticles. Nanomedicine., 3, 95–101.
Kwon, J.T., Hwang, S.K., Jin, H., Kim, D.S., Minai-Tehrani, A., Yoon, H.J., Choi, M., Yoon, T.J., Han, D.Y., Kang, Y.W., Yoon, B.I., Lee, J.K. and Cho, M.H. (2008). Body distribution of inhaled fluorescent magnetic nanoparticles in the mice. J. Occup. Health. 50, 1–6.
Lee, H.Y., Park, H.K., Lee, Y.M., Kim, K. and Park, S.B. (2007). A practical procedure for producing silver nanocoated fabric and its antibacterial evaluation for biomedical applications. Chem. Commun., 28, 2959–2961.
Lee, K. (1983). Change of particle size distribution during Brownian coagulation. J. Colloid. Interf. Sci., 92, 315–325.
Monteiller, C., Tran, L., MacNee, W., Faux, S., Jones, A., Miller, B. and Donaldson, K. (2007). The pro-inflammatory effects of low-toxicity low-solubility particles, nanoparticles and fine particles, on epithelial cells in vitro: the role of surface area. Occup. Environ. Med., 64, 609–615.
Moss, A.P., Sugar, A., Hargett, N.A., Atkin, A., Wolkstein, M. and Rosenman, K.D. (1979). The ocular manifestations and functional effects of occupational argyrosis. Arch. Ophthalmol., 97, 906–908.
Perez, J.M., Simeone, F.J., Saeki, Y., Josephson, L. and Weissleder, R. (2003). Viral-induced self-assembly of magnetic nano-particles allows the detection of viral particles in biological media. J. Am. Chem. Soc., 125, 10192–10193.
Roberts, E.S., Richards, J.H., Jaskot, R. and Dreher, K.L. (2003). Oxidative stress mediates air pollution particle-induced acute lung injury and molecular pathology. Inhal. Toxicol., 15, 1327–1346.
Rosenman, K.D., Moss, A. and Kon, S. (1979). Argyria: clinical implications of exposure to silver nitrate and silver oxide. J. Occup. Med., 21, 430–435.
Rosenman, K.D., Seixas, N. and Jacobs, I. (1987). Potential neph-rotoxic effects of exposure to silver. Br. J. Ind. Med., 44, 267–272.
Samet, J.M., Graves, L.M., Quay, J., Dailey, L.A., Devlin, R.B., Ghio, A.J., Wu, W., Bromberg, P.A. and Reed, W. (1998). Activation of MAPKs in human bronchial epithelial cells exposed to metals. Am. J. Physiol., 275, L551–L558.
Sung, J.H., Ji, J.H., Yoon, J.U., Kim, D.S., Song, M.Y., Jeong, J., Han, B.S., Han, J.H., Chung, Y.H., Kim, J., Kim, T.S., Chang, H.K., Lee, E.J., Lee, J.H. and Yu, I.J. (2008). Lung function changes in Sprague-Dawley rats after prolonged inhalation exposure to silver nanoparticles. Inhal. Toxicol., 20, 567–574.
Takenaka, S., Karg, E., Roth, C., Schulz, H., Ziesenis, A., Heinzmann, U., Schramel, P. and Heyder, J. (2001). Pulmonary and systemic distribution of inhaled ultrafine silver particles in rats. Environ. Health Perspect., 109, 547–551.
Tian, J., Wong, K.K., Ho, C.M., Lok, C.N., Yu, W.Y., Che, C.M., Chiu, J.F. and Tam, P.K. (2007). Topical delivery of silver nano-particles promotes wound healing. ChemMedChem., 2, 129–136.
Wang, X.B., Gao, H.Y., Hou, B.L., Huang, J., Xi, R.G. and Wu, L.J. (2007). Nanoparticle realgar powders induce apoptosis in U937 cells through caspase MAPK and mitochondrial pathways. Arch. Pharm. Res., 30, 653–658.
Warheit, D.B., Carakostas, M.C., Hartsky, M.A. and Hansen, J.F. (1991). Development of a short-term inhalation bioassay to assess pulmonary toxicity of inhaled particles: comparisons of pulmonary responses to carbonyl iron and silica. Toxicol. Appl. Pharmacol., 107, 350–368.
Warheit, D.B., Webb, T.R., Colvin, V.L., Reed, K.L. and Sayes, C.M. (2007). Pulmonary bioassay studies with nanoscale and fine-quartz particles in rats: toxicity is not dependent upon particle size but on surface characteristics. Toxicol. Sci., 95, 270–280.
Wu, W., Samet, J.M., Ghio, A.J. and Devlin, R.B. (2001). Activation of the EGF receptor signaling pathway in airway epithelial cells exposed to Utah Valley PM. Am. J. Physiol. Lung. Cell Mol. Physiol., 281, L483–L489.
Yu, K.N., Lee, S.M., Han, J.Y., Park, H., Woo, M.A., Noh, M.S., Hwang, S.K., Kwon, J.T., Jin, H., Kim, Y.K., Hergenrother, P.J., Jeong, D.H., Lee, Y.S. and Cho, M.H. (2007). Multiplex targeting, tracking, and imaging of apoptosis by fluorescent surface enhanced Raman spectroscopic dots. Bioconjug. Chem., 18, 1155–1162.
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Kwon, JT., Minai-Tehrani, A., Hwang, SK. et al. Acute Pulmonary Toxicity and Body Distribution of Inhaled Metallic Silver Nanoparticles. Toxicol Res. 28, 25–31 (2012). https://doi.org/10.5487/TR.2012.28.1.025
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DOI: https://doi.org/10.5487/TR.2012.28.1.025