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Pulmonary Toxicity Assessment of Aluminum Oxide Nanoparticles via Nasal Instillation Exposure

비강내 점적 노출을 통한 산화 알루미늄 나노입자의 폐독성 평가

  • Kwon, Jung-Taek (Environmental Health Research Department, National Institute of Environmental Research) ;
  • Seo, Gyun-Baek (Environmental Health Research Department, National Institute of Environmental Research) ;
  • Lee, Mimi (Environmental Health Research Department, National Institute of Environmental Research) ;
  • Kim, Hyun-Mi (Environmental Health Research Department, National Institute of Environmental Research) ;
  • Shim, Ilseob (Environmental Health Research Department, National Institute of Environmental Research) ;
  • Jo, Eunhye (Environmental Health Research Department, National Institute of Environmental Research) ;
  • Kim, Pilje (Environmental Health Research Department, National Institute of Environmental Research) ;
  • Choi, Kyunghee (Environmental Health Research Department, National Institute of Environmental Research)
  • 권정택 (국립환경과학원 환경건강연구부) ;
  • 서균백 (국립환경과학원 환경건강연구부) ;
  • 이미미 (국립환경과학원 환경건강연구부) ;
  • 김현미 (국립환경과학원 환경건강연구부) ;
  • 심일섭 (국립환경과학원 환경건강연구부) ;
  • 조은혜 (국립환경과학원 환경건강연구부) ;
  • 김필제 (국립환경과학원 환경건강연구부) ;
  • 최경희 (국립환경과학원 환경건강연구부)
  • Received : 2012.12.03
  • Accepted : 2013.01.30
  • Published : 2013.02.28

Abstract

Objective: The use of nanoparticle products is expected to present a potential harmful effect on consumers. Also, the lack of information regarding inhaled nanoparticles may pose a serious problem. In this study, we addressed this issue by studying pulmonary toxicity after nasal instillation of Al-NPs in SD rats. Methods: The animals were exposed to Al-NPs at 1 mg/kg body weight (low dose), 20 mg/kg body weight (medium dose) and 40 mg/kg body weight (high dose). To determine pulmonary toxicity, bronchoalveolar lavage (ts.AnBAL) fluid analysis and histopathological examination were conducted in rats. In addition, cell viability was investigated at 24 hours after the treatment with Al-NPs. Results: BAL fluid analysis showed that total cells (TC) count and total protein (TP) concentrations increased significantly in all treatment groups, approximately two to three times. Also, lactate dehydrogenase (LDH) and cytokines such as TNF-alpha and IL-6 dose-dependently increased following nasal instillation of Al-NPs. However, polymorphonuclear leukocytes (PMNs) levels showed no significant changes in a dose dependant manner in BAL fluid. In the cytotoxicity analysis, the treatment of Al-NPs significantly and dose-dependently induced cell viability loss (20 to 30%) and damage of cell membrane (5 to 10%) in rat normal lung epithelial cells (L2). Conclusions: Our results suggest that inhaled Al-NPs in the lungs may be removed quickly by alveolar macrophages with minimal inflammatory reaction, but Al-NPs have the potential to affect lung permeability. Therefore, extensive toxicity evaluations of Al-NPs are required prior to their practical application as consumer products.

Keywords

References

  1. Oberdorster G, Oberdörster E, Oberdörster J. Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles. Environ Health Perspect. 2005; 113(7): 823-839. https://doi.org/10.1289/ehp.7339
  2. Arora A. Ceramics in nanotech revolution. Adv Eng Mater. 2004; 6(4): 244-247. https://doi.org/10.1002/adem.200300532
  3. Roco MC. Broader societal issues of nanotechnology. J Nanopart Res. 2003; 5(3-4): 181-189. https://doi.org/10.1023/A:1025548512438
  4. OECD WPMN, "List of manufactured nanomaterials and list of endpoints for pahse one of the OECD testing programme", 2008, Paris, France
  5. Kim Y, Park J, Kim H, Lee J, Bae E, Lee S, et al. Investigation on the Main Exposure Sources of Nanomaterials for Nanohazards Assessment. J Environ Toxicol. 2008; 23(4): 257-265.
  6. Uner M, Wissing S, Yener G, Muller R. Influence of surfactants on the physical stability of solid lipid nanoparticle (SLN) formulations. Die Pharmazie-An International J. Pharm Sci. 2004; 59(4): 331-332.
  7. Kwon JT, Kim DS, Minai-Tehrani A, Hwang SK, Chang SH, Lee ES, et al. Inhaled fluorescent magnetic nanoparticles induced extramedullary hematopoiesis in the spleen of mice. J Occup Health. 2009; 51(5): 423-431. https://doi.org/10.1539/joh.L8159
  8. Warheit DB, Hoke RA, Finlay C, Donner EM, Reed KL, Sayes CM. Development of a base set of toxicity tests using ultrafine $TiO_{2}$ particles as a component of nanoparticle risk management. Toxicol Lett. 2007; 171(3): 99-110. https://doi.org/10.1016/j.toxlet.2007.04.008
  9. Dreher KL. Health and environmental impact of nanotechnology: toxicological assessment of manufactured nanoparticles. Toxicol Sci. 2004; 77(1): 3-5.
  10. Kim IS, Baek M, Choi SJ. Comparative cytotoxicity of $Al_{2}O_{3}$, $CeO_{2}$, $TiO_{2}$ and ZnO nanoparticles to human lung cells. J Nanosci Nanotechnol. 2010; 10(5): 3453-3458. https://doi.org/10.1166/jnn.2010.2340
  11. Wagner AJ, Bleckmann CA, Murdock RC, Schrand AM, Schlager JJ, Hussain SM. Cellular interaction of different forms of aluminum nanoparticles in rat alveolar macrophages. J Phys Chem B. 2007; 111(25): 7353-7359. https://doi.org/10.1021/jp068938n
  12. Hussain S, Hess K, Gearhart J, Geiss K, Schlager J. In vitro toxicity of nanoparticles in BRL 3A rat liver cells. In Vitro Toxicol. 2005; 19(7): 975-984. https://doi.org/10.1016/j.tiv.2005.06.034
  13. Chen L, Yokel RA, Hennig B, Toborek M. Manufactured aluminum oxide nanoparticles decrease expression of tight junction proteins in brain vasculature. J Neuroimmune Pharmacol. 2008; 3(4): 286-295. https://doi.org/10.1007/s11481-008-9131-5
  14. J Pauluhn. Pulmonary toxicity and fate of agglomerated 10 and 40 nm aluminum oxyhydroxides following 4-week inhalation exposure of rats: toxic effects are determined by agglomerated, not primary particle size. Toxicol Sci. 2009; 109(1): 152-167. https://doi.org/10.1093/toxsci/kfp046
  15. Green G. Pulmonary clearance of infectious agents. Annu Rev Med. 1968; 19: 315-336. https://doi.org/10.1146/annurev.me.19.020168.001531
  16. Kwon JT, Hwang SK, Jin H, Kim DS, Minai- Tehrani A, Yoon HJ, et al. Body distribution of inhaled fluorescent magnetic nanoparticles in the mice. J Occup Health. 2008; 50(1): 1-6. https://doi.org/10.1539/joh.50.1
  17. Warheit DB, Carakostas MC, Hartsky MA, Hansen JF. 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. 1991; 107(2): 350-368. https://doi.org/10.1016/0041-008X(91)90215-Z
  18. Warheit DB, Webb TR, Colvin VL, Reed KL, Sayes CM. Pulmonary bioassay studies with nanoscale and fine-quartz particles in rats: toxicity is not dependent upon particle size but on surface characteristics. Toxicol Sci. 2007; 95(1): 270-280. https://doi.org/10.1093/toxsci/kfl128
  19. Braydich-Stolle LK, Speshock JL, Castle A, Smith M, Murdock RC, Hussain SM. Nanosized aluminum altered immune function. ACS nano. 2010; 4(7): 3661-3670. https://doi.org/10.1021/nn9016789
  20. Kwon JT, Minai-Tehrani A, Hwang SK, Kim JE, Shin JY, Yu KN, et al. Acute Pulmonary Toxicity and Body Distribution of Inhaled Metallic Silver Nanoparticles. Toxicol Res. 2012; 28(1): 25-31. https://doi.org/10.5487/TR.2012.28.1.025
  21. Sung JH, Ji JH, Park JD, Yoon JU, Kim DS, Jeon KS, et al. Subchronic inhalation toxicity of silver nanoparticles. Toxicol Sci. 2009; 108(2): 452-461. https://doi.org/10.1093/toxsci/kfn246
  22. Sung JH, Ji JH, Yoon JU, Kim DS, Song MY, Jeong J, et al. Lung function changes in Sprague- Dawley rats after prolonged inhalation exposure to silver nanoparticles. Inhal Toxicol. 2008; 20(6): 567-574. https://doi.org/10.1080/08958370701874671
  23. Thorne PS, McCray PB, Howe TS, O'Neill MA. Early-onset inflammatory responses in vivo to adenoviral vectors in the presence or absence of lipopolysaccharide-induced inflammation. Am J Respir Cell Mol Biol. 1999; 20(6): 1155-1164. https://doi.org/10.1165/ajrcmb.20.6.3632

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