Nanoparticles and Neurotoxicity

International Journal of Molecular Sciences

Volumn 12, Issue 9, 2011, Pages 6267-6280

  Win Shwe, Tin Tin ^a   Fujimaki, Hidekazu ^a  

^a NATIONAL INSTITUTE FOR ENVIRONMENTAL STUDIES   (Japan)

Author keywords

Brain; Nanoparticles; Neuroinflammation; Neurotoxicity; Oxidative stress

Indexed keywords

ALUMINUM NANOPARTICLE; ALUMINUM OXIDE; BLACK CARBON; BRAIN DERIVED NEUROTROPHIC FACTOR; CARBON 13; COPPER NANOPARTICLE; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 1ALPHA; INTERLEUKIN 1BETA; MANGANESE NANOPARTICLE; MANGANESE OXIDE; MESSENGER RNA; MONOCYTE CHEMOTACTIC PROTEIN 1; N METHYL DEXTRO ASPARTIC ACID RECEPTOR; NANOMATERIAL; NANOPARTICLE; SILVER NANOPARTICLE; TITANIUM DIOXIDE; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; ZINC OXIDE;

COMBUSTION; ENVIRONMENTAL EXPOSURE; EXHAUST GAS; EXPERIMENTAL MOUSE; HEALTH HAZARD; HUMAN; IN VITRO STUDY; IN VIVO STUDY; NANOANALYSIS; NANOFABRICATION; NANOTOXICOLOGY; NEUROMONITORING; NEUROTOXICITY; NONHUMAN; OXIDATIVE STRESS; PARTICULATE MATTER; RECEPTOR UPREGULATION; REVIEW; TOXICITY TESTING; ANIMAL; BRAIN; EXPOSURE; METABOLISM; NEURODEGENERATIVE DISEASES; NEUROTOXICITY SYNDROMES; PATHOLOGY; RISK ASSESSMENT; RISK FACTOR;

ANIMALIA;

ANIMALS; BRAIN; HUMANS; INHALATION EXPOSURE; NANOPARTICLES; NEURODEGENERATIVE DISEASES; NEUROTOXICITY SYNDROMES; RISK ASSESSMENT; RISK FACTORS;

EID: 80053215779     PISSN: None     EISSN: 14220067     Source Type: Journal    
DOI: 10.3390/ijms12096267     Document Type: Review

References (83)

1. Oberdörster, G.; Oberdörster, E.; Oberdörster, J. Nanotoxicology: An emerging discipline evolving from studies of ultrafine particles. Environ. Health Perspect. 2005, 113, 823-839
2. Dockery, D.W.; Pope, C.A.; Xu, X.; Spengler, J.D.; Ware, J.H.; Fay, M.E.; Ferris, B.G., Jr.; Speizer, F.E. An association between air pollution and mortality in six US cities. N. Engl. J. Med. 1993, 329, 1753-1759
3. Pope, C.A.; Burnett, R.T.; Thun, M.J.; Calle, E.E.; Krewski, D.; Ito, K.; Thurston, G.D. Lung cancer, cardiopulmonary mortality, and long-term exposure to fine particulate air pollution. JAMA 2002, 287, 1132-1141
4. Peters, A.; Döring, A.; Wichmann, H.E.; Koenig, W. Increased plasma viscosity during an air pollution episode: A link to mortality? Lancet 1997, 349, 1582-1587
5. Penttinen, P.; Timonen, K.L.; Tittanen, P.; Mirme, A.; Ruuskanen, J.; Pekkanen, J. Ultrafine particles in urban air and respiratory health among adult asthmatics. Euro. Respir. J. 2001, 17, 428-435
6. Donaldson, K. Resolving the nanoparticles paradox. Nanomedicine 2006, 1, 229-234
7. Medina, C.; Santos-Martinez, M.J.; Radomski, A.; Corrigan, O.I.; Radomski, M.W. Nanoparticles: Pharmacological and toxicological significance. Br. J. Pharmacol. 2007, 150, 552-558
8. Linkov, I.; Satterstrom, F.K.; Corey, L.M. Nanotoxicology and nanomedicine: Making hard decisions. Nanomedicine 2008, 4, 167-171
9. Win-Shwe, T.T.; Yamamoto, S.; Kakeyama, M.; Kobayashi, T.; Fujimaki, H. Effect of intratracheal instillation of ultrafine carbon black on proinflammatory cytokine and chemokine release and mRNA expression in lung and lymph nodes of mice. Toxicol. Appl. Pharmacol. 2005, 209, 51-61
10. Oberdörster, G.; Sharp, Z.; Atudorei, V.; Elder, A.; Gelein, R.; Kreyling, W.; Cox, C. Translocation of inhaled ultrafine particles to the brain. Inhal. Toxicol. 2004, 16, 437-445
11. Block, M.L.; Wu, X.; Pei, Z.; Li, G.; Wang, T.; Qin, L.; Wilson, B.; Yang, J.; Hong, J.S.; Veronesi, B. Nanometer size diesel exhaust particles are selectively toxic to dopaminergic neurons: The role of microglia, phagocytosis, and NADPH oxidase. FASEB J. 2004, 18, 1618-1620
12. Peters, A.; Veronesi, B.; Calderon-Garciduenas, L.; Gehr, P.; Chen, L.C.; Geiser, M.; Reed, W.; Rothen-Rutishauser, B.; Schurch, S.; Schulz, H. Translocation and potential neurological effects of fine and ultrafine particles, A critical update. Part. Fibre Toxicol. 2006, 3, 1-13
13. Hu, Y.L.; Gao, J.Q. Potential neurotoxicity of nanoparticles. Int. J. Pharm. 2010, 394, 115-121
14. Donaldson, K.; Stone, V.; Clouter, A.; Renwick, L.; MacNee, W. Ultrafine particles. Occup. Environ. Med. 2001, 58, 211-216
15. Donaldson, K.; Stone, V.; Seaton, A.; MacNee, W. Ambient particle inhalation and the cardiovascular system: Potential mechanisms. Environ. Health Perspect. 2001, 109, 523-527
16. Morimoto, Y.; Kobayashi, N.; Shinohara, N.; Myojo, T.; Tanaka, I.; Nakanishi, J. Hazard assessments of manufactured nanomaterials. J. Occup. Health 2010, 52, 325-334
17. Farrer, L.A. Intercontinental epidemiology of Alzheimer disease: A global approach to bad gene hunting. JAMA 2001, 285, 796-798
18. Matés, J.M.; Pérez-Gómez, C.; Núñez de Castro, I. Antioxidant enzymes and human diseases. Clin. Biochem. 1999, 32, 595-603
19. Orringer, D.A.; Koo, Y.E.; Chen, T.; Kopelman, R.; Sagher, O.; Philbert, M.A. Small solutions for big problems: The application of nanoparticles to brain tumor diagnosis and therapy. Clin. Pharmacol. Ther. 2009, 85, 531-534
20. Burch, W.M. Passage of inhaled particles into the blood circulation in humans. Circulation 2002, 106, e141-e142.
21. Takenaka, S.; Karg, E.; Roth, C.; Schulz, H.; Ziesenis, A.; Heinzmann, U.; Schramel, P.; Heyder, J. Pulmonary and systemic distribution of inhaled ultrafine silver particles in rats. Environ. Health Perspect. 2001, 109, 547-551
22. Begley, D.J. The blood-brain barrier: Principles for targeting peptides and drugs to the central nervous system. J. Pharm. Pharmacol. 1996, 48, 136-146
23. Sharma, H.S.; Sharma, A. Nanoparticles aggravate heat stress induced cognitive deficits, blood-brain barrier disruption, edema formation and brain pathology. Prog. Brain Res. 2007, 162, 245-273
24. Sharma, H.S.; Sharma, A. Conference scene: Nanoneuroprotection and nanoneurotoxicity: Recent progress and future perspectives. Nanomedicine 2010, 5, 533-537
25. De Lorenzo, A.J.D. The olfactory neuron and the blood-brain barrier. In Taste and Smell in Vertebrates; Wolstenholme, G.E.W., Knight, J., Eds.; J. &A. Churchill: London, UK, 1970; pp. 151-176
26. Tjälve, H.; Henriksson, J.; Tallkvist, J.; Larsson, B.S.; Lindquist, N.G. Uptake of manganese and cadmium from the nasal mucosa into the central nervous system via olfactory pathways in rats. Pharmacol. Toxicol. 1996, 79, 347-356
27. Tallkvist, J.; Henriksson, J.; d'Argy, R.; Tjälve, H. Transport and subcellular distribution of nickel in the olfactory system of pikes and rats. Toxicol. Sci. 1998, 43, 196-203
28. Tjalve, H.; Henriksson, J. Uptake of metals in the brain via olfactory pathways. Neurotoxicology 1999, 20, 181-196
29. Henriksson, J.; Tjälve, H. Manganese taken up into the CNS via the olfactory pathway in rats affects astrocytes. Toxicol. Sci. 2000, 55, 392-398
30. Persson, E.; Henriksson, J.; Tjälve, H. Uptake of cobalt from the nasal mucosa into the brain via olfactory pathways in rats. Toxicol. Lett. 2003, 145, 19-27
31. Elder, A.; Gelein, R.; Silva, V.; Feikert, T.; Opanashuk, L.; Carter, J.; Potter, R.; Maynard, A.; Ito, Y.; Finkelstein, J.; Oberdorster, G. Translocation of inhaled ultrafine manganese oxide particles to the central nervous system. Environ. Health Perspect. 2006, 114, 1172-1178
32. Win-Shwe, T.T.; Yamamoto, S.; Ahmed, S.; Kakeyama, M.; Kobayashi, T.; Fujimaki, H. Brain cytokine and chemokine mRNA expression in mice induced by intranasal instillation with ultrafine carbon black. Toxicol. Lett. 2006, 163, 153-160
33. Zhang, Q.; Kusaka, Y.; Sato, K.; Nakakuki, K.; Kohyama, N.; Donaldson, K. Differences in the extent of inflammation caused by intratracheal exposure to three ultrafine metals: Role of free radicals. J. Toxicol. Environ. Health A. 1998, 53, 423-438
34. Dellinger, B.; Pryor, W.A.; Cueto, R.; Squadrito, G.L.; Hegde, V.; Deutsch, W.A. Role of free radicals in the toxicity of airborne fine particulate matter. Chem. Res. Toxicol. 2001, 14, 1371-1377
35. Li, N.; Sioutas, C.; Cho, A.; Schmitz, D.; Misra, C.; Sempf, J.; Wang, M.; Oberley, T.; Froines, J.; Nel, A. Ultrafine particulate pollutants induce oxidative stress and mitochondrial damage. Environ. Health Perspect. 2003, 111, 455-460
36. Veronesi, B.; Makwana, O.; Pooler, M.; Chen, L.C. Effects of subchronic exposures to concentrated ambient particles. VII. Degeneration of dopaminergic neurons in Apo E-/-mice. Inhal. Toxicol. 2005, 17, 235-241
37. Nel, A.; Xia, T.; Mädler, L.; Li, N. Toxic potential of materials at the nanolevel. Science 2006, 311, 622-627
38. Donaldson, K.; Stone, V. Current hypotheses on the mechanisms of toxicity of ultrafine particles. Ann. Ist. Super Sanita. 2003, 39, 405-410
39. Brown, D.M.; Stone, V.; Findlay, P.; MacNee, W.; Donaldson, K. Increased inflammation and intracellular calcium caused by ultrafine carbon black is independent of transition metals or other soluble components. Occup. Environ. Med. 2000, 57, 685-691
40. Brown, D.M.; Wilson, M.R.; MacNee, W.; Stone, V.; Donaldson, K. Size-dependent proinflammatory effects of ultrafine polystyrene particles: A role for surface area and oxidative stress in the enhanced activity of ultrafines. Toxicol. Appl. Pharmacol. 2001, 175, 191-199
41. Derfus, A.M.; Chan, W.C.W.; Bhatia, S.N. Probing the cytotoxicity of semiconductor quantum dots. Nano Lett. 2004, 4, 11-18
42. Joo, S.H.; Feitz, A.J.; Waite, T.D. Oxidative degradation of the carbothioate herbicide, molinate, using nanoscale zero-valent iron. Environ. Sci. Technol. 2004, 38, 2242-2247
43. Oberdörster, E. Manufactured nanomaterials (fullerenes, C60) induce oxidative stress in the brain of juvenile largemouth bass. Environ. Health Perspect. 2004, 112, 1058-1062
44. Sayes, C.; Fortner, J.; Guo, W.; Lyon, D.; Boyd, A.M.; Ausman, K.D.; Tao, Y.J.; Sitharaman, B.; Wilson, L.J.; Hughes, J.B.; West, J.L.; Colvin, V.L. The differential cytotoxicity of water-soluable fullerenes. Nano Lett. 2004, 4, 1881-1887
45. Shvedova, A.A.; Castranova, V.; Kisin, E.R.; Schwegler-Berry, D.; Murray, A.R.; Gandelsman, V.Z.; Maynard, A.; Baron, P. Exposure to carbon nanotube material: Assessment of nanotube cytotoxicity using human keratinocyte cells. J. Toxicol. Environ. Health A. 2003, 66, 1909-1926
46. Shvedova, A.A.; Kisin, E.R.; Murray, A.R.; Schwegler-Berry, D.; Gandelsnan, V.Z.; Baron, P.; Maynard, A.; Gunther, M.R.; Castranova, V. Exposue of human bronchial cells to carbon nanotubes caused oxidative stress and cytotoxicity. In Proceedings of the Society for Free Radical Research Meeting, Ioannina, Greece, 26-29 June 2003; Taylor & Francis Group: Philadelphia, PA, USA, 2003; pp. 91-103
47. Wilson, M.R.; Lightbody, J.H.; Donaldson, K.; Sales, J.; Stone, V. Interactions between ultrafine particles and transition metals in vivo and in vitro. Toxicol. Appl. Pharmacol. 2002, 184, 172-179
48. Yamakoshi, Y.; Umezawa, N.; Ryu, A.; Arakane, K.; Miyata, N.; Goda, Y.; Masumizu, T.; Nagano, T. Active oxygen species generated from photoexcited fullerene (C60) as potential medicines: O2-* versus 1O2. J. Am. Chem. Soc. 2003, 125, 1283-1289
49. Rahman, M.F.; Wang, J.; Patterson, T.A.; Saini, U.T.; Robinson, B.L.; Newport, G.D.; Murdock, R.C.; Schlager, J.J.; Hussain, S.M.; Ali, S.F. Expression of genes related to oxidative stress in the mouse brain after exposure to silver-25 nanoparticles. Toxicol. Lett. 2009, 187, 15-21
50. Shimizu, M.; Tainaka, H.; Oba, T.; Mizuo, K.; Umezawa, M.; Takeda, K. Maternal exposure to nanoparticulate titanium dioxide during the prenatal period alters gene expression related to brain development in the mouse. Part. Fibre Toxicol. 2009, 6, 1-8
51. Campbell, A.; Oldham, M.; Becaria, A.; Bondy, S.C.; Meacher, D.; Sioutas, C.; Misra, C.; Mendez, L.B.; Kleinman, M. Particulate matter in pollutant air may increase biomarkers of inflammation in mouse brain. Neurotoxicology 2005, 26, 133-140
52. Win-Shwe, T.T.; Mitsushima, D.; Yamamoto, S.; Fujitani, Y.; Funabashi, T.; Hirano, S.; Fujimaki, H. Extracellular glutamate level and NMDA receptor subunit expression in mouse olfactory bulb following nanoparticle-rich diesel exhaust exposure. Inhal. Toxicol. 2009, 21, 828-836
53. Borm, P.J.; Müller-Schulte, D. Nanoparticles in drug delivery and environmental exposure: Same size, same risks? Nanomedicine 2006, 1, 235-249
54. Win-Shwe, T.T.; Yamamoto, S.; Fujitani, Y.; Hirano, S.; Fujimaki, H. Spatial learning and memory function-related gene expression in the hippocampus of mouse exposed to nanoparticle-rich diesel exhaust. Neurotoxicology 2008, 29, 940-947
55. Win-Shwe, T.T.; Yamamoto, S.; Fujitani, Y.; Hirano, S.; Fujimaki, H. Nanoparticle-rich diesel exhaust affects hippocampal-dependent spatial learning and NMDA receptor subunit expression in female mice. Nanotoxicology 2011, DOI: 10.3109/17435390.2011.590904.
56. Tsukue, N.; Watanabe, M.; Kumamoto, T.; Takano, H.; Takeda, K. Perinatal exposure to diesel exhaust affects gene expression in mouse cerebrum. Arch. Toxicol. 2009, 83, 985-1000
57. Suzuki, T.; Oshio, S.; Iwata, M.; Saburi, H.; Odagiri, T.; Udagawa, T.; Sugawara, I.; Umezawa, M.; Takeda, K. In utero exposure to a low concentration of diesel exhaust affects spontaneous locomotor activity and monoaminergic system in male mice. Part. Fibre Toxicol. 2010, 7, 1-8
58. Win-Shwe, T.T.; Mitsushima, D.; Yamamoto, S.; Fukushima, A.; Funabashi, T.; Kobayashi, T.; Fujimaki, H. Changes in neurotransmitter levels and proinflammatory cytokine mRNA expressions in the mice olfactory bulb following nanoparticle exposure. Toxicol. Appl. Pharmacol. 2008, 226, 192-198
59. Kleinman, M.T.; Araujo, J.A.; Nel, A.; Sioutas, C.; Campbell, A.; Cong, P.Q.; Li, H.; Bondy, S.C. Inhaled ultrafine particulate matter affects CNS inflammatory processes and may act via MAP kinase signaling pathways. Toxicol. Lett. 2008, 178, 127-130
60. Zhang, Q.L.; Li, M.Q.; Ji, J.W.; Gao, F.P.; Bai, R.; Chen, C.Y.; Wang, Z.W.; Zhang, C.; Niu, Q. In vivo toxicity of nano-alumina on mice neurobehavioral profiles and the potential mechanisms. Int. J. Immunopathol. Pharmacol. 2011, 24, 23S-29S.
61. Takahashi, Y.; Mizuo, K.; Shinkai, Y.; Oshio, S.; Takeda, K. Prenatal exposure to titanium dioxide nanoparticles increases dopamine levels in the prefrontal cortex and neostriatum of mice. J. Toxicol. Sci. 2010, 35, 749-756
62. Takeda, K.; Suzuki, K.; Ishihara, A.; Kubo-Irie, M.; Fujimoto, R.; Tabata, M.; Oshio, S.; Nihei, Y.; Ihara, T.; Sugamata, M. Nanoparticles transferred from pregnant mice to their offspring can damage the genital and cranial nerve systems. J. Health Sci. 2009, 55, 95-102
63. Takeda, K.; Shinkai, Y.; Suzuki, K.; Yanagita, S.; Umezawa, M.; Yokota, S.; Tainaka, H.; Oshio, S.; Ihara, T.; Sugamata, M. Health effects of nanomaterials on next generation. Yakugaku Zasshi 2011, 131, 229-236
64. Hartz, A.M.; Bauer, B.; Block, M.L.; Hong, J.S.; Miller, D.S. Diesel exhaust particles induce oxidative stress, proinflammatory signaling, and P-glycoprotein up-regulation at the blood brain barrier. FASEB J. 2008, 22, 2723-2733
65. Levesque, S.; Taetzsch, T.; Lull, M.E.; Kodavanti, U.; Stadler, K.; Wagner, A.; Johnson, J.A.; Duke, L.; Kodavanti, P.; Surace, M.J.; Block, M.L. Diesel exhaust activates and primes microglia: Air pollution, neuroinflammation, and regulation of dopaminergic neurotoxicity. Environ. Health Perspect. 2011, 119, 1149-1155
66. Hussain, S.M.; Javorina, A.K.; Schrand, A.M.; Duhart, H.M.; Ali, S.F.; Schlager, J.J. The interaction of manganese nanoparticles with PC-12 cells induces dopamine depletion. Toxicol. Sci. 2006, 92, 456-463
67. Pisanic, T.R., Blackwell, J.D.; Shubayev, V.I.; Fiñones, R.R.; Jin, S. Nanotoxicity of iron oxide nanoparticle internalization in growing neurons. Biomaterials 2007, 28, 2572-2581
68. Wang, J.; Rahman, M.F.; Duhart, H.M.; Newport, G.D.; Patterson, T.A.; Murdock, R.C.; Hussain, S.M.; Schlager, J.J.; Ali, S.F. Expression changes of dopaminergic system-related genes in PC12 cells induced by manganese, silver, or copper nanoparticles. Neurotoxicology 2009, 30, 926-933
69. Wu, J.; Wang, C.; Sun, J.; Xue, Y. Neurotoxicity of silica nanoparticles: Brain localization and dopaminergic neurons damage pathways. ACS Nano. 2011, 5, 4476-4489
70. Wu, X.F.; Block, M.L.; Zhang, W.; Qin, L.; Wilson, B.; Zhang, W.Q.; Veronesi, B.; Hong, J.S. The role of microglia in paraquat-induced dopaminergic neurotoxicity. Antioxid. Redox Signal. 2005, 7, 654-661
71. Long, T.C.; Tajuba, J.; Sama, P.; Saleh, N.; Swartz, C.; Parker, J.; Hester, S.; Lowry, G.V.; Veronesi, B. Nanosize titanium dioxide stimulates reactive oxygen species in brain microglia and damages neurons in vitro. Environ. Health Perspect. 2007, 115, 1631-1637
72. Deng, X.; Luan, Q.; Chen, W.; Wang, Y.; Wu, M.; Zhang, H.; Jiao, Z. Nanosized zinc oxide particles induce neural stem cell apoptosis. Nanotechnology 2009, 20, 115101.
73. Calderón-Garcidueñas, L.; Reed, W.; Maronpot, R.R.; Henríquez-Roldán, C.; Delgado-Chavez, R.; Calderón-Garcidueñas, A.; Dragustinovis, I.; Franco-Lira, M.; Aragón-Flores, M.; Solt, A.C.; Altenburg, M.; Torres-Jardón, R.; Swenberg, J.A. Brain inflammation and Alzheimer's-like pathology in individuals exposed to severe air pollution. Toxicol. Pathol. 2004, 32, 650-658
74. United States Environmental Protection Agency (US EPA). Integrated Science Assessment for Particulate Matter. EPA/600/R-08/139F. EPA: Washington, DC, USA, December 2009.
75. Hoek, G.; Boogaard, H.; Knol, A.; de Hartog, J.; Slottje, P.; Ayres, J.G.; Borm, P.; Brunekreef, B.; Donaldson, K.; Forastiere, F.; Holgate, S.; Kreyling, W.G.; Nemery, B.; Pekkanen, J.; Stone, V.; Wichmann, H.E.; van der Sluijs, J. Concentration response functions for ultrafine particles and all-cause mortality and hospital admissions: Results of a European expert panel elicitation. Environ. Sci. Technol. 2010, 44, 476-482
76. Hesterberg, T.W.; Long, C.M.; Lapin, C.A.; Hamade, A.K.; Valberg, P.A. Diesel exhaust particulate (DEP) and nanoparticle exposures: What do DEP human clinical studies tell us about potential human health hazards of nanoparticles? Inhal. Toxicol. 2010, 22, 679-694
77. Kittelson, D.B.; Watts, W.F.; Johnson, J.P.; Remerowki, M.L.; Ische, E.E.; Oberdörster, G.; Gelein, R.M.; Elder, A.; Hopke, P.K.; Kim, E.; Zhao, W.; Zhou, L.; Jeong, C.H. On-road exposure to highway aerosols. 1. Aerosol and gas measurements. Inhal. Toxicol. 2004, 16S, 31-39
78. Kittelson, D.B. On-Road Particles-Characteristics and Measurement. In Proceedings of the International Workshop on Vehicle-related Nanoparticles and Environmental Health, Seoul, Korea, 2 February 2007; pp. 47-71
79. Crüts, B.; van Etten, L.; Törnqvist, H.; Blomberg, A.; Sandström, T.; Mills, N.L.; Borm, P.J. Exposure to diesel exhaust induces changes in EEG in human volunteers. Part. Fibre Toxicol. 2008, 5, 1-6
80. Frampton, M.W.; Utell, M.J.; Zareba, W.; Oberdörster, G.; Cox, C.; Huang, L.S.; Morrow, P.E.; Lee, F.E.; Chalupa, D.; Frasier, L.M.; Speers, D.M.; Stewart, J. Effects of exposure to ultrafine carbon particles in healthy subjects and subjects with asthma. Res. Rep. Health Eff. Inst. 2004, 126, 1-47
81. Beckett, W.S.; Chalupa, D.F.; Pauly-Brown, A.; Speers, D.M.; Stewart, J.C.; Frampton, M.W.; Utell, M.J.; Huang, L.S.; Cox, C.; Zareba, W.; Oberdörster, G. Comparing inhaled ultrafine versus fine zinc oxide particles in healthy adults: A human inhalation study. Am. J. Respir. Crit. Care Med. 2005, 171, 1129-1135
82. Song, Y.; Li, X.; Du, X. Exposure to nanoparticles is related to pleural effusion, pulmonary fibrosis and granuloma. Eur. Respir. J. 2009, 34, 559-567
83. Gwinn, M.R.; Vallyathan, V. Nanoparticles: Health effects-pros and cons. Environ. Health Perspect. 2006, 114, 1818-1825.