Journal of Korean Society of Occupational and Environmental Hygiene (한국산업보건학회지)

Korean Industrial Hygiene Association (한국산업보건학회)
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Size, Shape, and Crystal Structure-dependent Toxicity of Major Metal Oxide Particles Generated as Byproducts in Semiconductor Fabrication Facility

반도체 가공 작업환경에서 부산물로 발생되는 주요 금속산화물의 입자 크기, 형상, 결정구조에 따른 독성 고찰

  • Choi, Kwang-Min (Samsung Health Research Institute, Samsung Electronics Co. Ltd.)
  • Received : 2016.04.07
  • Accepted : 2016.06.24
  • Published : 2016.06.30
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Abstract

Objectives: The purpose of this study is to review size, shape, and crystal structure-dependent toxicity of major metal oxide particles such as silicon dioxide, tungsten trioxide, aluminum oxide, and titanium dioxide as byproducts generated in semiconductor fabrication facility. Methods: To review the toxicity of major metal oxide particles, we used various reported research and review papers. The papers were searched by using websites such as Google Scholar and PubMed. Keyword search terms included '$SiO_2$(or $WO_3$ or $Al_2O_3$ or $TiO_2$) toxicity', 'health effects $SiO_2$(or $WO_3$ or $Al_2O_3$ or $TiO_2$). Additional papers were identified in references cited in the searched papers. Results: In various cell lines and organs of human and animals, cytotoxicity, genotoxicity, hepatoxicity, fetotoxicity, neurotoxicity, and histopathological changes were induced by silicon dioxide, tungsten trioxide, aluminium oxide, and titanium dioxide particles. Differences in toxicity were dependent on the cell lines, organs, doses, as well as the chemical composition, size, surface area, shape, and crystal structure of the particles. However, the doses used in the reported papers were higher than the possible exposure level in general work environment. Oxidative stress induced by the metal oxide particles plays a significant role in the expression of toxicity. Conclusions: The results cannot guarantee human toxicity of the metal oxide particles, because there is still a lack of available information about health effects on humans. In addition, toxicological studies under the exposure conditions in the actual work environment are needed.

Keywords

References

  1. Agency for Toxic Substances and Disease Research (ATSDR), 2005. Toxicological Profile for Tungsten. US Department of Health and Human Services, Public Health Service, Atlanta, GA
  2. Alexander Jr FA, Huey EG, Price DT, Bhansail S. Real-time impedance analysis of silica nanowire toxicity on epithelial breast cancer cells. Aaalyst 2012;137: 5823-5828
  3. American Conference of Government Industrial Hygienists (ACGIH) TLVs and BEIs. Threshold Limit Values for Chemical Substances and Physical Agents and Biological Exposure Indices. Cincinnati, OH, 2008
  4. American Conference of Government Industrial Hygienists (ACGIH), 2001. Tungsten and Compounds
  5. American Conference of Government Industrial Hygienists (ACGIH): 2015 TLV and BEIs. Cincinnati, OH, 2015
  6. Baan R, Straif K, Grosse Y, Secretan B, Ghissassi FE, Cogliano V. Carcinogenicity of carbon black, titanium dioxide, and talc. Lancet Oncol 2006;7:295-296 https://doi.org/10.1016/S1470-2045(06)70651-9
  7. Balasubramanyam A, Sailaja N, Mahboob M, Rahman MF, Hussain SM, Grover P. In vivo genotoxicity assessment of aluminium oxide nanomaterials in rat peripheral blood cells using the comet assay and micronucleus test. Mutagenesis 2009;24(3):245-251 https://doi.org/10.1093/mutage/gep003
  8. Barnes CA, Elsaesser A, Arkusz J, Smok A, Palus J et al. Reproducible comet assay of amorphous silica nanoparticle detects no genotoxicity. Nano Lett 2008; 8(9):3069-3074 https://doi.org/10.1021/nl801661w
  9. Bhaskar R, Li J, Xu L.A comparatively study of particle size dependency of IR and XRD methods for quartz analysis. Am Ind Hyg Asso J 1994; 55:605-609 https://doi.org/10.1080/15428119491018682
  10. Brun E, Barreau F, Veronesi G, Fayard B, Sorieul S et al. Titanium dioxide nanoparticle impact and translocation through ex vivo, in vivo and in vitro gut epithelial. Part Fibre Toxicol 2014;11(1):13 https://doi.org/10.1186/1743-8977-11-13
  11. Byaydich-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
  12. Chen X, Mao SS. Synthesis of titanium dioxide ($TiO_{2}$) nanomaterials. J Nanosci Nanotechnol 2006;6:906-925 https://doi.org/10.1166/jnn.2006.160
  13. Cho WS, Cho M, Han BS, Cho M, Oh JH et al. Inflammatory mediators induced by intratracheal instillation of ultrafine amorphous silica particles. Toxicol Lett 2007;175:24-33 https://doi.org/10.1016/j.toxlet.2007.09.008
  14. Choi KM, Kim TH, Kim KS, Kim SG. Hazard identification of powder generated from a chemical vapor deposition process in the semiconductor manufacturing industry. J Occup Environ Hyg 2013;10(1):D1-D5 https://doi.org/10.1080/15459624.2012.734274
  15. Choi KM, Yeo JH, Jung MK, Kim KS, Cho SH. Size, shape, and crystal structure of silica particles generated as by-products in the semiconductor workplace. J Korean Soc Occup Environ Hyg 2015a;25(1):36-44 https://doi.org/10.15269/JKSOEH.2015.25.1.36
  16. Choi KM, An HC, Kim KS. Identifying the hazard characteristics of powder by-products generated semiconductor fabrication processes. J Occup Environ Hyg 2015b;12(2):114-122 https://doi.org/10.1080/15459624.2014.955178
  17. Choi KM, Kim JH, Park JH, Kim KS, Bae GN. Exposure characteristics of nanoparticles as process by-products for the semiconductor manufacturing industry. J Occup Environ Hyg 2015c;12(8):D153-D160 https://doi.org/10.1080/15459624.2015.1009983
  18. Chu Z, Huang Y, Li L, Tao Q, Li Q. Physiological pathway of human cell damage induced by genotoxic crystalline silica nanoparticle. Biomaterials 2012;33:7540-7546 https://doi.org/10.1016/j.biomaterials.2012.06.073
  19. Donaldson K, Stone V, Borm PJ, Jimenez LA, Gilmour PS et al. Oxidative stress and calcium signaling in the adverse effects of environmental particles (PM10). Free Radic Biol Med 2003;34:1369-1382 https://doi.org/10.1016/S0891-5849(03)00150-3
  20. Duan Y, Liu J, Ma L, Li N, Liu H et al. Toxicological characteristics of nanoparticulate anatase titanium dioxide in mice. Biomaterials 2010;31:894-899 https://doi.org/10.1016/j.biomaterials.2009.10.003
  21. Falck GCM, Lindgerg HK, Suhonen S, Vippola M, Vanhala E, Catalan J, Savolainen K, Norppa H. Genotoxic effects of nanosized and fine $TiO_{2}$. Hum Exp Toxicol 2009;28:339-352 https://doi.org/10.1177/0960327109105163
  22. Farcal LR, Uboldi C, Mehn d, Giudetti G, Nativo P et al. Mechanisms of toxicity induced by $SiO_{2}$ nanoparticles of in vitro human alveolar barrier: effects on cytokine production, oxidative stress induction, surfactant proteins A mRNA expression and nanoparticles uptake. Nanotoxicology 2012;7(6):1095-1110 https://doi.org/10.3109/17435390.2012.710658
  23. Gehrke H, Fruhmesser A, Pelka J, Esselen M, Hecht LL et al. In vitro toxicity of amorphous silica nanoparticles in human colon carcinoma cells. Nanotoxicology 2012;793:274-293
  24. Grassian VH, O'Shaughnessy PT, Adamcakova-Dodd A. Inhalation exposure study of titanium dioxide nanoparticles with a primary particle size of 2 to 5 nm. Environ Health Perspect 2007;115(3):397-402 https://doi.org/10.1289/ehp.10302R
  25. Guichard Y, Schmit J, Darne C, Gate L, Goutet M et al. Cytotoxicity and genotoxicity of nanosized and microsized titanium dioxide and iron oxide particles in Syrian hamster embryo cells. Ann Occup Hyg 2012; 56(5):631-644 https://doi.org/10.1093/annhyg/mes006
  26. Hackenberg S, Friehs G, Kessier M, Froelich K, Ginzkey C et al. Nanosized titanium dioxide particles do not induce DNA damage in human peripheral blood lymphocytes. Environ Mol Mutagen 2011;52(4):264-268 https://doi.org/10.1002/em.20615
  27. Hamilton Jr RF, Wu N, Porter D, Buford M, Wolfarth M, Holian A. Particle length-dependent titanium dioxide nanomaterials toxicity and bioactivity. Part Fibre Toxicol 2009;6:35 https://doi.org/10.1186/1743-8977-6-35
  28. Hasegawa G, Shimonaka M, Ishihara Y. Differential genotoxicity of chemical properties and particle size of rate metal and metal oxide nanoparticles. J Appl Toxicol 2012;32(1):72-80 https://doi.org/10.1002/jat.1719
  29. Hext PM, Tomenson JA, Thompson P. Titanium dioxide: inhalation toxicology and epidemiology. Ann Occup Hyg 2005;49(6):461-472 https://doi.org/10.1093/annhyg/mei012
  30. Iglesias EG, Perez-Arizti JA, Marquez-Ramirez SG, Delgado-Buenrostro NL, Chirino YI et al. Titanium dioxide nanoparticles induce strong oxidative stress and mitochondrial damage in glial cells. Free Radic Biol Med 2014;73:84-94 https://doi.org/10.1016/j.freeradbiomed.2014.04.026
  31. Ino K, Natori I, Ichikawa A, Vrtis RN, Ohmi T. Plasma enhanced in situ chamber cleaning evaluated by extracted-plasma-parameter analysis. IEEE Transactions on Semiconductor Manufacturing 1996;9(2):230-240 https://doi.org/10.1109/66.492817
  32. International Agency for Research on Cancer(IARC). "IARC Monographs Volume 100C: Arsenic, Metals, Fibres and Dusts; A Review of Human Carcinogens. 2012
  33. Ji B, Elder DL, Yang JH, Badowski PR, Karwacki EJ. Power dependence of $NF_{3}$ plasma stability for in situ chamber cleaning. J Appl Phys 2009;95:84446-84451
  34. Jin C, Tang Y, Yang G, Li XL, Xu S et al. Cellular toxicity of $TiO_{2}$ nanoparticles in anatase and rutile crystal phase. Biol Trace Element Res 2011;141(1):3-15 https://doi.org/10.1007/s12011-010-8707-0
  35. Johnston CJ, Driscoll KE, Finkestein JN, Baggs R, O'Reilly MA et al. Pulmonary chemokine and mutagenic responses in rats after subchronic inhalation of amorphous and crystalline silica. Toxicol Sci 2000; 56:405-413 https://doi.org/10.1093/toxsci/56.2.405
  36. Karlsson HL, Gustafsson J, Cronholm P, Moller L. Size-dependent toxicity of metal oxide particles-A comparison between nano- and micrometer size. Toxicol Lett 2009;188:112-118 https://doi.org/10.1016/j.toxlet.2009.03.014
  37. Keith LS, Moffett DB, Rosemond ZA, Wohlers DW. ATSDR evaluation of health effect of tungsten and relevance to public health. Toxicol Ind Health 2007;23(5-6): 347-387 https://doi.org/10.1177/0748233707076767
  38. 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
  39. Kobayashi N, Naya M, Endoh S, Maru J, Yamamoto K, Nakanishi J. Comparative pulmonary toxicity study of nano-$TiO_{2}$ particles of different sizes and agglomerations in rats : different short- and long- term post-instillation results. Toxicology 2009;264:110-118 https://doi.org/10.1016/j.tox.2009.08.002
  40. Krelying WG, Semmler M, Erbe F, Mayer P, Takenata S et al. Translocation of ultrafine insoluble iridium particles from lung epithelium to extrapulmonary organs is size dependent by very low. J Tox Environ Health 2002;65:1513-1530 https://doi.org/10.1080/00984100290071649
  41. Kumar C.(Ed) Nanomaterials-Toxicity, Health and Environmental Issues, Nanotechnologies for the Life Sciences Volume 5. Weinheim, Baden-Wurttemberg, Germay: Wiley-VCH, 2008, pp. 86-87
  42. Laulicht F, Cartularo L, Medict S, Peana MF, Zoroddu MA, Costa M. Investigating the potential carcinogenic effects of chronic tungsten(VI) oxide exposure to immortalize human lung cells. Soc Toxicol 2014;138(1):1297e
  43. Leanderson P, Sahle W. Formation of hydroxyl radicals and toxicity of tungsten oxide fibers. Toxic in Vitro 1995;9(2):175-183 https://doi.org/10.1016/0887-2333(94)00197-3
  44. Lesniak A, Fenaroli F, Monopoli MP, Aberg C, Dawson KA, Salvati A. Effects of the presence or absence of a protein corona silica nanoparticle uptake and impact on cells. ACS Nano 2012;6:5845-5857 https://doi.org/10.1021/nn300223w
  45. Li XB, Zheng H, Zhang ZR, Li B, Huang ZY et al. Glia activation induced by peripheral administration of aluminum oxide nanoparticles in rat brains. Nanomedicine: Nanotechnol Biol Med 2009;5:473-479 https://doi.org/10.1016/j.nano.2009.01.013
  46. Li Y, Sun L, Jin M, Du Z, Liu X et al. Size-dependent cytotoxicity of amorphous silica nanoparticles in human hepatoma HepG2 cells. Toxicol in Vitro 2011;25:1343-1352 https://doi.org/10.1016/j.tiv.2011.05.003
  47. Liang M, Lin IC, Whittaker MR, Minchin RF, Monteiro MU, Toth I. Cellular uptake of densely packed polymer coatings on gold nanoparticles. ACS Nano 2010;4:403-413 https://doi.org/10.1021/nn9011237
  48. Lin W, Huang YW, Zhou XD, Ma Y. In vitro toxicity of silica nanoparticle in human lung cancer cells. 2006;217:252-259 https://doi.org/10.1016/j.taap.2006.10.004
  49. Liu H, Ma L, Liu J, Zhao J, Yan J, Hong F. Toxicity of nano-anatase $TiO_{2}$ to mice: Liver injury, oxidative stress. Toxicol Environ Chem 2009;92(1):175-186 https://doi.org/10.1080/02772240902732530
  50. Lu X, Jin T, Jin Y, Wu L, Hu B et al. Toxicogenomic analysis of the particle dose- and size-response relationship of silica particles- induced toxicity in mice. Nanotechnol 2013;24(1):015106 https://doi.org/10.1088/0957-4484/24/1/015106
  51. McCarthy J, Inkielewicz-Stepniak I, Corbalan JJ, Radomski MW. Mechanism of toxicity of amorphous silica nanoparticles on human lung submucosal cells in vitro: protective effects of fisetin. Chem Res Toxicol 2012;25:2227-2235 https://doi.org/10.1021/tx3002884
  52. Mu Q, Hondow NS, Krzeminski L, Brown AP, Jeuken LJC et al. Mechanism of cellular uptake of genotoxic silica nanoparticles. Particle Fibre Toxicol 2012;9(1):29 https://doi.org/10.1186/1743-8977-9-29
  53. Nabeshi H, Yoshikawa T, Matsuyama K, Nakazato Y, Katsuo K et al. Systemic distribution, nuclear entry and cytotoxicity of amorphous nanosilica following topical application. Biomaterials 2011a;32:2713- 2724 https://doi.org/10.1016/j.biomaterials.2010.12.042
  54. Nabeshi H, Yoshikawa T, Matsuyama K, Nakazato Y, Tochigi S et al. Amorphous nanosilica induce endocytosis-dependent ROS generation and DNA damage in human keratinocytes. Particle Fibre Toxicol 2011b;8(1):1-10 https://doi.org/10.1186/1743-8977-8-1
  55. Napierska D, Thomassen LCJ, Rabolli V, Lison D, Gonzalez L et al. Size-dependent cytotoxicity of monodisperse silica nanoparticles in human endothelial cells. Small 2009;5(7):846-853 https://doi.org/10.1002/smll.200800461
  56. Napierska D, Thomassen LCJ, Lison D, Martens JA, Hoet PH. The nanosilica hazard: another variable entity. Part Fibre Toxicol 2010;7(1):39 https://doi.org/10.1186/1743-8977-7-39
  57. Nemmar A, Hoet PH, Nemery B. Translocation of ultrafine particles. Environ Health Perspect 2006;114(4):A211
  58. Nishimori H, Kondoh M, Isoda K, Tsunoda S, Tsutsumi Y, Yagi K. Silica nanoparticles as hepatotoxicant. European J Pharmaceutics Biopharmaceutics 2009;72:496-501 https://doi.org/10.1016/j.ejpb.2009.02.005
  59. Nordberg GF, Fowler BA, Nordberg M, Friberg LT. (third ed.). Handbook on the toxicology of metals. Academic Press. 2011
  60. Oberdorster G, Ferin J, Lehnert BE. Correlation between particle size, in vivo particle persistence, and lung injury. Environ Health Perspect 1994;102:173-179 https://doi.org/10.1289/ehp.94102s5173
  61. Oberdorster G, Sharp Z, Atudorei V, Elder A, Gelein R et al. Extrapulmonary translocation of ultrafine carbon particles following whole-body inhalation exposure of rats. J Toxicol Environ Health A 2002;65:1531-1543 https://doi.org/10.1080/00984100290071658
  62. Oberdorster G, Maynard A, Donaldson K, Castranova V, Fitzpatrick J et al. Principles for characterizing the potential human effects from exposure to nanomaterials: elements of a screening strategy. Part Fibre Toxicol 2005;2(1):8 https://doi.org/10.1186/1743-8977-2-8
  63. OECD. 2001. Guideline for the Testing of Chemicals: Acute Oral Toxicity-Fixed Dose Procedure. Guideline 420. Organization for Economic Cooperation and Development: Paris
  64. Oesterling E, Chopra N, Gavalas V, Arzuaga X, Lim EJ, Sultana R, Butterfield DA, Bachas L, Hennig B. Alumina nanoparticles induce expression of endothelial cell adhesion molecules. Toxicol Lett 2008;178:160-166 https://doi.org/10.1016/j.toxlet.2008.03.011
  65. Parks CG, Conrad K, Cooper GS. Occupational exposure to crystalline silica and autoimmune disease. Environ Health Perspect 1999;107 (Suppl.5):793-802 https://doi.org/10.1289/ehp.99107s5793
  66. Prabhakar PV, Reddy UA, Singh SP, Balasubramanyam A, Rahman MF et al. Oxidative stress induced by aluminum oxide nanomaterials after acute oral treatment in Wistar rats. J Appl Toxicol 2012;32:436-445 https://doi.org/10.1002/jat.1775
  67. Rabolli V, Thomassen LCJ, Uwambayinema F, Martens JA, Lison D. The cytotoxicity activiry of amorphous silica nanoparticles is mainly influenced by surface area and not by aggregation. Toxicol Lett 2011;206:197-203 https://doi.org/10.1016/j.toxlet.2011.07.013
  68. Radzium E, Dudkiewicz-Wilczynska J, Nowak K, Anuszewska E, Kunicki A. et al. Assessment of the cytotoxicity of aluminum oxide nanoparticles on selected mammalian cells. Toxicol In Vitro 2011;25:1694-1700 https://doi.org/10.1016/j.tiv.2011.07.010
  69. Rajiv S, Jerobin J, Saranya V, Nainawat M. Sharma A et al. Comparative cytotoxicity and genotoxicity of cobalt(II, III) oxide, iron (III) oxide, silicon dioxide, and aluminum oxide nanoparticles on human lymphocytes in vitro. Hum Exp Toxicol 2015;0960327105579208
  70. Saquib Q, Al-Khedhairy AA, Siddiqui MA, Abou-Tarboush FM, Azam A, Musarrat J. Titanium dioxide nanoparticles induced cytoxicity, oxidative stress and DNA damage in human amnion epithelial (WISH) cells. Toxicol In Vitro 2012;26:351-361 https://doi.org/10.1016/j.tiv.2011.12.011
  71. Sayes CM, Wahi R, Kurian PA, Liu Y, West JL et al. Correlating nanoscale titania structure with toxicity: a cytotoxicity and inflammatory response study with human dermal fibroblsts and human lung epithelial cells. Toxicol Sci 2006;92(1): 174-185 https://doi.org/10.1093/toxsci/kfj197
  72. Shi H, Magaye R, Castranova V, Zhao J. Titanium dioxide nanoparticles: a review of current toxicological data. Part Fibre Toxicol 2013;10(1): 15 https://doi.org/10.1186/1743-8977-10-15
  73. Simon-Deckers A, Gouget B, Mayne-Lhermite M, Herlin-Boime N, Reynaud C, Carrière M.. In vitro investigation of oxide nanoparticles and carbon nanotube toxicity and intracellular accumulation in A549 human pneumocytes. Toxicology, 2008;253:137-146 https://doi.org/10.1016/j.tox.2008.09.007
  74. Singh S, Shi T, Duffin R, Albrecht C, van Berlo D et al. Endocytosis, oxidative stress and IL-8 expression in human lung epithelial cells upon treatment with fine and ultrafine $TiO_{2}$: role of the specific surface area and of surface methylation of the particles. Toxicol Appl Pharmacol 2007;222:141-151 https://doi.org/10.1016/j.taap.2007.05.001
  75. Shukla RK, Kumar A, Gurbani D, Pandey AK, Singh S, Dhawan A. $TiO_2$ nano particles induce oxidative DNA damage and apoptosis in human liver cells. Nanotoxicology 2013;7(1):48-60 https://doi.org/10.3109/17435390.2011.629747
  76. Skuland T, Ovrevik J, Lag M, Refsnes M. Role of size and surface area for pro-inflammatory response to silica nanoparticles in epithelial lung cells: importance of exposure conditions. Toxicol in Vitro 2014;28:146-155 https://doi.org/10.1016/j.tiv.2013.10.018
  77. Sun L, Li Y, Liu X, Jin M, Zhang L et al. Cytotoxicity and mitochondrial damage caused by silica nanoparticles. Toxicol in Vitro 2011;25:1619-1629 https://doi.org/10.1016/j.tiv.2011.06.012
  78. Sycheva LP, Zhurkov VS, Iurchenko VV, Daugel-Dauge NO, Kovalenko MA et al. Investigation of genotoxic and cytotoxic effects of micro- and nanosized titanium dioxide in six organs of mice in vivo. Mutat Res 2011;726:8-14 https://doi.org/10.1016/j.mrgentox.2011.07.010
  79. Uboldi C, Giudetti G, Broggi F, Gilliland D, Ponti J, Rossi F. Amorphous silica nanoparticles do not induce cytotoxicity, cell transformation or genotoxicity in Balb/3T3 mouse fibroblasts. Mutation Research 2012;745:11-20 https://doi.org/10.1016/j.mrgentox.2011.10.010
  80. US Environmental Protection Agency (EPA), 2010. Nanomaterial Case Studies: Nanoscale Titanium Dioxide in Water Treatment and in Topical Sunscreen. US EPA, Triangle Park, NC
  81. Wang F, Gao F, Lan M, Yuan H, Huang Y et al. Oxidative stress contributes to silica nanoparticle-induced cytotoxicity in human embryonic kidney cells. Toxicol in Vitro 2009;23:808-815 https://doi.org/10.1016/j.tiv.2009.04.009
  82. Wang FS, Liu LF, Chen NM, Li YR. A study on cellular reactions and fibrogenic effects of mineral dusts. Biomed Environ Sci 1994;7(2):116-121
  83. Wang J, Zhou G, Chen C, Yu H, Wang T et al. Acute toxicity and biodistribution of different sized titanium dioxide particles in mice after oral administration. Toxicol Lett 2007;168(1):176-185 https://doi.org/10.1016/j.toxlet.2006.12.001
  84. Warheit DB, Webb TR, Sayes CM, Colvin VL, Reed KL. Pulmonary instillation studies with nanoscale $TiO_2$rods and dots in rats: toxicity is not dependent upon particle size and surface area. Toxicol Sci 2006;91(1):227-236 https://doi.org/10.1093/toxsci/kfj140
  85. Warheit DB, Webb TR, Reed KL, Frerichs S, Sayes CM. Pulmonary toxicity study in rats with three forms of ultrafine-$TiO_2$ particles: different responses related to surface properties. Toxicology 2007;230(1):90-104 https://doi.org/10.1016/j.tox.2006.11.002
  86. Xue C, Wu J, Lan F, Liu W, Yang X et al. Nano titanium dioxide induces the generation of ROS and potential damage in HaCaT cells under UVA irradiation. J Nanosci Nanotechnol 2010; 10(12):8500-8507 https://doi.org/10.1166/jnn.2010.2682
  87. Yamashita K, Yoshioka Y, Higashisaka K, Mimura K, Morishita Y et al. Silica and titanium dioxide nanoparticles cause pregnancy complications in mice. Nature nanotechnol 2011;6(5):321-328 https://doi.org/10.1038/nnano.2011.41
  88. Yang H, Liu C, Yang D, Zhang H, Xi Zhuge. Comparative study of cytotoxicity, oxidative stress and genotoxicity induced by four typical nanomaterials: the role of particle size, shape and composition. J Appl Toxicol 2009;29(1):69-78 https://doi.org/10.1002/jat.1385
  89. Ye Y, Liu J, Chen M, Sun L, Lan M. In vitro toxicity of silica nanoparticles in myocardial cells. Environ Toxicol Pharmacol 2010a;29:131-137 https://doi.org/10.1016/j.etap.2009.12.002
  90. Ye Y, Liu J, Xu J, Sun L, Chen M et al. Nano-$SiO_2$ induces apoptosis via activation of p53 and Bax mediated by oxidative stress in human hepati ccell line. Toxicol in Vitro 2010b;24:751-758 https://doi.org/10.1016/j.tiv.2010.01.001
  91. Yu KO, Grabinski CM, Schrand AM, Murdock RC, Wang W, Gu B et al. Toxicity of amorphous silica nanoparticles in mouse keratinocytes. J Nanopartticle Research 2009;11(1):15-24 https://doi.org/10.1007/s11051-008-9417-9
  92. Zhang Y, Hu L, Yu D, Gao C. Influence of silica particle internalization on adhesion and migration of human dermal fibroblasts. Biomaterials 2010;31:8465-8474 https://doi.org/10.1016/j.biomaterials.2010.07.060
  93. Zhang XQ, Yin LH, Tang M, Pu YP. ZnO, $TiO_{2}$, $SiO_{2}$, and $Al_{2}O_{3}$ nanoparticles-induced toxic effects on human fetal lung fibroblasts. Biomed Environ Sci 2011;24(6): 661-669 https://doi.org/10.3967/0895-3988.2011.06.011