Các hạt nano titanium dioxide: tổng quan về dữ liệu độc học hiện tại

Kisin ER, Murray AR, Keane MJ, Shi XC, Schwegler-Berry D, Gorelik O, Arepalli S, Castranova V, Wallace WE, Kagan VE, Shvedova AA: Single-walled carbon nanotubes: geno- and cytotoxic effects in lung fibroblast V79 cells. J Toxicol Environ Health A 2007, 70: 2071–2079. 10.1080/15287390701601251

Robertson TA, Sanchez WY, Roberts MS: Are commercially available nanoparticles safe when applied to the skin? J Biomed Nanotechnol 2010, 6: 452–468. 10.1166/jbn.2010.1145

EU - European Commission Recommendation on the definition of nanomaterial. http://osha.europa.eu/en/news/eu-european-commission-recommendation-on-the-definition-of-nanomaterial

Riu J, Maroto A, Rius FX: Nanosensors in environmental analysis. Talanta 2006,69(2):288–301. 10.1016/j.talanta.2005.09.045

Ruth Magaye JZ, Linda B, Min D: Genotoxicity and carcinogenicity of cobalt-, nickel- and copper-based nanoparticles (Review). Exp Ther Med 2012, 4: 551–561.

American Conference of Governmental Industrial Hygienists (ACGIH): Threshold limit values and biological exposure indices for 1992–1993. Cincinnati: Ohio: American Conference of Governmental industrial hygienists; 1992.

Participants IRSIW: The relevance of the rat lung response to particle overload for human risk assessment: a workshop consensus report. Inhal Toxicol 2000, 12: 1–17.

Zhao J, Bowman L, Zhang X, Vallyathan V, Young SH, Castranova V, Ding M: Titanium dioxide (TiO2) nanoparticles induce JB6 cell apoptosis through activation of the caspase-8/Bid and mitochondrial pathways. J Toxicol Environ Health A 2009, 72: 1141–1149. 10.1080/15287390903091764

Lee KP, Trochimowicz HJ, Reinhardt CF: Pulmonary response of rats exposed to titanium dioxide (TiO2) by inhalation for two years. Toxicol Appl Pharmacol 1985, 79: 179–192. 10.1016/0041-008X(85)90339-4

IARC: Cobalt in Hard Metals and Cobalt Sulfate, Gallium Arsenide, Indium Phosphide and Vanadium Pentoxide. IARC Sci Publ 2006., 86:

Maynard AD, Kuempel ED: Airborne nanostructured particles and occupational health. J Nanopart Res 2005, 6: 587–614.

Tsuji JS, Maynard AD, Howard PC, James JT, Lam CW, Warheit DB, Santamaria AB: Research strategies for safety evaluation of nanomaterials, part IV: risk assessment of nanoparticles. Toxicol Sci 2006, 89: 42–50.

Fabian E, Landsiedel R, Ma-Hock L, Wiench K, Wohlleben W, van Ravenzwaay B: Tissue distribution and toxicity of intravenously administered titanium dioxide nanoparticles in rats. Arch Toxicol 2008, 82: 151–157. 10.1007/s00204-007-0253-y

Oberdorster G: Pulmonary effects of inhaled ultrafine particles. Int Arch Occup Environ Health 2001, 74: 1–8.

Oberdorster G, Ferin J, Lehnert BE: Correlation between particle size, in vivo particle persistence, and lung injury. Environ Health Perspect 1994,102(Suppl 5):173–179. 10.1289/ehp.94102s5173

Sager TM, Kommineni C, Castranova V: Pulmonary response to intratracheal instillation of ultrafine versus fine titanium dioxide: role of particle surface area. Part Fibre Toxicol 2008, 5: 17. 10.1186/1743-8977-5-17

Long TC, Tajuba J, Sama P, Saleh N, Swartz C, Parker J, Hester S, Lowry GV, Veronesi B: Nanosize titanium dioxide stimulates reactive oxygen species in brain microglia and damages neurons in vitro. Environ Health Perspect 2007, 115: 1631–1637. 10.1289/ehp.10216

Warheit DB, Webb TR, Reed KL, Frerichs S, Sayes CM: Pulmonary toxicity study in rats with three forms of ultrafine-TiO2 particles: differential responses related to surface properties. Toxicology 2007, 230: 90–104. 10.1016/j.tox.2006.11.002

Sayes CM, Wahi R, Kurian PA, Liu Y, West JL, Ausman KD, Warheit DB, Colvin VL: Correlating nanoscale titania structure with toxicity: a cytotoxicity and inflammatory response study with human dermal fibroblasts and human lung epithelial cells. Toxicol Sci 2006, 92: 174–185. 10.1093/toxsci/kfj197

Xue C, Wu J, Lan F, Liu W, Yang X, Zeng F, Xu H: Nano titanium dioxide induces the generation of ROS and potential damage in HaCaT cells under UVA irradiation. J Nanosci Nanotechnol 2010, 10: 8500–8507. 10.1166/jnn.2010.2682

Petkovic J, Zegura B, Stevanovic M, Drnovsek N, Uskokovic D, Novak S, Filipic M: DNA damage and alterations in expression of DNA damage responsive genes induced by TiO2 nanoparticles in human hepatoma HepG2 cells. Nanotoxicology 2011, 5: 341–353. 10.3109/17435390.2010.507316

Wang C, Li Y: Interaction and nanotoxic effect of TiO(2) nanoparticle on fibrinogen by multi-spectroscopic method. Sci Total Environ 2012, 429: 156–160.

Andersson POLC, Ekstrand-Hammarstrom B, Akfur C, Ahlinder L, Bucht A, Osterlund L: Polymorph- and Size-Dependent Uptake and Toxicity of TiO2 Nanoparticles in Living Lung Epithelial Cells. Small 2011, 7: 514–523. 10.1002/smll.201001832

Tedja R, Lim M, Amal R, Marquis C: Effects of serum adsorption on cellular uptake profile and consequent impact of titanium dioxide nanoparticles on human lung cell lines. ACS Nano 2012, 6: 4083–4093. 10.1021/nn3004845

Saber AT, Jensen KA, Jacobsen NR, Birkedal R, Mikkelsen L, Moller P, Loft S, Wallin H, Vogel U: Inflammatory and genotoxic effects of nanoparticles designed for inclusion in paints and lacquers. Nanotoxicology 2012, 6: 453–471. 10.3109/17435390.2011.587900

Ortlieb M: White Giant or White Dwarf?: Particle Size Distribution Measurements of TiO2. GIT Lab J Eur 2010, 14: 42–43.

Baan R, Straif K, Grosse Y, Secretan B, El Ghissassi F, Cogliano V: Carcinogenicity of carbon black, titanium dioxide, and talc. Lancet Oncol 2006, 7: 295–296. 10.1016/S1470-2045(06)70651-9

Shukla RK, Sharma V, Pandey AK, Singh S, Sultana S, Dhawan A: ROS-mediated genotoxicity induced by titanium dioxide nanoparticles in human epidermal cells. Toxicol In Vitro 2011, 25: 231–241. 10.1016/j.tiv.2010.11.008

Kaida T, Kobayashi K, Adachi M, Suzuki F: Optical characteristics of titanium oxide interference film and the film laminated with oxides and their applications for cosmetics. J Cosmet Sci 2004, 55: 219–220.

Wang JJ, Sanderson BJ, Wang H: Cyto- and genotoxicity of ultrafine TiO2 particles in cultured human lymphoblastoid cells. Mutat Res 2007, 628: 99–106. 10.1016/j.mrgentox.2006.12.003

Wolf R, Matz H, Orion E, Lipozencic J: Sunscreens–the ultimate cosmetic. Acta Dermatovenerol Croat 2003, 11: 158–162.

Trouiller B, Reliene R, Westbrook A, Solaimani P, Schiestl RH: Titanium dioxide nanoparticles induce DNA damage and genetic instability in vivo in mice. Cancer Res 2009, 69: 8784–8789. 10.1158/0008-5472.CAN-09-2496

Jacobs JJ, Skipor AK, Black J, Urban R, Galante JO: Release and excretion of metal in patients who have a total hip-replacement component made of titanium-base alloy. J Bone Joint Surg Am 1991, 73: 1475–1486.

Sul YT: Electrochemical growth behavior, surface properties, and enhanced in vivo bone response of TiO2 nanotubes on microstructured surfaces of blasted, screw-shaped titanium implants. Int J Nanomedicine 2010, 5: 87–100.

Patri A, Umbreit T, Zheng J, Nagashima K, Goering P, Francke-Carroll S, Gordon E, Weaver J, Miller T, Sadrieh N: Energy dispersive X-ray analysis of titanium dioxide nanoparticle distribution after intravenous and subcutaneous injection in mice. J Appl Toxicol 2009, 29: 662–672. 10.1002/jat.1454

Ni M, Leung MKH, Leung DYC, Sumathy K: A review and recent developments in photocatalytic water-splitting using TiO2 for hydrogen production. Renewable and Sustainable Energy Reviews 2007, 11: 401–425. 10.1016/j.rser.2005.01.009

Yuan Y, Ding J, Xu J, Deng J, Guo J: TiO2 nanoparticles co-doped with silver and nitrogen for antibacterial application. J Nanosci Nanotechnol 2010, 10: 4868–4874. 10.1166/jnn.2010.2225

Montazer M, Seifollahzadeh S: Enhanced self-cleaning, antibacterial and UV protection properties of nano TiO2 treated textile through enzymatic pretreatment. Photochem Photobiol 2011, 87: 877–883. 10.1111/j.1751-1097.2011.00917.x

Szacilowski K, Macyk W, Drzewiecka-Matuszek A, Brindell M, Stochel G: Bioinorganic photochemistry: frontiers and mechanisms. Chem Rev 2005, 105: 2647–2694. 10.1021/cr030707e

Wiesenthal A, Hunter L, Wang S, Wickliffe J, Wilkerson M: Nanoparticles: small and mighty. Int J Dermatol 2011, 50: 247–254. 10.1111/j.1365-4632.2010.04815.x

Montazer M, Behzadnia A, Pakdel E, Rahimi MK, Moghadam MB: Photo induced silver on nano titanium dioxide as an enhanced antimicrobial agent for wool. J Photochem Photobiol B 2011, 103: 207–214. 10.1016/j.jphotobiol.2011.03.009

Schkroeder HA, Balassa JJ, Tipton IH: Abnormal trace metals in man: titanium. J Chronic Dis 1963, 16: 55–69. 10.1016/0021-9681(63)90019-5

Dankovic D, Kuempel E, Wheeler M: An approach to risk assessment for TiO2. Inhal Toxicol 2007,19(Suppl 1):205–212.

Weir A, Westerhoff P, Fabricius L, Hristovski K, von Goetz N: Titanium dioxide nanoparticles in food and personal care products. Environ Sci Technol 2012, 46: 2242–2250. 10.1021/es204168d

Zhao J, Castranova V: Toxicology of nanomaterials used in nanomedicine. J Toxicol Environ Health B Crit Rev 2011, 14: 593–632. 10.1080/10937404.2011.615113

Saber AT, Jacobsen NR, Mortensen A, Szarek J, Jackson P, Madsen AM, Jensen KA, Koponen IK, Brunborg G, Gutzkow KB: Nanotitanium dioxide toxicity in mouse lung is reduced in sanding dust from paint. Part Fibre Toxicol 2012, 9: 4. 10.1186/1743-8977-9-4

FDA: Listing of color additives exempt from certification. In Code of Federal Regulations Title 21-Food and Drugs. 21 CFR 73.2575. Washington, DC: US Government Printing Office; 2002.

ACGIH: Titanium dioxide. In Documentation of the threshold limit values for chemical substances. 7th edition. Cincinnati, OH: American Conference of Governmental Industrial Hygienists; 2001.

Kitchin KT, Prasad RY, Wallace K: Oxidative stress studies of six TiO(2) and two CeO(2) nanomaterials: Immuno-spin trapping results with DNA. Nanotoxicology 2010, 5: 546–556.

NIOSH: Occupational Exposure to Titanium Dioxide. In Current Intelligence Bulletin 63. Cincinnati: National Institute for Occupational Safety and Health; 2011.

Morimoto Y, Kobayashi N, Shinohara N, Myojo T, Tanaka I, Nakanishi J: Hazard Assessments of Manufactured Nanomaterials. J Occup Health 2010, 52: 325–324. 10.1539/joh.R10003

Curwin B, Bertke S: Exposure characterization of metal oxide nanoparticles in the workplace. J Occup Environ Hyg 2011, 8: 580–587. 10.1080/15459624.2011.613348

Lee JH, Kwon M, Ji JH, Kang CS, Ahn KH, Han JH, Yu IJ: Exposure assessment of workplaces manufacturing nanosized TiO2 and silver. Inhal Toxicol 2011, 23: 226–236. 10.3109/08958378.2011.562567

Methner MM: Effectiveness of a custom-fitted flange and local exhaust ventilation (LEV) system in controlling the release of nanoscale metal oxide particulates during reactor cleanout operations. Int J Occup Environ Health 2010, 16: 475–487. 10.1179/107735210799160039

Hagens WI, Oomen AG, de Jong WH, Cassee FR, Sips AJ: What do we (need to) know about the kinetic properties of nanoparticles in the body? Regul Toxicol Pharmacol 2007, 49: 217–229. 10.1016/j.yrtph.2007.07.006

Lomer MC, Thompson RP, Powell JJ: Fine and ultrafine particles of the diet: influence on the mucosal immune response and association with Crohn's disease. Proc Nutr Soc 2002, 61: 123–130. 10.1079/PNS2001134

Hillyer JF, Albrecht RM: Gastrointestinal persorption and tissue distribution of differently sized colloidal gold nanoparticles. J Pharm Sci 2001, 90: 1927–1936. 10.1002/jps.1143

Jania P, McCarthya D, Florence AT: Titanium dioxide (rutile) particle uptake from the rat GI tract and translocation to systemic organs after oral administration. Int J Pharm 1994, 105: 157–168. 10.1016/0378-5173(94)90461-8

Wang J, Zhou G, Chen C, Yu H, Wang T, Ma Y, Jia G, Gao Y, Li B, Sun J: Acute toxicity and biodistribution of different sized titanium dioxide particles in mice after oral administration. Toxicol Lett 2007, 168: 176–185. 10.1016/j.toxlet.2006.12.001

Senzui M, Tamura T, Miura K, Ikarashi Y, Watanabe Y, Fujii M: Study on penetration of titanium dioxide (TiO(2)) nanoparticles into intact and damaged skin in vitro. J Toxicol Sci 2010, 35: 107–113. 10.2131/jts.35.107

Schulz J, Hohenberg H, Pflucker F, Gartner E, Will T, Pfeiffer S, Wepf R, Wendel V, Gers-Barlag H, Wittern KP: Distribution of sunscreens on skin. Adv Drug Deliv Rev 2002,54(Suppl 1):S157–163.

Pflucker F, Wendel V, Hohenberg H, Gartner E, Will T, Pfeiffer S, Wepf R, Gers-Barlag H: The human stratum corneum layer: an effective barrier against dermal uptake of different forms of topically applied micronised titanium dioxide. Skin Pharmacol Appl Skin Physiol 2001,14(Suppl 1):92–97.

Gamer AO, Leibold E, van Ravenzwaay B: The in vitro absorption of microfine zinc oxide and titanium dioxide through porcine skin. Toxicol In Vitro 2006, 20: 301–307. 10.1016/j.tiv.2005.08.008

Sadrieh N, Wokovich AM, Gopee NV, Zheng J, Haines D, Parmiter D, Siitonen PH, Cozart CR, Patri AK, McNeil SE: Lack of significant dermal penetration of titanium dioxide from sunscreen formulations containing nano- and submicron-size TiO2 particles. Toxicol Sci 2010, 115: 156–166. 10.1093/toxsci/kfq041

Newman MD, Stotland M, Ellis JI: The safety of nanosized particles in titanium dioxide- and zinc oxide-based sunscreens. J Am Acad Dermatol 2009, 61: 685–692. 10.1016/j.jaad.2009.02.051

Lademann J, Weigmann H, Rickmeyer C, Barthelmes H, Schaefer H, Mueller G, Sterry W: Penetration of titanium dioxide microparticles in a sunscreen formulation into the horny layer and the follicular orifice. Skin Pharmacol Appl Skin Physiol 1999, 12: 247–256. 10.1159/000066249

Escobar-Chavez JJ, Merino-Sanjuan V, Lopez-Cervantes M, Urban-Morlan Z, Pinon-Segundo E, Quintanar-Guerrero D, Ganem-Quintanar A: The tape-stripping technique as a method for drug quantification in skin. J Pharm Pharm Sci 2008, 11: 104–130.

Tan MH, Commens CA, Burnett L, Snitch PJ: A pilot study on the percutaneous absorption of microfine titanium dioxide from sunscreens. Australas J Dermatol 1996, 37: 185–187. 10.1111/j.1440-0960.1996.tb01050.x

Bennat C, Muller-Goymann CC: Skin penetration and stabilization of formulations containing microfine titanium dioxide as physical UV filter. Int J Cosmet Sci 2000, 22: 271–283. 10.1046/j.1467-2494.2000.00009.x

Sagawa Y, Futakuchi M, Xu J, Fukamachi K, Sakai Y, Ikarashi Y, Nishimura T, Suzui M, Tsuda H, Morita A: Lack of promoting effect of titanium dioxide particles on chemically-induced skin carcinogenesis in rats and mice. J Toxicol Sci 2012, 37: 317–327. 10.2131/jts.37.317

Xu J, Sagawa Y, Futakuchi M, Fukamachi K, Alexander DB, Furukawa F, Ikarashi Y, Uchino T, Nishimura T, Morita A: Lack of promoting effect of titanium dioxide particles on ultraviolet B-initiated skin carcinogenesis in rats. Food Chem Toxicol 2011, 49: 1298–1302. 10.1016/j.fct.2011.03.011

Monteiro-Riviere NA, Wiench K, Landsiedel R, Schulte S, Inman AO, Riviere JE: Safety evaluation of sunscreen formulations containing titanium dioxide and zinc oxide nanoparticles in UVB sunburned skin: an in vitro and in vivo study. Toxicol Sci 2011, 123: 264–280. 10.1093/toxsci/kfr148

Miquel-Jeanjean C, Crepel F, Raufast V, Payre B, Datas L, Bessou-Touya S, Duplan H: Penetration Study of Formulated Nanosized Titanium Dioxide in Models of Damaged and Sun-Irradiated Skins. Photochem Photobiol 2012, 88: 1513–1521. 10.1111/j.1751-1097.2012.01181.x

Filipe P, Silva JN, Silva R, Cirne de Castro JL, Marques Gomes M, Alves LC, Santus R, Pinheiro T: Stratum corneum is an effective barrier to TiO2 and ZnO nanoparticle percutaneous absorption. Skin Pharmacol Physiol 2009, 22: 266–275. 10.1159/000235554

Simko M, Mattsson MO: Risks from accidental exposures to engineered nanoparticles and neurological health effects: a critical review. Part Fibre Toxicol 2010, 7: 42. 10.1186/1743-8977-7-42

Kuempel ED, Tran CL, Castranova V, Bailer AJ: Lung dosimetry and risk assessment of nanoparticles: evaluating and extending current models in rats and humans. Inhal Toxicol 2006, 18: 717–724. 10.1080/08958370600747887

Muhlfeld C, Geiser M, Kapp N, Gehr P, Rothen-Rutishauser B: Re-evaluation of pulmonary titanium dioxide nanoparticle distribution using the "relative deposition index": Evidence for clearance through microvasculature. Part Fibre Toxicol 2007, 4: 7. 10.1186/1743-8977-4-7

Driscoll KE, Costa DL, Hatch G, Henderson R, Oberdorster G, Salem H, Schlesinger RB: Intratracheal instillation as an exposure technique for the evaluation of respiratory tract toxicity: uses and limitations. Toxicol Sci 2000, 55: 24–35. 10.1093/toxsci/55.1.24

Li Y, Li J, Yin J, Li W, Kang C, Huang Q, Li Q: Systematic influence induced by 3 nm titanium dioxide following intratracheal instillation of mice. J Nanosci Nanotechnol 2010, 10: 8544–8549. 10.1166/jnn.2010.2690

Wang J, Liu Y, Jiao F, Lao F, Li W, Gu Y, Li Y, Ge C, Zhou G, Li B: Time-dependent translocation and potential impairment on central nervous system by intranasally instilled TiO(2) nanoparticles. Toxicology 2008, 254: 82–90. 10.1016/j.tox.2008.09.014

Wang J, Chen C, Liu Y, Jia F, Li W, Lao F, Lia Y, Lia B, Ge C, Zhou G: Potential neurological lesion after nasal instillation of TiO 2 nanoparticles in the anatase and rutile crystal phases. Toxicol Lett 2008, 183: 72–80. 10.1016/j.toxlet.2008.10.001

Deng ZJ, Mortimer G, Schiller T, Musumeci A, Martin D, Minchin RF: Differential plasma protein binding to metal oxide nanoparticles. Nanotechnology 2009, 20: 455101. 10.1088/0957-4484/20/45/455101

Cedervall T, Lynch I, Lindman S, Berggard T, Thulin E, Nilsson H, Dawson KA, Linse S: Understanding the nanoparticle-protein corona using methods to quantify exchange rates and affinities of proteins for nanoparticles. Proc Natl Acad Sci U S A 2007, 104: 2050–2055. 10.1073/pnas.0608582104

Mikkelsen L, Sheykhzade M, Jensen KA, Saber AT, Jacobsen NR, Vogel U, Wallin H, Loft S, Moller P: Modest effect on plaque progression and vasodilatory function in atherosclerosis-prone mice exposed to nanosized TiO(2). Part Fibre Toxicol 2011, 8: 32. 10.1186/1743-8977-8-32

Rothen-Rutishauser BM, Schurch S, Haenni B, Kapp N, Gehr P: Interaction of fine particles and nanoparticles with red blood cells visualized with advanced microscopic techniques. Environ Sci Technol 2006, 40: 4353–4359. 10.1021/es0522635

Geiser M: Update on macrophage clearance of inhaled micro- and nanoparticles. J Aerosol Med Pulm Drug Deliv 2010, 23: 207–217. 10.1089/jamp.2009.0797

Wick P, Malek A, Manser P, Meili D, Maeder-Althaus X, Diener L, Diener PA, Zisch A, Krug HF, von Mandach U: Barrier capacity of human placenta for nanosized materials. Environ Health Perspect 2010, 118: 432–436. 10.1289/ehp.118-a432

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: 20. 10.1186/1743-8977-6-20

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 Heal Sci 2009, 55: 95–102. 10.1248/jhs.55.95

Hougaard KS, Jackson P, Jensen KA, Sloth JJ, Loschner K, Larsen EH, Birkedal RK, Vibenholt A, Boisen AM, Wallin H, Vogel U: Effects of prenatal exposure to surface-coated nanosized titanium dioxide (UV-Titan). A study in mice. Part Fibre Toxicol 2010, 7: 16. 10.1186/1743-8977-7-16

Geiser M, Kreyling WG: Deposition and biokinetics of inhaled nanoparticles. Part Fibre Toxicol 2010, 7: 2. 10.1186/1743-8977-7-2

Eydner M, Schaudien D, Creutzenberg O, Ernst H, Hansen T, Baumgartner W, Rittinghausen S: Impacts after inhalation of nano- and fine-sized titanium dioxide particles: morphological changes, translocation within the rat lung, and evaluation of particle deposition using the relative deposition index. Inhal Toxicol 2012, 24: 557–569. 10.3109/08958378.2012.697494

Scherbart AM, Langer J, Bushmelev A, van Berlo D, Haberzettl P, van Schooten FJ, Schmidt AM, Rose CR, Schins RP, Albrecht C: Contrasting macrophage activation by fine and ultrafine titanium dioxide particles is associated with different uptake mechanisms. Part Fibre Toxicol 2011, 8: 31. 10.1186/1743-8977-8-31

Ferin J, Oberdorster G, Penney DP: Pulmonary retention of ultrafine and fine particles in rats. Am J Respir Cell Mol Biol 1992, 6: 535–542. 10.1165/ajrcmb/6.5.535

Churg A, Stevens B, Wright JL: Comparison of the uptake of fine and ultrafine TiO2 in a tracheal explant system. Am J Physiol 1998, 274: L81–86.

Chen J, Dong X, Zhao J, Tang G: In vivo acute toxicity of titanium dioxide nanoparticles to mice after intraperitioneal injection. J Appl Toxicol 2009, 29: 330–337. 10.1002/jat.1414

Liu H, Ma L, Zhao J, Liu J, Yan J, Ruan J, Hong F: Biochemical toxicity of nano-anatase TiO2 particles in mice. Biol Trace Elem Res 2009, 129: 170–180. 10.1007/s12011-008-8285-6

Ma L, Liu J, Li N, Wang J, Duan Y, Yan J, Liu H, Wang H, Hong F: Oxidative stress in the brain of mice caused by translocated nanoparticulate TiO2 delivered to the abdominal cavity. Biomaterials 2010, 31: 99–105. 10.1016/j.biomaterials.2009.09.028

World Health Organization (WHO): Environmental Health Criteria 24-Titanium. In International Programme on Chemical Safety. Geneva: World Health Organization; 1982.

Huggins CB, Froehlich JP: High concentration of injected titanium dioxide in abdominal lymph nodes. J Exp Med 1966, 124: 1099–1106. 10.1084/jem.124.6.1099

Geiser M, Casaulta M, Kupferschmid B, Schulz H, Semmler-Behnke M, Kreyling W: The role of macrophages in the clearance of inhaled ultrafine titanium dioxide particles. Am J Respir Cell Mol Biol 2008, 38: 371–376. 10.1165/rcmb.2007-0138OC

Tang M, Zhang T, Xue Y, Wang S, Huang M, Yang Y, Lu M, Lei H, Kong L, Yuepu P: Dose dependent in vivo metabolic characteristics of titanium dioxide nanoparticles. J Nanosci Nanotechnol 2010, 10: 8575–8583. 10.1166/jnn.2010.2482

Ma-Hock L, Burkhardt S, Strauss V, Gamer AO, Wiench K, van Ravenzwaay B, Landsiedel R: Development of a short-term inhalation test in the rat using nano-titanium dioxide as a model substance. Inhal Toxicol 2009, 21: 102–118. 10.1080/08958370802361057

Grassian VH, O'Shaughnessy PT, Adamcakova-Dodd A, Pettibone JM, Thorne PS: Inhalation exposure study of titanium dioxide nanoparticles with a primary particle size of 2 to 5 nm. Environ Health Perspect 2007, 115: 397–402. 10.1289/ehp.10302R

Nurkiewicz TR, Porter DW, Hubbs AF, Cumpston JL, Chen BT, Frazer DG, Castranova V: Nanoparticle inhalation augments particle-dependent systemic microvascular dysfunction. Part Fibre Toxicol 2008, 5: 1. 10.1186/1743-8977-5-1

Nurkiewicz TR, Porter DW, Hubbs AF, Stone S, Moseley AM, Cumpston JL, Goodwill AG, Frisbee SJ, Perrotta PL, Brock RW: Pulmonary particulate matter and systemic microvascular dysfunction. Res Rep Health Eff Inst 2011, 3–48.

LeBlanc AJ, Cumpston JL, Chen BT, Frazer D, Castranova V, Nurkiewicz TR: Nanoparticle inhalation impairs endothelium-dependent vasodilation in subepicardial arterioles. J Toxicol Environ Health A 2009, 72: 1576–1584. 10.1080/15287390903232467

Sun Q, Hong X, Wold LE: Cardiovascular effects of ambient particulate air pollution exposure. Circulation 2010, 121: 2755–2765. 10.1161/CIRCULATIONAHA.109.893461

Liu R, Yin L, Pu Y, Liang G, Zhang J, Su Y, Xiao Z, Ye B: Pulmonary toxicity induced by three forms of titanium dioxide nanoparticles via intra-tracheal instillation in rats. Prog Nat Sci 2009, 19: 573–579. 10.1016/j.pnsc.2008.06.020

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. 10.1016/j.tox.2009.08.002

Liu R, Zhang X, Pu Y, Yin L, Li Y, Liang G, Li X, Zhang J: Small-sized titanium dioxide nanoparticles mediate immune toxicity in rat pulmonary alveolar macrophages in vivo. J Nanosci Nanotechnol 2010, 10: 5161–5169. 10.1166/jnn.2010.2420

Liu R, Yin LH, Pu YP, Li YH, Zhang XQ, Liang GY, Li XB, Zhang J, Li YF, Zhang XY: The immune toxicity of titanium dioxide on primary pulmonary alveolar macrophages relies on their surface area and crystal structure. J Nanosci Nanotechnol 2010, 10: 8491–8499. 10.1166/jnn.2010.2685

Hussain S, Vanoirbeek JA, Luyts K, De Vooght V, Verbeken E, Thomassen LC, Martens JA, Dinsdale D, Boland S, Marano F: Lung exposure to nanoparticles modulates an asthmatic response in a mouse model. Eur Respir J 2011, 37: 299–309. 10.1183/09031936.00168509

Warheit DB, Hoke RA, Finlay C, Donner EM, Reed KL, Sayes CM: Development of a base set of toxicity tests using ultrafine TiO2 particles as a component of nanoparticle risk management. Toxicol Lett 2007, 171: 99–110. 10.1016/j.toxlet.2007.04.008

Liu Q, Hong Z, Guo B, Zhang Y, Li Y, Liu J: Experimental Study on Toxicity of Nanosized Titanium Dioxide. Mod Preventive Med 2006, 33: 1211–1212.

Unnithan J, Rehman MU, Ahmad FJ, Samim M: Aqueous synthesis and concentration-dependent dermal toxicity of TiO2 nanoparticles in Wistar rats. Biol Trace Elem Res 2011, 143: 1682–1694. 10.1007/s12011-011-9010-4

Ma L, Zhao J, Wang J, Liu J, Duan Y, Liu H, Li N, Yan J, Ruan J, Wang H, Hong F: The Acute Liver Injury in Mice Caused by Nano-Anatase TiO2. Nanoscale Res Lett 2009, 4: 1275–1285. 10.1007/s11671-009-9393-8

Chen EY, Garnica M, Wang YC, Mintz AJ, Chen CS, Chin WC: A mixture of anatase and rutile TiO(2) nanoparticles induces histamine secretion in mast cells. Part Fibre Toxicol 2012, 9: 2. 10.1186/1743-8977-9-2

Li SQ, Zhu RR, Zhu H, Xue M, Sun XY, Yao SD, Wang SL: Nanotoxicity of TiO(2) nanoparticles to erythrocyte in vitro. Food Chem Toxicol 2008, 46: 3626–3631. 10.1016/j.fct.2008.09.012

Aisaka Y, Kawaguchi R, Watanabe S, Ikeda M, Igisu H: Hemolysis caused by titanium dioxide particles. Inhal Toxicol 2008, 20: 891–893. 10.1080/08958370802304123

Zhang J, Song W, Guo J, Sun Z, Li L, Ding F, Gao M: Cytotoxicity of different sized TiO2 nanoparticles in mouse macrophages. Toxicol Ind Health 2012. http://tih.sagepub.com/content/early/2012/04/16/0748233712442708.abstract

Qi K, Deng FR, Guo XB: [Effects of nanoscale titanium dioxide on intercellular gap junction communication in human lung fibroblasts]. Beijing Da Xue Xue Bao 2009, 41: 297–301.

Rossi EMPL, Koivisto AJ, Vippopa M, Jensen KA, Miettinen M, Sirola K, Nykasenoja H, Karisola P, Stjernvall T, Vanhala E, Kiilunen M, Pasanen P, Makinen M, Hameri K, Joutsensaari J, Tuomi T, Jokiniemi J, Wolff H, Savolainen K, Matikainen S, Alenius H: Airway Exposure to Silica-Coated TiO2 Nanoparticles Induces Pulmonary Neutrophilia in Mice. Toxicol Sci 2010, 113: 422–433. 10.1093/toxsci/kfp254

Zhang Y, Tao J, He P, Tang Y, Wang Y: Bio-effects of nano-TiO2 on lungs of mice. Sheng Wu Yi Xue Gong Cheng Xue Za Zhi 2009, 26: 803–806.

Oberdorster G, Finkelstein JN, Johnston C, Gelein R, Cox C, Baggs R, Elder AC: Acute pulmonary effects of ultrafine particles in rats and mice. Res Rep Health Eff Inst 2000, 95: 5–74.

Hu JQ, Chen CY, Bai R, Zhen S, Du XM, Zang JJ, Li JC, Gu YQ, Jia G: [Effect of nano-TiO(2) intratracheal instillation on lipid metabolism of AopE gene-knockout mice]. Zhonghua Yu Fang Yi Xue Za Zhi 2010, 44: 780–784.

Larsen ST, Roursgaard M, Jensen KA, Nielsen GD: Nano titanium dioxide particles promote allergic sensitization and lung inflammation in mice. Basic Clin Pharmacol Toxicol 2010, 106: 114–117. 10.1111/j.1742-7843.2009.00473.x

Bu Q, Yan G, Deng P, Peng F, Lin H, Xu Y, Cao Z, Zhou T, Xue A, Wang Y: NMR-based metabonomic study of the sub-acute toxicity of titanium dioxide nanoparticles in rats after oral administration. Nanotechnology 2010, 21: 125105. 10.1088/0957-4484/21/12/125105

Bermudez E, Mangum JB, Wong BA, Asgharian B, Hext PM, Warheit DB, Everitt JI: Pulmonary responses of mice, rats, and hamsters to subchronic inhalation of ultrafine titanium dioxide particles. Toxicol Sci 2004, 77: 347–357. 10.1093/toxsci/kfh019

Warheit DB, Webb TR, Sayes CM, Colvin VL, Reed KL: Pulmonary instillation studies with nanoscale TiO2 rods and dots in rats: toxicity is not dependent upon particle size and surface area. Toxicol Sci 2006, 91: 227–236. 10.1093/toxsci/kfj140

Roursgaard M, Jensen KA, Poulsen SS, Jensen NE, Poulsen LK, Hammer M, Nielsen GD, Larsen ST: Acute and subchronic airway inflammation after intratracheal instillation of quartz and titanium dioxide agglomerates in mice. Sci World J 2011, 11: 801–825.

Wang JX, Li YF, Zhou GQ, Li B, Jiao F, Chen CY, Gao YX, Zhao YL, Chai ZF: [Influence of intranasal instilled titanium dioxide nanoparticles on monoaminergic neurotransmitters of female mice at different exposure time]. Zhonghua Yu Fang Yi Xue Za Zhi 2007, 41: 91–95.

Wu J, Liu W, Xue C, Zhou S, Lan F, Bi L, Xu H, Yang X, Zeng FD: Toxicity and penetration of TiO2 nanoparticles in hairless mice and porcine skin after subchronic dermal exposure. Toxicol Lett 2009, 191: 1–8. 10.1016/j.toxlet.2009.05.020

Hu R, Gong X, Duan Y, Li N, Che Y, Cui Y, Zhou M, Liu C, Wang H, Hong F: Neurotoxicological effects and the impairment of spatial recognition memory in mice caused by exposure to TiO2 nanoparticles. Biomaterials 2010, 31: 8043–8050. 10.1016/j.biomaterials.2010.07.011

Baskerville A, Fitzgeorge RB, Gilmour MI, Dowsett AB, Williams A, Featherstone AS: Effects of inhaled titanium dioxide dust on the lung and on the course of experimental Legionnaires' disease. Br J Exp Pathol 1988, 69: 781–792.

Warheit DB, Yuen IS, Kelly DP, Snajdr S, Hartsky MA: Subchronic inhalation of high concentrations of low toxicity, low solubility particulates produces sustained pulmonary inflammation and cellular proliferation. Toxicol Lett 1996, 88: 249–253. 10.1016/0378-4274(96)82678-6

Warheit DB, Hansen JF, Yuen IS, Kelly DP, Snajdr SI, Hartsky MA: Inhalation of high concentrations of low toxicity dusts in rats results in impaired pulmonary clearance mechanisms and persistent inflammation. Toxicol Appl Pharmacol 1997, 145: 10–22. 10.1006/taap.1997.8102

Bermudez E, Mangum JB, Asgharian B, Wong BA, Reverdy EE, Janszen DB, Hext PM, Warheit DB, Everitt JI: Long-term pulmonary responses of three laboratory rodent species to subchronic inhalation of pigmentary titanium dioxide particles. Toxicol Sci 2002, 70: 86–97. 10.1093/toxsci/70.1.86

Sang X, Zheng L, Sun Q, Li N, Cui Y, Hu R, Gao G, Cheng Z, Cheng J, Gui S: The chronic spleen injury of mice following long-term exposure to titanium dioxide nanoparticles. J Biomed Mater Res A 2012, 100: 894–902.

Lu PJ, Ho IC, Lee TC: Induction of sister chromatid exchanges and micronuclei by titanium dioxide in Chinese hamster ovary-K1 cells. Mutat Res 1998, 414: 15–20. 10.1016/S1383-5718(98)00034-5

IARC: Titanium dioxide. In IARC monographs on the evaluation of carcinogenic risks to humans, volume 47. Lyon; 1989:307–328.

Yazdi AS, Guarda G, Riteau N, Drexler SK, Tardivel A, Couillin I, Tschopp J: Nanoparticles activate the NLR pyrin domain containing 3 (Nlrp3) inflammasome and cause pulmonary inflammation through release of IL-1alpha and IL-1beta. Proc Natl Acad Sci U S A 2010, 107: 19449–19454. 10.1073/pnas.1008155107

Kan H, Wu Z, Young SH, Chen TH, Cumpston JL, Chen F, Kashon ML, Castranova V: Pulmonary exposure of rats to ultrafine titanium dioxide enhances cardiac protein phosphorylation and substance P synthesis in nodose ganglia. Nanotoxicology 2011, 6: 736–745.

Driscoll KE, Deyo LC, Carter JM, Howard BW, Hassenbein DG, Bertram TA: Effects of particle exposure and particle-elicited inflammatory cells on mutation in rat alveolar epithelial cells. Carcinogenesis 1997, 18: 423–430. 10.1093/carcin/18.2.423

Cui Y, Liu H, Zhou M, Duan Y, Li N, Gong X, Hu R, Hong M, Hong F: Signaling pathway of inflammatory responses in the mouse liver caused by TiO2 nanoparticles. J Biomed Mater Res A 2011, 96: 221–229.

Gui S, Zhang Z, Zheng L, Cui Y, Liu X, Li N, Sang X, Sun Q, Gao G, Cheng Z: Molecular mechanism of kidney injury of mice caused by exposure to titanium dioxide nanoparticles. J Hazard Mater 2011, 195: 365–370.

Sun Q, Tan D, Ze Y, Sang X, Liu X, Gui S, Cheng Z, Cheng J, Hu R, Gao G: Pulmotoxicological effects caused by long-term titanium dioxide nanoparticles exposure in mice. J Hazard Mater 2012, 235–236: 47–53.

Li N, Duan Y, Hong M, Zheng L, Fei M, Zhao X, Wang J, Cui Y, Liu H, Cai J: Spleen injury and apoptotic pathway in mice caused by titanium dioxide nanoparticules. Toxicol Lett 2010, 195: 161–168. 10.1016/j.toxlet.2010.03.1116

Jackson P, Halappanavar S, Hougaard KS, Williams A, Madsen AM, Lamson JS, Andersen O, Yauk C, Wallin H, Vogel U: Maternal inhalation of surface-coated nanosized titanium dioxide (UV-Titan) in C57BL/6 mice: effects in prenatally exposed offspring on hepatic DNA damage and gene expression. Nanotoxicology 2011, 7: 85–96.

Halappanavar S, Jackson P, Williams A, Jensen KA, Hougaard KS, Vogel U, Yauk CL, Wallin H: Pulmonary response to surface-coated nanotitanium dioxide particles includes induction of acute phase response genes, inflammatory cascades, and changes in microRNAs: a toxicogenomic study. Environ Mol Mutagen 2011, 52: 425–439. 10.1002/em.20639

Boisen AM, Shipley T, Jackson P, Hougaard KS, Wallin H, Yauk CL, Vogel U: NanoTIO2 (UV-Titan) does not induce ESTR mutations in the germline of prenatally exposed female mice. Part Fibre Toxicol 2012, 9: 19. 10.1186/1743-8977-9-19

Lindberg HK, Falck GC, Catalan J, Koivisto AJ, Suhonen S, Jarventaus H, Rossi EM, Nykasenoja H, Peltonen Y, Moreno C: Genotoxicity of inhaled nanosized TiO(2) in mice. Mutat Res 2012, 745: 58–64. 10.1016/j.mrgentox.2011.10.011

Gallagher J, Heinrich U, George M, Hendee L, Phillips DH, Lewtas J: Formation of DNA adducts in rat lung following chronic inhalation of diesel emissions, carbon black and titanium dioxide particles. Carcinogenesis 1994, 15: 1291–1299. 10.1093/carcin/15.7.1291

Zucker RM, Massaro EJ, Sanders KM, Degn LL, Boyes WK: Detection of TiO2 nanoparticles in cells by flow cytometry. Cytometry A 2010, 77: 677–685.

Jugan ML, Barillet S, Simon-Deckers A, Herlin-Boime N, Sauvaigo S, Douki T, Carriere M: Titanium dioxide nanoparticles exhibit genotoxicity and impair DNA repair activity in A549 cells. Nanotoxicology 2012, 6: 501–513. 10.3109/17435390.2011.587903

Saquib Q, Al-Khedhairy AA, Siddiqui MA, Abou-Tarboush FM, Azam A, Musarrat J: Titanium dioxide nanoparticles induced cytotoxicity, oxidative stress and DNA damage in human amnion epithelial (WISH) cells. Toxicol In Vitro 2012, 26: 351–361. 10.1016/j.tiv.2011.12.011

Bhattacharya K, Davoren M, Boertz J, Schins RP, Hoffmann E, Dopp E: Titanium dioxide nanoparticles induce oxidative stress and DNA-adduct formation but not DNA-breakage in human lung cells. Part Fibre Toxicol 2009, 6: 17. 10.1186/1743-8977-6-17

Bhattacharya K, Cramer H, Albrecht C, Schins R, Rahman Q, Zimmermann U, Dopp E: Vanadium pentoxide-coated ultrafine titanium dioxide particles induce cellular damage and micronucleus formation in V79 cells. J Toxicol Environ Health A 2008, 71: 976–980. 10.1080/15287390801989218

Morishige T, Yoshioka Y, Tanabe A, Yao X, Tsunoda S, Tsutsumi Y, Mukai Y, Okada N, Nakagawa S: Titanium dioxide induces different levels of IL-1beta production dependent on its particle characteristics through caspase-1 activation mediated by reactive oxygen species and cathepsin B. Biochem Biophys Res Commun 2010, 392: 160–165. 10.1016/j.bbrc.2009.12.178

Vamanu CI, Cimpan MR, Hol PJ, Sornes S, Lie SA, Gjerdet NR: Induction of cell death by TiO2 nanoparticles: studies on a human monoblastoid cell line. Toxicol In Vitro 2008, 22: 1689–1696. 10.1016/j.tiv.2008.07.002

Wilhelmi V, Fischer U, van Berlo D, Schulze-Osthoff K, Schins RP, Albrecht C: Evaluation of apoptosis induced by nanoparticles and fine particles in RAW 264.7 macrophages: facts and artefacts. Toxicol In Vitro 2012, 26: 323–334. 10.1016/j.tiv.2011.12.006

Kang SJ, Kim BM, Lee YJ, Hong SH, Chung HW: Titanium dioxide nanoparticles induce apoptosis through the JNK/p38-caspase-8-Bid pathway in phytohemagglutinin-stimulated human lymphocytes. Biochem Biophys Res Commun 2009, 386: 682–687. 10.1016/j.bbrc.2009.06.097

Shi Y, Wang F, He J, Yadav S, Wang H: Titanium dioxide nanoparticles cause apoptosis in BEAS-2B cells through the caspase 8/t-Bid-independent mitochondrial pathway. Toxicol Lett 2010, 196: 21–27. 10.1016/j.toxlet.2010.03.014

Kang SJ, Kim BM, Lee YJ, Chung HW: Titanium dioxide nanoparticles trigger p53-mediated damage response in peripheral blood lymphocytes. Environ Mol Mutagen 2008, 49: 399–405. 10.1002/em.20399

Xue C, Liu W, Wu J, Yang X, Xu H: Chemoprotective effect of N-acetylcysteine (NAC) on cellular oxidative damages and apoptosis induced by nano titanium dioxide under UVA irradiation. Toxicol In Vitro 2011, 25: 110–116. 10.1016/j.tiv.2010.09.014

Ghosh M, Bandyopadhyay M, Mukherjee A: Genotoxicity of titanium dioxide (TiO2) nanoparticles at two trophic levels: plant and human lymphocytes. Chemosphere 2010, 81: 1253–1262. 10.1016/j.chemosphere.2010.09.022

Falck GC, Lindberg HK, Suhonen S, Vippola M, Vanhala E, Catalan J, Savolainen K, Norppa H: Genotoxic effects of nanosized and fine TiO2. Hum Exp Toxicol 2009, 28: 339–352. 10.1177/0960327109105163

Mano SSKK, Sonezaki S, Taniguchi A: Effect of Polyethylene Glycol Modification of TiO2 Nanoparticles on Cytotoxicity and Gene Expressions in Human Cell Lines. Int J Mol Sci 2012, 13: 3703–3717. 10.3390/ijms13033703

Gerloff K, Fenoglio I, Carella E, Kolling J, Albrecht C, Boots AW, Forster I, Schins RP: Distinctive toxicity of TiO2 rutile/anatase mixed phase nanoparticles on Caco-2 cells. Chem Res Toxicol 2012, 25: 646–655. 10.1021/tx200334k

Gurr JR, Wang AS, Chen CH, Jan KY: Ultrafine titanium dioxide particles in the absence of photoactivation can induce oxidative damage to human bronchial epithelial cells. Toxicology 2005, 213: 66–73. 10.1016/j.tox.2005.05.007

Huang S, Chueh PJ, Lin YW, Shih TS, Chuang SM: Disturbed mitotic progression and genome segregation are involved in cell transformation mediated by nano-TiO2 long-term exposure. Toxicol Appl Pharmacol 2009, 241: 182–194. 10.1016/j.taap.2009.08.013

Rahman Q, Lohani M, Dopp E, Pemsel H, Jonas L, Weiss DG, Schiffmann D: Evidence that ultrafine titanium dioxide induces micronuclei and apoptosis in Syrian hamster embryo fibroblasts. Environ Health Perspect 2002, 110: 797–800.

Guichard Y, Schmit J, Darne C, Gate L, Goutet M, Rousset D, Rastoix O, Wrobel R, Witschger O, Martin A: Cytotoxicity and genotoxicity of nanosized and microsized titanium dioxide and iron oxide particles in Syrian hamster embryo cells. Ann Occup Hyg 2012, 56: 631–644.

Di Virgilio AL, Reigosa M, Arnal PM, Fernandez Lorenzo De Mele M: Comparative study of the cytotoxic and genotoxic effects of titanium oxide and aluminium oxide nanoparticles in Chinese hamster ovary (CHO-K1) cells. J Hazard Mater 2010, 177: 711–718. 10.1016/j.jhazmat.2009.12.089

Wang S, Hunter LA, Arslan Z, Wilkerson MG, Wickliffe JK: Chronic exposure to nanosized, anatase titanium dioxide is not cyto- or genotoxic to Chinese hamster ovary cells. Environ Mol Mutagen 2011, 52: 614–622. 10.1002/em.20660

Setyawati MI, Khoo PK, Eng BH, Xiong S, Zhao X, Das GK, Tan TT, Loo JS, Leong DT, Ng KW: Cytotoxic and genotoxic characterization of titanium dioxide, gadolinium oxide, and poly(lactic-co-glycolic acid) nanoparticles in human fibroblasts. J Biomed Mater Res A 2012, 101: 633–640.

Prasad RY, Chastain PD, Nikolaishvili-Feinberg N, Smeester L, Kaufmann WK, Fry RC: Titanium dioxide nanoparticles activate the ATM-Chk2 DNA damage response in human dermal fibroblasts. Nanotoxicology 2012. 10.3109/17435390.2012.710659

Li N, Ma L, Wang J, Zheng L, Liu J, Duan Y, Liu H, Zhao X, Wang S, Wang H: Interaction Between Nano-Anatase TiO(2) and Liver DNA from Mice In Vivo. Nanoscale Res Lett 2009, 5: 108–115.

Wan R, Mo Y, Feng L, Chien S, Tollerud DJ, Zhang Q: DNA damage caused by metal nanoparticles: involvement of oxidative stress and activation of ATM. Chem Res Toxicol 2012, 25: 1402–1411. 10.1021/tx200513t

Aueviriyavit S, Phummiratch D, Kulthong K, Maniratanachote R: Titanium dioxide nanoparticles-mediated in vitro cytotoxicity does not induce hsp70 and grp78 expression in human bronchial epithelial a549 cells. Biol Trace Elem Res 2012, 149: 123–132. 10.1007/s12011-012-9403-z

Woodruff RS, Li Y, Yan J, Bishop M, Jones MY, Watanabe F, Biris AS, Rice P, Zhou T, Chen T: Genotoxicity evaluation of titanium dioxide nanoparticles using the Ames test and Comet assay. J Appl Toxicol 2012, 32: 934–943. 10.1002/jat.2781

Linnainmaa K, Kivipensas P, Vainio H: Toxicity and cytogenetic studies of ultrafine titanium dioxide in cultured rat liver epithelial cells. Toxicol In Vitro 1997, 11: 329–335. 10.1016/S0887-2333(97)00000-3

Fisichella M, Berenguer F, Steinmetz G, Auffan M, Rose J, Prat O: Intestinal toxicity evaluation of TiO2 degraded surface-treated nanoparticles: a combined physico-chemical and toxicogenomics approach in caco-2 cells. Part Fibre Toxicol 2012, 9: 18. 10.1186/1743-8977-9-18

Wilson D, Zaqout M, Heo JH, Park EK, Oak CH, Ueno S: Nuclear factor-kappa B is not involved in titanium dioxide-induced inflammation. J UOEH 2012, 34: 183–191.

Yu M, Mo Y, Wan R, Chien S, Zhang X, Zhang Q: Regulation of plasminogen activator inhibitor-1 expression in endothelial cells with exposure to metal nanoparticles. Toxicol Lett 2010, 195: 82–89. 10.1016/j.toxlet.2010.02.010

Wan R, Mo Y, Zhang X, Chien S, Tollerud DJ, Zhang Q: Matrix metalloproteinase-2 and −9 are induced differently by metal nanoparticles in human monocytes: The role of oxidative stress and protein tyrosine kinase activation. Toxicol Appl Pharmacol 2008, 233: 276–285. 10.1016/j.taap.2008.08.022

Wang J, Zhu X, Zhang X, Zhao Z, Liu H, George R, Wilson-Rawls J, Chang Y, Chen Y: Disruption of zebrafish (Danio rerio) reproduction upon chronic exposure to TiO nanoparticles. Chemosphere 2011, 83: 461–467. 10.1016/j.chemosphere.2010.12.069

Zhu X, Zhu L, Duan Z, Qi R, Li Y, Lang Y: Comparative toxicity of several metal oxide nanoparticle aqueous suspensions to Zebrafish (Danio rerio) early developmental stage. J Environ Sci Health, Part A: Tox Hazard Subst Environ Eng 2008, 43: 278–284. 10.1080/10934520701792779

Takeda K, Suzuki K, Ishihara A, Kubo-Irie M, Fujimoto R, Tabota M, Oshio S, Nihei Y, Ihara T, Sugamata M: Nanoparticles Transferred from Pregnent Mice to Their Offspring can Damage the Genital and Cranial Nerve Systems. J Health Sci 2009, 55: 95–102. 10.1248/jhs.55.95

Yamashita K, Yoshioka Y, Higashisaka K, Mimura K, Morishita Y, Nozaki M, Yoshida T, Ogura T, Nabeshi H, Nagano K: Silica and titanium dioxide nanoparticles cause pregnancy complications in mice. Nat Nanotechnol 2011, 6: 321–328. 10.1038/nnano.2011.41

Komatsu T, Tabata M, Kubo-Irie M, Shimizu T, Suzuki K, Nihei Y, Takeda K: The effects of nanoparticles on mouse testis Leydig cells in vitro. Toxicol In Vitro 2008, 22: 1825–1831. 10.1016/j.tiv.2008.08.009

Borm PJ, Schins RP, Albrecht C: Inhaled particles and lung cancer, part B: paradigms and risk assessment. Int J Cancer 2004, 110: 3–14. 10.1002/ijc.20064

Trochimowicz HJ, Lee KP, Reinhardt CF: Chronic inhalation exposure of rats to titanium dioxide dust. J Appl Toxicol 1988, 8: 383–385.

Heinrich UF R, Rittinghausen S, Creutzenberg O, Bellmann B, Koch W, Levsen K: Chronic inhalation exposure of Wistar rats and two different strains of mice to diesel engine exhaust, carbon black, and titanium dioxide. Inhal Toxicol 1995, 7: 533–556. 10.3109/08958379509015211

Pott F, Roller M: Carcinogenicity study with nineteen granular dusts in rats. Eur J Oncol 2005, 10: 249.

Rittinghausen S, Mohr U, Dungworth DL: Pulmonary cystic keratinizing squamous cell lesions of rats after inhalation/instillation of different particles. Exp Toxicol Pathol 1997, 49: 433–446. 10.1016/S0940-2993(97)80131-5

Bernard BK, Osheroff MR, Hofmann A, Mennear JH: Toxicology and carcinogenesis studies of dietary titanium dioxide-coated mica in male and female Fischer 344 rats. J Toxicol Environ Health 1990, 29: 417–429. 10.1080/15287399009531402

Boffetta P, Gaborieau V, Nadon L, Parent MF, Weiderpass E, Siemiatycki J: Exposure to titanium dioxide and risk of lung cancer in a population-based study from Montreal. Scand J Work Environ Health 2001, 27: 227–232. 10.5271/sjweh.609

Fryzek JP, Chadda B, Marano D, White K, Schweitzer S, McLaughlin JK, Blot WJ: A cohort mortality study among titanium dioxide manufacturing workers in the United States. J Occup Environ Med 2003, 45: 400–409. 10.1097/01.jom.0000058338.05741.45

Boffetta P, Soutar A, Cherrie JW, Granath F, Andersen A, Anttila A, Blettner M, Gaborieau V, Klug SJ, Langard S: Mortality among workers employed in the titanium dioxide production industry in Europe. Cancer Causes Control 2004, 15: 697–706.

Suttiponparnit KJJ, Sahu M, Suvachittanont S, Charinpanitkul T, Biswas P: Role of Surface Area, Primary Particle Size, and Crystal Phase on Titanium Dioxide Nanoparticle Dispersion Properties. Nanoscale Res Lett 2011, 6: 27.

Baan RA: Carcinogenic hazards from inhaled carbon black, titanium dioxide, and talc not containing asbestos or asbestiform fibers: recent evaluations by an IARC Monographs Working Group. Inhal Toxicol 2007,19(Suppl 1):213–228.

Waris G, Ahsan H: Reactive oxygen species: role in the development of cancer and various chronic conditions. J Carcinog 2006, 5: 14. 10.1186/1477-3163-5-14

Buechter DD: Free radicals and oxygen toxicity. Pharm Res 1988, 5: 253–260. 10.1023/A:1015914418014

Susin SA, Daugas E, Ravagnan L, Samejima K, Zamzami N, Loeffler M, Costantini P, Ferri KF, Irinopoulou T, Prevost MC: Two distinct pathways leading to nuclear apoptosis. J Exp Med 2000, 192: 571–580. 10.1084/jem.192.4.571

Freyre-Fonseca V, Delgado-Buenrostro NL, Gutierrez-Cirlos EB, Calderon-Torres CM, Cabellos-Avelar T, Sanchez-Perez Y, Pinzon E, Torres I, Molina-Jijon E, Zazueta C: Titanium dioxide nanoparticles impair lung mitochondrial function. Toxicol Lett 2011, 202: 111–119. 10.1016/j.toxlet.2011.01.025

Jaeger A, Weiss DG, Jonas L, Kriehuber R: Oxidative stress-induced cytotoxic and genotoxic effects of nano-sized titanium dioxide particles in human HaCaT keratinocytes. Toxicology 2012, 296: 27–36. 10.1016/j.tox.2012.02.016

Sanders K, Degn LL, Mundy WR, Zucker RM, Dreher K, Zhao B, Roberts JE, Boyes WK: In vitro phototoxicity and hazard identification of nano-scale titanium dioxide. Toxicol Appl Pharmacol 2012, 258: 226–236. 10.1016/j.taap.2011.10.023

Yin JJ, Liu J, Ehrenshaft M, Roberts JE, Fu PP, Mason RP, Zhao B: Phototoxicity of nano titanium dioxides in HaCaT keratinocytes-Generation of reactive oxygen species and cell damage. Toxicol Appl Pharmacol 2012, 263: 81–88. 10.1016/j.taap.2012.06.001

Yoo KC, Yoon CH, Kwon D, Hyun KH, Woo SJ, Kim RK, Lim EJ, Suh Y, Kim MJ, Yoon TH, Lee SJ: Titanium dioxide induces apoptotic cell death through reactive oxygen species-mediated Fas upregulation and Bax activation. Int J Nanomedicine 2012, 7: 1203–1214.

Sun Q, Tan D, Zhou Q, Liu X, Cheng Z, Liu G, Zhu M, Sang X, Gui S, Cheng J: Oxidative damage of lung and its protective mechanism in mice caused by long-term exposure to titanium dioxide nanoparticles. J Biomed Mater Res A 2012, 100: 2554–2562.

Liu S, Xu L, Zhang T, Ren G, Yang Z: Oxidative stress and apoptosis induced by nanosized titanium dioxide in PC12 cells. Toxicology 2010, 267: 172–177. 10.1016/j.tox.2009.11.012

Meena R, Rani M, Pal R, Rajamani P: Nano-TiO2-induced apoptosis by oxidative stress-mediated DNA damage and activation of p53 in human embryonic kidney cells. Appl Biochem Biotechnol 2012, 167: 791–808. 10.1007/s12010-012-9699-3

Wu J, Sun J, Xue Y: Involvement of JNK and P53 activation in G2/M cell cycle arrest and apoptosis induced by titanium dioxide nanoparticles in neuron cells. Toxicol Lett 2010, 199: 269–276. 10.1016/j.toxlet.2010.09.009

Winter M, Beer HD, Hornung V, Kramer U, Schins RP, Forster I: Activation of the inflammasome by amorphous silica and TiO2 nanoparticles in murine dendritic cells. Nanotoxicology 2011, 5: 326–340. 10.3109/17435390.2010.506957

Wang J, Li N, Zheng L, Wang S, Wang Y, Zhao X, Duan Y, Cui Y, Zhou M, Cai J: P38-Nrf-2 signaling pathway of oxidative stress in mice caused by nanoparticulate TiO2. Biol Trace Elem Res 2011, 140: 186–197. 10.1007/s12011-010-8687-0

Uchino T, Tokunaga H, Ando M, Utsumi H: Quantitative determination of OH radical generation and its cytotoxicity induced by TiO(2)-UVA treatment. Toxicol In Vitro 2002, 16: 629–635. 10.1016/S0887-2333(02)00041-3

Onuma K, Sato Y, Ogawara S, Shirasawa N, Kobayashi M, Yoshitake J, Yoshimura T, Iigo M, Fujii J, Okada F: Nano-scaled particles of titanium dioxide convert benign mouse fibrosarcoma cells into aggressive tumor cells. Am J Pathol 2009, 175: 2171–2183. 10.2353/ajpath.2009.080900

Toyooka T, Amano T, Ibuki Y: Titanium dioxide particles phosphorylate histone H2AX independent of ROS production. Mutat Res 2012, 742: 84–91. 10.1016/j.mrgentox.2011.12.015

Moon C, Park HJ, Choi YH, Park EM, Castranova V, Kang JL: Pulmonary inflammation after intraperitoneal administration of ultrafine titanium dioxide (TiO2) at rest or in lungs primed with lipopolysaccharide. J Toxicol Environ Health A 2010, 73: 396–409. 10.1080/15287390903486543

Goncalves DM, Chiasson S, Girard D: Activation of human neutrophils by titanium dioxide (TiO2) nanoparticles. Toxicol In Vitro 2010, 24: 1002–1008. 10.1016/j.tiv.2009.12.007