Journal of Nanoparticle Research

, Volume 13, Issue 2, pp 511–524 | Cite as

Generation and characterization of stable, highly concentrated titanium dioxide nanoparticle aerosols for rodent inhalation studies

  • Wolfgang G. Kreyling
  • Pratim Biswas
  • Maria E. Messing
  • Neil Gibson
  • Marianne Geiser
  • Alexander Wenk
  • Manoranjan Sahu
  • Knut Deppert
  • Izabela Cydzik
  • Christoph Wigge
  • Otmar Schmid
  • Manuela Semmler-Behnke
Research Paper

Abstract

The intensive use of nano-sized titanium dioxide (TiO2) particles in many different applications necessitates studies on their risk assessment as there are still open questions on their safe handling and utilization. For reliable risk assessment, the interaction of TiO2 nanoparticles (NP) with biological systems ideally needs to be investigated using physico-chemically uniform and well-characterized NP. In this article, we describe the reproducible production of TiO2 NP aerosols using spark ignition technology. Because currently no data are available on inhaled NP in the 10–50 nm diameter range, the emphasis was to generate NP as small as 20 nm for inhalation studies in rodents. For anticipated in vivo dosimetry analyses, TiO2 NP were radiolabeled with 48V by proton irradiation of the titanium electrodes of the spark generator. The dissolution rate of the 48V label was about 1% within the first day. The highly concentrated, polydisperse TiO2 NP aerosol (3–6 × 106 cm−3) proved to be constant over several hours in terms of its count median mobility diameter, its geometric standard deviation, and number concentration. Extensive characterization of NP chemical composition, physical structure, morphology, and specific surface area was performed. The originally generated amorphous TiO2 NP were converted into crystalline anatase TiO2 NP by thermal annealing at 950 °C. Both crystalline and amorphous 20-nm TiO2 NP were chain agglomerated/aggregated, consisting of primary particles in the range of 5 nm. Disintegration of the deposited TiO2 NP in lung tissue was not detectable within 24 h.

Keywords

Titanium dioxide Anatase Amorphous TiO2 Spark ignition Chain aggregate/agglomerate Nanoparticle generation Transmission electron microscopy Elemental microanalysis Electron tomography Environmental, health and safety (EHS) 

References

  1. Almquist CB, Sahle-Demessie E, Enriquez J, Biswas P (2003) The photocatalytic oxidation of low concentration MTBE on titanium dioxide from groundwater in a falling film reactor. Environ Prog 22(1):14–24CrossRefGoogle Scholar
  2. Barnard AS (2010) One-to-one comparison of sunscreen efficacy, aesthetics and potential nanotoxicity. Nat Nanotechnol 5(4):271–274CrossRefGoogle Scholar
  3. Baron PA, Willeke K (2001) Aerosol measurement. Wiley Interscience, New YorkGoogle Scholar
  4. Baumeister W (2002) Electron tomography: towards visualizing the molecular organization of the cytoplasm. Curr Opin Struct Biol 12:679–684CrossRefGoogle Scholar
  5. Boffetta P, Soutar A, Cherrie JW, Granath F, Andersen A, Anttila A, Blettner M, Gaborieau V, Klug SJ, Langard S, Luce D, Merletti F, Miller B, Mirabelli D, Pukkala E, Adami HO, Weiderpass E (2004) Mortality among workers employed in the titanium dioxide production industry in Europe. Cancer Causes Control 15:697–706CrossRefGoogle Scholar
  6. Borm PJ, Schins RP, Albrecht C (2004) Inhaled particles and lung cancer, part B: paradigms and risk assessment. Int J Cancer 110:3–14CrossRefGoogle Scholar
  7. Chen X, Mao SS (2007) Titanium dioxide nanomaterials: synthesis, properties, modifications, and applications. Chem Rev 107:2891–2959CrossRefGoogle Scholar
  8. Dankovic D, Kuempel E, Wheeler M (2007) An approach to risk assessment for TiO2. Inhal Toxicol 19(Suppl 1):205–212CrossRefGoogle Scholar
  9. Fryzek JP, Chadda B, Marano D, White K, Schweitzer S, McLaughlin JK, Blot WJ (2003) A cohort mortality study among titanium dioxide manufacturing workers in the United States. J Occup Environ Med 45:400–409CrossRefGoogle Scholar
  10. Geiser M, Kreyling WG (2010) Deposition and biokinetics of inhaled nanoparticles. Particle Fibre Toxicol 7:2. doi:10.1186/1743-8977-7-2 CrossRefGoogle Scholar
  11. Geiser M, Rothen-Rutishauser B, Kapp N, Schürch S, Kreyling W, Schulz H, Semmler M, Im Hof V, Heyder J, Gehr P (2005) Ultrafine particles cross cellular membranes by non-phagocytic mechanisms in lungs and in cultured cells. Environ Health Perspect 113:1555–1560CrossRefGoogle Scholar
  12. Geiser M, Casaulta M, Kupferschmid B, Schulz H, Semmler-Behnke M, Kreyling W (2008) The role of macrophages in the clearance of inhaled ultrafine titanium dioxide particles. Am J Respir Cell Mol Biol 38:371–376CrossRefGoogle Scholar
  13. Gribb AA, Banfield JF (1997) Particle size effects on transformation kinetics and phase stability in nanocrystalline TiO2. Am Mineral 82:717–728Google Scholar
  14. Heinrich U, Fuhst R, Rittinghausen S, Creutzenberg O, Bellmann B, Koch W, Levsen K (1995) Chronic inhalation exposure of Wistar rats and two different strains of mice to diesel engine exhaust, carbon black, and titanium dioxide. Inhal Toxicol 7:533–556CrossRefGoogle Scholar
  15. Jani PU, McCarthy DE, Florence AT (1994) Titanium dioxide (rutile) particle uptake from the rat GI tract and translocation to systemic organs after oral administration. Int J Pharm 105:157–168CrossRefGoogle Scholar
  16. Jiang J, Oberdörster G, Elder A, Gelein R, Mercer P, Biswas P (2008) Does nanoparticle activity depend upon size and crystal phase? Nanotoxicology 2(1):33–42CrossRefGoogle Scholar
  17. Kapp N, Kreyling W, Schulz H, Im Hof V, Semmler M, Gehr P, Geiser M (2004) Identification of inhaled ultrafine titanium oxide particles by analytical electron microscopy in rat lungs. Microsc Res Tech 63:298–305CrossRefGoogle Scholar
  18. Karlsson MNA, Deppert K, Karlsson LS, Magnusson MH, Malm J-O, Srinivasan NS (2005) Compaction of agglomerates of aerosol nanoparticles: a compilation of experimental data. J Nanopart Res 7:43–49. doi:10.1007/s11051-004-7218-3 CrossRefGoogle Scholar
  19. Kreyling WG, Semmler M, Erbe F, Mayer P, Takenaka S, Oberdörster G, Ziesenis A (2002) Translocation of ultrafine insoluble iridium particles from lung epithelium to extrapulmonary organs is size dependent but very low. J Toxicol Environ Health 65(20):1513–1530CrossRefGoogle Scholar
  20. Kreyling WG, Semmler-Behnke M, Seitz J, Scymczak W, Wenk A, Mayer P, Oberdörster G (2009) Size dependence of the translocation of inhaled iridium and carbon nanoparticle aggregates from the lung of rats to the blood and secondary target organs. Inhal Toxicol 21(S1):55–60CrossRefGoogle Scholar
  21. Lekki J, Stachura Z, Dabros W, Stachura J, Menzel F, Reinert T, Butz T, Pallon J, Gontier E, Ynsa MD, Moretto P, Kertesz Z, Szikszai Z, Kiss AZ (2007) On the follicular pathway of percutaneous uptake of nanoparticles: ion microscopy and autoradiography studies. Nucl Instrum Methods Phys Res B 260:174–177CrossRefGoogle Scholar
  22. Li Q, Mahendra S, Lyon DY, Brunet L, Liga MV, Li D, Alvarez PJJ (2008) Antimicrobial nanomaterials for water disinfection and microbial control: potential applications and implications. Water Res 42:4591–4602CrossRefGoogle Scholar
  23. Lomer MC, Hutchinson C, Volkert S, Greenfield SM, Catterall A, Thompson RP, Powell JJ (2004) Dietary sources of inorganic microparticles and their intake in healthy subjects and patients with Crohn’s disease. Br J Nutr 92(6):947–955CrossRefGoogle Scholar
  24. Ma-Hock L, Gamer AO, Landsiedel R, Leibold E, Frechen T, Sens B et al (2007) Generation and characterization of test atmospheres with nanomaterials. Inhal Toxicol 19(10):833–848CrossRefGoogle Scholar
  25. Nohynek GJ, Dufour EK, Roberts MS (2008) Nanotechnology, cosmetics and the skin: is there a health risk? Skin Pharmacol Physiol 21:136–149CrossRefGoogle Scholar
  26. Rehman S, Ullah R, Butt AM, Gohar ND (2009) Strategies of making TiO2 and ZnO visible light active. J Hazard Mater 170:560–569CrossRefGoogle Scholar
  27. Semmler M, Seitz J, Erbe F, Mayer P, Heyder J, Oberdörster G, Kreyling WG (2004) Long-term clearance kinetics of inhaled ultrafine insoluble iridium particles from the rat lung, including transient translocation into secondary organs. Inhal Toxicol 16(6–7):453–459CrossRefGoogle Scholar
  28. Semmler-Behnke M, Kreyling W, Lipka J, Fertsch S, Wenk A, Takenaka S, Schmid G, Brandau W (2008) Biodistribution of 1.4- and 18-nm gold particles in rats. Small 4(12):2108–2111CrossRefGoogle Scholar
  29. Seto T, Shimada M, Okuyama K (1995) Evaluation of sintering of nanometer-sized titania using aerosol method. Aerosol Sci Technol 23(2):183–200CrossRefGoogle Scholar
  30. Takaoka A, Hasegawa T, Yoshida K, Mori H (2008) Microscopic tomography with ultra-HVEM and applications. Ultramicroscopy 108:230–238CrossRefGoogle Scholar
  31. Weber AP, Baltensperger U, Gaggeler HW, Schmidt-Ott A (1996) In situ characterization and structure modification of agglomerated aerosol particles. J Aerosol Sci 27(6):915–929CrossRefGoogle Scholar
  32. Yang GM, Zhuang H, Biswas P (1996) Characterization and sinterability of nanophase titania particles processed in flame reactors. NanoStruct Mater 7(6):675–689CrossRefGoogle Scholar
  33. Zhang H, Banfield JF (2000) Understanding polymorphic phase transformation behavior during growth of nanocrystalline aggregates: Insights from TiO2. J Phys Chem B 104:3481–3487CrossRefGoogle Scholar
  34. Zhang H, Finnegan M, Banfield JF (2001) Preparing single-phase nanocrystalline anatase from amorphous titania with particle sizes tailored by temperature. Nano Lett 1(2):81–85CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Wolfgang G. Kreyling
    • 1
  • Pratim Biswas
    • 2
  • Maria E. Messing
    • 3
  • Neil Gibson
    • 4
  • Marianne Geiser
    • 5
  • Alexander Wenk
    • 1
  • Manoranjan Sahu
    • 2
  • Knut Deppert
    • 3
  • Izabela Cydzik
    • 4
  • Christoph Wigge
    • 5
  • Otmar Schmid
    • 1
  • Manuela Semmler-Behnke
    • 1
  1. 1.Comprehensive Pneumology Center, Institute of Lung Biology and Disease and Focus Network Nanoparticles and HealthHelmholtz Zentrum München—Research Center for Environmental HealthNeuherberg, MunichGermany
  2. 2.Department of Energy, Environmental and Chemical EngineeringWashington University in St. LouisSt. LouisUSA
  3. 3.Solid State PhysicsLund UniversityLundSweden
  4. 4.Institute for Health and Consumer ProtectionJoint Research Centre of the European CommissionIspraItaly
  5. 5.Institute of AnatomyUniversity of BernBern 9Switzerland

Personalised recommendations