Skip to main content
Log in

Aerosol characterization and lung deposition of synthesized TiO2 nanoparticles for murine inhalation studies

  • Research paper
  • Published:
Journal of Nanoparticle Research Aims and scope Submit manuscript

Abstract

This study presents a novel exposure protocol for synthesized nanoparticles (NPs). NPs were synthesized in gas phase by thermal decomposition of metal alkoxide vapors in a laminar flow reactor. The exposure protocol was used to estimate the deposition fraction of titanium dioxide (TiO2) NPs to mice lung. The experiments were conducted at aerosol mass concentrations of 0.8, 7.2, 10.0, and 28.5 mg m−3. The means of aerosol geometric mobility diameter and aerodynamic diameter were 80 and 124 nm, and the geometric standard deviations were 1.8 and 1.7, respectively. The effective density of the particles was approximately from 1.5 to 1.7 g cm−3. Particle concentration varied from 4 × 105 cm−3 at mass concentrations of 0.8 mg m−3 to 12 × 106 cm−3 at 28.5 mg m−3. Particle phase structures were 74% of anatase and 26% of brookite with respective crystallite sized of 41 and 6 nm. The brookite crystallites were approximately 100 times the size of the anatase crystallites. The TiO2 particles were porous and highly agglomerated, with a mean primary particle size of 21 nm. The specific surface area of TiO2 powder was 61 m2 g−1. We defined mice respiratory minute volume (RMV) value during exposure to TiO2 aerosol. Both TiO2 particulate matter and gaseous by-products affected respiratory parameters. The RMV values were used to quantify the deposition fraction of TiO2 matter by using two different methods. According to individual samples, the deposition fraction was 8% on an average, and when defined from aerosol mass concentration series, it was 7%. These results show that the exposure protocol can be used to study toxicological effects of synthesized NPs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Adlakha-Hutcheon G, Khaydarov R, Korenstein R, Varma R, Vaseashta A, Stamm H, Abdel-Mottaleb M (2009) Nanomaterials, nanotechnology: applications, consumer products, and benefits. In: Linkov I, Steevens J (eds) Nanomaterials: risks and benefits. Springer, Dordrecht

    Google Scholar 

  • Aitken RJ, Chaudhry MQ, Boxall ABA, Hull M (2006) Manufacture and use of nanomaterials: current status in the UK and global trends. Occup Med 56:300–306

    Article  CAS  Google Scholar 

  • Alarie Y (1998) Computer-based bioassay for evaluation of sensory irritation of airborne chemicals and its limit of detection. Arch Toxicol Suppl 72:277–282

    Article  CAS  Google Scholar 

  • ASTM (1984) American Society for Testing and Materials. Designation E981-84, Philadelphia, PA, ASTM

  • Backman U, Tapper U, Jokiniemi JK (2004) An aerosol method to synthesize supported metal catalyst nanoparticles. Synth Met 142:169–176

    Article  CAS  Google Scholar 

  • Balas F, Arruebo M, Urrutia J, Santamaria J (2010) Reported nanosafety practices in research laboratories worldwide. Nat Nanotechnol 5:93–96

    Article  CAS  Google Scholar 

  • Borm PJA (2002) Particle toxicology: from coal mining to nanotechnology. Inhalation Toxicol 14:311–324

    Article  CAS  Google Scholar 

  • Borm PJA, Robbins D, Haubold S, Kuhlbusch T, Fissan H, Donaldson K, Schins R, Stone V, Kreyling W, Lademann J, Krutmann J, Warheit D, Oberdörster E (2006) The potential risks of nanomaterials: a review carried out for ECETOC. Part Fibre Toxicol 3:11

    Article  Google Scholar 

  • Boylstein LA, Anderson SJ, Thomson RD, Alarie Y (1995) Characterization of the effects of an airborne mixture of chemicals on the respiratory tract and smoothing polynomial spline analysis of the data. Arch Toxicol Suppl 69:579–589

    Article  CAS  Google Scholar 

  • Boylstein LA, Luo J, Stock MF, Alarie Y (1996) An attempt to define a just detectable effect for airborne chemicals on the respiratory tract in mice. Arch Toxicol Suppl 70:567–578

    Article  CAS  Google Scholar 

  • Gwinn MR, Vallyathan V (2006) Nanoparticles: health effects—pros and cons. Environ Health Perspect 114:1818–1825

    CAS  Google Scholar 

  • Guyton AC (1947) Measurement of the respiratory volume of laboratory animals. Am J Physiol Lung Cell Mol Physiol 150:70–77

    CAS  Google Scholar 

  • Hinds WC (1999) Aerosol technology. Wiley, New York

    Google Scholar 

  • Hoet PHM, Brüske-Hohlfeld I, Salata OV (2004) Nanoparticles—known and unknown health risks. J Nanobiotechnol 2:12

    Article  Google Scholar 

  • Hsieh TH, Yu CP, Oberdörster G (1999) A dosimetry model of nickel compounds in the rat lung. Inhalation Toxicol 11:229–248

    Article  CAS  Google Scholar 

  • Kirkbir F, Komiyama H (1987) Formation and growth mechanism of porous, amorphous, and fine particles prepared by chemical vapor deposition. Titania from titanium tetraisopropoxide. Can J Chem Eng 65:759–766

    Article  CAS  Google Scholar 

  • Keskinen H, Mäkelä JM, Aromaa M, Ristimäki J, Kanerva T, Levänen E, Mäntylä T, Keskinen J (2007) Effect of silver addition on the formation and deposition of titania nanoparticles produced by Liquid Flame Spray. J Nanopart Res 9:569–588

    Article  CAS  Google Scholar 

  • Kobata A, Kusakabe K, Morooka S (1991) Growth and transformation of TiO2 crystallites in aerosol reactor. AICHE J 37:347–359

    Article  CAS  Google Scholar 

  • Kominami H, Takada Y, Yamagiwa H, Kera Y (1996) Synthesis of thermally stable nanocrystalline anatase by high-temperature hydrolysis of titanium alkoxide with water dissolved in organic solvent from gas phase. J Mater Sci Lett 15:197–200

    Article  CAS  Google Scholar 

  • Komiyama H, Kanai T, Inoue H (1984) Preparation of porous, amorphous, and ultrafine TiO2 particles by chemical vapor deposition. Chem Lett 8:1283–1286

    Article  Google Scholar 

  • Ku BK, Maynard AD (2005) Comparingaerosol surface-area measurements of monodisperse ultrafine silver agglomerates by mobility analysis, transmission electron microscopy and diffusion charging. J Aerosol Sci 36:1108–1124

    Article  CAS  Google Scholar 

  • Kuhlbusch TAJ, Fissan H, Asbach C (2009) Nanotechnologies and environmental risks: measurement technologies and strategies. In: Linkov I, Steevens J (eds) Nanomaterials: risks and benefits. Springer, Dordrecht

    Google Scholar 

  • Lindberg HK, Falck GC-M, Catalán J, Santonen T, Norppa H (2010) Micronucleus assay for mouse alveolar Type II and Clara cells. Environ Mol Mutagen 51:164–172

    CAS  Google Scholar 

  • Lutterotti L, Matthies S, Wenk HR (1999) MAUD: a friendly Java program for Material Analysis Using Diffraction. CPD Newsl 21:14–15

    Google Scholar 

  • Peters A, Wichmann HE, Tuch T, Heinrich J, Heyder J (1997) Respiratory effects are associated with the number of ultrafine particles. Am J Respir Crit Care Med 155:1376–1383

    CAS  Google Scholar 

  • Ristimäki J, Virtanen A, Marjamaki M, Rosted A, Keskinen J (2002) On-line measurement ofsize distribution and effective density of submicron aerosol particles. J Aerosol Sci 33:1541–1557

    Article  Google Scholar 

  • Marjamäki M, Keskinen J, Chen D-R, Pui DYH (2000) Performance evaluation of the electrical low-pressure impactor (ELPI). J Appl Crystallogr 31:249–261

    Google Scholar 

  • Mertes S, Schröder F, Wiedensohler A (1995) The particle detection efficiency curve of the TSI–3010 CPC as a function of the temperature difference between saturator and condenser. Aerosol Sci Technol 23:257–261

    Article  CAS  Google Scholar 

  • Mauad T, Rivero DHRF, Oliveira RC, Lichtenfels AJFC, Guimarães ET, Andre PA, Kasahara DI, Bueno HMS, Saldiva PHN (2008) Chronic exposure to ambient levels of urban particles affects mouse lung development. Am J Respir Crit Care Med 178:721–728

    Article  Google Scholar 

  • Miettinen M, Riikonen J, Tapper U, Backman U, Joutsensaari J, Auvinen A, Lehto V-P, Jokiniemi J (2009) Developement of a highly controlled gas-phase nanoparticle generator for inhalation exposure studies. Hum Exp Toxicol 28:413–419

    Article  CAS  Google Scholar 

  • Moravec P, Smolík J, Levdansky VVE (2001) Preparation of TiO2 fine particles by thermal decomposition of titanium tetraisopropoxide vapor. J Mater Sci Lett 20:2033–2037

    Article  CAS  Google Scholar 

  • Nakaso K, Fujimoto T, Seto T, Shimada M, Okuyama K, Lunden MM (2001) Size distribution change of titania nano-particle agglomerates generated by gas phase reaction. Agglomeration and sintering. Aerosol Sci Technol 35:929–947

    Article  CAS  Google Scholar 

  • Nakaso K, Okuyama K, Shimada M, Pratsinis SE (2003) Effect of reaction temperature on CVD-made TiO2 primary particle diameter. Chem Eng Sci 58:3327–3335

    Article  CAS  Google Scholar 

  • Nel A (2005) Air pollution-related illness: effects of particles. Sci Agric 308:804–806

    CAS  Google Scholar 

  • Nel A (2006) Toxic potential of materials at the nanolevel. Sci Agric 311:622–627

    CAS  Google Scholar 

  • Oberdörster G (2001) Pulmonary effects of inhaled ultrafine particles. Int Arch Occup Environ Health 74:1–8

    Article  Google Scholar 

  • Oberdörster G, Sharp Z, Atudorei V, Elder A, Gelein R, Lunts A, Kreyling W, Cox C (2002) Extrapulmonary translocation of ultrafine carbon particles following whole-body inhalation exposure of rats. J Toxicol Environ Health 65:1531–1543

    Article  Google Scholar 

  • Oberdörster G, Oberdörster E, Oberdörster J (2005) Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles. Environ Health Perspect 113:823–839

    Article  Google Scholar 

  • Oberdörster G, Oberdörster E, Oberdörster J (2007) Concepts of nanoparticle dose metric and response metric. Environ Health Perspect 115:A290–A290

    Article  Google Scholar 

  • Okuyama K, Kousaka Y, Tohge N, Yamamoto S, Wu JJ, Flagan RC, Seinfeld JH (1986) Production of ultrafine metal oxide aerosol particles by thermal decomposition of metal alkoxide vapors. AICHE J 32:2010–2019

    Article  CAS  Google Scholar 

  • Okuyama K, Ushio R, Kousaka Y, Flagan RC, Seinfeld HJ (1990) Particle generation in a chemical vapor deposition process with seed particles. AICHE J 36:409–419

    Article  CAS  Google Scholar 

  • Rietveld HM (1969) A profile refinement method for nuclear and magnetic structures. J Appl Crystallogr 2:65–71

    Article  CAS  Google Scholar 

  • Rossi EM, Pylkkänen L, Koivisto AJ, Vippola M, Jensen KA, Miettinen M, Sirola K, Nykäsenoja H, Karisola P, Stjernvall T, Vanhala E, Kiilunen M, Pasanen P, Mäkinen M, Hämeri K, Joutsensaari J, Tuomi T, Jokiniemi J, Wolff H, Savolainen K, Matikainen S, Alenius H (2010) Airway exposure to silica coated TiO2 nanoparticles induces pulmonary neutrophilia in mice. Toxicol Sci 113:422–433

    Article  CAS  Google Scholar 

  • Seaton A, MacNee W, Donaldson K, Godden D (1995) Particlucate air pollution and acute health effects. Lancet 345:176–178

    Article  CAS  Google Scholar 

  • Service RF (2005) Calls rise for more research on toxicology of nanomaterials. Sci Agric 300:243

    Google Scholar 

  • Seto T, Shimada M, Okuyama K (1995) Evaluation of sintering of nanometer-sized titania using aerosol method. Aerosol Sci Technol 23:183–200

    Article  CAS  Google Scholar 

  • Seto T, Hirota A, Fujimoto T, Shimada M, Okuyama K (1997) Sintering of polydisperse nanometer-sized agglomerates. Aerosol Sci Technol 27:422–438

    Article  CAS  Google Scholar 

  • Snipes MB (1989) Long-term retention and clearance of particles inhaled by mammalian species. Crit Rev Toxicol 20:175–211

    Article  CAS  Google Scholar 

  • Ryman-Rasmussen JP, Cesta MF, Brody AR, Shipley-Phillips JK, Everitt JI, Tewksbury EW, Moss OR, Wong BA, Dodd DE, Andersen ME, Bonner JC (2009) Inhaled carbon nanotubes reach the subpleural tissue in mice. Nat Nanotechnol 4:747–751

    Article  CAS  Google Scholar 

  • U.S. Environmental Protection Agency (US EPA) (1998) Health effects test guidelines: OPPTS 87.1300. Acute Inhalation Toxicity, EPA 712-C-98-193

  • Vijayaraghavan R, Schaper M, Thompson R, Stock MF, Alarie Y (1993) Characteristic modifications of the breathing pattern of mice to evaluate the effects of airborne chemicals on the respiratory tract. Arch Toxicol Suppl 67:478–490

    Article  CAS  Google Scholar 

  • Vijayaraghavan R, Schaper M, Thompson R, Stock MF, Boylstein LA, Luo JE, Alarie Y (1994) Computer assisted recognition and quantification of the effects of airborne chemicals acting at different areas of the respiratory tract in mice. Arch Toxicol Suppl 68:490–499

    Article  CAS  Google Scholar 

  • Wang SC, Flagan RC (1990) Scanning electrical mobility spectrometer. Aerosol Sci Technol 1990(13):230–240

    Google Scholar 

  • Wong AW (2007) Inhalation exposure systems: design, methods and operation. Toxicol Pathol 35(1):3–14

    Article  CAS  Google Scholar 

  • Xia T, Li N, Nel AE (2009) Potential health impact of nanoparticles. Annu Rev Public Health 30:137–150

    Article  Google Scholar 

Download references

Acknowledgements

The article was supported by the Academy of Finland, FinNano-program, Engineered Nanoparticles: Synthesis, Characterization, Exposure and Health Hazards (NANOHEALTH)-project (project number 117 924).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Antti J. Koivisto.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Koivisto, A.J., Mäkinen, M., Rossi, E.M. et al. Aerosol characterization and lung deposition of synthesized TiO2 nanoparticles for murine inhalation studies. J Nanopart Res 13, 2949–2961 (2011). https://doi.org/10.1007/s11051-010-0186-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11051-010-0186-x

Keywords

Navigation