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Pulmonary toxicity study in rats with three forms of ultrafine-TiO2 particles: differential responses related to surface properties

Toxicology. 2007 Jan 25;230(1):90-104. doi: 10.1016/j.tox.2006.11.002. Epub 2006 Nov 10.

Abstract

Surface properties are critical to assess effects of ultrafine-TiO(2) particles. The aim of this study was to assess lung toxicity in rats of newly developed, well characterized, ultrafine-TiO(2) particles and compare them to TiO(2) samples in two different size ranges and surface modifications. Groups of rats were intratracheally instilled with doses of 1 or 5mg/kg of either two ultrafine rutile TiO(2) particles (uf-1 or uf-2); rutile R-100 fine-TiO(2) (F-1); 80/20 anatase/rutile P25 ultrafine-TiO(2) (uf-3); or alpha-quartz particles. Phosphate-buffered saline (PBS) solution instilled rats served as vehicle controls. Following exposures, the lungs of PBS and particle-exposed rats were evaluated for bronchoalveolar lavage (BAL) fluid inflammatory markers, cell proliferation, and by histopathology at post-instillation time points of 24h, 1 week, 1 and 3 months. The ranking of lung inflammation/cytotoxicity/cell proliferation and histopathological responses was quartz>uf-3>F-1=uf-1=uf-2. Exposures to quartz and to a lesser degree, uf-3 anatase/rutile TiO(2) particles produced pulmonary inflammation, cytotoxicity and adverse lung tissue effects. In contrast, exposures to F-1 fine-TiO(2) particles or to uf-1/uf-2 ultrafine-TiO(2) particle-types produced transient inflammation. We conclude that differences in responses to anatase/rutile uf-3 TiO(2) particles versus the rutile uf-1 and uf-2 TiO(2) particles could be related to crystal structure, inherent pH of the particles, or surface chemical reactivity. Thus, based on these results, inhaled rutile ultrafine-TiO(2) particles are expected to have a low risk potential for producing adverse pulmonary health effects. Finally, the results demonstrate that exposures to ultrafine-TiO(2) particle-types can produce differential pulmonary effects, based upon their composition, and crystal structure. Thus, the lung toxicity of anatase/rutile uf-3 should not be viewed as representative for all ultrafine-TiO(2) particle-types.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bronchoalveolar Lavage Fluid / cytology
  • Cell Count
  • Cell Proliferation / drug effects
  • Chemical Phenomena
  • Chemistry, Physical
  • Inflammation / chemically induced
  • Inflammation / pathology
  • L-Lactate Dehydrogenase / metabolism
  • Lung / pathology
  • Lung Diseases / chemically induced*
  • Lung Diseases / pathology*
  • Male
  • Nanoparticles / chemistry
  • Nanoparticles / toxicity*
  • Neutrophils / drug effects
  • Organ Size / drug effects
  • Particle Size
  • Quartz / toxicity
  • Rats
  • Surface Properties
  • Therapeutic Irrigation
  • Titanium / chemistry
  • Titanium / toxicity*

Substances

  • Quartz
  • titanium dioxide
  • Titanium
  • L-Lactate Dehydrogenase