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ToxSci Advance Access published online on February 22, 2006
Toxicological Sciences, doi:10.1093/toxsci/kfj140
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© The Author 2006. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received November 28, 2005
Accepted January 31, 2006

Respiratory Toxicology

Pulmonary Instillation Studies with Nanoscale TiO2 Rods and Dots in Rats: Toxicity is not Dependent Upon Particle Size and Surface Area

DB Warheit 1 *, TR Webb 1, CM Sayes 2, VL Colvin 2, and KL Reed 1

1 DuPont Haskell Laboratory for Health and Environmental Sciences, Newark, DE
2 DuPont Haskell Laboratory for Health and Environmental Sciences, Newark, DE; Dept. of Chemistry, Rice University, Houston, TX

* To whom correspondence should be addressed.
DB Warheit, E-mail: david.b.warheit{at}usa.dupont.com


  Abstract

Pulmonary toxicology studies in rats demonstrate that nanoparticles administered to the lung are more toxic than larger, fine-sized particles of similar chemistry at identical mass concentrations. The aim of this study was to evaluate the acute lung toxicity in rats of intratracheally instilled pigment-grade TiO2 particles (rutile-type- particle size = ~300 nm) vs. Nanoscale TiO2 rods (anatase - 200 nm x 35 nm) or Nanoscale TiO2 dots (anatase - ~10 nm) compared with a positive control particle-type, quartz. Groups of rats were instilled either with doses of 1 or 5 mg/kg of the various particle- types in phosphate-buffered saline (PBS). Subsequently, the lungs of PBS and particle-exposed rats were assessed using bronchoalveolar lavage (BAL) fluid biomarkers, cell proliferation methods, and by histopathological evaluation of lung tissue at 24 hrs, 1 week, 1 month and 3 months post-instillation exposure.

Exposures to Nanoscale TiO2 rods or Nanoscale TiO2 dots produced transient inflammatory and cell injury effects at 24 hours postexposure (pe) and were not different from the pulmonary effects of larger-sized TiO2 particle exposures. In contrast, pulmonary exposures to quartz particles in rats produced a dose-dependent lung inflammatory response characterized by neutrophils and foamy lipid-containing alveolar macrophage accumulation as well as evidence of early lung tissue thickening consistent with the development of pulmonary fibrosis.

The results described herein provide the first example of nanoscale particle-types which are not more cytotoxic or inflammogenic to the lung compared to larger-sized particles of similar composition. Furthermore, these findings run counter to the postulation that surface area is a major factor associated with the pulmonary toxicity of nanoscale particle-types.

Keywords: titanium dioxide particles; pulmonary toxicity; Nanoscale TiO2 Rods and Dots; particle size; particle surface area.
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