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ToxSci Advance Access published online on October 9, 2006
Toxicological Sciences, doi:10.1093/toxsci/kfl128
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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 August 13, 2006
Accepted September 26, 2006

Respiratory Toxicology

Pulmonary Bioassay Studies with Nanoscale and Fine Quartz Particles in Rats: Toxicity is not dependent upon Particle Size but on Surface Characteristics

David B. Warheit 1 *, Thomas R. Webb 1, Vicki L. Colvin 2, Kenneth L. Reed 1, and Christie M. Sayes 1

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

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


  Abstract

Pulmonary toxicology studies in rats demonstrate that nanoparticles are more toxic than fine-sized particles of similar chemistry. This study, however, provides evidence to contradict this theory. The aims of the study were 1) to compare the toxicity of synthetic 50 nm nanoquartz-I particles vs. (mined) Min-U-Sil quartz (~500 nm); the toxicity of synthetic 12 nm nanoquartz-II particles vs. (mined) Min-U-Sil (~500 nm) vs. (synthetic) fine quartz particles (300 nm); and 2) to evaluate the surface activities among the samples as they relate to toxicity. Well characterized samples were tested for surface activity and hemolytic potential. In addition, groups of rats were instilled either with doses of 1 or 5 mg/kg of carbonyl iron or various {alpha}-quartz particle-types in phosphate buffered saline solution and subsequently assessed using bronchoalveolar lavage fluid biomarkers, cell proliferation, and histopathological evaluation of lung tissue at 24 hrs, 1 week, 1 month and 3 months postexposure.

Exposures to the various {alpha}-quartz particles produced differential degrees of pulmonary inflammation and cytotoxicity, which were not always consistent with particle size but correlated with surface activity, particularly hemolytic potential. Lung tissue evaluations of three of the quartz samples demonstrated "typical" quartz-related effects - dose-dependent lung inflammatory macrophage accumulation responses concomitant with early development of pulmonary fibrosis. The various {alpha}-quartz related effects were similar qualitatively but with different potencies. The range of particle-related toxicities and histopathological effects in descending order were nanoscale quartz II = Min-U-Sil quartz > fine quartz > nanoscale quartz I > carbonyl iron particles. The results demonstrate that the pulmonary toxicities of {alpha}-quartz particles appear to correlate better with surface activity than particle size and surface area.

Keywords: {alpha}-quartz particles; pulmonary toxicity; nanoscale quartz particles; particle size; particle characterization; surface activity.
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