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ToxSci Advance Access originally published online on October 9, 2006
Toxicological Sciences 2007 95(1):270-280; 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

COVER ARTICLE

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*, Vicki L. Colvin{dagger}, Kenneth L. Reed* and Christie M. Sayes*

* DuPont Haskell Laboratory for Health and Environmental Sciences, Newark, Delaware 19714-0050; and {dagger} Department of Chemistry, Rice University, Houston, TX 77005

1 To whom correspondence should be addressed at DuPont Haskell Lab, 1090 Elkton Rd., PO Box 50, Newark, DE 19714-0050. Fax: (302) 366-5207. E-mail: david.b.warheit{at}usa.dupont.com.

Received August 13, 2006; accepted September 26, 2006


  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 versus (mined) Min-U-Sil quartz (~500 nm); the toxicity of synthetic 12 nm nanoquartz II particles versus (mined) Min-U-Sil (~500 nm) versus (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 with either doses of 1 or 5 mg/kg of carbonyl iron (CI) 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 h, 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 > CI 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.

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


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