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ToxSci Advance Access originally published online on April 12, 2006
Toxicological Sciences 2006 92(1):174-185; doi:10.1093/toxsci/kfj197
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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

Correlating Nanoscale Titania Structure with Toxicity: A Cytotoxicity and Inflammatory Response Study with Human Dermal Fibroblasts and Human Lung Epithelial Cells

Christie M. Sayes*,1, Rajeev Wahi*, Preetha A. Kurian*, Yunping Liu*, Jennifer L. West{dagger},{ddagger}, Kevin D. Ausman{ddagger}, David B. Warheit§ and Vicki L. Colvin*,{ddagger}

* Department of Chemistry, {dagger} Department of Bioengineering, and {ddagger} Center for Biological and Environmental Nanotechnology, Rice University, Houston, Texas 77005; and § DuPont Haskell Lab, Newark, Delaware 19714

Received December 19, 2005; accepted April 7, 2006

Nanocrystalline titanium dioxide (nano-TiO2) is an important material used in commerce today. When designed appropriately it can generate reactive species (RS) quite efficiently, particularly under ultraviolet (UV) illumination; this feature is exploited in applications ranging from self-cleaning glass to low-cost solar cells. In this study, we characterize the toxicity of this important class of nanomaterials under ambient (e.g., no significant light illumination) conditions in cell culture. Only at relatively high concentrations (100 µg/ml) of nanoscale titania did we observe cytotoxicity and inflammation; these cellular responses exhibited classic dose-response behavior, and the effects increased with time of exposure. The extent to which nanoscale titania affected cellular behavior was not dependent on sample surface area in this study; smaller nanoparticlulate materials had effects comparable to larger nanoparticle materials. What did correlate strongly to cytotoxicity, however, was the phase composition of the nanoscale titania. Anatase TiO2, for example, was 100 times more toxic than an equivalent sample of rutile TiO2. The most cytotoxic nanoparticle samples were also the most effective at generating reactive oxygen species; ex vivo RS species generation under UV illumination correlated well with the observed biological response. These data suggest that nano-TiO2 samples optimized for RS production in photocatalysis are also more likely to generate damaging RS species in cell culture. The result highlights the important role that ex vivo measures of RS production can play in developing screens for cytotoxicity.

Key Words: nanoscale titanium dioxide; titania; nano-TiO2 particles; cytotoxicity; inflammation mediators; photocatalysis; reactive oxygen species.


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