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In Vitro Vascular Toxicity of Metal Oxide Nanoparticles
Citation:
ODEGAARD, M. L. AND K. L. DREHER. In Vitro Vascular Toxicity of Metal Oxide Nanoparticles. Presented at Society of Toxicology Annual meeting, Washington, DC, March 06 - 10, 2011.
Impact/Purpose:
The purpose of the current studies was to screen a variety of commercially-available Ti02 (6 types) and Ce02 (2 types) NPs varying in size and composition for vascular endothelial cell (EC) toxicity.
Description:
Engineered nanoparticles (NPs) are designed to possess unique physicochemical properties, but may also produce atypical and unforeseen exposure scenarios with adverse health effects. The ability ofNPs to translocate into systemic circulation following either inhalation or ingestion makes the vascular system a prime target for potential adverse health effects. The purpose of the current studies was to screen a variety of commercially-available Ti02 (6 types) and Ce02 (2 types) NPs varying in size and composition for vascular endothelial cell (EC) toxicity. A moderate-throughput in vitro approach was used to determine effects on EC viability, cytotoxicity, and oxidative stress. Because ECs derived from different anatomical locations display substantial heterogeneity, three different types of primary human ECs were used for these studies: coronary artery (HCAEC), aortic (HAEC), and lung microvascular cells (HMVECL). NP dispersion conditions were tested and optimized, and ECs were exposed overnight to a range of doses (6.25-200 ug/ml). NP exposure resulted in significant dose-dependent decreases in cell viability and increases in cytotoxicity (LDH release). Effects were independent of particle size, while HCAEC and HAEC cells showed greater sensitivity than HMVEC-L cells. All three cell types showed similar effects ofNP exposure on oxidative stress, with slightly greater sensitivity in the HAECs. Importantly, oxidative stress was most strongly increased after exposure to Ti02 but not Ce02 NPs, and was not directly correlated with changes in viability or cytotoxicity. In summary, these data reveal that exposure of human endothelial cells to metal oxide NPs results in gross detrimental health effects. Overall, the observed effects were particle, cell-type and endpoint-specific. Our approach of directly comparing different commerciallyavailable NPs in vitro provides a useful screening system for assessing health effects and prioritizing future in vivo toxicity testing, as well as identifying alternative test methods to predict NP vascular toxicity. This abstract does not reflect EPA policy.