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193713 
Meetings & Symposia 
Toxicology of titanium dioxide (TiO2) nanoparticles: Immunological effects in subcutaneously and intravenously injected mice 
Weaver, J; Umbreit, TH; Miller, TJ; Zhang, J; Stratmeyer, ME; Tomazic-Jezic, FJ 
2007 
no. 1391 Nanoparticles that are internalized are very likely to interact with the reticuloendothelial system (RES). This will be more important with therapeutic nanoparticles that may require multiple injections in significant quantities. We evaluated effects of TiO2 particles injected either subcutaneously (SC) or intravenously (IV) on several standard measures of the immune response. Suspensions of ~ 4.7 nm uncoated TiO2 (W470X, Degussa) particles were injected at total doses of 5600 mg/kg (SC) or 560 mg/kg (IV) over two days. At +1 day, there was no significant change in any cell population in peripheral blood except CD8+ in SC mice. In contrast, at day +5 there was a dramatic increase in granulocytes in circulation in SC as well as proportional decreases in circulating lymphocyte percentages. Macrophage percentages were not affected. No changes were observed in any cell population in draining lymph nodes. In SC mice, there was an increase in granulocyte number in the spleen, mirroring the increase in peripheral blood. In the spleen of IV injected mice a number of macrophages containing TiO2 aggregates were observed in the marginal zone of the white pulp, suggesting a pathway for the interaction of TiO2 with T cells. After 3 days of culture with Con-A, an apparent lack of T-cell proliferation was seen in lymph nodes from SC but not IV injected animals. This was seen by both direct measurement of proliferation and from B-cell:T-cell ratios after culture. Cytokine analyses of the mitogen stimulated spleen and lymph node cells indicated increased production of TNF-alpha, IL-6 and gamma-interferon. These results indicate that the acute inflammatory response seen in SC injected mice may well have secondary effects on the immune response. These findings, along with earlier results with polystyrene nanoparticles suggest that the immune system may be especially sensitive to effects of nanoparticles. 
Society of Toxicology 46th Annual Meeting 
Charlotte, NC 
March 25-29, 2007