Toxicology Of Titanium Dioxide (Tio2) Nanoparticles: In Vitro And In Vivo Evaluation Of Macrophage Uptake Of Tio2

New Hampshire Ave, Silver Spring, MD, 20993 Potential health risks from TiO2 in sunscreens and medical products remains unknown. Balb/C mice were injected IV with TiO2 in saline (size 4.7 nm, 5.6 mg /mouse/day for 2 days) and necropsied on days 3 & 5. The mice showed white discoloration of lungs, liver, and spleen, as well as phagocytosis of TiO2 aggregates by macrophages in these organs by light microscopy. Kidney and brain of treated mice appeared unchanged. To model macrophage response to TiO2 in vitro, cultured J774 cells were treated with TiO2 (0.025–6.3 mg/mL) up to 24 hours and examined for viability, oxidative stress, and cytokine production. TiO2-treated J774 cells showed dose & time dependent loss of viability via MTT assay. Increased ROS production and loss of cell membrane integrity was observed at higher TiO2 doses and longer exposure times, by fluorescence microscopy. However, antioxidants α-tocopherol & trolox failed to prevent TiO2-induced ROS and cell death, suggesting that oxidative stress may not be the predominant mechanism of TiO2 toxicity. Cytokine analysis of treated cells revealed an increased release of TNF-α, IL-1β, IL-6, and MIP-2 with increasing dose and time of exposure to TiO2. These data suggest that macrophage uptake and accumulation of large amounts of TiO2 aggregates may result in cytokine release and potential cytotoxicity in cells and tissues responsible for clearance of TiO2 from circulation.