title: Tissue distribution and toxicity of intravenously administered titanium dioxide nanoparticles in rats.
abstract: The tissue distribution and toxicity of intravenously administered nanoparticles of titanium dioxide (TiO2) (>10 wt.% at <100 nm size) were investigated because of the fundamental importance to obtain information on the kinetics of this widely used nanoparticle in a situation of 100% bioavailability. Male Wistar rats were treated with single intravenous injections of a suspension of TiO2 in serum (5 mg/kg body weight), and the tissue content of TiO2 was determined 1, 14, and 28 days later. Biochemical parameters and antigens in serum were also assessed to determine potential pathological changes. The health and behavior of the animals were normal throughout the study. There were no detectable levels of TiO2 in blood cells, plasma, brain, or lymph nodes. The TiO2 levels were highest in the liver, followed in decreasing order by the levels in the spleen, lung, and kidney, and highest on day 1 in all organs. TiO2 levels were retained in the liver for 28 days, there was a slight decrease in TiO2 levels from day 1 to days 14 and 28 in the spleen, and a return to control levels by day 14 in the lung and kidney. There were no changes in the cytokines and enzymes measured in blood samples, indicating that there was no detectable inflammatory response or organ toxicity. Overall, rats exposed to TiO2 nanoparticles by a route that allows immediate systemic availability showed expected tissue distribution, no obvious toxic health effects, no immune response, and no change in organ function. Therefore, even with 100% bioavailability of the 5 mg/kg TiO2 dose afforded by the intravenous route of administration, there were no remarkable toxic effects evident in the experimental animals. These results indicate that TiO2 nanoparticles could be used safely in low doses.
authors.affiliation: BASF Product Safety, BASF Aktiengesellschaft, Ludwigshafen, Germany.
authors.forename: Eric
authors.initials: E
authors.lastname: Fabian
authors.forename: Robert
authors.initials: R
authors.lastname: Landsiedel
authors.forename: Lan
authors.initials: L
authors.lastname: Ma-Hock
authors.forename: Karin
authors.initials: K
authors.lastname: Wiench
authors.forename: Wendel
authors.initials: W
authors.lastname: Wohlleben
authors.forename: Ben
authors.initials: B
authors.lastname: van Ravenzwaay
mesh_terms: D000818:Animals; D007275:Injections, Intravenous; D008297:Male; D053768:Metal Nanoparticles; D009929:Organ Size / Q000187:drug effects; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D013473:Sunscreening Agents / Q000633:toxicity*; D014018:Tissue Distribution; D014025:Titanium / Q000633:toxicity*; D018675:Toxicity Tests; D014874:Water Pollutants, Chemical
chemical_list: D013473:Sunscreening Agents; D014874:Water Pollutants, Chemical; C009495:titanium dioxide; D014025:Titanium