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Tissue distribution and histopathological effects of titanium dioxide nanoparticles after intravenous or subcutaneous injection in mice†
Article first published online: 25 AUG 2011
Published 2011. This article is a US Government work and is in the public domain in the USA.
Journal of Applied Toxicology
Volume 32, Issue 5, pages 350–357, May 2012
How to Cite
Umbreit, T. H., Francke-Carroll, S., Weaver, J. L., Miller, T. J., Goering, P. L., Sadrieh, N. and Stratmeyer, M. E. (2012), Tissue distribution and histopathological effects of titanium dioxide nanoparticles after intravenous or subcutaneous injection in mice. J. Appl. Toxicol., 32: 350–357. doi: 10.1002/jat.1700
- Issue published online: 23 MAR 2012
- Article first published online: 25 AUG 2011
- Manuscript Accepted: 20 APR 2011
- Manuscript Revised: 7 APR 2011
- Manuscript Received: 28 FEB 2011
- titanium dioxide;
- in vivo
Nanoparticles can be formed following degradation of medical devices such as orthopedic implants. To evaluate the safety of titanium alloy orthopedic materials, data are needed on the long-term distribution and tissue effects of injected titanium nanoparticles in experimental animals. In this study, we evaluated the tissue distribution and histopathological effects of titanium dioxide (TiO2) nanoparticles (approximately 120 nm diameter) in mice after intravenous (i.v.; 56 or 560 mg kg−1 per mouse) or subcutaneous (s.c.; 560 or 5600 mg kg−1 per mouse) injection on two consecutive days. Animals were examined 1 and 3 days, and 2, 4, 12 and 26 weeks after the final injection. When examined by light microscopy, particle agglomerates identified as TiO2 were observed mainly in the major filtration organs – liver, lung and spleen – following i.v. injection. Particles were still observed 26 weeks after injection, indicating that tissue clearance is limited. In addition, redistribution within the histological micro-compartments of organs, especially in the spleen, was noted. Following s.c. injection, the largest particle agglomerates were found mainly in the draining inguinal lymph node, and to a lesser extent, the liver, spleen and lung. With the exception of a foreign body response at the site of s.c. injection and the appearance of an increased number of macrophages in the lung and liver, there was no histopathological evidence of tissue damage observed in any tissue at any time point. Published 2011. This article is a US Government work and is in the public domain in the USA.