The importance of a validated standard methodology to define in vitro toxicity of nano-TiO2
- 496 Downloads
Several in vitro studies on the potential toxicity of nano-TiO2 have been published and recent reviews have summarised them. Most of these reports concluded that physicochemical properties of nanoparticles are fundamental to their toxicological effects. No published review has compared in vitro tests with similar test strategies in terms of exposure duration and measured endpoints and for this reason we have attempted to assess the degree of homogeneity among in vitro tests and to assess if they afford reliable data to support risk assessment. The responses in different in vitro tests appeared to be unrelated to primary particle size. The biologically effective concentrations in different tests can be seen to differ by as many as two orders of magnitude and such differences could be explained either by different sensitivities of cell lines to nanoparticles or by effect of the test media. Our review indicates that even when the in vitro tests measure the same biomarkers with the same exposure duration and known primary particle sizes, it is insufficient merely to use such data for risk assessment. In the future, validated standard methods should include a limited number of cell lines and an obligatory selection of biomarkers. For routine purposes, it is important that assays can be easily conducted, false negatives and false positives are excluded and unbiased interpretation of results is provided. Papers published to date provide an understanding of the mode on nano-TiO2 action but are not suitable for assessment and management of risk.
KeywordsTiO2 nanoparticles Risk assessment Risk management Nanotoxicity Size-dependent effects
We would like to thank the Slovenian Research Agency (project number J1-9475), and G.W.A. Milne for editorial assistance.
Conflict of interest
The authors declare that they have no conflict of interest.
- Erickson BE (2008) Grassroots effort aims to improve quality of nanotoxicology studies. Chem Eng Tools 86(50):25–26Google Scholar
- Fujita K, Horie M, Kato H, Endoh S, Suzuki M, Nakamura A, Miyauchi A, Yamamoto K, Kinugasa S, Nishio K, Yoshida Y, Iwahashi H, Nakanishi J (2009) Effects of ultrafine TiO2 particles on gene expression profile in human keratinocytes without illumination: involvement of extracellular matrix and cell adhesion. Toxicol Lett 191(2–3):109–117PubMedCrossRefGoogle Scholar
- Hackenberg S, Friehs G, Froelich K, Ginzkey C, Koehler C, Scherzed A, Burghartz M, Hagen R, Kleinsasser N (2010) Intracellular distribution, geno- and cytotoxic effects of nanosized titanium dioxide particles in the anatase crystal phase on human nasal mucosa cells. Toxicol Lett 195(1):9–14. doi: 10.1016/j.toxlet.2010.02.022 PubMedCrossRefGoogle Scholar
- Han X, Gelein R, Corson N, Wade-Mercer P, Jiang J, Biswas P, Finkelstein JN, Elder A, Oberdörster G (2011) Validation of an LDH assay for assessing nanoparticle toxicity. Toxicology In pressGoogle Scholar
- Horie M, Nishio K, Fujita K, Kato H, Endoh S, Suzuki M, Nakamura A, Miyauchi A, Kinugasa S, Yamamoto K, Iwahashi H, Murayama H, Niki E, Yoshida Y (2010) Cellular responses by stable and uniform ultrafine titanium dioxide particles in culture-medium dispersions when secondary particle size was 100 nm or less. Toxicol in vitro 24(6):1629–1638PubMedCrossRefGoogle Scholar
- Hussain SM, Hess KL, Gearhart JM, Geiss KT, Schlager JJ (2005) in vitro toxicity of nanoparticles in BRL 3A rat liver cells. Toxicol in vitro 19(7):975–983Google Scholar
- Komatsu T, Tabata M, Kubo-Irie M, Shimizu T, Suzuki K, Nihei Y, Takeda K (2008) The effects of nanoparticles on mouse testis Leydig cells in vitro. Toxicol in vitro 22(8):1825–1831Google Scholar
- Oberdörster G, Maynard A, Donaldson K, Castranova V, Fitzpatrick J, Ausman K, Carter J, Karn B, Kreyling W, Lai D, Olin S, Monteiro-Riviere N, Warheit DB, Yang H (2005) Principles for characterizing the potential human health effects from exposure to nanomaterials: elements of a screening strategy. Part Fibre Toxicol 2(8)Google Scholar
- Park YH, Jeong SH, Yi SM, Choi BH, Kim YR, Kim IK, Kim MK, Son SW (2011) Analysis for the potential of polystyrene and TiO2 nanoparticles to induce skin irritation, phototoxicity, and sensitization. Toxicol in vitro In press Google Scholar
- Petković J, Žegura B, Stevanović M, Drnovšek N, Uskoković D, Novak S, Filipič M (2010) DNA damage and alterations in expression of DNA damage responsive genes induced by TiO2 nanoparticles in human hepatoma HepG2 cells. Nanotoxicology in pressGoogle Scholar
- Sayes CM, Wahi R, Kurian PA, Liu YP, West JL, Ausman KD, Warheit DB, Colvin VL (2006) Correlating nanoscale titania structure with toxicity: a cytotoxicity and inflammatory response study with human dermal fibroblasts and human lung epithelial cells. Toxicol Sci 92(1):174–185PubMedCrossRefGoogle Scholar
- Thybaud V, Aardema M, Clements J, Dearfield K, Galloway S, Hayashi M, Jacobson-Kram D, Kirkland D, MacGregor JT, Marzin D, Ohyama W, Schuler M, Suzuki H, Zeiger E (2007) Strategy for genotoxicity testing: hazard identification and risk assessment in relation to in vitro testing. Mutat Res Gen Toxicol Eng 627(1):41–58CrossRefGoogle Scholar
- Uchino T, Tokunaga H, Ando M, Utsumi H (2002) Quantitative determination of OH radical generation and its cytotoxicity induced by TiO2-UVA treatment. Toxicol in vitro 16(5):629–635Google Scholar
- Wadhwa S, Rea C, O’Hare P, Mathur A, Roy SS, Dunlop PSM, Byrne JA, Burke G, Meenan B, McLaughlin JA (2011) Comparative in vitro cytotoxicity study of carbon nanotubes and titania nanostructures on human lung epithelial cells. J Hazard Mater 191(1–3):56–61. doi: 10.1016/j.jhazmat.2011.04.035 PubMedCrossRefGoogle Scholar
- Wang S, Yu H, Wickliffe JK (2011) Limitation of the MTT and XTT assays for measuring cell viability due to superoxide formation induced by nano-scale TiO2. Toxicol in vitro In press Google Scholar
- Xu A, Chai YF, Nohmi T, Hei TK (2009) Genotoxic responses to titanium dioxide nanoparticles and fullerene in gpt delta transgenic MEF cells. Part Fibre Toxicol 6: in pressGoogle Scholar