Administration of very high doses of nanoscale titanium dioxide (TiO2) causes damage to cells. There are no such high doses in everyday life though.


Numerous in vitro studies have shown that, depending on their type and origin, cells react to TiO2 exposure differently. Depending on the dose, TiO2 nanoparticles may cause secretion of inflammation markers, formation of reactive oxygen species (ROS), cytotoxicity, and apoptosis [1,2,3]. However, only very high concentrations of nanoscale TiO2 (primary particle size must be 15 nm) can definitively damage the cells [4,5,6]. In spite of the presence of some particles and an increased amount of agglomerates, no DNA or cell damage was detected in studies of cells from human nasal mucosa and lymphocytes [7,8].


Within the project NanoCare, titanium dioxide served as reference material to be applied in all tests. Studies of different cell lines showed that the vitality of cells was reduced only after administration of very high doses (50 µg/cm2) of the different variants of TiO2. That concentration is not only far above the concentration of natural TiO2 but also above the one occurring as industrial TiO2 is used appropriately. Besides, TiO2 tends to strongly agglomerate. The concentration of free nanoparticles thus is reduced accordingly [9].


The so-called vector model, which represents some of the elementary cell functions [10], shows that the cells get damaged in the presence of a concentration of approximately 60 µg particles per 106 phagocytes. Reactive oxygen species (ROS) were also found to only form inside the cells when exposed to such doses [9].


Other in vitro tests within the project NanoCare were carried out using a bioassay exposure system developed at the Karlsruhe Institute of Technology (KIT) to determine the toxicity of gas-borne nanoparticles. Flowing over the cell surfaces, the aerosol can trigger dose-dependent reactions, e.g. inflammation, in the cells through action of the particles deposited. At the same time, the particle dose deposited per surface is recorded using a quartz crystal microbalance [11,12].

Human lung cells were exposed to TiO2 for two and four hours, respectively. None of the applied concentrations was found to decrease the vitality of the exposed cells or cause acute cytotoxicity [9].


TiO2 (P25, Evonik/Degussa) was also used as reference material within the BMBF-supported joint project INOS. All of the relevant in-vitro tests showed that concentrations of 50 µg/ml of TiO2 applied over 3 hours and 3 days, respectively, had no cytotoxic effect on the human cell lines A549, HaCaT, CaCo2, and on the cells of rainbow trout [13].


Literatur arrow down

  1. Val, S et al. (2009), Inhal Toxicol, 21 Suppl 1 115-122.
  2. Liu, S et al. (2010), Toxicology, 267(1-3): 172-177.
  3. Hussain, S et al. (2010), Part Fibre Toxicol, 7 10.
  4. Gerloff, K et al. (2009), Nanotoxicology, 3(4): 355-364.
  5. L'Azou, B et al. (2008), Part Fibre Toxicol, 5 22.
  6. Shukla, RK et al. (2011), Toxicol In Vitro, 25(1): 231-241.
  7. Hackenberg, S et al. (2010), Toxicol Lett, 195(1): 9-14.
  8. Hackenberg, S et al. (2011), Environ Mol Mutagen, 52(4): 264-268.
  9. NanoCare 2009, Final Scientific Report, ISBN 978-3-89746-108-6. (PDF-Document, 19 MB).
  10. Bruch, J et al. (2004), Int J Hyg Environ Health, 207(3): 203-216.
  11. Muelhopt, S et al (2007). In vitro Testing of inhalable fly ash at the air liquid interface, p.402-414. Advanced Environmental Monitoring, Kim Y J and Platt U (eds.), Springer Verlag Netherlands. ISBN 9048114632.
  12. KIT-Flyer Karlsruhe Exposure System for Bioassays (PDF-Document, in German)
  13. INOS Scientific Reports (see Publications of the Project INOS)


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