Titanium Dioxide

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Titanium dioxide (TiO2) nanoparticles are the main component of sunscreens and wall paints. Thus humans generally come into contact with TiO2 nanoparticles via the skin. Titanium dioxide nanoparticles are classified to be non-toxic. Therefore unintentional swallowing is considered to be harmless. There is no significant evidence for a nano-specific risk. Coarse titanium dioxide which contains no nanoparticles is allowed for use in food and is used as a whitener in toothpaste.


How can I come into contact with this material?

child with sunscreen © Sunny-studio /fotolia.com

By applying sunscreen to your skin you also apply titanium dioxide nanoparticles. These particles however do not pass through healthy or sunburnt skin. Wounds however should be treated with wound ointment instead. Self-cleaning wall paints contain TiO2 nanoparticles which are fixed within the paintwork after drying, thus humans do not get exposed to these particles. In addition, titanium dioxide contained in tiles, flagstones and solar panels are also present in a bound manner. As there are no titanium dioxide nanoparticles released during the day-to-day use it is highly unlikely for these particles to enter the human body.

However, in all major applications the bound titanium dioxide nanoparticles may eventually leach out into the environment, but as yet there have been no negative effects shown for humans or wildlife. Nevertheless this requires further research.

Is there any risk from this material to humans and the environment?

Only very high concentrations of titanium dioxide show toxic effects. This means that inhalation of titanium dioxide particles, as for all dusty particles, should be avoided even though there is no evidence for significant impairment of the human lung. If swallowed titanium dioxide nanoparticles are not toxic. Indeed, titanium dioxide is approved and sold as white food colouring agent with the identification code E171, but without any further specification of the particle size.


Titanium dioxide nanoparticles do not enter the human body through intact skin. In other applications than sunscreen the nanoparticles are generally not free to move, because they are firmly bound in a matrix. Food can only be whitened with micro-scaled titanium dioxide particles.


By the way…

  • All grinding work causes dust which always contains a certain amount of nanoparticles regardless of whether the ground material previously did contain any nanoparticle. The amount of particles in the air (dust) can be reduced by wet grinding, which also reduces the generation of nanoparticles.
  • Sunscreen with a sun protection factor higher than 25 can’t be realised without usage of titanium dioxide. High rating sun factor lotions are important in reducing the number of casualties through skin cancer. The only available alternative to titanium dioxide to manufacture sunscreens with a sun protection factor equal to 25 would be using chemicals which evidently show health side effects.

Properties and Applications

Titanium dioxide (TiO2) has become part of our everyday lives. It is found in various consumer goods and products of daily use such as cosmetics, paints, dyes and varnishes, textiles, paper and plastics, food and drugs, and even paving stones. 4.68 million tons of titanium dioxide were produced worldwide in 2009 [1]; 1,5 million tons/year are produced in the European Union [2]. Production was even higher before the financial crisis in 2007 and 2008.The great versatility of titanium dioxide is owing to its various forms and sizes. Titanium dioxides may be used in the form of microscale pigments or as nano-objects. Their crystal structures may vary: Depending on the arrangement of TiO2 atoms, one differentiates between rutile and anatase modifications.

Due to its high diffraction index and strong light scattering and incident-light reflection capability, TiO2 is mostly used as white pigment. It is these properties and a high UV resistance that make TiO2 the standard pigment found in white dispersion paints with high hiding power. Since light scattering does not occur anymore in nanoscale particles, the white titanium dioxide pigments used are almost exclusively rutile modification particles with grain sizes in the micrometer range. These white pigments are not only found in paints and dyes but also in varnishes, plastics, paper, and textiles. Having E number E171, they are used as food additives and occur in toothpastes, several other cosmetics, and drugs. TiO2 pigments for use in plastics constitute the fastest growing market. It is in particular due to the packaging industry’s strong demand that the consumption of titanium dioxide pigments is on the increase.

bottle of unlabelled sunscreen possitioned in the sand next to the drawing of a sun made from sunscreen as an application example for titanium dioxide particles

bottle of sunscreen in the sand © vimarovi / Fotolia.com

Nanoscale titanium dioxide that is manufactured for specific applications is by approximately a factor of 100 finer than the TiO2 pigments and has other physical properties. The production volume of nanoscale TiO2 amounts to less than 1 percent that of TiO2 pigments [3]. Unlike TiO2 pigments, nanoscale titanium dioxides are not used as food additives. Currently, they are mainly found in high-factor sun protection creams, textile fibers or wood preservatives. For a long time, suncreams have been manufactured adding titanium oxide microparticles that gave the products a pasty, sticky consistency. Leaving a visible film, application of such suncreams was not easy and not pleasing to the skin. Suncreams that contain the transparent nanoscale titanium dioxides can be applied much more easily. In addition, their protective effect against harmful UV radiation is much better. At present, high sun protection factors can only be achieved using nanoscale titanium dioxides [4].

The German Association for Cosmetic, Toiletry, Perfumery and Detergent (Industrieverband Körperpflege und Waschmittel e.V. - IKW) has been reporting that only nanoscale titanium dioxides are used in sunscreens presently [5].


sunflower in front of a wall of solar cell panels as application example of titanium dioxide in solar cell panels

solar cells © Jürgen Fälchle / Fotolia.com

To achieve better dispersion properties and ensure photostability, these TiO2, moreover, are coated with further materials [6]. The photocatalytic activity, which is another property of TiO2, is increased considerably through the high surface-to-volume ratio of the nanoparticles as compared to that of microparticles. However, not each of the above modifications can be used for photocatalytic purposes. While, as has been shown above, rutile TiO2 are applied mainly in suncreams, paints, and dyes, anatase modifications are rather suited for photocatalysis. In the presence of UV radiation, anatase TiO2 can form radicals from air or water which can degrade oxidatively organic pollutants. In the German town of Fulda, Franz Carl Nüdling Basaltwerke has developed paving stones which by means of titanium dioxide can “free” the air from exhaust emissions. Similar paving stones and tiles are used already in Japan along the traffic routes. Researchers at Universität Kassel have found a method of interlocking nanoscale TiO2 with dye molecules in such a way that the photocatalytic process can be triggered also by visible light and not exclusively by UV radiation.

Due to the hydrophilic character of titanium dioxide, water forms a closed film on the surface in which pollutants and degradation products can be easily carried away. House paints or tiles containing TiO2 particles thus are self-cleaning and pollutant-degrading. Besides, so-called anti-fog coatings benefit from the hydrophilic properties of nanoscale titanium dioxide. The ultra-thin water film on a glass pane coated with a transparent layer of nanoscale TiO2 impedes the formation of water droplets and, thus, avoids fogging. Nanoscale titanium dioxides are also suited for use in dye-sensitized solar cells (Graetzel cells).

Titandioxid is not self-inflammable as nanometer-sized powder. Also as a mixture with air (dust) under the influence of an ignition source, it is not inflammable, so there is no possibility of a dust explosion.


Natural Occurence and Manufacture

Titanium dioxide mostly occurs together with other types of rock, thus must be separated from these. Ilmenite (FeTiO3) is one of the most well-known minerals. Different methods are used for refinement.

In the European Union, 70 percent of all titanium dioxide are extracted from natural minerals using the sulfate method while the remaining 30 percent are obtained by means of the chloride method. In Germany, both methods are used equally. The sulfate method came under criticism some decades ago for producing dilute sulfuric acid (referred to as dilute acid) which through to the eighties was dumped in the North Sea. North Sea dumping has been forbidden in Germany since 1990. Today, dilute acid is being treated or fed into manufacturing processes. During the chloride method, TiO2 ores react with chloride gas while forming hydrochloric acid. Being much more significant to industry than dilute acid, hydrochloric acid can be recycled into production or be sold.

Further processes are necessary for production of nanoscale TiO2. The so-called titanium alkoxylates can be hydrolysed and subsequently be treated thermally. The particles’ crystal modification depends on the temperature applied during the process. Moreover, nanoscale titanium oxide particles can be obtained by reacting titanium chloride compounds with ammonia. Under the influence of heat, the titanium oxide hydrate forming during that reaction turns into rutile TiO2. The aerosol method that was developed by Degussa in the forties for silicon dioxide was applied to titanium dioxide in the fifties. It enables production of nanoscale titanium dioxide from titanium chloride compounds through reaction of the latter with water vapor.


NanoCare Data Sheets


  1. PR Web.com (EN) (30.08.2010) . Global Titanium Dioxide Industry Stabilises and Heads for Recovery, TZMI Pressemitteilung.
  2. Cefig.org (EN): Titanium Dioxide Manufacturers Association (TDMA) (Stand letzter Zugang: Sep 2011).
  3. Cefig.org (EN): Industry responds to Nano-TiO2 study published in American Association for Cancer Research Journal, Offener Brief des Titanium Dioxide Stewardship Council vom 3. März 2010. (PDF-Document).
  4. Schweizer Kosmetik- und Waschmittelverband (SKW) (02.09.2014). Nanomaterialien in Kosmetika. (PDF; 38 KB, in GERMAN Only)
  5. NanoTrust Dossier No.008en (Dec 2010). Nanotechnology in Cosmetics, NanoTrust, Institute of Technology Assessment (ITA), Vienna Austria.
  6. Scientific Committee on Consumer Products (SCCP) (19.06.2007). Safety of nanomaterials in cosmetic products.

General Hazard

The studies conducted so far have not indicated any increased risk for people employed in production to incur lung cancer or other types of cancer. The death rate was not increased either [1,2]. Workplace exposure studies within the project NanoCare have shown that particles released during TiO2 powder filling mostly are larger than 450 nm and, thus, are not considered nanoparticles [3].

schematic workflow of the different life cycle steps of titanium dioxide nanoparticles from production to processing into applications to disposal highlighing potential hot sports fro nanoparticle release

Life cycle and possible paths of titanium dioxide release. © Kuhlbusch et al., UBA-Studie.


  1. Ellis, ED et al. (2010), J Occup Environ Med, 52(3): 303-309.
  2. Wild, P et al. (2009)."Lung Cancer and Exposure to Metals: The Epidemiological Evidence", in Cancer Epidemiology. vol. 472, Verma, Humana Press, pp. 139-167. ISBN:978-1-60327-491-3
  3. NanoCare 2009, Final Scientific Report, ISBN 978-3-89746-108-6. (PDF-Document, 19 MB).
  4. Kuhlbusch, T. (Oct 2010). Emissionen von Nanopartikeln aus ausgewählten Produkten in ihrem Lebenszyklus. UBA-Studie, Umweltbundesamt, ISSN 1862-4804.

Studies on Living Organisms - in vivo

A five-day inhalation study within the project NanoCare has revealed that inhaled TiO2 particles are deposited in the lung as agglomerates and can get into the lung-associated lymph nodes [1]. They are mostly found in phagocytes. In addition, instillation studies carried out within that project applying low (0,6 mg/lung) and high doses (4,8 mg/lung) showed a slight dose-dependent increase in the number of macrophages. These cells are important to immune defense and serve to remove foreign matter such as particles by phagocytosis [1].

Further instillation studies have shown that low doses of TiO2 particles are deposited in the lungs and can also get into the liver and kidneys. Small amounts of TiO2 had no negative effects on the lung but caused temporary changes in the metabolites in the liver and kidney. At high doses, the strong aggregation and disposal of particles in the lung was observed to cause severe inflammatory reactions. There was no detectable further transport of TiO2 particles in the liver and kidneys. Since the macrophages were no longer able to mediate phagocytosis, the lung became overcharged with particles [2,5]. Also according to Kobayashi and colleagues particles in the lung can cause short-term effects (24 h). The observed inflammatory reactions were found to have healed after approximately 1 month [3].

The effects described above cause acute reactions in the lung. Only few studies are available so far of the chronic effects of nanoscale TiO2 particles on the body. Park et al. have inferred from their studies that TiO2 may possibly cause chronic inflammation of the lung after instillation [4].


  1. NanoCare 2009, Final Scientific Report, ISBN 978-3-89746-108-6. (PDF-Document, 19 MB).
  2. Tang, M et al. (2010), J Nanosci Nanotechnol, 10(12): 8575-8583.
  3. Kobayashi, N et al. (2009), Toxicology, 264(1-2): 110-118.
  4. Park, EJ et al. (2009), Toxicology, 260(1-3): 37-46.
  5. Li, J et al. (2007), Environ Toxicol Pharmacol, 24(3): 239-244.
  6. Ma-Hock, L et al. (2009), Inhal Toxicol, 21(2): 102-118.

Studies Outside of Organisms - in vitro

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 15nm) 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 (50µg/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 60µg 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 50µg/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].


  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)

It is not easy to detect TiO2 nanoparticles in the environment. However, titanium dioxide nanoparticles were found to leach from facades painted with TiO2-based paint [1]. The particles run down with the rain water in form of aggregates, and often embedded in the paint components, and reached surface waters.

On examination of sediment samples from a region in China, engineered TiO2 particles were detected by electron microscopy and it was possible to distinguish them from naturally occurring titanium [2]. At the same time, this study showed that the accumulation of Ti in sediments has been going on for decades, since also coarser particles produced earlier are detectable. As the sources of Ti pollution, the introduction of treated and untreated waste water is assumed.

An investigation of effluent from sewage treatment plants [3] showed that a large proportion of titanium particles is removed from the wastewater, however, the very small (<700nm) particles remain in the water, and so again may reach rivers and lakes. The titanium concentrations in the effluent of the treatment plant were 5 to 15µg/l. During the purification process, most of the titanium particles are bound to solids and get into the sludge. The latter, in turn, is either disposed of as landfill or spread on fields as fertilizer, so that the coarser titanium particles are more likely to get into the soil.

Because the TiO2 concentrations in the environment are so low, both the development of measurement methods [4,5] and the simulation of exposure to titanium dioxide nanoparticles in the environment [6] are currently in the focus of research and development.

By means of computer programs, it has been attempted to simulate the probable behavior of titanium dioxide nanoparticles in the environment. Therefore, they most likely occur in natural surface waters and their sediments and in sewage sludge and soils on which sewage sludge was disposed [7,8]. Comparing these predicted environmental concentrations (PEC values) with concentrations not just hazardous for environmental organisms, (PNEC value), it is apparent that currently; particularly TiO2 nanoparticles in discharge from sewage treatment plants may pose an environmental risk. However, for surface water, soil, and air no risk is expected at present. The figure explains in more detail how such a risk is calculated.

Risk Ratios for TiO2 in different Regions

Environmental compartment Europe USA Switzerland
Surface waters 0,015 0,002 0,02
STP effluent 3,5 1,8 4,3
Air <0,0005 <0,0005 <0,0005


The risk ratio is calculated from the predicted environmental concentrations (PEC) divided by the concentrations that have no effects on environmental organisms (PNEC). If the risk ratio is less than 1, there is no immediate risk to the environment, whereas at levels above 1, there is a risk and further investigations must be carried out [7].

Another computer simulation assumes that in the future, the amount of produced TiO2 will continue to rise and that the proportion of nanoscale TiO2 also further increases [9]. From this, it is concluded that the environmental concentrations will increase in the future.

Generally, there are still large gaps in knowledge in this area which are mainly due to inadequate methods of measurement and, hence, accurate knowledge of the environmental concentrations is missing. Further, data are lacking on accurate amounts of substance, as well as on the behavior and distribution in the three environmental compartments water, soil, and air.


  1. Kaegi, R et al. (2008), Environ Pollut, 156(2): 233-239.
  2. Luo, Z et al. (2011), J Environ Monit, 13(4): 1046-1052.
  3. Kiser, MA et al. (2009), Environ Sci Technol, 43(17): 6757-6763.
  4. Tiede, K et al. (2009), Water Res, 43(13): 3335-3343.
  5. Contado, C et al. (2008), Anal Chem, 80(19): 7594-7608.
  6. Gottschalk, F et al. (2010), Environ Modell Softw, 25(3): 320-332.
  7. Gottschalk, F et al. (2009), Environ Sci Technol, 43(24): 9216-9222.
  8. Mueller, NC et al. (2008), Environ Sci Technol, 42(12): 4447-4453.
  9. Robichaud, CO et al. (2009), Environ Sci Technol, 43(12): 4227-4233.

Uptake via the Lung - Inhalation

Within the project NanoCare, in vitro tests were carried out on human lung cells. Only very high doses (50 µg/cm2) of different variants of titanium dioxide were found to have caused losses in vitality. To simulate the formation of dust, the cells were exposed to titanium dioxide particles for two and four hours, respectively, using the Karlsruhe Exposure System. None of the applied concentrations was found to have caused losses in the cell vitality or signs of acute cell cytotoxicity [1].

Moreover, animal experiments conducted within NanoCare revealed that inhaled TiO2 particles that are deposited in the lungs of the subjects may trigger temporary inflammatory reactions [1]. Please see also the sections on "exposure – in vitro" and "exposure - in vivo".


  1. NanoCare 2009, Final Scientific Report, ISBN 978-3-89746-108-6. (PDF-Document, 19 MB).

Uptake via the Skin - Dermal Uptake

schematic image of the different layers of human skin starting from the stratum conreum at the top down to the stratum basale at the bottom

Human Skin Layer (epidermis). © Wikipedia.de

These results have been confirmed within the EU project NanoDerm for nanoscale TiO2 particles used in cosmetics [2]. Coating of the TiO2 particles contained in suncreams ensures good dispersion properties and photostability [3] and avoids the formation of reactive oxygen species (ROS). It remains to clarify the question how injured, inflamed or particularly sensitive skin, for example sunburnt skin, reacts? A study from 2011 could show that neither titanium dioxide nor zinc oxide nanoparticles penetrate UVB-damaged skin (sunburn) [6]. The particles remain in the upper layers of the epidermis (see also the article "Basics - Dermal Uptake").

Sunscreens with titanium dioxide and zinc oxide nanoparticles provide an efficient protection against skin damage from ultraviolet light (UVB). In their report from 2011 the American Nanodermatology Society (NDS) compiles and summarises the results of numerous studies and confirms that TiO2 particles do not penetrate the skin (the stratum corneum) and do not enter living cell layers [7].


  1. Gamer, AO et al. (2006), Toxicol In Vitro, 20(3): 301-307.
  2. Pfluecker, F et al. (2001), Skin Pharmacol Appl Skin Physiol, 14 Suppl 1(Suppl. 1): 92-97.
  3. NanoDerm final scientific report (2007). Quality of Skin as a Barrier to ultra-fine Particles. QLK4-CT-2002-02678.
  4. Scientific Committee on Consumer Products (SCCP) (19.06.2007). Safety of nanomaterials in cosmetic products.
  5. Nohynek, GJ et al. (2007), Crit Rev Toxicol, 37(3): 251-277.
  6. Monteiro-Riviere, NA et al. (2011), Toxicol Sci, 123(1): 264-280.
  7. Nanodermatology Society (NDS) (17.05.2011). The 2011 Nanodermatology Society Position Statement on Sunscreens, http://www.nanodermsociety.org/news.php (PDF, 243 KB).

Uptake via the Gastro-Intestinal Tract

Usually, such particles are excreted via the stool. So far, only few analyses on this topic exist.

In vitro studies with human intestinal cells showed that high doses (20 and 80μg/cm2) on TiO2 cause after 24 h of incubation, significant membrane damage, leading to a loss of vitality and may induce toxicity. After 4 h, the cells, however, showed no reactions. TiO2 particles in this study caused no DNA strand breaks or oxidative DNA damage. When different versions of TiO2 with different surfaces were used, so surface dependent effects could not be found. The authors conclude from their in vitro studies on intestinal cells (as a model for a healthy intestine) that ingestion of TiO2 particles poses no risk [1].


  1. Gerloff, K et al. (2009) Nanotoxicology 3(4): 355-364.

However, the studies are not easily comparable because the particle manufacturers and, thus, usually also the properties of titanium dioxide particles differ from study to study [1].

The rainbow trout as aquatic test organism has been very well studied and was confronted with titanium dioxide nanoparticles via the water, food, and the bloodstream. In coarser form (microscale), titanium dioxide particles have long been used in nutritional studies in fish and are considered nontoxic. TiO2 nanoparticles ingested via the food can be detected in the gills, intestine, liver, brain, and spleen. Thus, there is a systemic distribution of the particles in the body, but this had no effect on the health of the animals [2]. Titanium dioxide nanoparticles taken up directly from the water are only slightly absorbed into the fish's body [3].

In another study, rainbow trout were injected with TiO2 nanoparticles directly into the bloodstream and the distribution in the organs was observed. A non-environmentally relevant exposure, however, it serves to clarify mechanisms of action and effects on the uptake of very high doses, e.g. for a possible industrial accident [4]. The particles were enriched in the kidney and liver without affecting the functions of these important organs.

Zebrafish can also take up TiO2 particles from the water. The egg of fish embryos is not permeable for particles. If embryos are exposed to the particles in the presence of strong lighting, occurrence of malformations and increased mortality of the embryos is observed [5]. This effect does not occur under normal lighting conditions and is therefore due to the photocatalytic properties of the TiO2 particles. Adult zebrafish showed no effects after exposure to TiO2; the gills showed no morphological changes [6,7]. However, there were changes in the activity of certain genes; these changes were partly consistent with those observed after copper and silver nanoparticle exposure.

Water fleas (Daphnia magna) are among the most commonly used test organisms. In the often used two-day test, in which the daphnia are exposed for 48 h to the particles, no or only minimal effects (mobility, mortality) were observed in several studies [6,8,9,10]. However, when the observation period was extended to 3-21 days, effects on molting and reproductive ability became apparent, some leading to the death of all test organisms [8,9,10]. These indirect toxic effects are due, on the one hand, to the attachment of particles on the exoskeleton (carapace) of the animals, on the other hand, to particle absorption in the intestine. The latter may inhibit food intake in the chronic tests [10].

Water flea accumulate titanium dioxide nanoparticles (black coloured areas) in their gut. © Zhu et al., 2010.

Water flea accumulate titanium dioxide nanoparticles (black coloured areas) in their gut. © Zhu et al., 2010.

An important question in risk research is the extent to which a transfer of nanoparticles through the food chain takes place. In a "small" food chain, consisting of water fleas and zebrafish, it was shown that transfer of nanoparticles from TiO2-fed daphnids to zebrafish occurs [11].

For other freshwater and saltwater organisms (mussels, snails) titanium dioxide nanoparticles were not acutely toxic [12,13], but the activities of certain enzymes showed a response to particle exposure [13,14].

Lugworms living in marine sediments did not internalize particles via the skin or the gut into the body tissue [15]. At very high concentrations, the worms’ food intake was reduced, a typical response to contaminants in the sediment. Also in high concentrations, TiO2 nanoparticles induced DNA and cell damage.

As an example of soil-dwelling organisms, woodlice were fed with titanium dioxide-soaked leaves. The nanoparticles had little influence on the metabolism and no effect on feed intake, body weight or mortality [16,17], although the concentrations used were very high. Similar to water fleas, however, longer duration of exposure had an influence on the effect of TiO2, an indication that unlike the commonly used short-term tests also chronic tests with longer exposure times should be performed. After 7 days of TiO2 exposure via the soil, a worm species showed DNA damage and evidence of oxidative stress, also in very high concentrations [18]. Similar observations were made for a nematode; here, also growth and number of offspring was reduced [19].

TiO2 nanoparticles were tested on various plants. In the onion and in willow trees, the toxicity was low and all growth parameters were unchanged [20,21]. Another study examined tobacco and onion plants; here, high, non-environmentally relevant concentrations caused genotoxic effects [22]. For a freshwater green alga exposed to 3 different TiO2 nanoparticles, growth inhibitory effects were observed, but these do not only depend on differences in particle sizes, but also on other characteristics such as different crystal structures [23]. Further, it is unclear, whether the nanoparticles hinder the necessary light and thereby inhibit algae growth.

In conclusion, from the studies available so far, a low toxicity of titanium dioxide nanoparticles to environmental organisms can be derived. Effects were always observed at concentrations well above the predicted environmental concentrations (PEC value).

The particles are taken up, however, without a doubt in organisms and cells, so we must consider for the future, that the effects of very low concentrations of these substances over a longer period, as it would comply with the conditions in the environment, have not yet been adequately examined (in Daphnia and woodlice).


  1. Menard, A et al. (2011), Environ Pollut, 159(3): 677-684.
  2. Ramsden, CS et al. (2009), Ecotoxicology, 18(7): 939-951.
  3. Federici, G et al. (2007), Aquat Toxicol, 84(4): 415-430.
  4. Scown, TM et al. (2009), Toxicol Sci, 109(2): 372-380.
  5. Bar-Ilan, O et al. (2012), Nanotoxicology, 6(6): 670-679.
  6. Griffitt, RJ et al. (2008), Environ Toxicol Chem, 27(9): 1972-1978.
  7. Griffitt, RJ et al. (2009), Toxicol Sci, 107(2): 404-415.
  8. Dabrunz, A et al. (2011), PLoS One, 6(5): e20112.
  9. Wiench, K et al. (2009), Chemosphere, 76(10): 1356-1365.
  10. Zhu, X et al. (2010), Chemosphere, 78(3): 209-215.
  11. Zhu, X et al. (2010), Chemosphere, 79(9): 928-933.
  12. Canesi, L et al. (2010), Aquat Toxicol, 100(2): 168-177.
  13. Musee, N et al. (2010), Chemosphere, 81(10): 1196-1203.
  14. Canesi, L et al. (2010), Aquat Toxicol, 96(2): 151-158.
  15. Galloway, T et al. (2010), Environ Pollut, 158(5): 1748-1755.
  16. Drobne, D et al. (2009), Environ Pollut, 157(4): 1157-1164.
  17. Jemec, A et al. (2008), Environ Toxicol Chem, 27(9): 1904-1914.
  18. Hu, CW et al. (2010), Soil Biol Biochem, 42(4): 586-591.
  19. Wang, H et al. (2009), Environ Pollut, 157(4): 1171-1177.
  20. Klancnik, K et al. (2011), Ecotoxicol Environ Saf, 74(1): 85-92.
  21. Seeger, EM et al. (2008), J Soils Sediments, 9(1): 46-53.
  22. Ghosh, M et al. (2010), Chemosphere, 81(10): 1253-1262.
  23. Hartmann, NB et al. (2010), Toxicology, 269(2-3): 190-197.

Behaviour at the Blood-Brain Barrier

Given the fact that the blood-brain barrier is a good protection against penetration of pathogens, it remains to be found out whether or not at all TiO2 particles can get into the brain. Besides passing the blood-brain barrier, particles, when inhaled, can get directly into the brain via the olfactory nerve.

In a study with rats, no increased amounts of TiO2 nanoparticles were found in the brains after injection into the bloodstream [2]. No titanium was detected in the brains of mice after instillation with TiO2[3].


  1. Long, TC et al. (2006), Environ Sci Technol, 40(14): 4346-4352.
  2. Fabian, E et al. (2008), Arch Toxicol, 82(3): 151-157.
  3. Li, Y et al. (2010), J Nanosci Nanotechnol, 10(12): 8544-8549.

Behaviour of Uptake in somatic cells

Most of the TiO2 particles are taken up in the cells as large intracellular aggregates in vesicles, vacuoles or lamellar bodies by means of phagocytosis. High doses, however, impede phagocytosis thus causing overloading of the cells, for example in the lungs [5]. Pinocytotic uptake was observed only in the case of small aggregates (< 30nm) and single particles. After uptake, the TiO2 particles are mostly bound to the cytoplasmic membranes of the cells. No particles have been found so far in the nuclei of the cells [1,2]. In vitro multi-cell systems are preferred to simple cell culture models with only one cell type for simulation of the interaction of different cells in the body and of in vivo situations. Using sensitive methods, TiO2 was shown to occur in all cell types of a triple co-culture system as membrane-bound larger aggregates but also freely in the cytoplasm as smaller aggregates or single particles [3].

In contrast, transcytosis, i.e. the vesicular transport of macromolecules from one cell to the other, has hardly been investigated in vitro. Measurements that have been taken within the project NanoCare to assess the transport of nanoparticles through the cells have shown that TiO2 particles are not transported through monolayer cells [4]. Besides, exocytosis, a process where substances are transported from the cell interior to the cell environment, does not take place according to in vitro tests.


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  2. Zucker, RM et al. (2010), Cytometry A, 77(7): 677-685.
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(1) Studies on the influence of environmental conditions on the mobility are concerned in particular with naturally occurring substances in soil or water and their interaction with the nanoparticles. This is particularly the influence of agglomeration , as well as stability and deposition of particles. The natural materials include organic materials (degradation products of plants or animals), such as humic or fulvic acids, which are included in all waters and soils in different proportions.

In most cases, binding of such materials to TiO2 leads to stabilisation of the suspension particles and prevents their agglomeration [1,2,3,4,5,6,7]. As a result, particles rather "float" in the water, thus remain mobile and do not sediment. Stabilisation by organic materials is largely independent of the pH and salinity of the environment, i.e. takes place under various environmental conditions. The agglomeration-preventing effect of proteins is similar to that of organic materials [8].

However, certain substances like organic acids, e.g. oxalic acid, can also have opposite effects or may not exert any stabilising effect [9]. Minerals or salts also increase agglomeration of the particles [10] and reduce their mobility [1].

The behaviour of the particles is also influenced by their chemical and physical properties. Hence, contaminants (e.g. residues from production) may affect the surface charge and, thus, the behaviour of the particles [11,5]. However, according to the present studies, the different crystalline structures of TiO2 and different shapes and sizes have no effect on sedimentation and agglomeration of the particles.

(2) In addition to the natural organic substances, also inorganic substancescan bind to titanium dioxide particles and thereby influence their behaviour in the environment and their effects on environmental organisms. Titanium dioxide particles can bind toxic heavy metals such as cadmium and arsenic [12,13,14].

Carp exposed to cadmium and arsenic-containing water and titanium dioxide particles took up more cadmium and arsenic than carp in particle-free water [13,14]. In algae, however, this effect was not observed, because algae do not absorb cadmium-laden particles [12]. Due to the photocatalytic effect of TiO2, arsenic is transformed into a less toxic form [15]. Similarly, an increased binding of phosphorus to TiO2 has been described [16].

Thus, TiO2 nanoparticles in principle bind many substances and increase the bioavailability for organisms. Whether TiO2 particles have a significant impact on the availability of other pollutants under field conditions has not been investigated yet.

(3) TiO2 nanoparticles can also affect processes in the environment, e.g. by changing the properties of sediments with respect to surface area, pore size, and ability to bind to other substances [16]. This could for example increase the binding of nutrients in TiO2-contaminated soils. The precise effects of TiO2 enrichment, however, are still unexplored.

Also, water-purification processes in water treatment plants can be affected by high TiO2 concentrations. Effects on the removal of nitrogen compounds have been described [17].


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  11. Liu, X et al. (2011), J Colloid Interface Sci, 363(1): 84-91.
  12. Hartmann, NB et al. (2010), Toxicology, 269(2-3): 190-197.
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  14. Zhang, X et al. (2007), Chemosphere, 67(1): 160-166.
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Further Materials

Quantum Dots
Barium Sulphate
Iron and Iron Oxides
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