Titanium dioxide can be taken up via the lungs or the gastrointestinal tract. Due to its many layers, the skin is a good barrier for particles. The addition of titanium dioxide in nano form to food or food packaging was never permitted in Germany. Since August 2022, titanium dioxide (E171) in any form and size has been banned as a food additive.
Uptake via the Lung
As part of the NanoCare project, in vitro tests were carried out with human lung cells. Different variants of titanium dioxide only caused loss of vitality after administration of very high doses (≥ 50 µg/cm2). Cells exposed to titanium dioxide particles for 2 and 4 hours in the so-called "Karlsruhe exposure system" to simulate dust formation showed no loss of vitality at any of the concentrations used and there were no signs of acute cytotoxicity .
A 5-day inhalation study conducted in the NanoCare project showed that inhaled titanium dioxide particles are deposited as agglomerates in the lungs, are then taken up by macrophages and are also deposited in lung-associated lymph nodes when high doses are administered (50 mg/m3). In contrast, nanoparticles were not detected in the liver, kidneys, spleen or basal brain with attached olfactory bulb in these studies [.
Instillation studies with low (0.6 mg/lung) and high doses (4.8 mg/lung) also carried out as part of the NanoCare project showed a slight dose-dependent increase in the number of macrophages in the lungs. These cells are important for immune defence and serve to remove foreign substances, such as particles, by phagocytosis.
Further instillation studies have shown that titanium dioxide particles can be deposited in the lungs at low doses and can also be transported to the liver and kidneys. The low doses of titanium dioxide had no negative effects on the lungs, but led to a temporary change in the metabolites in the liver and kidneys. In contrast, a strong aggregation and deposition of particles in the lungs was observed at high doses. This led to strong inflammatory reactions. However, no further transport of titanium dioxide particles into the liver and kidneys was detected. The macrophages could no longer perform phagocytosis, so the lungs were overloaded with particles .
Kobayashi and colleagues also describe in their studies that particles in the lungs can cause short-term effects (24 h) However, the inflammatory reactions observed had subsided again after approx. 1 month .
In 2021, the ECHA reclassified titanium dioxide on the basis of several studies with high-dose experiments on rats. Everyday products containing titanium dioxide, regardless of size, must be labelled according to EUH212 as follows: "Warning! Hazardous respirable dust may be generated during use. Do not inhale dust". However, on 23 November 2022, the European Court of Justice annulled the Commission Regulation from 2019 insofar as it concerns the harmonised classification and labelling of titanium dioxide in certain powder forms as a carcinogenic substance if inhaled. In its judgement, the General Court states that the Commission had made a serious mistake in assessing the reliability and recognition of the studies. The classification was based on this erroneous assessment.
Uptake via the Skin
Human Skin Layer © Wikipedia.de
Titanium dioxide particles are not taken up into the body via the skin. This was investigated and confirmed in the EU project NanoDerm for nano-titanium dioxide particles as a component of cosmetics . Further studies confirm this by investigating pig skin, which is very similar to that of humans . Another very good overview on the safety of titanium dioxide particles in sunscreens comes from France, which also found no concerns for the use of titanium dioxide in sunscreens from all the studies consulted .
In order to obtain good dispersion properties of the sun cream, to ensure photostability and to prevent the formation of harmful so-called reactive oxygen species (ROS), the titanium dioxide particles are also coated (see also NanoDerm final report, 2007).
The question remains as to how injured, inflamed or particularly sensitive skin, such as skin damaged by sunburn, reacts? A study from 2011 was able to show that titanium dioxide and zinc oxide nanoparticles are also unable to penetrate UVB-damaged skin (sunburn) .
The particles remain in the upper layers of the epidermis (see the article under "Basics Basic Information - How can innovative materials (e.g.nanomaterials) enter the body or the environment?")
Sun creams with titanium dioxide and zinc oxide nanoparticles offer efficient protection against skin damage caused by ultraviolet light (UVB).
Uptake via the Gastro-Intestinal Tract
Orally ingested insoluble mineral particles are usually excreted in the faeces. To date, however, only a few analyses have been carried out on this topic.
Studies with treated human intestinal cells (20 and 80 µg/cm2) certainly showed toxic effects after 24 hours of treatment. However, DNA damage was not observed . Titanium dioxide was authorised as a food additive E171 in 2008. A re-evaluation of the studies from 2015 to 2020 by the European Food Safety Agency (EFSA) in 2021 revealed a different picture . Due to the existing safety concerns, Titanium dioxide (E171) was banned as a food additive in the EU in August 2022.
There are scientific doubts about this ban. In 2022, the Canadian health authority concluded that there is no evidence of a carcinogenic effect. In Canada, titanium dioxide remains permitted in food (Health Canada, 2022). In the UK, there is also certainty that titanium dioxide has no such effect and the Food Standards Agency (FSA) https://www.food.gov.uk/ has no safety concerns and titanium dioxide also remains permitted there (COT, 2022).
Furthermore, international expert groups have doubts about the EFSA's evaluation and are calling for this decision to be reconsidered in the EU .
Uptake via medical applications
Titanium dioxide is contained in many medicines as a filler and excipient. Irrespective of the ban in foodstuffs, it may continue to be used in medicines as there is no alternative available and an immediate ban would lead to further bottlenecks in the supply and production of medicines.
However, the European Medicines Agency (EMA) has called on the pharmaceutical industry to look for alternatives as quickly as possible . The EMA is due to submit a report to the EU in April 2024 and the EU will then decide whether and how titanium dioxide may continue to be used in medicines (see also: EMA )
However, the quantities of titanium dioxide in the individual tablets or other dosage forms are very low. None of the many studies have so far been able to prove a recognisable risk from such low levels of titanium dioxide.
The intake of titanium dioxide via food is currently not given, but is still possible via medication. However, titanium dioxide is also absorbed from natural sources via food. To date, no valid study has been able to plausibly demonstrate a risk from orally ingested titanium dioxide. Titanium dioxide is not absorbed via the skin. Titanium dioxide can be absorbed via the lungs, primarily due to exposure in the workplace. However, the risk assessment of this material has been under discussion for several years (2018 to 2022). Titanium dioxide is regulated very differently around the world.