Apart from its use as a food additive (E171), titanium dioxide is used as a white pigment in a wide variety of other products such as paints and plastics. Human uptake can also result from components of food supplements and medicines. In addition, small children sometimes swallow their toothpaste, which can contain titanium dioxide. In the list of ingredients, it is then labelled as CI77891. Titanium dioxide may also be found naturally in certain foods.

Size, form and coating of titanium dioxide particles

To provide the characteristic white colour of titanium dioxide, a large part of the particles must be between 200 and 300 nanometres in size. Particles of this size are not considered nanoparticles. However, the titanium dioxide production process results in a small fraction of the particles being nanoparticles. In addition, titanium dioxide can exist in various crystalline forms, and a coating may be added to the particles as well. The potential differences in terms of size, crystalline form, and surface characteristics complicate the risk assessment of titanium dioxide.

Uncertain risks

The effects of titanium dioxide in case of a realistic, long-term, low level of human exposure via food consumption are unclear. Previous studies with laboratory animals have indicated that the ingestion of very large quantities of titanium dioxide can cause damage to various organs, including the liver. It has been shown excretion of titanium dioxide nanoparticles from the body is a very slow process, leading to potential accumulation in tissues. Such accumulation does not automatically mean that there is a health risk involved, but it is an indication that additional studies may be needed. This stresses the particular importance to conduct long-term exposure studies.

In 2016, RIVM used computer modelling to estimate the concentration of titanium dioxide nanoparticles in various human organs based on the estimated exposure to titanium dioxide nanoparticles via food, food supplements, and toothpaste (for small children). This estimated exposure concentration was then compared with the concentration that causes negative effects in the liver of laboratory animals. The modelling study also took into account the long-term accumulation of titanium dioxide nanoparticles in the body. Based on this study and considering the differences between humans and animals and sensitive groups within the population, it was shown that effects on the liver cannot be excluded.

In 2018, RIVM and the RIKILT research institute, for the first time, actually detected titanium dioxide particles to be present in the liver and spleen of humans. At least 24% of the titanium dioxide particles were found to be nanoparticles. The concentrations measured in the spleen matched the computer estimations. The concentration measured in the liver is somewhat higher than estimated. The concentration of titanium dioxide particles found in the human liver did not yet result in adverse health effects in laboratory animals, but it exceeded the level that RIVM considers safe for humans. In this assessment, safety factors were applied for the possible differences in sensitivity between humans and animals and between different human individuals.

These analyses confirm the possibility that the use of titanium dioxide may lead to adverse effects in the liver. Therefore, the safety of the present use cannot be fully guaranteed.

Re-evaluation by EFSA

In 2016, the European Food Safety Authority EFSA published the re-evaluation of titanium dioxide (E171) as a food additive. This publication also dealt with the potential risks of titanium dioxide nanoparticles for humans. Despite the inclusion of RIVM’s computer estimations, EFSA concludes that, based on the information currently available, there is no reason for concern. RIVM is more cautious in its conclusions as a result of a different way of considering the lifelong accumulation of titanium dioxide nanoparticles in organs.

In 2018, the European Commission requested EFSA to further re-examine a number of studies, including the RIVM study.

Publications

Titanium dioxide particles in the liver and spleen of humans (Heringa et al. 2018):

https://doi.org/10.1186/s12989-018-0251-7

Computer modelling of the accumulation of titanium dioxide nanoparticles in the liver (Heringa et al. 2016):

https://doi.org/10.1080/17435390.2016.1238113

Ingestion estimate for (nano)titanium dioxide (Rompelberg et al. 2016):

https://doi.org/10.1080/17435390.2016.1222457

Distribution in and removal from the (rat) body (Geraets et al. 2014):

https://doi.org/10.1186/1743-8977-11-30