Titanium dioxide (TiO₂) is a food additive authorized since the 1960s. Used for its whitening properties, it is included in confectionery, pastries and other industrial preparations under code E171 in the European Union. Its initial authorization file states that it poses no health risk and that its intestinal absorption is minimal. Its re-evaluation by the European Health Authority (EFSA), published in 2016, led the experts to conclude that the available data indicated that dietary exposure to this substance was not a health problem for consumers. Nevertheless, they emphasized the lack of data on some organs, particularly reproductive organs, and recommended to conduct studies to fill these voids.

In 2017, a study was published by the French National Institute of Agronomic Research and Environment (INRAE), highlighting its promoter effect in colorectal carcinogenesis on rats exposed by gastric gavage or drinking water at realistic doses of E171, as well as disturbances of the immune system of exposed animals ^[1].
Researchers at our Institute have been studying the effects of TiO₂ nanoparticles on in vitro models of intestinal epithelial cells for about ten years. These models combine enterocytes and cells secreting mucus, thus reconstituting the most superficial layer of the epithelium bordering the terminal part of the small intestine - the ileum. While prior results of the researchers have shown a transfer of TiO₂ nanoparticles from the intestinal lumen to the internal environment ^[2], their most recent data point out significant cellular effects, although of small magnitude. Thus, E171 does not result in a decrease in cell viability or chromosomal breaks or damage in the DNA of exposed cells, but disrupts the oxidative balance (homeostasis) of the cell, in particular by causing the accumulation of reactive oxygen species, toxic for the cell, coupled with the appearance of oxidized bases of DNA ^[3]. These disturbances do not cause endoplasmic reticulum stress but are associated with an inflammatory pattern, an increased expression of efflux pumps responsible for the release of xenobiotics out of intestinal epithelial cells, and with increased mucus production by Goblet cells ^[4].

On the basis of these results, E171 therefore appears to cause sub-lethal perturbations in intestinal epithelial cells, leading these cells to put in place defense mechanisms.



E171 seen in scanning electron microscopy.

Collaboration: Institut de Recherche en Santé Digestive, Inserm, Toulouse; Toxalim, Inra, Toulouse; Laboratoire Chimie et Biologie des Métaux, CNRS-CEA-UGA, Grenoble.
Enterocytes are one of the four main types of cells in the intestinal epithelium, within the intestinal mucosa.
Epithelium: a fundamental tissue forming either an outer (on the surface of the skin) or an internal (on the surface of a mucous membrane) surface, or a gland composed of epithelial cells.