Effect of food additive E171 (titanium dioxide) on the development of colorectal cancer
The food additive E171 (titanium dioxide) is present in many different food products, including sweets, cookies, icing and chewing gum. Consumers are exposed between 1 and 2 mg/kg bw/day depending on the age, it is important to evaluate the potential risk of this compound on human health. E171 comprised titanium dioxide (TiO2) particles of various sizes, among others in the nanoparticle size range. In view of its chemical nature, TiO2 was considered to be inert in humans after ingestion and allowed as food additive on the European market. In 2016, the European Food Safety Authority (EFSA) published an opinion in which it was concluded that after ingestion, no health effects for humans were to be expected. However, in 2017, the European Chemicals Agency (ECHA) published an opinion which proposes that TiO2 be classified as a category 2 carcinogen after inhalation, and the International Agency for Research on Cancer (IARC) has designated titanium dioxide as possibly carcinogenic to humans after inhalation.
After publication of the EFSA opinion in 2016, a number of new studies were published in scientific literature, reporting harmful effects of exposure to E171 in laboratory animals. In addition, a coherent sequence of studies has demonstrated that the basis of insolubility and inertia, it is no longer valid to assume that E171 has no toxic effects. These studies demonstrated in vitro damage to human colonic cells, and identified relevant molecular processes in different types of animal studies that raise concern about human safety (Proquin 2018). A recent ANSES report (ANSES, 2019) is in line with this notion. In order to establish if the molecular mechanisms induced in animal studies, and which are linked to cancer promotion, are also induced in humans, a dietary intervention study is needed.
Therefore, the main core of the present PhD project will consist of a human dietary intervention study for which the protocol is already approved by the METC of the Maastricht UMC+. In addition, the PhD candidate will set up an in vitro study with human colon organoids, to evaluate gene expression responses in a relevant human model. Furthermore, the kinetics of TiO2 micro and nanoparticles will be studied, focusing on the relevance of different colonic cell types