Liver Titanium Dioxide Toxicology: Investigating the Mechanisms of Liver Toxicity Induced by the Food Additive E171 (Titanium Dioxide, TiO2) Using In Vitro, In Vivo, and In Silico Approaches

The oral intake of the food additive E171 (titanium dioxide, TiO2 nanoparticles) has raised significant public health concerns due to its potential adverse health effects. It was recently banned in the European Union after a reassessment by the European Food Safety Authority (EFSA) due to genotoxicity risks. However, it is still widely used in many countries, and the mechanisms underlying E171's toxicity, particularly its effects on the liver, remain poorly understood. The LiTiTox project aims to address this by investigating the molecular mechanisms of E171-induced liver toxicity, focusing on inflammation, cell death, and the role of pannexin1 (Panx1) channels, which are crucial for inflammasome activation but remain unexplored in this context. LiTiTox will employ a multidisciplinary approach, combining advanced in vitro liver spheroid co-culture models, in vivo mouse studies, and in silico molecular simulations. Liver spheroid models will simulate human liver responses to TiO2 exposure, while in vivo mouse studies will explore the effects of oral E171 exposure on liver toxicity. Molecular docking and dynamics simulations, conducted during the secondment, will predict interactions between E171 TiO2 and liver toxicity-related molecular events (MIEs). The project will also equip the researcher with advanced skills in in vitro toxicology, experimental hepatology, molecular biology, and computational modelling, enhancing career development and leadership in scientific research. The secondment will provide specialised training in chemoinformatics, machine learning, and predictive toxicology. Ultimately, LiTiTox’s findings will offer a deeper understanding of how E171 TiO2 nanoparticles affect liver health, contributing to the development of global regulatory policies. LiTiTox will play a crucial role in promoting food safety, sustainable nutrition, and safeguarding public health.