Since its discovery in the late eighteenth century and mass production in the early twentieth century, titanium dioxide has been used in a wide range of applications such as paints, cosmetics, energy storage, photocatalysis and food. Health concerns regarding TiO 2 use as a food additive, named E171 in Europe, are mainly due to the presence of nanoparticles, whereas it should contain only microparticles. Here we present the history of the increasing use of TiO 2 since the end of the Second World War, followed by rising concerns at the beginning of the twenty-first century, until the European decision to ban the use of TiO 2 in food in 2022. We discuss the evolution of TiO 2 regulation, within the regulation of chemicals products, particularly in Europe. We highlight the specific role played by the stakeholders: regulatory agencies, companies, scientists and associations. Two periods were identified. In the first period (1945–2000), marked by the growing use of chemical products, and of food additives in industry, the regulation of chemical products progressed with the double aim to master and adapt to risks. In the second period, beginning in the 2000s, the regulation of TiO 2 as a food additive in Europe has evolved in the context of the regulation of nanotechnology. The liberal approach associating nanotechnologies with progress and the competitiveness of companies and of the economies has gradually been challenged by the accumulation of scientific work pointing out the risks to human health during the last period. In the context of a food safety governance based on the separation of risk assessment and risk management, the TiO 2 case reveals the signaling role played by academic work, while civil society groups promote mediatization and can impose the precautionary principle as a basis for this regulation.