Safety assessment of titanium dioxide (E171) as a food additive

Maged Younes, Gabriele Aquilina, Laurence Castle, Karl-Heinz Engel, Paul Fowler, Maria Jose Frutos Fernandez, Peter Fürst, Ursula Gundert-Remy, Rainer Gürtler, Trine Husøy, Melania Manco, Wim Mennes, Peter Moldeus, Sabina Passamonti, Romina Shah, Ine Waalkens-Berendsen, Detlef Wölfle, Emanuela Corsini, Francesco Cubadda, Didima De GrootRex FitzGerald, Sara Gunnare, Arno Christian Gutleb, Jan Mast, Alicja Mortensen, Agnes Oomen, Aldert Piersma, Veronika Plichta, Beate Ulbrich, Henk Van Loveren, Diane Benford, Margherita Bignami, Claudia Bolognesi, Riccardo Crebelli, Maria Dusinska, Francesca Marcon, Elsa Nielsen, Josef Schlatter, Christiane Vleminckx, Stefania Barmaz, Maria Carfí, Consuelo Civitella, Alessandra Giarola, Ana Maria Rincon, Rositsa Serafimova, Camilla Smeraldi, Jose Tarazona, Alexandra Tard, Matthew Wright, EFSA Panel on Food Additives and Flavourings (FAF)

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The present opinion deals with an updated safety assessment of the food additive titanium dioxide (E 171) based on new relevant scientific evidence considered by the Panel to be reliable, including data obtained with TiO2 nanoparticles (NPs) and data from an extended one-generation reproductive toxicity (EOGRT) study. Less than 50% of constituent particles by number in E 171 have a minimum external dimension < 100 nm. In addition, the Panel noted that constituent particles < 30 nm amounted to less than 1% of particles by number. The Panel therefore considered that studies with TiO2 NPs < 30 nm were of limited relevance to the safety assessment of E 171. The Panel concluded that although gastrointestinal absorption of TiO2 particles is low, they may accumulate in the body. Studies on general and organ toxicity did not indicate adverse effects with either E 171 up to a dose of 1,000 mg/kg body weight (bw) per day or with TiO2 NPs (> 30 nm) up to the highest dose tested of 100 mg/kg bw per day. No effects on reproductive and developmental toxicity were observed up to a dose of 1,000 mg E 171/kg bw per day, the highest dose tested in the EOGRT study. However, observations of potential immunotoxicity and inflammation with E 171 and potential neurotoxicity with TiO2 NPs, together with the potential induction of aberrant crypt foci with E 171, may indicate adverse effects. With respect to genotoxicity, the Panel concluded that TiO2 particles have the potential to induce DNA strand breaks and chromosomal damage, but not gene mutations. No clear correlation was observed between the physico-chemical properties of TiO2 particles and the outcome of either in vitro or in vivo genotoxicity assays. A concern for genotoxicity of TiO2 particles that may be present in E 171 could therefore not be ruled out. Several modes of action for the genotoxicity may operate in parallel and the relative contributions of different molecular mechanisms elicited by TiO2 particles are not known. There was uncertainty as to whether a threshold mode of action could be assumed. In addition, a cut-off value for TiO2 particle size with respect to genotoxicity could not be identified. No appropriately designed study was available to investigate the potential carcinogenic effects of TiO2 NPs. Based on all the evidence available, a concern for genotoxicity could not be ruled out, and given the many uncertainties, the Panel concluded that E 171 can no longer be considered as safe when used as a food additive.

Original languageEnglish
Article numbere06585
Number of pages130
JournalEFSA Journal
Issue number5
Early online date6 May 2021
Publication statusPublished - 6 May 2021

Bibliographical note

Acknowledgements: The Panel wishes to thank the following for the support provided to this scientific output: Ana Campos Fernandes, Laura Ciccolallo, Esraa Elewa, Galvin Eyong, Christina Kyrkou, Irene Munoz, Giorgia Vianello, the members of the SCER Cross-cutting WG nanotechnologies: Jacqueline Castenmiller, Mohammad Chaudhry, Roland Franz, David Gott, Stefan Weigel and the former member of the SCER Cross-cutting WG Genotoxicity Maciej Stepnik. The FAF Panel wishes to acknowledge all European competent institutions, Member State bodies and other organisations that provided data for this scientific output.


  • Titanium dioxide
  • E 171
  • CAS No 13463-67-7


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