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

49siThe 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, includingdata obtained with TiO2nanoparticles (NPs) and data from an extended one-generation reproductivetoxicity (EOGRT) study. Less than 50% of constituent particles by number in E 171 have a minimumexternal dimension30 nm) up to the highest dose tested of100 mg/kg bw per day. No effects on reproductive and developmental toxicity were observed up to adose 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 withTiO2NPs, together with the potential induction of aberrant crypt foci with E 171, may indicate adverseeffects. With respect to genotoxicity, the Panel concluded that TiO2particles have the potential toinduce DNA strand breaks and chromosomal damage, but not gene mutations. No clear correlationwas observed between the physico-chemical properties of TiO2particles and the outcome of eitherin vitroorin vivogenotoxicity assays. A concern for genotoxicity of TiO2particles that may be presentin E 171 could therefore not be ruled out. Several modes of action for the genotoxicity may operate inparallel and the relative contributions of different molecular mechanisms elicited by TiO2particles arenot known. There was uncertainty as to whether a threshold mode of action could be assumed. Inaddition, a cut-off value for TiO2particle size with respect to genotoxicity could not be identified. Noappropriately designed study was available to investigate the potential carcinogenic effects of TiO2NPs. Based on all the evidence available, a concern for genotoxicity could not be ruled out, and giventhe many uncertainties, the Panel concluded that E 171 can no longer be considered as safe whenused as a food additive.©2021 European Food Safety Authority. EFSA Journalpublished by John Wiley and Sons Ltd on behalfof European Food Safety Authority.Keywords:Titanium dioxide, E 171, CAS No 13463-67-7EFSA Journal 2021;19(5):6585www.efsa.europa.eu/efsajournalopenopenYounes, Maged; Aquilina, Gabriele; Castle, Laurence; Engel, Karl‐Heinz; Fowler, Paul; Frutos Fernandez, Maria Jose; Fürst, Peter; Gundert‐Remy, Ursula; Gürtler, Rainer; Husøy, Trine; Manco, Melania; Mennes, Wim; Moldeus, Peter; Passamonti, Sabina; Shah, Romina; Waalkens‐Berendsen, Ine; Wölfle, Detlef; Corsini, Emanuela; Cubadda, Francesco; De Groot, Didima; FitzGerald, Rex; Gunnare, Sara; Gutleb, Arno Christian; Mast, Jan; Mortensen, Alicja; Oomen, Agnes; Piersma, Aldert; Plichta, Veronika; Ulbrich, Beate; Van Loveren, Henk; Benford, Diane; Bignami, Margherita; Bolognesi, Claudia; Crebelli, Riccardo; Dusinska, Maria; Marcon, Francesca; Nielsen, Elsa; Schlatter, Josef; Vleminckx, Christiane; Barmaz, Stefania; Carfí, Maria; Civitella, Consuelo; Giarola, Alessandra; Rincon, Ana Maria; Serafimova, Rositsa; Smeraldi, Camilla; Tarazona, Jose; Tard, Alexandra; Wright, MatthewYounes, Maged; Aquilina, Gabriele; Castle, Laurence; Engel, Karl‐heinz; Fowler, Paul; Frutos Fernandez, Maria Jose; Fürst, Peter; Gundert‐remy, Ursula; Gürtler, Rainer; Husøy, Trine; Manco, Melania; Mennes, Wim; Moldeus, Peter; Passamonti, Sabina; Shah, Romina; Waalkens‐berendsen, Ine; Wölfle, Detlef; Corsini, Emanuela; Cubadda, Francesco; De Groot, Didima; Fitzgerald, Rex; Gunnare, Sara; Gutleb, Arno Christian; Mast, Jan; Mortensen, Alicja; Oomen, Agnes; Piersma, Aldert; Plichta, Veronika; Ulbrich, Beate; Van Loveren, Henk; Benford, Diane; Bignami, Margherita; Bolognesi, Claudia; Crebelli, Riccardo; Dusinska, Maria; Marcon, Francesca; Nielsen, Elsa; Schlatter, Josef; Vleminckx, Christiane; Barmaz, Stefania; Carfí, Maria; Civitella, Consuelo; Giarola, Alessandra; Rincon, Ana Maria; Serafimova, Rositsa; Smeraldi, Camilla; Tarazona, Jose; Tard, Alexandra; Wright, Matthe