TY - JOUR T1 - Safety assessment of titanium dioxide (E171) as a food additive JF - EFSA Journal Y1 - 2021 A1 - Younes Maged A1 - Gabriele Aquilina A1 - Laurence Castle A1 - Karl‐Heinz Engel A1 - Paul Fowler A1 - Maria Jose Frutos Fernandez A1 - Peter Fürst A1 - Ursula Gundert‐Remy A1 - Rainer Gürtler A1 - Trine Husøy A1 - Melania Manco A1 - Wim Mennes A1 - Peter Moldeus A1 - Sabina Passamonti A1 - Romina Shah A1 - Ine Waalkens‐Berendsen A1 - Detlef Wölfle A1 - Emanuela Corsini A1 - Francesco Cubadda A1 - Didima De Groot A1 - Rex FitzGerald A1 - Sara Gunnare A1 - Arno Christian Gutleb A1 - Jan Mast A1 - Mortensen, Alicja A1 - Agnes Oomen A1 - Aldert Piersma A1 - Veronika Plichta A1 - Beate Ulbrich A1 - Henk van Loveren A1 - Diane Benford A1 - Margherita Bignami A1 - Claudia Bolognesi A1 - Riccardo Crebelli A1 - Maria Dusinska A1 - Francesca Marcon A1 - Elsa Nielsen A1 - Josef Schlatter A1 - Christiane Vleminckx A1 - Stefania Barmaz A1 - Maria Carfí A1 - Consuelo Civitella A1 - Alessandra Giarola A1 - Ana Maria Rincon A1 - Rositsa Serafimova A1 - Camilla Smeraldi A1 - Jose Tarazona A1 - Alexandra Tard A1 - Wright, Matthew KW - CAS No 13463-67-7 KW - E 171 KW - titanium dioxide AB -

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.

VL - 19 CP - 5 M3 - 10.2903/j.efsa.2021.6585 ER -