Safety of iron hydroxide adipate tartrate as a novel food pursuant to Regulation (EU) 2015/2283 and as a source of iron in the context of Directive 2002/46/EC

Abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on iron hydroxide adipate tartrate as a novel food (NF) pursuant to Regulation (EU) 2015/2283 and as a source of iron in the context of Directive 2002/46/EC. The NF is intended to be used in food supplements up to a maximum dose of 100 mg per day, corresponding to a maximum daily intake of iron of 36 mg. The target population proposed by the applicant is the general population above 3 years of age. The NF which is the subject of the application is an engineered nanomaterial having primary particles, of almost spherical morphology, with a diameter typically smaller than 5 nm. The studies provided for absorption, distribution, metabolism and excretion (ADME) and bioavailability indicate that iron, once taken up into the epithelial cells of the gut, is subject to the same mechanisms of regulation and absorption as that of other forms of iron. Further studies provided in the context of the toxicological assessment indicate that the NF does not lead to iron bioaccumulation in tissues and organs at the doses tested. The Panel notes that the NF contains nickel at concentrations that may increase the risk of flare‐up reactions in nickel‐sensitised young individuals up to 10 years of age. In the 90‐day toxicity study, findings related to haematology, clinical biochemistry and organ weights were observed and the Panel defined a no observed adverse effect level (NOAEL) of 231 mg/kg body weight (bw) per day, that is, the mid‐dose used in the study. The Panel considers that the NF is a source from which iron is bioavailable and it is safe under the proposed conditions of use.

Agglomeration Behavior and Fate of Food-Grade Titanium Dioxide in Human Gastrointestinal Digestion and in the Lysosomal Environment

“…The results of the present study are opposite to those obtained in a series of studies in which light-scattering techniques, such as DLS and laser diffraction, were inappropriately used to obtain information they cannot deliver, i.e., data on titania agglomeration in GID [ 17 , 18 , 19 , 20 , 21 , 22 , 23 ]. Whereas DLS can provide some size-related information for pure monodisperse nanomaterials [ 48 ], it cannot be used for polydisperse materials and, as such, is not an accepted technique for regulatory safety assessment in the EU [ 8 ]. We showed herein that DLS produces biased results for E 171 dispersed in water, and we consider that its use in complex suspensions, where the TiO 2 particles coexist with proteins (digestive enzymes) and other particulate agents with light-scattering properties, is analytically unjustifiable.…”

“…However, as shown in Figure 2a, food-grade TiO 2 is a highly polydisperse material, with Fmean values spanning a range of 30-300 nm and a few constituent particles having Fmean diameters around 400 nm. This polydispersity makes it impossible to establish a complete PSD using a single isotope in spICP-MS. 48 Ti, which is the most sensitive isotope-i.e., the one providing the lowest background equivalent diameters (BED, instrumental particle size detection limit)-for this same reason is prone to detector saturation when large TiO 2 particles are atomized [26][27][28]. 47 Ti and 49 Ti are less abundant isotopes (7.44% and 5.41%, respectively) and provide BEDs increased by a factor of 2.15 to 2.39, respectively [29].…”

“…This technique can accurately measure the agglomeration state since it detects discrete particles in suspensions irrespective of their being 'primary' (i.e., individual constituent particles) or agglomerates (i.e., 'secondary particles' formed through the clustering of two or more constituent particles). PSDs derived from spICP-MS measurements were obtained using the isotope combination approach, whereby both 47 Ti and 48 Ti are monitored and the data integrated in such a way as to achieve numberbased PSDs covering a wider size range, i.e., avoiding the underestimation of the fraction of larger agglomerates caused by considering 48 Ti alone, a common approach used in the vast majority of studies [30]. Further characterization of the material was achieved via centrifugal liquid sedimentation (CLS), volume-specific surface area (VSSA) determination via the BET method, zeta potential and isoelectric point (IEP) determination via electrophoretic light scattering (ELS), whereas DLS was used to enable comparisons with data from other studies.…”

Scientific opinion on the tolerable upper intake level for iron

“…Iron hydroxide adipate tartrate and iron milk proteinate/caseinate have recently been assessed by the NDA Panel as novel nutrient sources intended to be used in food supplements and were deemed safe under the proposed conditions of use (EFSA NDA Panel, 2021 , 2022b ).…”

Application of Single Particle ICP-MS for the Determination of Inorganic Nanoparticles in Food Additives and Food: A Short Review

“…Engineered NPs might be intentionally added to food. Currently, no engineered NPs are approved for addition to food in Europe; however, the first novel food in nanoparticulate form, iron hydroxide adipate tartrate, was recently evaluated as safe by the European Food Safety Authority [ 2 ]. Engineered NPs have the potential of release from food contact materials or can enter the food chain via the environment when they are used in other applications, e.g., construction and buildings.…”