waterglass, with a diluted acid (e.g. The Panel noted that the highest exposure estimates were always much lower than the no observed adverse effect levels (NOAELs) identified in the different toxicity studies available. Silicon dioxide (E 551) is also authorised according the Annex III to Regulation (EC) No 1333/2008 (Parts 1, 2, 3, 4 and 5 A and B) in many other food‐improving agents (additives, enzymes, flavourings) and nutrients and can as such be found in many foods via carry‐over. When the test substance was administered in the feed or in the drinking water, but doses were not explicitly reported by the authors as mg/kg bw per day based on actual feed or water consumption, the daily intake was calculated by the Panel using the relevant default values as indicated in the EFSA Scientific Committee Guidance document (EFSA Scientific Committee, 2012) for studies in rodents or, in the case of other animal species, by JECFA (2000a,b). According to the authors, interactions between proteins and nanomaterials play important roles in the biological effects and bio‐distribution of nanomaterials. This opinion was formulated following the principles described in the EFSA Guidance on transparency with regard to scientific aspects of risk assessment (EFSA Scientific Committee, 2009) and following the relevant existing guidance documents from the EFSA Scientific Committee. Study No. Nevertheless, the EFSA Comprehensive Database represents the currently best available source of food consumption data across Europe. Given the absence of information about the particle size distribution for silicon dioxide (E 551) in the current EU specifications, the Panel considered that no SAS preparation used in any single study might be fully representative of the food additive E 551. The composition of this corona may have consequence on the biological reactivity of the particles as, for instance, it has been reported that some proteins of the complement system, which have significant roles in the development of inflammation, are present in the corona after incubation of silicon dioxide nanoparticles in serum (Strojan et al., 2017). However, these developmental studies were not well documented; the statistical analysis was not described and they were not performed in accordance with the current guidelines. Necropsy of rats after 45 or 90 days of treatment revealed no test item related effects. The Panel agreed with this conclusion. According to the authors, corona formation affected haemolysis, thrombocyte activation, nanoparticle uptake and endothelial cell death. The list of food additives currently used in the European Union: 1 ‘Sweeteners’ give a sweet taste to foods or table-top sweeteners.They are used to make low calorie versions of foods and drinks. The Panel noted some effects were reported but it was only when nano‐silica was injected via routes (e.g. After a 4.5‐month premating exposure period, one male was mated with five females for 14 days in each group. 01.7.6 Cheese products, only sliced or grated hard and semi‐hard products; 02.2.2 Other fat and oil emulsions including spreads as defined by Council Regulation (EC) No 1234/2007 and liquid emulsions, only tin greasing products; 02.3 Vegetable oil pan spray, only tin greasing products; 01.7.2 Ripened cheese, only sliced or grated cheese hard and semi‐hard cheese. The Panel considered that it would be possible to derive an ADI should the limitations in the toxicological database be reduced. These methods measure different particle characteristics, which are reflected in the different numerical size‐values obtained (see Table 2). Overall, the Panel noted that the SAS test items used in the biological and toxicological studies available were different in their physicochemical properties (e.g. The Scientific Committee on Food (SCF) established a group acceptable daily intake (ADI) ‘not specified’ for silicon dioxide and silicates. Submitted to EFSA by CEFIC, October 2017. The study is not well reported and lacks some important details on, among others, the characterisation of the silica nanoparticles both in the feed and in the organs. Once ultrasonicated then suspended in culture medium the two SAS materials formed aggregates with mean diameters of 147 and 127 nm. The food products were prepared as indicated on their labels for a homemade preparation. Food Addititive Code Breaker and Guide - Mineral salts and Anti-Caking Agents (E500 - E597) In the high‐dose group, the average fetal weight was reduced (31.5 g vs 37.5 g in control; no statistical evaluation). ). This approach was considered the most appropriate and realistic scenario for risk characterisation of E 551 because it is assumed that the population is most likely to be exposed long‐term to the food additive E 551 present at the mean reported use in processed food. Due to the non‐availability of the full report, the Panel could not assess the biological significance of this observation. The NDA Panel considered silicon to be sufficiently characterised but that the claimed effect ‘immune health’ was not sufficiently defined. AEROSIL 300F‐ primary particles 7 nm (no information on the % of number of particles). ). OJ L 80, 26.3.2010, p. 19–27. Test items are burned and alkali‐soluble silicon dioxide is dissolved in sodium hydroxide. The Scientific Committee on Food (SCF) established a group acceptable daily intake (ADI) ‘not specified’ for silicon dioxide and silicates. The Panel noted that three different analytical methods were used (i.e. As regards silicon dioxide, given the high surface reactivity of the particle, the primary particles spontaneously aggregate and agglomerate giving rise mainly to structures with sizes > 100 nm. Degussa, Frankfurt, Germany, Dispersion of nanoparticles in different media importantly determines the composition of their protein corona, Oral ingestion of syloid to mice and rats and its chronic toxicity and carcinogenicity, Genotoxicity of synthetic amorphous silica nanoparticles in rats following short‐term exposure. This was the case for four food categories and may have resulted in an underestimation of the exposure. They finally concluded that: ‘Additional studies seem warranted to further evaluate the biological relevance of the observed fibrosis in liver of NM‐202 exposed animals’. The induction of tolerance by OVA, the production of anti‐OVA IgG antibodies, and proliferation of splenocytes in response to OVA was inhibited by silica nanoparticles in conjunction with OVA and was dose‐related. These aggregates can further agglomerate to form larger structures. Silicon in urine was determined after alkaline hydrolysis; other excretion routes were not evaluated. (2011) investigated the bio‐distribution and excretion of mesoporous silica particles and polyethylene glycol‐treated mesoporous silica particles (PEG–MSNs) of different particle sizes (80, 120, 200 and 360 nm) in groups of male ICR mice (n = 5) and Sprague–Dawley rats (n = 3) injected with 20 mg/kg bw of the suspensions via the tail‐vein. Another subchronic toxicity study with rats receiving a diet containing up to 3,500 mg/kg bw per day fumed silica (only limited information available) for 90 days confirmed the low toxicity of high doses (Cabot, 1958 (Documentation provided to EFSA n. 4)). AF4‐ICPMS: in 7 out of the 11 samples particles < 100 nm (number of particles/L 10−11 range 0.1–11.4). Transmission electron microscopy revealed intracellular uptake of nanomaterial, the particles were encapsulated in endocytic vacuoles but free particles were also evident in the cytoplasm. The expression of interferon IFN‐γ, IL‐4 and IL‐5 (Th2) and IL‐17 (Th17) was also stimulated (dose‐related) by silica nanoparticles in splenocytes stimulated ex vivo with OVA. Yoshida et al. Cabot, Tuscola, Illinois, USA (as referred to Cabot GmbH, 1995m by ECETOC, 2006), CAB‐O‐SIL TS‐720, chromosome aberrations in Chinese hamster ovary (CHO) cells, laboratory study G94BN11.330, In Handbook of Nutritionally Essential Mineral Elements, Consideration of interaction between nanoparticles and food components for the safety assessment of nanoparticles following oral exposure: a review, Study of the genotoxic effects induced by two kinds of silica nanoparticles on human bronchial (BEAS‐2B) epithelial cells, The impact of size on tissue distribution and elimination by single intravenous injection of silica nanoparticles, Physicochemical and toxicological evaluation of silica nanoparticles suitable for food and consumer products collected by following the EC recommendation, Size characterization by Sedimentation Field Flow Fractionation of silica particles used as food additives, Amorphous silica nanoparticles trigger nitric oxide/peroxynitrite imbalance in human endothelial cells: inflammatory and cytotoxic effects, Gewerbehygienisch‐toxikologische Untersuchung der Kieselsäure FK700, Presence and risks of nanosilica in food products, Proinflammatory effects of pyrogenic and precipitated amorphous silica nanoparticles in innate immunity cells, The protein corona protects against size‐ and dose‐dependent toxicity of amorphous silica nanoparticles, Silica nanoparticles administered at the maximum tolerated dose induce genotoxic effects through an inflammatory reaction while gold nanoparticles do not, Toxic effect of silica nanoparticles on endothelial cells through DNA damage response via chk1‐dependent G2/M checkpoint, Scientific opinion of the Scientific Committee related to uncertainties in dietary exposure assessment, Guidance of the Scientific Committee on transparency in the scientific aspects of risk assessments carried out by EFSA. 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