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BACKGROUND: The characterization of phytoestrogen intake and cancer risk has been hindered by the absence of accurate dietary phytoestrogen values. OBJECTIVE: We examined the risk of breast, colorectal, and prostate cancers relative to phytoestrogen intake on the basis of a comprehensive database. DESIGN: Demographic and anthropometric characteristics, a medical history, and 7-d records of diet were collected prospectively from participants (aged 40-79 y) in the European Prospective Investigation into Cancer and Nutrition-Norfolk (EPIC-Norfolk). Five hundred nine food items were analyzed by liquid chromatography-mass spectrometry/mass spectrometry, and (13)C(3)-labeled internal standards were analyzed for isoflavones (genistein, daidzein, glycitein, biochanin A, and formononetin), lignans (secoisolariciresinol and matairesinol), and enterolignans from gut microbial metabolism in animal food sources (equol and enterolactone). From the direct analysis, values for 10,708 foods were calculated. Odds ratios (ORs) for breast (244 cases, 941 controls), colorectal (221 cases, 886 controls), and prostate (204 cases, 812 controls) cancers were calculated relative to phytoestrogen intake. RESULTS: Phytoestrogen intake was not associated with breast cancer among women or colorectal cancer among men. Among women, colorectal cancer risk was inversely associated with enterolactone (OR: 0.33; 95% CI: 0.14, 0.74) and total enterolignans (OR: 0.32; 95% CI: 0.13, 0.79), with a positive trend detected for secoisolariciresinol (OR: 1.60; 95% CI: 0.96, 2.69). A positive trend between enterolignan intake and prostate cancer risk (OR: 1.27; 95% CI: 0.97, 1.66) was attenuated after adjustment for dairy intake (OR: 1.19; 95% CI: 0.77, 1.82). CONCLUSION: Dietary phytoestrogens may contribute to the risk of colorectal cancer among women and prostate cancer among men. © 2010 American Society for Nutrition. [ABSTRACT FROM AUTHOR]

Scope: It has been proposed that endogenously form N-nitroso compounds (NOCs) are partly responsible for the link between red meat consumption and colorectal cancer (CRC) risk. As nitrite has been indicated as critical factor in the formation of NOCs, the impact of replacing the additive sodium nitrite (E250) by botanical extracts in the PHYTOME project is evaluated., Method and Results: A human dietary intervention study is conducted in which healthy subjects consume 300 g of meat for 2 weeks, in subsequent order: conventional processed red meat, white meat, and processed red meat with standard or reduced levels of nitrite and added phytochemicals. Consumption of red meat products enriched with phytochemicals leads to a significant reduction in the faecal excretion of NOCs, as compared to traditionally processed red meat products. Gene expression changes identify cell proliferation as main affects molecular mechanism. High nitrate levels in drinking water in combination with processed red meat intake further stimulates NOC formation, an effect that could be mitigated by replacement of E250 by natural plant extracts., Conclusion: These findings suggest that addition of natural extracts to conventionally processed red meat products may help to reduce CRC risk, which is mechanistically support by gene expression analyses., (© 2021 The Authors. Molecular Nutrition & Food Research published by Wiley-VCH GmbH.)

Purpose: To examine the association between fructose intake in adolescence and fatty liver indices (hepatic steatosis index (HSI), fatty liver index (FLI)) in young adulthood., Methods: Overall, 246 participants of the Dortmund Nutritional and Anthropometric Longitudinally Designed (DONALD) study who had a fasting blood sample in adulthood (18-36 years), at least two 3-day weighed dietary records for calculating fructose intakes and other fructose-containing sugars (total (TS), free (FS), added sugar (AS)) as well as two complete 24-h urine samples for calculating sugar excretion (fructose excretion (FE), fructose + sucrose excretion (FE + SE)) in adolescence (males: 9.5-16.5 years; females: 8.5-15.5 years) were analysed using multivariable linear regression analyses., Results: On the level of dietary intake, no prospective associations were observed between adolescent fructose intake and both adult fatty liver indices, whereas higher FS intakes were associated with lower levels of HSI (P trend  = 0.02) and FLI (P trend  = 0.03). On the urinary excretion level, however, a higher FE (P trend  = 0.03) and FE + SE (P trend  = 0.01) in adolescence were prospectively related to higher adult FLI values. No associations were observed between adolescent sugar excretion and adult HSI., Conclusion: The present study does not provide unambiguous support for a detrimental impact of adolescent fructose intake on adult liver health. Nonetheless, further examinations estimating exposure by means of urinary excretion as well as dietary intake levels appear warranted., (© 2021. The Author(s).)

[Table: see text] This guidance describes the scientific data required to allow an evaluation of the safety of new substances that are proposed for use as sources of nutrients in food supplements, foods for the general population or foods for specific groups and an assessment of the bioavailability of the nutrient from the proposed source. This guidance describes the scientific data required to allow an evaluation of the safety of the source within the established framework for risk assessment of food additives and novel food ingredients and the bioavailability of the nutrient from this source. This document is arranged in five main sections: one on technical data aimed at characterising the proposed source and at identifying potential hazards resulting from its manufacture and stability in food; one on existing authorisations and evaluation, providing an overview of previous assessments on the proposed source and their conclusions; one on proposed uses and exposure assessment section, allowing an estimate of the dietary exposure to the source and the nutrient based on the proposed uses and use levels; one on toxicological data, describing approaches which can be used to identify (in conjunction with data on manufacture and composition) and to characterise hazards of the source and any relevant breakdown products; the final section on bioavailability focuses on determining the extent to which the nutrient from the proposed source is available for use by the body in comparison with one or more forms of the same nutrient that are already permitted for use on the positive lists. This guidance was adopted by the Panel on Food Additives and Nutrient Sources added to Food (ANS Panel) on 16 May 2018. Upon request from EFSA, the present guidance has been revised to inform applicants of new provisions set out in Regulation (EC) No 178/2002, as amended by Regulation (EU) 2019/1381 on the transparency and sustainability of the EU risk assessment in the food chain., (© 2021 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

The global increases in life expectancy and population have resulted in a growing ageing population and with it a growing number of people living with age-related neurodegenerative conditions and dementia, shifting focus towards methods of prevention, with lifestyle approaches such as nutrition representing a promising avenue for further development. This overview summarises the main themes discussed during the 3 rd Symposium on "Nutrition for the Ageing Brain: Moving Towards Clinical Applications" held in Madrid in August 2018, enlarged with the current state of knowledge on how nutrition influences healthy ageing and gives recommendations regarding how the critical field of nutrition and neurodegeneration research should move forward into the future. Specific nutrients are discussed as well as the impact of multi-nutrient and whole diet approaches, showing particular promise to combatting the growing burden of age-related cognitive decline. The emergence of new avenues for exploring the role of diet in healthy ageing, such as the impact of the gut microbiome and development of new techniques (imaging measures of brain metabolism, metabolomics, biomarkers) are enabling researchers to approach finding answers to these questions. But the translation of these findings into clinical and public health contexts remains an obstacle due to significant shortcomings in nutrition research or pressure on the scientific community to communicate recommendations to the general public in a convincing and accessible way. Some promising programs exist but further investigation to improve our understanding of the mechanisms by which nutrition can improve brain health across the human lifespan is still required., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Trend analyses based on dietary records suggest decreases in the intakes of total sugar (TS), added and free sugar since 2005 among children and adolescents in Germany. In terms of age trends, TS intake decreased with increasing age. However, self-reported sugar intake in epidemiological studies is criticised, as it may be prone to bias due to selective underreporting. Furthermore, adolescents are more susceptible to underreporting than children. We thus analysed time and age trends in urinary fructose excretion (FE), sucrose excretion (SE) and the sum of both (FE + SE) as biomarkers for sugar intake among 8·5-16·5-year-old adolescents. Urinary sugar excretion was measured by UPLC-MS/MS in 997 24-h urine samples collected from 239 boys and 253 girls participating in the Dortmund Nutritional and Anthropometric Longitudinally Designed (DONALD) study cohort between 1990 and 2016. Time and age trends of log-transformed FE, SE and FE + SE were analysed using polynomial mixed-effects regression models. Between 1990 and 2016, FE as well as FE + SE decreased (linear time trend: P = 0·0272 and P < 0·0001, respectively). A minor increase in excretion during adolescence was confined to FE (linear age trend: P = 0·0017). The present 24-h excretion measurements support a previously reported dietary record-based decline in sugar intake since 2005. However, the previously seen dietary record-based decrease in TS from childhood to late adolescence was not confirmed by our biomarker analysis, suggesting a constant sugar intake for the period of adolescence.

Background: Nitrate is converted to nitrite in the human body and subsequently can react with amines and amides in the gastrointestinal tract to form N-nitroso compounds (NOCs), which are known to be carcinogenic in animals. Humans can be exposed to nitrate via consumption of drinking water and diet, especially green leafy vegetables and cured meat. The contribution of nitrate from drinking water in combination with meat intake has not been investigated thoroughly. Therefore, in the present pilot study, we examined the effect of nitrate from drinking water, and its interaction with the consumption of white and processed red meat, on the endogenous formation of NOCs, taking into account the intake of vitamin C, a nitrosation inhibitor., Methods: Twenty healthy subjects were randomly assigned to two groups consuming either 3.75 g/kg body weight (maximum 300 g per day) processed red meat or unprocessed white meat per day for two weeks. Drinking water nitrate levels were kept low during the first week (< 1.5 mg/L), whereas in week 2, nitrate levels in drinking water were adjusted to the acceptable daily intake level of 3.7 mg/kg bodyweight. At baseline, after 1 and 2 weeks, faeces and 24 h urine samples were collected for analyses of nitrate, apparent total N-nitroso compounds (ATNC), compliance markers, and genotoxic potential in human colonic Caco-2 cells., Results: Urinary nitrate excretion was significantly increased during the high drinking water nitrate period for both meat types. Furthermore, levels of compliance markers for meat intake were significantly increased in urine from subjects consuming processed red meat (i.e. 1-Methylhistidine levels), or unprocessed white meat (i.e. 3-Methylhistidine). ATNC levels significantly increased during the high drinking water nitrate period, which was more pronounced in the processed red meat group. Genotoxicity in Caco-2 cells exposed to faecal water resulted in increased genotoxicity after the interventions, but results were only significant in the low drinking water nitrate period in subjects consuming processed red meat. Furthermore, a positive correlation was found between the ratio of nitrate/vitamin C intake (including drinking water) and the level of ATNC in faecal water of subjects in the processed red meat group, but this was not statistically significant., Conclusions: Drinking water nitrate significantly contributed to the endogenous formation of NOC, independent of the meat type consumed. This implies that drinking water nitrate levels should be taken into account when evaluating the effect of meat consumption on endogenous formation of NOC., Trial Registration: Dutch Trialregister: 29707 . Registered 19th of October 2018. Retrospectively registered.

Consumption of nitrate-rich beetroot juice (BRJ) by athletes induces a number of beneficial physiological health effects, which are linked to the formation of nitric oxide (NO) from nitrate. However, following a secondary pathway, NO may also lead to the formation of N -nitroso compounds (NOCs), which are known to be carcinogenic in 39 animal species. The extent of the formation of NOCs is modulated by various other dietary factors, such as vitamin C. The present study investigates the endogenous formation of NOCs after BRJ intake and the impact of vitamin C on urinary NOC excretion. In a randomized, controlled trial, 29 healthy recreationally active volunteers ingested BRJ with or without additional vitamin C supplements for one week. A significant increase of urinary apparent total N -nitroso Compounds (ATNC) was found after one dose (5 to 47 nmol/mmol: p < 0.0001) and a further increase was found after seven consecutive doses of BRJ (104 nmol/mmol: p < 0.0001). Vitamin C supplementation inhibited ATNC increase after one dose (16 compared to 72 nmol/mmol, p < 0.01), but not after seven daily doses. This is the first study that shows that BRJ supplementation leads to an increase in formation of potentially carcinogenic NOCs. In order to protect athlete's health, it is therefore important to be cautious with chronic use of BRJ to enhance sports performances.

The present opinion deals with the evaluation of the proposed increase of the currently authorised maximum amounts of ferric sodium ethylenediaminetetraacetic acid (EDTA) as a novel food ingredient used as a source of iron, and its extension of use in processed cereal-based foods and baby foods. The applicant also provided information on two forms of ferric sodium EDTA, one previously assessed by EFSA and a new one of finer consistency. To support the proposed changes to the uses of ferric sodium EDTA, the applicant proposed a revision of the current acceptable daily intake (ADI) for EDTA, derived from that set for the food additive calcium disodium EDTA (E 385). The Panel confirmed that ferric sodium EDTA is a source from which iron is bioavailable. In assessing the safety of the proposed revision to the existing specifications for the novel food ingredient ferric sodium EDTA, the Panel noted that this would not discriminate between the previously evaluated substance and the one of finer consistency. In particular, the Panel noted that particle size was not one of the proposed parameters for the revised specifications. The Panel noted that it was not possible to determine whether particles of ferric sodium EDTA in the nano range were present in the product with finer consistency in the solid form. The toxicological data submitted did not add any new relevant information to the database on which the current ADI for EDTA is based. Consequently, the Panel concluded that there was no sound scientific justification to increase the ADI for EDTA and hence increase the use levels of ferric sodium EDTA or introduce additional uses as proposed by the applicant. The Panel recommended that additional toxicological data should be provided to address the shortcomings in the available toxicity database prior to the re-evaluation of calcium disodium EDTA (E 385)., (© 2018 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

The Panel on Food Additives and Nutrient Sources added to Food (ANS) was asked to deliver a scientific opinion on the safety of monacolins in red yeast rice (RYR) and to provide advice on a dietary intake of monacolins that does not give rise to concerns about harmful effects to health. The Panel reviewed the scientific evidences available as well as the information provided by interested parties in response of a public 'Call for data' launched by EFSA. The Panel considered that monacolin K in lactone form is identical to lovastatin, the active ingredient of several medicinal products authorised for the treatment of hypercholesterolaemia in the EU. On the basis of the information available, the Panel concluded that intake of monacolins from RYR via food supplements, could lead to estimated exposure to monacolin K within the range of the therapeutic doses of lovastatin. The Panel considered that the available information on the adverse effects reported in humans were judged to be sufficient to conclude that monacolins from RYR when used as food supplements were of significant safety concern at the use level of 10 mg/day. The Panel further considered that individual cases of severe adverse reactions have been reported for monacolins from RYR at intake levels as low as 3 mg/day. The Panel concluded that exposure to monacolin K from RYR could lead to severe adverse effects on musculoskeletal system, including rhabdomyolysis, and on the liver. In the reported cases, the product contained other ingredients in addition to RYR. However, these reported effects in particular musculoskeletal effects, have both occurred after ingestion of monacolin K and lovastatin independently. On the basis of the information available and several uncertainties highlighted in this opinion, the Panel was unable to identify a dietary intake of monacolins from RYR that does not give rise to concerns about harmful effects to health, for the general population, and as appropriate, for vulnerable subgroups of the population., (© 2018 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

The EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS) provides a scientific opinion on the refined exposure assessment of extracts of rosemary (E 392) when used as a food additive. Extracts of rosemary (E 392) was evaluated by the AFC Panel in 2008. Following this EFSA evaluation, extracts of rosemary (E 392) was authorised for use as a food additive in the EU in several food categories with maximum levels. In 2015, the ANS Panel provided a scientific opinion on the safety of the proposed extensions of use for extracts of rosemary (E 392) in fat-based spreads. In 2016, the Joint FAO/WHO Expert Committee on Food Additives (JECFA) has evaluated this food additive and established a temporary acceptable daily intake (ADI) of 0-0.3 mg/kg body weight (bw) for rosemary extract, expressed as carnosic acid plus carnosol. Based on the data provided by food industry, the Panel was able to refine the exposure estimates of extracts of rosemary (E 392). The highest mean refined exposure estimate (non-brand loyal scenario) was 0.09 mg/kg bw per day in children (3-9 years) and the highest 95th percentile of exposure was 0.20 mg/kg bw per day in children. Taking uncertainties into account, the Panel concluded that these exposure estimates very likely overestimate the real exposure to extracts of rosemary (E 392) from its use as a food additive according to Annex II. Margins of safety were estimated for children and adults using the refined exposure estimate; these are higher than the ones calculated in 2015. Intake of carnosic acid and carnosol from natural diet (herbs) was estimated. It was maximally 1.66 mg/kg bw per day (p95)., (© 2018 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

The EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS) provides a scientific opinion re-evaluating the safety of calcium silicate (E 552), magnesium silicate (E 553a) and talc (E 553b) when used as food additives. In 1991, the Scientific Committee on Food (SCF) established a group acceptable daily intake (ADI) 'not specified' for silicon dioxide and silicates. The EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS) recently provided a scientific opinion re-evaluating the safety of silicon dioxide (E 551) when used as a food additive. The Panel noted that the absorption of silicates and talc was very low; there was no indication for genotoxicity or developmental toxicity for calcium and magnesium silicate and talc; and no confirmed cases of kidney effects have been found in the EudraVigilance database despite the wide and long-term use of high doses of magnesium trisilicate up to 4 g/person per day over decades. However, the Panel considered that accumulation of silicon from calcium silicate in the kidney and liver was reported in rats, and reliable data on subchronic and chronic toxicity, carcinogenicity and reproductive toxicity of silicates and talc were lacking. Therefore, the Panel concluded that the safety of calcium silicate (E 552), magnesium silicate (E 553a(i)), magnesium trisilicate (E 553a(ii)) and talc (E 553b) when used as food additives cannot be assessed. The Panel considered that there is no mechanistic rationale for a group ADI for silicates and silicon dioxide and the group ADI established by the SCF is obsolete. Based on the food supplement scenario considered as the most representative for risk characterisation, exposure to silicates (E 552-553) for all population groups was below the maximum daily dose of magnesium trisilicate used as an antacid (4 g/person per day). The Panel noted that there were a number of approaches, which could decrease the uncertainties in the current toxicological database. These approaches include - but are not limited to - toxicological studies as recommended for a Tier 1 approach as described in the EFSA Guidance for the submission of food additives and conducted with an adequately characterised material. Some recommendations for the revision of the EU specifications were proposed by the Panel., (© 2018 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

The present opinion deals with the re-evaluation of propane-1,2-diol alginate (E 405) when used as a food additive. The Panel noted that absorption, distribution, metabolism and excretion (ADME) data on propane-1,2-diol alginate gave evidence for the hydrolysis of this additive into propane-1,2-diol and alginic acid. These two compounds have been recently re-evaluated for their safety of use as food additives (EFSA ANS Panel, 2017, 2018). Consequently, the Panel considered in this opinion the major toxicokinetic and toxicological data of these two hydrolytic derivatives. No adverse effects were reported in subacute and subchronic dietary studies with propane-1,2-diol alginate. The available data did not indicate a genotoxic concern for propane-1,2-diol alginate (E 405) when used as a food additive. Propane-1,2-diol alginate, alginic acid and propane-1,2-diol were not of concern with respect to carcinogenicity. The Panel considered that any adverse effect of propane-1,2-diol alginate would be due to propane-1,2-diol. Therefore, the acceptable daily intake (ADI) of the food additive E 405 is determined by the amount of free propane-1,2-diol and the propane-1,2-diol released from the food additive after hydrolysis. According to the EU specification, the concentration of free and bound propane-1,2-diol amounts to a maximum of 45% on a weight basis. On the worst-case assumption that 100% of propane-1,2-diol would be systemically available and considering the ADI for propane-1,2-diol of 25 mg/kg body weight (bw) per day, the Panel allocated an ADI of 55 mg/kg bw per day for propane-1,2-diol alginate. The Panel concluded that exposure estimates did not exceed the ADI in any of the population groups from the use of propane-1,2-diol alginate (E 405) as a food additive. Therefore, the Panel concluded that there is no safety concern at the authorised use levels., (© 2018 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

The Panel on Food Additives and Nutrient Sources added to Food (ANS) provided a scientific opinion re-evaluating the safety of aluminium sulphates (E 520-523) and sodium aluminium phosphate, acidic (E 541) as food additives. The Panel considered that adequate exposure and toxicity data were available. Aluminium sulphates (E 520-523) and sodium aluminium phosphate, acidic (E 541) are permitted as food additives in only a few specific products and the exposure is probably near zero. Aluminium compounds have low bioavailability and low acute toxicity. There is no concern with respect to genotoxicity and carcinogenicity. The no observed adverse effect level (NOAEL) for aluminium compounds in subchronic studies was 52 mg Al/kg body weight (bw) per day in rats and 90 mg Al/kg bw per day in dogs and the lowest NOAEL for neurotoxicity in rats was 30 mg Al/kg bw per day and for developing nervous system was 10-42 mg Al/kg bw per day in studies in mice and rats. The Panel concluded that aluminium sulphates (E 520-523) and sodium aluminium phosphate, acidic (E 541) are of no safety concern in the current authorised uses and use levels., (© 2018 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

The present opinion deals with the re-evaluation of glycerol esters of wood rosin (GEWR, E 445) when used as a food additive. Regarding GEWR originating from Pinus palustris (longleaf pine) and Pinus elliottii (slash pine), based on the overall toxicity database, and given the absence of reproductive and developmental toxicity data, the Panel concluded that the current acceptable daily intake (ADI) of 12.5 mg/kg body weight (bw) per day for GEWR (E 445) as established by the Scientific Committee on Food (SCF) in 1994 should be temporary pending the provision of such data. This assessment is restricted to GEWR derived from P. palustris (longleaf pine) and P. elliottii (slash pine) and with a chemical composition in compliance with GEWR used in the toxicological testing. The Panel concluded that the mean and the high exposure levels (P95) of the brand-loyal refined exposure scenario did not exceed the temporary ADI in any of the population groups from the use of GEWR (E 445) as a food additive at the reported use levels. For GEWR originating from Pinus halepensis and Pinus brutia , the Panel noted that concentrations of the fractions of 'glycerol monoesters', 'free resin acids' and 'neutrals', which are considered to be of particular toxicological relevance, are not known; therefore, the evaluation of chemical equivalence with GEWR originating from P. palustris (longleaf pine) and P. elliottii (slash pine) is not possible; no data on stability were available; no toxicological data were available. Therefore, the Panel concluded that a safety assessment of GEWR originating from P. halepensis and P. brutia could not be performed. The Panel recommended the European Commission to consider an update of the definition of GEWR (E 445) in the EU specifications. It should be indicated that GEWR (E 445) (i) contain, besides the mentioned glycerol di- and triesters, a residual fraction of glycerol monoesters, and (ii) contain residual free resin acids and neutrals (non-acidic other saponifiable and unsaponifiable substances)., (© 2018 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

The Panel on Food Additives and Nutrient Sources added to Food (ANS) provided a scientific opinion re-evaluating the safety of sodium ferrocyanide (E 535), potassium ferrocyanide (E 536), and evaluating the safety of calcium ferrocyanide (E 538) as food additives. The Panel considered that adequate exposure and toxicity data were available. Ferrocyanides (E 535-538) are solely authorised in two food categories as salt substitutes. To assess the dietary exposure to ferrocyanides (E 535-538) from their use as food additives, the exposure was calculated based on regulatory maximum level exposure assessment scenario (maximum permitted level (MPL)) and the refined exposure assessment scenario. Dietary exposure to ferrocyanides was calculated based on mean and high levels consumption of salts in both the regulatory maximum level and the refined scenario. In the MPL scenario, the exposure to ferrocyanides (E 535-538) from their use as a food additive was up to 0.009 mg/kg body weight (bw) per day in children and adolescents. In the refined estimated exposure scenario, the exposure was up to 0.003 mg/kg bw per day in children and adolescents. Absorption of ferrocyanides is low and there is no accumulation in human. There is no concern with respect to genotoxicity and carcinogenicity. Reproductive studies were not available, but a no observed adverse effect level (NOAEL) of 1,000 mg sodium ferrocyanide/kg bw per day (highest dose tested) was identified from a prenatal developmental toxicity study. The kidney appeared to be the target organ for ferrocyanides toxicity and 4.4 mg sodium ferrocyanide/kg bw per day was identified as the NOAEL for the renal effects in a chronic (2-year) study in rats. Assuming that the toxicity of this compound is due to the ferrocyanide ion only, the Panel established a group acceptable daily intake (ADI) for sodium, potassium and calcium ferrocyanide of 0.03 mg/kg bw per day expressed as ferrocyanide ion. The Panel concluded that ferrocyanides (E 535-538) are of no safety concern at the current authorised use and use levels., (© 2018 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

The European Commission requested EFSA to carry out a scientific evaluation on four studies on the potential toxicity of titanium dioxide (TiO 2 ) used as a food additive (E 171) and to indicate whether they would merit re-opening the existing opinion of EFSA on the safety of TiO 2 (E 171) as a food additive. The results of the Bettini et al. (2017) study did not provide enough justification for a new carcinogenicity study, but, should additional useful mechanistic information become available, this could be reconsidered in future. The new in vitro findings in the Proquin et al. (2017) study did not modify the conclusion on the genotoxicity of TiO 2 as stated in the previous EFSA opinion of 2016 on the safety of TiO 2 (E 171) as a food additive. The effects of engineered TiO 2 nanoparticles reported by the Guo et al. (2017) study were of uncertain biological significance and therefore of limited relevance for the risk assessment of the food additive TiO 2 (E 171). There was significant uncertainty in the risk assessment performed by Heringa et al. (2016), which did not include a weight of evidence analysis of the whole database. The Panel considered that the four studies evaluated, highlighted some concerns but with uncertainties, therefore their relevance for the risk assessment was considered limited and further research would be needed to decrease the level of uncertainties. Overall, three of the studies, reporting that TiO 2 induced various effects in in vitro and in vivo models, may be useful for hazard identification of TiO 2 . In the fourth study by Heringa et al. (2016), numerous assumptions were made, which resulted in large uncertainty in their conclusion. Altogether, the Panel concluded that the outcome of the four studies did not merit re-opening the existing opinion of EFSA related to the safety of TiO 2 (E 171) as a food additive., (© 2018 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

Whenever new substances are proposed for use as sources of nutrients in food supplements, foods for the general population or foods for specific groups, EFSA is requested by the European Commission to perform an assessment of their safety and of the bioavailability of the nutrient from the proposed source. This guidance describes the scientific data required to allow an evaluation of the safety of the source within the established framework for risk assessment of food additives and novel food ingredients and the bioavailability of the nutrient from this source. This document is arranged in five main sections: one on technical data aimed at characterising the proposed source and at identifying potential hazards resulting from its manufacture and stability in food; one on existing authorisations and evaluation, providing an overview of previous assessments on the proposed source and their conclusions; one on proposed uses and exposure assessment section, allowing an estimate of the dietary exposure to the source and the nutrient based on the proposed uses and use levels; one on toxicological data, describing approaches which can be used to identify (in conjunction with data on manufacture and composition) and to characterise hazards of the source and any relevant breakdown products; the final section on bioavailability focuses on determining the extent to which the nutrient from the proposed source is available for use by the body in comparison with one or more forms of the same nutrient that are already permitted for use on the positive lists. This guidance document should replace the previous guidance issued by the Scientific Committee for Food and published in 2001., (© 2018 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

The Panel on Food Additives and Nutrient Sources added to Food (ANS) provides a scientific opinion re-evaluating the safety of stannous chloride and stannous chloride dihydrate (E 512) as food additives. The Panel considered that adequate exposure and toxicity data were available. Stannous chloride is only permitted as food additives in one food category and no reply on the actual use level of stannous chloride (E 512) as a food additive and on its concentration in food was provided by any interested party. According to the Mintel's Global New Products Database (GNPD), stannous chloride was not labelled on any products in the EU nor in Norway. The regulatory maximum level exposure assessment scenario is based on the maximum permitted levels (MPLs) for stannous chloride (E 512), which is 25 mg Sn/kg. The mean exposure to stannous chloride (E 512) from its use as a food additive was below 1.3 μg Sn/kg body weight (bw) per day for all age groups. The 95th percentile of exposure to stannous chloride (E 512) ranged from 0.0 μg Sn/kg bw per day in all groups to 11.2 μg Sn/kg bw per day in adults. Absorption of stannous chloride from the gastrointestinal tract is low there is no concern with respect to carcinogenicity and genotoxicity. Gastrointestinal irritation was reported in humans after ingestion of a bolus dose of 40 mg Sn. The Panel concluded that stannous chloride (E 512) is of no safety concern in this current authorised use and use levels., (© 2018 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

The EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS) provides a scientific opinion on the refined exposure assessment of polyethylene glycol (E 1521) when used as a food additive. Polyethylene glycols were evaluated by several international bodies and the AFC Panel previously adopted scientific opinions on the safety polyethylene glycol (E 1521). In 2006, the Panel concluded that based on all the data, consumption of PEG through use as plasticisers in film-coating formulations for food supplement tablets and/or capsules at the intended use level are not of safety concern. In 2007, in another opinion of the AFC Panel related to d-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) in use for food for particular nutritional purposes, the Panel noted that TPGS intakes would correspond to intake to PEG 1000 at levels equivalent to 3.3-8.5 mg/kg body wieght (bw) per day which are within the range of group acceptable daily intakes (ADIs) of the SCF (1997) and JECFA (1980). This assessment could only take into account the use of polyethylene glycol (E 1521) in food supplements and thus the food supplements consumers only scenario was performed. It resulted in exposure estimates of polyethylene glycol (E 1521) up to 3.5 mg/kg bw per day at the mean and up to 6.1 mg/kg bw per day at the high level. The current exposure assessment is based on the methodology used in the re-evaluation of food additives together with reported use levels received following a call for data in 2017. Considering the uncertainties of the exposure assessment, these estimates very likely overestimated the real exposure to polyethylene glycol (E 1521). The Panel also noted that the highest calculated exposure estimate falls within the range of the group ADI previously established by SCF (5 mg/kg bw per day for PEG 300-4000) and of the one set by JECFA (10 mg/kg bw per day for PEG 200-10000)., (© 2018 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

The Panel on Food Additives and Nutrient Sources added to Food (ANS) provides a scientific opinion re-evaluating the safety of gellan gum (E 418) as a food additive. Following the conceptual framework for the risk assessment of certain food additives re-evaluated under Commission Regulation (EU) No 257/2010, the Panel considered that adequate exposure and toxicity data were available. Based on the reported use levels, a refined exposure of up to 72.4 mg/kg body weight (bw) per day in toddlers at the 95th percentile was estimated. Gellan gum is unlikely to be absorbed intact and would not be fermented by human intestinal microbiota. There is no concern with respect to carcinogenicity and genotoxicity. No adverse effects were reported in chronic studies at the highest doses tested in mice and rats (3,627 and 1,460 mg gellan gum/kg bw per day, respectively). Repeated oral intake up to 200 mg/kg bw per day for 3 weeks had no adverse effects in humans. The Panel concluded that there is no need for a numerical acceptable daily intake (ADI) for gellan gum (E 418), and that there is no safety concern at the refined exposure assessment for the reported uses and use levels of gellan gum (E 418) as a food additive. The Panel recommended to better define the specifications of gellan gum including the absence of viable cells of the microbial source and the presence of polyhydroxybutyrate (PHB), protein and residual bacterial enzymatic activities., (© 2018 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

The present scientific opinion deals with the evaluation of the safety of di-magnesium malate (DMM) proposed as a novel food ingredient and as a source of magnesium for use in foods for the general population, food supplements, total diet replacement for weight control and food for special medical purposes (FSMP), and with the bioavailability of magnesium from this source. Additional information was sought from the applicant during the assessment process. However, despite several requests, the applicant did not provide the additional data. Consequently, the Panel performed this assessment on the basis of the available data and concluded that there was insufficient scientific evidence of a difference between the proposed novel food ingredient named as DMM and magnesium malate already authorised as a source of magnesium included in Annex II to Directive 2002/46/EC. Accordingly, the Panel was unable to assess the safety of DMM as a novel food ingredient. The Panel concluded that based on the data provided it was not possible to assess the dissociation of DMM into magnesium and malic acid. The Panel further concluded that if DMM dissociates, magnesium would be available following ingestion of DMM and the availability would appear similar to values reported for other sources of magnesium already permitted. Finally, the Panel noted that the proposed use levels could result in exposures to magnesium greater than its upper level (UL) (250 mg/day) for food supplements and for food for special medical purposes., (© 2018 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

The present scientific opinion deals with the evaluation of the safety of di-calcium malate (DCM) proposed as a novel food ingredient and as a source of calcium for use in foods for the general population, food supplements, total diet replacement for weight control and food for special medical purposes (FSMP), and with the bioavailability of calcium from this source. The structural formula of the proposed complex is based on expert judgement and not supported by any analytical data. On the basis of the available data, the Panel concluded that there was insufficient scientific evidence of a difference between the proposed novel food ingredient named as di-calcium malate (DCM) and calcium malate already authorised as a source of calcium included in Annex II to Directive 2002/46/EC. Accordingly, the Panel was unable to assess the safety of DCM as a novel food ingredient. On the basis of the results provided, the Panel considered that DCM does not completely dissociate into calcium and malic acid. The Panel concluded that when DCM dissociates, calcium would be available following ingestion of DCM and the bioavailability would appear similar to values reported for other sources of calcium already permitted. Furthermore, the Panel concluded that on the basis of the information available it was not possible to calculate the exposure to DCM as a source of calcium to foods for the general population, food supplements, total diet replacement for weight control and FSMP., (© 2018 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

The present opinion deals with the re-evaluation of the safety of food-grade carrageenan (E 407) and processes Eucheuma seaweed (E 407a) used as food additives. Because of the structural similarities, the Panel concluded that processed Eucheuma seaweed can be included in the evaluation of food-grade carrageenan. Poligeenan (average molecular weight 10-20 kDa) has not been authorised as a food additive and is not used in any food applications. In its evaluation of carrageenan (E 407) and processed Eucheuma seaweed (E 407a), the Panel noted that the ADME database was sufficient to conclude that carrageenan was not absorbed intact; in a subchronic toxicity study performed with carrageenan almost complying with the EU specification for E 407 in rats, the no-observed-adverse-effect level (NOAEL) was 3,400-3,900 mg/kg body weight (bw) per day, the highest dose tested; no adverse effects have been detected in chronic toxicity studies with carrageenan in rats up to 7,500 mg/kg bw per day, the highest dose tested; there was no concern with respect to the carcinogenicity of carrageenan; carrageenan and processed Eucheuma seaweed did not raise a concern with respect to genotoxicity; the NOAEL of sodium and calcium carrageenan for prenatal developmental dietary toxicity studies were the highest dose tested; the safety of processed Eucheuma seaweed was sufficiently covered by the toxicological evaluation of carrageenan; data were adequate for a refined exposure assessment for 41 out of 79 food categories. However, the Panel noted uncertainties as regards the chemistry, the exposure assessment and biological and toxicological data. Overall, taking into account the lack of adequate data to address these uncertainties, the Panel concluded that the existing group acceptable daily intake (ADI) for carrageenan (E 407) and processed Eucheuma seaweed (E 407a) of 75 mg/kg bw per day should be considered temporary, while the database should be improved within 5 years after publication of this opinion., (© 2018 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

The EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS) provides a scientific opinion re-evaluating the safety of propane-1,2-diol (E 1520) when used as a food additive. In 1996, the Scientific Committee on Food (SCF) established an acceptable daily intake (ADI) of 25 mg/kg body weight (bw) per day for propane-1,2-diol. Propane-1,2-diol is readily absorbed from the gastrointestinal and is expected to be widely distributed to organs and tissues. The major route of metabolism is oxidation to lactic acid and pyruvic acid. At high concentrations, free propane-1,2-diol is excreted in the urine. No treatment-related effects were observed in subchronic toxicity studies. The available data did not raise concern with respect to genotoxicity. Haematological changes suggestive of an increased red blood cell destruction with a compensatory increased rate of haematopoiesis were observed at the highest dose level (5,000 mg/kg bw per day) in a 2-year study in dogs. No adverse effects were reported in a 2-year chronic study in rats with propane-1,2-diol (up to 2,500 mg/kg bw per day). The SCF used this study to derive the ADI. No adverse effects were observed in the available reproductive and developmental toxicity studies. Propane-1,2-diol (E 1520) is authorised according to Annex III in some food additives, food flavourings, enzymes and nutrients and it is then carried over to the final food. Dietary exposure to E 1520 was assessed based on the use levels and analytical data. The Panel considered that for the food categories for which information was available, the exposure was likely to be overestimated. Considering the toxicity database, the Panel concluded that there was no reason to revise the current ADI of 25 mg/kg bw per day. The Panel also concluded that the mean and the high exposure levels (P95) of the brand-loyal refined exposure scenario did not exceed the ADI in any of the population groups from the use of propane-1,2-diol (E 1520) at the reported use levels and analytical results., (© 2018 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

The EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS) provides a scientific opinion on the safety and bioavailability of silver hydrosol as a source of silver added for nutritional purposes to food supplements. Silver hydrosol is a suspension comprised of a mixture of positively charged silver ions and silver metal particles in water. The study report submitted, being a gastric disappearance study performed in six individuals, did not provide information on the systemic absorption of silver as such, and was not able to provide information on the bioavailability of silver from silver hydrosol. If silver from silver hydrosol is systematically available a complete toxicological evaluation is needed for its assessment. The application dossier was limited to an acute toxicity study with silver hydrosol and references to toxicological studies performed with forms of silver (e.g. salts of silver) which were considered neither relevant nor adequate to the risk assessment of silver hydrosol. The Panel concluded that the submitted data are insufficient to characterise the silver hydrosol regarding its nano specific properties and to assess either the bioavailability of silver from the source or the safety of the silver hydrosol as a source of silver added for nutritional purposes to food supplements., (© 2018 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

The EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS) provides a scientific opinion on the safety of proposed amendment of the specifications of the food additive steviol glycosides (E 960). The applicant asked to amend the existing EU specifications for steviol glycosides to allow for the inclusion of all steviol glycosides identified in Stevia rebaudiana Bertoni leaves, including both 'major' and 'minor' glycosides, that may comprise the assay value of not less than 95% total steviol glycosides. According to the applicant, all steviol glycosides are subject to microbial metabolism in a similar manner, ultimately generating the common primary metabolite steviol. There are uncertainties on the rate and extent of the metabolism of different steviol glycosides to steviol in the evidence provided and they did not allow the Panel to endorse the applicant's argumentation that all steviol glycosides generate the common metabolite steviol when subjected to microbial metabolism under realistic conditions. The available information was not sufficient to assess the safety of the proposed amendment of the specifications for E 960 and the conclusions on the previous assessments on steviol glycosides cannot be extrapolated to any other mixture of steviol glycosides (containing not less than 95% of any steviol glycosides) extracted from S. rebaudiana Bertoni leaves. Therefore, the Panel concluded that the submitted data were insufficient to assess the safety of proposed amendment of the specifications of the food additive steviol glycosides (E 960)., (© 2018 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

The EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS) provides a scientific opinion re-evaluating the safety of sodium, potassium and calcium salts of fatty acids (E 470a) and magnesium salts of fatty acids (E 470b) when used as food additives. In 1991, the Scientific Committee on Food (SCF) established a group acceptable daily intake (ADI) 'not specified' for the fatty acids (myristic-, stearic-, palmitic- and oleic acid) and their salts. The sodium, potassium, calcium and magnesium salts of fatty acids are expected to dissociate in the gastrointestinal tract to fatty acid carboxylates and their corresponding cations. There were no data on subchronic toxicity, chronic toxicity, reproductive and developmental toxicity of the salts of fatty acids. There was no concern for mutagenicity of calcium caprylate, potassium oleate and magnesium stearate. From a carcinogenicity study with sodium oleate, a no observed adverse effect level (NOAEL) could not be identified but the substance was considered not to present a carcinogenic potential. Palmitic- and stearic acid which are the main fatty acids in E 470a and E 470b were already considered of no safety concern in the re-evaluation of the food additive E 570. The fatty acid moieties of E 470a and E 470b contributed maximally for 5% to the overall intake of saturated fatty acids from all dietary sources. Overall, the Panel concluded that there was no need for a numerical ADI and that the food additives sodium, potassium, calcium and magnesium salts of fatty acids (E 470a and E 470b) were of no safety concern at the reported uses and use levels., (© 2018 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

The EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS) provides a scientific opinion on the safety of glucosylated steviol glycosides proposed for use as a new food additive in different food categories. According to the applicant, glucosylated steviol glycosides preparations consist of not less than 95% (on anhydrous basis) total steviol glycosides, made up of glucosylated steviol glycosides of different molecular weights as well as any remaining steviol glycosides. The applicant proposed that glucosylated steviol glycosides and parent steviol glycosides undergo a common metabolic process in pathway following ingestion and suggested that data from steviol glycosides can be used for read-across to glucosylated steviol glycosides. The limited evidence provided in the application dossier did not demonstrate the complete hydrolysis of the glucosylated steviol glycosides. No toxicological studies on glucosylated steviol glycoside preparations under evaluation have been provided for its assessment. The Panel concluded that the submitted data are insufficient to assess the safety of the glucosylated steviol glycoside preparations to be used as a new food additive., (© 2018 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

The Panel on Food Additives and Nutrient Sources added to Food (ANS) was asked to deliver a scientific opinion on the safety of hydroxyanthracene derivatives and to provide advice on a daily intake that does not give rise to concerns about harmful effects to health. Hydroxyanthracene derivatives are a class of chemical substances naturally occurring in different botanical species and used in food to improve bowel function. The ANS Panel reviewed the available scientific data on a possible relationship between hydroxyanthracene derivatives exposure and genotoxic and carcinogenic effects. On the basis of the data currently available, the Panel noted that emodin, aloe-emodin and the structurally related substance danthron have shown evidence of in vitro genotoxicity. Aloe extracts have also been shown to be genotoxic in vitro possibly due to the presence of hydroxyanthracene derivatives in the extract. Furthermore, aloe-emodin was shown to be genotoxic in vivo and the whole-leaf aloe extract and the structural analogue danthron were shown to be carcinogenic. Epidemiological data suggested an increased risk for colorectal cancer associated with the general use of laxatives, several of which contain hydroxyanthracene derivatives. Considering the possible presence of aloe-emodin and emodin in extracts, the Panel concluded that hydroxyanthracene derivatives should be considered as genotoxic and carcinogenic unless there are specific data to the contrary, such as for rhein, and that there is a safety concern for extracts containing hydroxyanthracene derivatives although uncertainty persists. The Panel was unable to provide advice on a daily intake of hydroxyanthracene derivatives that does not give rise to concerns about harmful effects to health., (© 2018 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

Low-substituted hydroxypropyl cellulose (L-HPC) is a low-substituted poly(hydroxypropyl) ether of cellulose. L-HPC is proposed for use as a food additive in food supplements in solid form (tablet), with a maximum use level of 20,000 mg/kg and a typical use level of 10,000 mg/kg. Exposure estimates to L-HPC from its proposed use were calculated for both typical and maximum use levels. Due to the close chemical relationship between L-HPC and other celluloses recently re-evaluated by EFSA, the Panel decided to read-across the biological data already evaluated in the context of the re-evaluation programme. The Panel concluded that there was no safety concern from the proposed use and use levels of L-HPC., (© 2018 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

The EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS) provides a scientific opinion re-evaluating the safety of silicon dioxide (E 551) when used as a food additive. The forms of synthetic amorphous silica (SAS) used as E 551 include fumed silica and hydrated silica (precipitated silica, silica gel and hydrous silica). The Scientific Committee on Food (SCF) established a group acceptable daily intake (ADI) 'not specified' for silicon dioxide and silicates. SAS materials used in the available biological and toxicological studies were different in their physicochemical properties; their characteristics were not always described in sufficient detail. Silicon dioxide appears to be poorly absorbed. However, silicon-containing material (in some cases presumed to be silicon dioxide) was found in some tissues. Despite the limitations in the subchronic, reproductive and developmental toxicological studies, including studies with nano silicon dioxide, there was no indication of adverse effects. E 551 does not raise a concern with respect to genotoxicity. In the absence of a long-term study with nano silicon dioxide, the Panel could not extrapolate the results from the available chronic study with a material, which does not cover the full-size range of the nanoparticles that could be present in the food additive E 551, to a material complying with the current specifications for E 551. These specifications do not exclude the presence of nanoparticles. The highest exposure estimates were at least one order of magnitude lower than the no observed adverse effect levels (NOAELs) identified (the highest doses tested). The Panel concluded that the EU specifications are insufficient to adequately characterise the food additive E 551. Clear characterisation of particle size distribution is required. Based on the available database, there was no indication for toxicity of E 551 at the reported uses and use levels. Because of the limitations in the available database, the Panel was unable to confirm the current ADI 'not specified'. The Panel recommended some modifications of the EU specifications for E 551., (© 2018 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

The EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS) provides a scientific opinion on the exposure assessment of sucrose esters of fatty acids (E 473) when used as a food additive. The Panel previously adopted scientific opinions on the safety of sucrose esters of fatty acids (E 473). In the 2010 opinion, the Panel concluded that, based on the data available, the additional use of the sucrose esters of fatty acids (E 473) may lead to exposures in excess of the acceptable daily intake (ADI) of 40 mg/kg body weight (bw) per day for sucrose esters of fatty acids (E 473) and sucroglycerides (E 474) established by EFSA in 2004. In 2012, an update on the exposure assessment of sucrose esters of fatty acids (E 473) was delivered as new data were submitted to EFSA providing use levels of sucrose esters of fatty acids as a surface treatment for fresh fruits and the resulting residual levels in fruit. This assessment also resulted in exposure estimates of sucrose esters of fatty acids (E 473) exceeding the ADI, although considerably lower than those estimated in 2010. The current exposure assessment is based on the recent methodology used in the re-evaluation of food additives together with reported use levels received following a call for data in 2014. New consumption data were also available since then. The Panel noted that the current exposure estimates to sucrose esters of fatty acids (E 473) exceeded the ADI of 40 mg/kg bw per day for many population groups; especially toddlers and children and that assuming that sucrose esters of fatty acids (E 473) is not used in the 24 food categories where data was not provided, these estimates very likely overestimated the real exposure to sucrose esters of fatty acids (E 473)., (© 2018 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

The present scientific opinion deals with the safety of orthosilicic acid-vanillin complex (OSA-VC) as a novel food ingredient for use as a source of silicon (Si) in food supplements and with the bioavailability of Si from this source. OSA-VC is stable in liquid solution at low pH values. OSA from OSA-VC was available as revealed by the increase in plasma Si concentrations after oral ingestion in human volunteers. The toxicological data provided in support of the current application were not in accordance with the Tier 1 requirement of the 'Guidance for submission for food additive evaluations'; however, this was considered justified by the Panel given that OSA-VC at pH 6.8 dissociates into orthosilicic acid and vanillin. The daily consumption of OSA-VC at the dose recommended by the applicant would provide a supplemental intake of Si of approximately 10-18 mg Si/day which would result in an estimated total intake of roughly 30-70 mg Si/day. The maximum vanillin intake resulting from the consumption of OSA-VC would be less than 5% of the acceptable daily intake (ADI) value for vanillin of 10 mg/kg body weight (bw) per day established by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) in 2002. The Panel concluded that there would be no safety concern with the proposed use and use level of OSA-VC as a novel food ingredient intended to be used as a source of Si in food supplements for the adult population. The Panel concluded that OSA, measured as Si, is bioavailable following ingestion of OSA-VC and appears similar to values reported in the literature for other established sources of OSA., (© 2018 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

The EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS) provides a scientific opinion re-evaluating the safety of polyglycerol esters of fatty acids (PEFA) (E 475) when used as a food additive. In 1978, the Scientific Committee on Food (SCF) endorsed an acceptable daily intake (ADI) of 25 mg/kg body weight (bw) per day previously established by the Joint FAO/WHO Expert Committee on Food Additives (JECFA). Absorption of intact PEFA in the gastrointestinal tract was extremely low. PEFA was rapidly and almost fully hydrolysed to polyglycerols and fatty acids in the gastrointestinal tract. The safety of polyglycerols and specific fatty acids has recently been assessed and no adverse effects were identified in the available studies. No adverse effects of PEFA at any dose have been observed in short-term, subchronic or chronic toxicity studies. A no observed adverse effect level (NOAEL) of 9,000 mg/kg bw per day was identified from subchronic studies and of 2,500 mg/kg bw per day from chronic studies, the highest doses tested. No genotoxic potential of PEFA was identified from the limited information available. The reproductive toxicity studies showed no adverse effects of PEFA but had major limitations. Clinical chemistry and urinalysis, from a clinical study with limited information, did not reveal any adverse effects in volunteers receiving up to 300 mg/kg bw per day for 3 weeks. The highest exposure to PEFA used as a food additive was 2.6 and 6.4 mg/kg bw per day in children at the mean and the 95th percentile, respectively, for the non-brand loyal scenario. Considering all the above, the Panel concluded that the food additive PEFA (E 475) was not of safety concern at the reported uses and use levels and that there was no need for a numerical ADI. The Panel recommended some modifications of the EU specifications for E 475., (© 2017 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

The present scientific opinion deals with the evaluation of the safety of nisin (E 234) in the light of new toxicological data and with the proposed extension of use in unripened cheese and heat-treated meat products. Nisin (E 234) is currently an authorised food additive in the EU under Annex II of Regulation (EC) 1333/2008 for use in several food categories. The safety of nisin (E 234) as a food additive has been evaluated in 2006 by the EFSA Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food, where an acceptable daily intake (ADI) of 0.13 mg/kg body weight (bw) was confirmed as previously established by Scientific Committee on Food (SCF). In addition to the studies previously evaluated by EFSA in 2006, the Panel considered in the present opinion, data from a new subchronic toxicity study. No adverse effects were observed in a repeated dose oral toxicity study in which rats were administered nisin A for 90 days. A no observed adverse effect level (NOAEL) of 225 mg nisin A/kg bw per day, the highest dose tested, was identified for this study. Using this NOAEL, an ADI of 1 mg nisin A/kg bw per day for nisin (E 234) was calculated applying a default uncertainty factor of 200 for extrapolation of subchronic to chronic exposure and inter- and intra-species variability. The Panel calculated exposure estimates for both the current and the proposed uses based on the data available in the EFSA Comprehensive Database. The Panel considered that the overall exposure estimate was below the new ADI for nisin A for all population groups. The Panel concluded that the proposed extension of use of nisin (E 234) as a food additive in unripened cheese (at maximum level of 12 mg/kg) and in heat-treated meat products (at maximum level of 25 mg/kg) would not be of safety concern., (© 2017 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

The present scientific opinion deals with the safety of the extension of use of lycopene (E 160d) in certain meat preparations, meat products and fruit and vegetable preparations. Lycopene (E 160d) is an authorised food additive in the EU for use in several food categories and an acceptable daily intake (ADI) of 0.5 mg/kg body weight (bw) per day was established. In the present opinion, the Panel decided that a comparison of the exposure resulting from the current uses and use levels with the exposure resulting from this additional proposed extension of uses would be sufficient to address the safety of lycopene. The Panel calculated that, considering the current maximum permitted levels (MPLs) and the proposed extension of uses and use levels, the mean dietary exposure to lycopene (E 160d) in the total population ranged from 0.01 mg/kg bw per day in infants to 0.82 mg/kg bw per day in toddlers. At the high level, dietary exposure to lycopene (E 160d) ranged from 0.03 mg/kg bw per day in infants to 1.39 mg/kg bw per day in toddlers. The Panel concluded that the proposed extension of uses of lycopene (E 160d) as a food additive in meat preparations, meat products and fruit and vegetable preparations up to 60 mg/kg would not add significantly to the intake of the food additive at its current MPL. However, the Panel noted that the overall intake at the MPL scenario would exceed the currently established ADI. The Panel acknowledged the uncertainties in the current estimates which could result in an overestimation of the exposure to lycopene (E 160d) as a food additive in European countries and therefore concluded that a refined exposure estimate would be recommended focusing on food categories contributing the most to its estimates, in order to decrease uncertainties in its current estimates., (© 2017 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

The EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS) provides a scientific opinion re-evaluating the safety of mono- and di-glycerides of fatty acids (E 471) when used as a food additive. The Panel considered that it is very likely that hydrolysis of mono- and di-glycerides of fatty acids by lipases in the gastrointestinal tract would occur, resulting in the release of glycerol and fatty acids. Glycerol (E 422) and fatty acids (E 570) have been re-evaluated and the Panel concluded that there was no safety concern regarding their use as food additives. Toxicological studies with mono- and di-glycerides rich in unsaturated fatty acids were considered for the re-evaluation of E 471. No evidence for adverse effects was reported in short-term, subchronic studies, chronic, reproductive and developmental toxicity studies. Neither carcinogenic potential nor a promotion effect in initiation/promotion was reported. The available studies did not raise any concern with regard to genotoxicity. The refined estimates were based on 31 out of 84 food categories in which E 471 is authorised. The Panel noted that the contribution of E 471 represented at the mean only 0.8-3.5% of the recommended daily fat intake. Based on the approach described in the conceptual framework for the risk assessment of certain food additives re-evaluated under Commission Regulation (EU) No 257/2010 and taking into account the considerations mentioned above, the Panel concluded that there was no need for a numerical acceptable daily intake (ADI) and that the food additive mono- and di-glycerides of fatty acids (E 471) was of no safety concern at the reported uses and use levels. The Panel recommended some modifications of the EU specifications for E 471., (© 2017 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

The present opinion deals with the re-evaluation of alginic acid and its sodium, potassium, ammonium and calcium salts (E 400-E 404) when used as food additives. Alginic acid and its salts (E 400-E 404) are authorised food additives in the EU in accordance with Annex II and Annex III to Regulation (EC) No 1333/2008. Following the conceptual framework for the risk assessment of certain food additives re-evaluated under Commission Regulation (EU) No 257/2010, the Panel concluded that there was no need for a numerical Acceptable Daily Intake (ADI) for alginic acid and its salts (E 400, E 401, E 402, E 403 and E 404), and that there was no safety concern at the level of the refined exposure assessment for the reported uses of alginic acid and its salts (E 400, E 401, E 402, E 403 and E 404) as food additives. The Panel further concluded that exposure of infants and young children to alginic acid and its salts (E 400, E 401, E 402, E 403 and E 404) by the use of these food additives should stay below therapeutic dosages for these population groups at which side-effects could occur. Concerning the use of alginic acid and its salts (E 400, E 401, E 402, E 403 and E 404) in 'dietary foods for special medical purposes and special formulae for infants' (Food category 13.1.5.1) and 'in dietary foods for babies and young children for special medical purposes as defined in Directive 1999/21/EC' (Food category 13.1.5.2), the Panel further concluded that the available data did not allow an adequate assessment of the safety of alginic acid and its salts (E 400, E 401, E 402, E 403 and E 404) in infants and young children consuming the food belonging to the categories 13.1.5.1 and 13.1.5.2., (© 2017 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

Nitrate (NO 3 - )-rich foods such as green leafy vegetables are not only part of a healthy diet, but increasingly marketed for primary prevention of cardiovascular disease (CVD) and used as ergogenic aids by competitive athletes. While there is abundant evidence for mild hypotensive effects of nitrate on acute application there is limited data on chronic intake in humans, and results from animal studies suggest no long-term benefit. This is important as nitrate can also promote the formation of nitrosamines. It is therefore classified as 'probably carcinogenic to humans', although a beneficial effect on CVD risk might compensate for an increased cancer risk. Dietary nitrate requires reduction to nitrite (NO 2 - ) by oral commensal bacteria to contribute to the formation of nitric oxide (NO). The extensive crosstalk between NO and hydrogen sulfide (H 2 S) related metabolites may further affect nitrate's bioactivity. Using nitrate and nitrite concentrations of drinking water - the only dietary source continuously monitored for which detailed data exist - in conjunction with data of >14,000 participants of the EPIC-Norfolk study, we found no inverse associations with blood pressure or CVD risk. Instead, we found a strong interaction with sulfate (SO 4 2- ). At low sulfate concentrations, nitrate was inversely associated with BP (-4mmHg in top quintile) whereas this was reversed at higher concentrations (+3mmHg in top quintile). Our findings have a potentially significant impact for pharmacology, physiology and public health, redirecting our attention from the oral microbiome and mouthwash use to interaction with sulfur-containing dietary constituents. These results also indicate that nitrate bioactivation is more complex than hitherto assumed. The modulation of nitrate bioactivity by sulfate may render dietary lifestyle interventions aimed at increasing nitrate intake ineffective and even reverse potential antihypertensive effects, warranting further investigation., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Processed meat intake is carcinogenic to humans. We have shown that intake of a workshop-made cured meat with erythorbate promotes colon carcinogenesis in rats. We speculated that polyphenols could inhibit this effect by limitation of endogenous lipid peroxidation and nitrosation. Polyphenol-rich plant extracts were added to the workshop-made cured meat and given for 14 days to rats and 100 days to azoxymethane-induced rats to evaluate the inhibition of preneoplastic lesions. Colons of 100-d study were scored for precancerous lesions (mucin-depleted foci, MDF), and biochemical end points of peroxidation and nitrosation were measured in urinary and fecal samples. In comparison with cured meat-fed rats, dried red wine, pomegranate extract, α-tocopherol added at one dose to cured meat and withdrawal of erythorbate significantly decreased the number of MDF per colon (but white grape and rosemary extracts did not). This protection was associated with the full suppression of fecal excretion of nitrosyl iron, suggesting that this nitroso compound might be a promoter of carcinogenesis. At optimized concentrations, the incorporation of these plant extracts in cured meat might reduce the risk of colorectal cancer associated with processed meat consumption.

Background: The beneficial cardiovascular effects of vegetables may be underpinned by their high inorganic nitrate content., Objective: We sought to examine the effects of a 6-wk once-daily intake of dietary nitrate (nitrate-rich beetroot juice) compared with placebo intake (nitrate-depleted beetroot juice) on vascular and platelet function in untreated hypercholesterolemics., Design: A total of 69 subjects were recruited in this randomized, double-blind, placebo-controlled parallel study. The primary endpoint was the change in vascular function determined with the use of ultrasound flow-mediated dilatation (FMD)., Results: Baseline characteristics were similar between the groups, with primary outcome data available for 67 patients. Dietary nitrate resulted in an absolute increase in the FMD response of 1.1% (an ∼24% improvement from baseline) with a worsening of 0.3% in the placebo group (P < 0.001). A small improvement in the aortic pulse wave velocity (i.e., a decrease of 0.22 m/s; 95% CI: -0.4, -0.3 m/s) was evident in the nitrate group, showing a trend (P = 0.06) to improvement in comparison with the placebo group. Dietary nitrate also caused a small but significant reduction (7.6%) in platelet-monocyte aggregates compared with an increase of 10.1% in the placebo group (P = 0.004), with statistically significant reductions in stimulated (ex vivo) P-selectin expression compared with the placebo group (P < 0.05) but no significant changes in unstimulated expression. No adverse effects of dietary nitrate were detected. The composition of the salivary microbiome was altered after the nitrate treatment but not after the placebo treatment (P < 0.01). The proportions of 78 bacterial taxa were different after the nitrate treatment; of those taxa present, 2 taxa were responsible for >1% of this change, with the proportions of Rothia mucilaginosa trending to increase and Neisseria flavescens (P < 0.01) increased after nitrate treatment relative to after placebo treatment., Conclusions: Sustained dietary nitrate ingestion improves vascular function in hypercholesterolemic patients. These changes are associated with alterations in the oral microbiome and, in particular, nitrate-reducing genera. Our findings provide additional support for the assessment of the potential of dietary nitrate as a preventative strategy against atherogenesis in larger cohorts. This trial was registered at clinicaltrials.gov as NCT01493752.

Cocoa flavanol (CF) intake improves endothelial function in patients with cardiovascular risk factors and disease. We investigated the effects of CF on surrogate markers of cardiovascular health in low risk, healthy, middle-aged individuals without history, signs or symptoms of CVD. In a 1-month, open-label, one-armed pilot study, bi-daily ingestion of 450 mg of CF led to a time-dependent increase in endothelial function (measured as flow-mediated vasodilation (FMD)) that plateaued after 2 weeks. Subsequently, in a randomised, controlled, double-masked, parallel-group dietary intervention trial (Clinicaltrials.gov: NCT01799005), 100 healthy, middle-aged (35-60 years) men and women consumed either the CF-containing drink (450 mg) or a nutrient-matched CF-free control bi-daily for 1 month. The primary end point was FMD. Secondary end points included plasma lipids and blood pressure, thus enabling the calculation of Framingham Risk Scores and pulse wave velocity. At 1 month, CF increased FMD over control by 1·2 % (95 % CI 1·0, 1·4 %). CF decreased systolic and diastolic blood pressure by 4·4 mmHg (95 % CI 7·9, 0·9 mmHg) and 3·9 mmHg (95 % CI 6·7, 0·9 mmHg), pulse wave velocity by 0·4 m/s (95 % CI 0·8, 0·04 m/s), total cholesterol by 0·20 mmol/l (95 % CI 0·39, 0·01 mmol/l) and LDL-cholesterol by 0·17 mmol/l (95 % CI 0·32, 0·02 mmol/l), whereas HDL-cholesterol increased by 0·10 mmol/l (95 % CI 0·04, 0·17 mmol/l). By applying the Framingham Risk Score, CF predicted a significant lowering of 10-year risk for CHD, myocardial infarction, CVD, death from CHD and CVD. In healthy individuals, regular CF intake improved accredited cardiovascular surrogates of cardiovascular risk, demonstrating that dietary flavanols have the potential to maintain cardiovascular health even in low-risk subjects.

Objective: The objective of the present study was to investigate associations between sugar intake and overweight using dietary biomarkers in the Norfolk cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Norfolk)., Design: Prospective cohort study., Setting: EPIC-Norfolk in the UK, recruitment between 1993 and 1997., Subjects: Men and women (n 1734) aged 39-77 years. Sucrose intake was assessed using 7 d diet diaries. Baseline spot urine samples were analysed for sucrose by GC-MS. Sucrose concentration adjusted by specific gravity was used as a biomarker for intake. Regression analyses were used to investigate associations between sucrose intake and risk of BMI>25·0 kg/m2 after three years of follow-up., Results: After three years of follow-up, mean BMI was 26·8 kg/m2. Self-reported sucrose intake was significantly positively associated with the biomarker. Associations between the biomarker and BMI were positive (β=0·25; 95 % CI 0·08, 0·43), while they were inverse when using self-reported dietary data (β=-1·40; 95 % CI -1·81, -0·99). The age- and sex-adjusted OR for BMI>25·0 kg/m2 in participants in the fifth v. first quintile was 1·54 (95 % CI 1·12, 2·12; P trend=0·003) when using biomarker and 0·56 (95 % CI 0·40, 0·77; P trend<0·001) with self-reported dietary data., Conclusions: Our results suggest that sucrose measured by objective biomarker but not self-reported sucrose intake is positively associated with BMI. Future studies should consider the use of objective biomarkers of sucrose intake.

Experimental evidence suggests that nitric oxide (NO) and hydrogen sulfide (H2S) signaling pathways are intimately intertwined, with mutual attenuation or potentiation of biological responses in the cardiovascular system and elsewhere. The chemical basis of this interaction is elusive. Moreover, polysulfides recently emerged as potential mediators of H2S/sulfide signaling, but their biosynthesis and relationship to NO remain enigmatic. We sought to characterize the nature, chemical biology, and bioactivity of key reaction products formed in the NO/sulfide system. At physiological pH, we find that NO and sulfide form a network of cascading chemical reactions that generate radical intermediates as well as anionic and uncharged solutes, with accumulation of three major products: nitrosopersulfide (SSNO(-)), polysulfides, and dinitrososulfite [N-nitrosohydroxylamine-N-sulfonate (SULFI/NO)], each with a distinct chemical biology and in vitro and in vivo bioactivity. SSNO(-) is resistant to thiols and cyanolysis, efficiently donates both sulfane sulfur and NO, and potently lowers blood pressure. Polysulfides are both intermediates and products of SSNO(-) synthesis/decomposition, and they also decrease blood pressure and enhance arterial compliance. SULFI/NO is a weak combined NO/nitroxyl donor that releases mainly N2O on decomposition; although it affects blood pressure only mildly, it markedly increases cardiac contractility, and formation of its precursor sulfite likely contributes to NO scavenging. Our results unveil an unexpectedly rich network of coupled chemical reactions between NO and H2S/sulfide, suggesting that the bioactivity of either transmitter is governed by concomitant formation of polysulfides and anionic S/N-hybrid species. This conceptual framework would seem to offer ample opportunities for the modulation of fundamental biological processes governed by redox switching and sulfur trafficking.

Increased vascular stiffness, endothelial dysfunction, and isolated systolic hypertension are hallmarks of vascular aging. Regular cocoa flavanol (CF) intake can improve vascular function in healthy young and elderly at-risk individuals. However, the mechanisms underlying CF bioactivity remain largely unknown. We investigated the effects of CF intake on cardiovascular function in healthy young and elderly individuals without history, signs, or symptoms of cardiovascular disease by applying particular focus on functional endpoints relevant to cardiovascular aging. In a randomized, controlled, double-masked, parallel-group dietary intervention trial, 22 young (<35 years) and 20 elderly (50-80 year) healthy, male non-smokers consumed either a CF-containing drink (450 mg CF) or nutrient-matched, CF-free control drink bi-daily for 14 days. The primary endpoint was endothelial function as measured by flow-mediated vasodilation (FMD). Secondary endpoints included cardiac output, vascular stiffness, conductance of conduit and resistance arteries, and perfusion in the microcirculation. Following 2 weeks of CF intake, FMD improved in young (6.1 ± 0.7 vs. 7.6 ± 0.7 %, p < 0.001) and elderly (4.9 ± 0.6 vs. 6.3 ± 0.9 %, p < 0.001). Secondary outcomes demonstrated in both groups that CF intake decreased pulse wave velocity and lowered total peripheral resistance, and increased arteriolar and microvascular vasodilator capacity, red cell deformability, and diastolic blood pressure, while cardiac output remained affected. In the elderly, baseline systolic blood pressure was elevated, driven by an arterial-stiffness-related augmentation. CF intake decreased aortic augmentation index (-9 %) and thus systolic blood pressure (-7 mmHg; Clinicaltrials.gov: NCT01639781). CF intake reverses age-related burden of cardiovascular risk in healthy elderly, highlighting the potential of dietary flavanols to maintain cardiovascular health.

Background: Flavonoids are a group of phenolic secondary plant metabolites that are ubiquitous in plant-based diets. Data from anthropological, observational and intervention studies have shown that many flavonoids are bioactive. For this reason, there is an increasing interest in investigating the potential health effects of these compounds. The translation of these findings into the context of the health of the general public requires detailed information on habitual dietary intake. However, only limited data are currently available for European populations., Objective: The objective of this study is to determine the habitual intake and main sources of anthocyanidins, flavanols, flavanones, flavones, flavonols, proanthocyanidins, theaflavins and thearubigins in the European Union., Design: We use food consumption data from the European Food Safety Authority (EFSA) and the FLAVIOLA Food Composition Database to estimate intake of flavonoids., Results: Mean (±SEM) intake of total flavonoids in Europe was 428±49 mg/d, of which 136±14 mg/d were monomeric compounds. Gallated flavan-3-ols (53±12 mg/d) were the main contributor. The lowest flavonoid intake was observed in Mediterranean countries (monomeric compounds: 95±11 mg/d). The distribution of intake was skewed in many countries, especially in Germany (monomeric flavonoids; mean intake: 181 mg/d; median intake: 3 mg/d)., Conclusions: The habitual intake of flavonoids in Europe is below the amounts found to have a significant health effect.