Safety of an extension of use of Yarrowia lipolytica yeast biomass as a novel food pursuant to Regulation (EU) 2015/2283.

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of an extension of use of Yarrowia (Y.) lipolytica yeast biomass as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The extension of use pertains to the use of the NF as a food ingredient in a number of food categories, in foods for special medical purposes and in foods for total diet replacement for weight control. In 2018, Y. lipolytica was attributed the qualified presumption of safety (QPS) status for production purposes, including food and feed products based on biomass. The Panel considers that the data provided sufficient information with respect to the stability of the NF, also when used as a food ingredient. The concentrations of the analysed processing contaminants do not raise safety concerns. The Panel also considers that consumption of the NF is not nutritionally disadvantageous under the proposed conditions of use. The Panel concludes that the NF, Y. lipolytica yeast biomass, is safe under the proposed conditions of use.

Safety of paramylon as a novel food pursuant to Regulation (EU) 2015/2283.

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on paramylon as a novel food (NF) pursuant to Regulation (EU) 2015/2283. Paramylon is a linear, unbranched beta-1,3-ᴅ-glucan polymer that is isolated from the single-cell microalga Euglena gracilis. The NF consists of at least 95% beta-glucan and minor amounts of protein, fat, ash and moisture. The applicant proposed to use the NF in food supplements, as a food ingredient added to a number of food categories and in foods for total diet replacement for weight control. In 2019, E. gracilis was attributed the qualified presumption of safety (QPS) status with the qualification 'for production purposes only', which includes food products based on microbial biomass of the microalga. Based on the information provided, E. gracilis is not expected to survive the manufacturing process. The submitted toxicity studies did not raise safety concerns. No adverse effects were observed in the subchronic toxicity studies, up to the highest dose tested, i.e. 5,000 mg NF/kg body weight per day. In view of the QPS status of the source of the NF, supported by the manufacturing process, compositional data and lack of toxicity observed in the toxicity studies, the Panel has no safety concerns and concludes that the NF, i.e. paramylon, is safe under the proposed uses and use levels.

Safety of iron milk proteinate as a novel food pursuant to Regulation (EU) 2015/2283 and bioavailability of iron from this source in the context of Directive 2002/46/EC.

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on iron milk proteinate as a novel food (NF) pursuant to Regulation (EU) 2015/2283 and to address the bioavailability of iron from this source in the context of Directive 2002/46/EC. The NF is a complex of iron, casein and phosphate, which is produced from iron salts (i.e. ferric chloride or ferric sulfate), sodium caseinate and potassium orthophosphate. The NF is proposed by the applicant to be used as a source of iron, of which the NF contains 2-4%. The applicant intends to market the NF as an ingredient in a number of food categories; in food supplements, in total diet replacement for weight control and in foods for special medical purposes. The Panel considers that, taking into account the composition of the NF and the proposed conditions of use, consumption of the NF is not nutritionally disadvantageous. The studies provided for ADME and bioavailability indicate that iron from the NF is bioavailable. Overall, the evidence indicates that upon ingestion the NF undergoes digestion into small peptides to yield iron-bound caseinophosphopeptides that are normal constituents of the human diet, and that the iron from the NF does not bypass the homeostatic control of iron as a nutrient. The Panel concludes that the NF, iron milk proteinate, is safe under the proposed conditions of use. The Panel also concludes that the NF is a source from which iron is bioavailable.

Safety of an extension of use of Yarrowia lipolytica yeast biomass as a novel food pursuant to Regulation (EU) 2015/2283.

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of an extension of use for Yarrowia lipolytica yeast biomass as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The extension of use pertains to the use of the NF as a food ingredient in single meal replacement products for weight reduction for adults at a maximum amount of 6 g NF per day, which is the same amount of NF as already authorised in food supplements for this population group. According to the applicant, food supplements with Yarrowia lipolytica biomass (as already authorised) should not be consumed concomitantly with the meal replacement products in order not to exceed the 6 g NF per day. The Panel considers that the consumption of the NF is not nutritionally disadvantageous under the proposed conditions of use. The Panel concludes that the NF, Yarrowia lipolytica yeast biomass, is safe under the proposed conditions of use.

Safety of pasteurised Akkermansia muciniphila as a novel food pursuant to Regulation (EU) 2015/2283.

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on pasteurised Akkermansia muciniphila as a novel food (NF) pursuant to Regulation (EU) 2015/2283. A. muciniphila is a well-characterised non-toxin producing, avirulent microorganism that has been reported as part of normal gut microbiota. The NF, pasteurised A. muciniphila, is proposed by the applicant to be used as a food supplement at max. 5 × 1010 cells/day by adults excluding pregnant and lactating women, and in foods for special medical purposes. The Panel considers that the production process of the NF is sufficiently described and that the information provided on the composition of the NF is sufficient for its characterisation. Taking into account the composition of the NF and the proposed conditions of use, the consumption of the NF is not nutritionally disadvantageous. Based on literature data, and by applying an uncertainty factor of 200 to the no observed adverse effect level (NOAEL) of a 90-day repeated dose oral toxicity study in rats, the Panel concludes that the consumption of 3.4 × 1010 cells/day is safe for the target population under the provision that the number of viable cells in the NF is < 10 colony forming units (CFU)/g (i.e. limit of detection).

Safety of tetrahydrocurcuminoids from turmeric (Curcuma longa L.) as a novel food pursuant to Regulation (EU) 2015/2283.

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on tetrahydrocurcuminoids from turmeric (Curcuma longa L.) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. Tetrahydrocurcuminoids are derivatives of curcuminoids, produced chemically by hydrogenation of curcuminoids extracted from the rhizomes of C. longa L. The NF consists of more than 95% of tetrahydrocurcuminoids. The applicant proposed to use the NF in food supplements at a maximum dose of 300 mg/day for adults excluding pregnant and lactating women. Taking into account the composition of the NF and the proposed conditions of use, consumption of the NF is not nutritionally disadvantageous. There are no concerns regarding genotoxicity of the NF. Based on a 90-day oral toxicity study and a reproduction/developmental toxicity screening test performed with the NF, the Panel derives a safe level of 2 mg/kg body weight per day. For the target population this level corresponds to 140 mg/day, which is lower than the use level as proposed by the applicant. The Panel concludes that the NF, tetrahydrocurcuminoids from turmeric (C. longa L.), is safe for the target population at 140 mg/day.

Novel foods in the European Union: Scientific requirements and challenges of the risk assessment process by the European Food Safety Authority.

The European Food Safety Authority (EFSA) has been involved in the risk assessment of novel foods since 2003. The implementation of the current novel food regulation in 2018 rendered EFSA the sole entity of the European Union responsible for such safety evaluations. The risk assessment is based on the data submitted by applicants in line with the scientific requirements described in the respective EFSA guidance document. The present work aims to elaborate on the rationale behind the scientific questions raised during the risk assessment of novel foods, with a focus on complex mixtures and whole foods. Novel foods received by EFSA in 2003-2019 were screened and clustered by nature and complexity. The requests for additional or supplementary information raised by EFSA during all risk assessments were analyzed for identifying reoccurring issues. In brief, it is shown that applications concern mainly novel foods derived from plants, microorganisms, fungi, algae, and animals. A plethora of requests relates to the production process, the compositional characterization of the novel food, and the evaluation of the product's toxicological profile. Recurring issues related to specific novel food categories were noted. The heterogeneous nature and the variable complexity of novel foods emphasize the challenge to tailor aspects of the evaluation approach to the characteristics of each individual product. Importantly, the scientific requirements for novel food applications set by EFSA are interrelated, and only a rigorous and cross-cutting approach adopted by the applicants when preparing the respective application dossiers can lead to scientifically sound dossiers. This is the first time that an in-depth analysis of the experience gained by EFSA in the risk assessment of novel foods and of the reasoning behind the most frequent scientific requests by EFSA to applicants is made.

Safety of astaxanthin for its use as a novel food in food supplements.

Following a request from the European Commission, the Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of astaxanthin when used as a novel food in food supplements at maximum levels of 8 mg/day, taking into account the overall cumulative intake of astaxanthin from all food sources. In 2014, the NDA Panel assessed the safety of the novel astaxanthin-rich ingredient derived from microalgae Haematococcus pluvialis in the context of an application submitted under Regulation (EC) No 258/1997. In that opinion, the NDA Panel considered that the acceptable daily intake (ADI) for astaxanthin was 0.034 mg/kg body weight (bw) set by the EFSA FEEDAP Panel in 2014. In 2019, the FEEDAP Panel adopted an opinion which concerned the renewal of the authorisation of dimethyldisuccinate-astaxanthin and a new use of the additive for crustaceans and other fish than salmonids. In that assessment, the FEEDAP Panel derived a new ADI of 0.2 mg astaxanthin/kg bw which replaced the ADI of 0.034 mg/kg bw established in 2014. By taking into account an updated exposure assessment for astaxanthin from the background diet (fish and crustaceans) in combination with 8 mg from food supplements, the NDA Panel concludes that (i) such combined exposure to astaxanthin is safe for adults, (ii) 14 to < 18 years old adolescents reach the ADI, and (iii) the ADI is exceeded by 28% in children aged 10 to < 14 years and up to 524% in infants aged 4-6 months.

Safety of chromium-enriched biomass of Yarrowia lipolytica as a novel food pursuant to Regulation (EU) 2015/2283.

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on chromium-enriched biomass of Yarrowia lipolytica as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is the dried and heat-killed chromium-enriched biomass of Y. lipolytica. This yeast species is widespread in nature, can be found in the environment and in foods, and was attributed the qualified presumption of safety (QPS) status for production purposes in 2018, including food and feed products based on biomass of the yeast. The production process, fermentation in the presence of chromium chloride, includes a heat-killing step of the yeast, resulting in the absence of viable Y. lipolytica in the NF. The maximum total chromium content of the NF is 23 µg Cr/g, with the chromium present as Cr(III). The applicant proposed to use the NF as a food supplement. The target population proposed by the applicant is the general population from 3 years of age onwards, with maximum proposed use levels of 2 g/day for children from 3 to 9 years of age and 4 g/day thereafter. At the proposed use levels of the NF, the combined intake of chromium provided by the NF, in addition to a background diet high in chromium, would result in total chromium intakes well below the tolerable daily intake (TDI) for chromium(III) for all target population groups. The Panel concludes that the NF, chromium-enriched biomass of Y. lipolytica, is safe under the proposed conditions of use.

Safety of dried whole cell Euglena gracilis as a novel food pursuant to Regulation (EU) 2015/2283.

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of dried whole cell Euglena gracilis as a novel food (NF) pursuant to Regulation (EU) 2015/2283. E. gracilis is a single-cell microalga which occurs widely in nature and is commonly found in freshwater habitats. The NF, the dried biomass of E. gracilis, is produced by fermentation and its major constituent (> 50%) is a ß-glucan polysaccharide. The applicant proposed to use the NF in food supplements, in foods for total diet replacement for weight control and as a food ingredient added to a number of food products. The target population proposed by the applicant is the general population, except for food supplements and for foods for total diet replacement for which the target population is the general population from 12 months of age onwards. In 2019, E. gracilis was attributed the qualified presumption of safety (QPS)-status with the qualification 'for production purposes only', which includes food products based on microbial biomass of the microalga. Based on the information provided, E. gracilis is not expected to survive the manufacturing process. The submitted toxicity studies did not raise safety concerns. No adverse effects were observed in the subchronic toxicity study, up to the highest dose tested, i.e. 3,300 mg NF/kg body weight, considered as the no observed adverse effect level (NOAEL). The margins of exposure between this dose and the high (95th percentile) intake estimates, range from 33 for infants to 192 for adults. The Panel considers that in view of the QPS status of the source of the NF, supported by the compositional data and lack of toxicity observed in the 90-day study, the margins of exposure are sufficient. The Panel considers that the NF, i.e. dried whole cell Euglena gracilis, is safe at the proposed uses and use levels.

Safety of a botanical extract derived from Panax notoginseng and Astragalus membranaceus (AstraGin™) as a novel food pursuant to Regulation (EU) 2015/2283.

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on a botanical extract derived from both Panax notoginseng and Astragalus membranaceus (AstraGin™) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is a combination of an ethanol extract of the roots of A. membranaceus and a hot water extract of the roots of P. notoginseng. The NF contains 1.5-5% total saponins, 0.1-0.5% ginsenoside Rb1 and 0.01-0.1% astragaloside I. Both plants that are used to produce the NF have a long history of use, especially in traditional Chinese medicine. Information on the production process and the composition of the NF is sufficient and does not raise safety concerns. The applicant proposed to use the NF as a food supplement for the general adult population, excluding pregnant women, at a maximum daily amount of 350 mg. Taking into account these conditions of use, the Panel considers that the consumption of the NF is not nutritionally disadvantageous. The provided genotoxicity studies do not raise concerns for genotoxicity of the NF. Based on the findings of a subchronic toxicity study, supported by a subacute toxicity study, the Panel identified the overall no observed adverse effect level (NOAEL) of the NF at 100 mg/kg body weight (bw) per day. By applying an uncertainty factor of 200, the Panel concludes that the NF is safe at an intake level of 0.5 mg/kg bw per day, corresponding to a maximum daily intake of 35 mg of the NF for the target population, i.e. adults excluding pregnant women.

Safety and efficacy of astaxanthin-dimethyldisuccinate (Carophyll® Stay-Pink 10%-CWS) for salmonids, crustaceans and other fish.

Following a request from the European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the safety and efficacy of astaxanthin-dimethyldisuccinate (ATX-DMDS) for salmonids, crustaceans and other fish. The applicant has provided evidence that ATX-DMDS currently on the market complies with the conditions of authorisation for salmon and trout. ATX and ATX-DMDS are safe for salmonids, crustaceans and fish up to 100 mg ATX/kg complete diet, corresponding to 138 mg ATX-DMDS/kg. The FEEDAP Panel re-assessed the toxicological profile of ATX based on data already considered in 2014, the literature review performed by the applicant and the data available in the context of an EFSA public call for data on ATX. The acceptable daily intake (ADI) of 0.2 mg astaxanthin/kg body weight (bw) per day obtained by applying an uncertainty factor of 200 to a lowest observed adverse effect level (LOAEL) of 40 mg/kg bw per day for the increased incidence of multinucleated hepatocytes observed in a 2-year carcinogenicity study replaces the one of 0.034 mg/kg bw established by the FEEDAP Panel in 2014. The use of ATX-DMDS in the nutrition of salmonids, other fish and crustaceans up to the maximum permitted dietary level is of no concern for the safety of the consumer. No dermal or ocular risk for the users is likely to occur under practical conditions. In the absence of inhalation toxicology study, the Panel is not in the position to establish the inhalation toxicity of the additive. The use of synthetic ATX-DMDS does not pose a significant additional risk to the environment compared with natural astaxanthin. ATX-DMDS is efficacious in colouring the flesh of salmonids and other fish. ATX-DMDS is an effective pigment for crustaceans at the proposed conditions of use.

Safety of Yarrowia lipolytica yeast biomass as a novel food pursuant to Regulation (EU) 2015/2283.

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on Yarrowia lipolytica yeast biomass as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is the dried and heat-killed biomass of Yarrowia lipolytica, a yeast species that is widespread in nature and which can be found in the environment as well as in foods. The production process is sufficiently described and does not raise safety concerns. The information provided on the composition of the NF is sufficient and does not raise safety concerns. The applicant proposed to use the NF as a food supplement in the form of capsules, tablets or powder. The target population for the NF is the general population above 3 years of age. The maximum proposed daily use levels are 3 g/day for children from 3 years to less than 10 years of age and 6 g/day thereafter. Taking into account the composition of the NF and the proposed use levels, the consumption of the NF is not nutritionally disadvantageous. No relevant toxicological information was provided. The Panel considers that given the qualified presumption of safety (QPS) status for production purposes of Yarrowia lipolytica and the fact that the production process of the NF does not raise safety concerns, no toxicological studies are needed for the safety assessment of the NF. The Panel concludes that the NF, Yarrowia lipolytica yeast biomass, is safe under the proposed conditions of use.

Safety of egg membrane hydrolysate as a novel food pursuant to Regulation (EU) 2015/2283.

Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver a scientific opinion on egg membrane hydrolysate as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is a water-soluble hydrolysate of egg membrane, produced by alkaline treatment of the thin layer lining the shells of chicken eggs. The main constituents of the NF are elastin, collagen and glycosaminoglycans. The information provided on the production process, batch-to-batch variability, composition and specifications of the NF is sufficient and does not raise safety concerns. The NF is proposed to be used as a food supplement for adults, at a maximum daily amount of 450 mg. The consumption of the NF is not nutritionally disadvantageous. One human study, which was not designed for safety but included a number of endpoints pertaining to safety, did not raise safety concerns. The Panel considers that taking into account the information provided and considering the nature, the source and the production process of the NF, there are no safety concerns for the NF at the proposed conditions of use. The Panel concludes that the NF, egg membrane hydrolysate, is safe as a food supplement at a dose of 450 mg/day. The target population for the NF is the general adult population.

Safety of dried aerial parts of Hoodia parviflora as a novel food pursuant to Regulation (EC) No 258/97.

Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver a scientific opinion on the dried aerial parts of Hoodia parviflora as a novel food (NF) submitted pursuant to Regulation (EC) No 258/97. The information provided on the composition, the specifications, the production process, the batch-to-batch variability and the stability of the NF is sufficient and does not raise safety concerns. The applicant intends to use the NF in a number of energy-reduced/sugar-free/no-added-sugar foods in quantities of up to 15 mg per serving. The applicant also proposes to provide the NF as a food supplement. The target population proposed by the applicant is adults. The highest intake estimates were found in the group of elderly (≥ 65 years) individuals, with a high intake of 1.0 mg/kg body weight (bw) per day. One 90-day toxicity study in rodents was provided from which a benchmark dose lower confidence limit (BMDL 05) of 53.5 mg/kg bw per day was derived for effects of the NF on bodyweight. The Panel concludes that the addition of the NF to foods as a food ingredient at the uses and use levels as proposed by the applicant would exceed intake levels considered safe in humans. The Panel considers that the NF is safe to be used as a food supplement at a maximum dose of 9.4 mg/day. The target population is adults.

Safety of Ecklonia cava phlorotannins as a novel food pursuant to Regulation (EC) No 258/97.

Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver a scientific opinion on the safety of Ecklonia cava phlorotannins (marketed as SeaPolynol™) as a novel food submitted pursuant to Regulation (EC) No 258/97. The novel food is a phlorotannin-rich alcohol extract of Ecklonia cava, which is an edible marine brown alga species. The information provided on the composition, the specifications, the production process and the batch-to-batch variability of the novel food is sufficient and does not raise safety concerns. The intention is to market the novel food as a food supplement for healthy individuals over the age of 12 years. A subchronic repeated dose oral toxicity study in rodents tested the novel food at daily doses of 0, 375, 750 and 1,500 mg/kg body weight (bw). The Panel considers the mid-dose as the no-observed-adverse-effect-level (NOAEL) of the study. Taking into account this NOAEL of 750 mg/kg bw per day and by applying an uncertainty factor of 200, the Panel considers an intake level of 3.75 mg/kg bw per day as safe. The Panel concludes that the novel food, Ecklonia cava phlorotannins, is safe for the use in food supplements at a maximum daily intake level of 163 mg/day for adolescents from 12 to 14 years of age, 230 mg/day for adolescents above 14 years of age and 263 mg/day for adults.

Statement on the safety of synthetic l-ergothioneine as a novel food - supplementary dietary exposure and safety assessment for infants and young children, pregnant and breastfeeding women.

Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to provide a supplementary dietary exposure and safety assessment of synthetic l-ergothioneine for those groups of the population which had been excluded by the applicant in the original application, i.e. infants and young children (i.e. toddlers), pregnant and breastfeeding women. Thus, intake estimates were calculated for these population groups and the following maximum anticipated daily intakes of l-ergothioneine from the NF, in addition to the background diet, were calculated: 2.82 mg/kg body weight (bw) per day for infants, 3.39 mg/kg bw per day for toddlers and 1.31 mg/kg bw per day for adults including pregnant and breastfeeding women. The Panel considers that based on the overall toxicological data the no-observed-adverse-effect level (NOAEL) of 800 mg/kg bw per day as established in the original assessment also pertains to pregnant and breastfeeding women as well as to young children (i.e. toddlers) and infants. The corresponding margins of exposure (i.e. the ratio between the NOAEL and the maximum anticipated daily intakes) are 284 for infants, 236 for young children and 610 for pregnant and breastfeeding women. These margins of exposure are considered sufficient. The Panel concludes that the novel food, synthetic l-ergothioneine, is safe under the proposed uses and use levels for infants, young children (i.e. toddlers) and pregnant and breastfeeding women.

Conditional targeting of plectin in prenatal and adult mouse stratified epithelia causes keratinocyte fragility and lesional epidermal barrier defects.

Plectin, a widespread intermediate filament-based cytolinker protein capable of interacting with a variety of cytoskeletal structures and plasma membrane-bound junctional complexes, serves essential functions in maintenance of cell and tissue cytoarchitecture. We have generated a mouse line bearing floxed plectin alleles and conditionally deleted plectin in stratified epithelia. This strategy enabled us to study the consequences of plectin deficiency in this particular type of tissues in the context of the whole organism without plectin loss affecting other tissues. Conditional knockout mice died early after birth, showing signs of starvation and growth retardation. Blistering was observed on their extremities and on the oral epithelium after initial nursing, impairing food uptake. Knockout epidermis was very fragile and showed focal epidermal barrier defects caused by the presence of small skin lesions. Stratification, proliferation and differentiation of knockout skin seemed unaffected by epidermis-restricted plectin deficiency. In an additionally generated mouse model, tamoxifen-induced Cre-ER(T)-mediated recombination led to mice with a mosaic plectin deletion pattern in adult epidermis, combined with microblister formation and epidermal barrier defects. Our study explains the early lethality of plectin-deficient mice and provides a model to ablate plectin in adult animals which could be used for developing gene or pharmacological therapies.