Safety of oil from Schizochytrium limacinum (strain TKD-1) for use in infant and follow-on formula 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 Schizochytrium sp. (TKD-1) oil as a novel food (NF) pursuant to Regulation (EU) 2015/2283. Schizochytrium sp. is a single-cell microalga. The strain TKD-1, used by the applicant (ATK Biotech Co. Ltd.), belongs to the species Schizochytrium limacinum. The NF is a mixture of triglycerides in which docosahexaenoic acid (DHA) represents 53%-61% of fatty acids. The applicant proposed to use the NF in infant formulae (IF) and follow-on formulae (FOF). The use levels proposed by the applicant were derived from Regulation (EU) 2016/127, which states the mandatory addition of DHA to IF and FOF at the level of 20-50 mg/100 kcal. S. limacinum was attributed the qualified presumption of safety (QPS) status with the qualification 'for production purposes only'. Data provided by the applicant demonstrated the absence of viable cells in the NF. No toxicological studies were performed with the NF. However, based on the available toxicological data on oils derived from Schizochytrium sp., the QPS status of the source of the NF, the production process, the composition of the NF and the absence of marine biotoxins and viable cells in the NF, the Panel considers there are no concerns with regard to toxicity of the NF. The Panel concludes that the NF is safe under the proposed conditions of use.

Safety of oil from Schizochytrium sp. (strain CABIO-A-2) for use in infant and follow-on formula 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 Schizochytrium sp. (strain CABIO-A-2) oil as a novel food (NF) pursuant to Regulation (EU) 2015/2283. S. sp. is a single-cell microalga. The NF is a mixture of triglycerides in which docosahexaenoic acid (DHA) represents 38%-44% of fatty acids. The applicant proposed to use the NF in infant formulae (IF) and follow-on formulae (FOF). The use levels proposed by the applicant were derived from Regulation (EU) 2016/127, which states the mandatory addition of DHA to IF and FOF at the level of 20-50 mg/100 kcal. The evidence provided demonstrated that the strain S. sp. CABIO-A-2 is phylogenetically closely related to the strain S. sp. ATCC 20888. The assessment of some already authorised S. sp. oils in the Union list were also based on similarities with the strain ATCC 20888. The applicant provided a 90-day repeated dose toxicity study in rats with the NF. No adverse effects were observed up to the highest dose tested, i.e. 10.2 g/kg body weight (bw) per day. Taking into account the toxicity studies performed with the NF and with DHA-oils derived from strains belonging to the genus Schizochytrium, its phylogenetical profile, the production process, the composition of the NF and the absence of marine biotoxins and viable cells in the NF, the Panel considers that there are no concerns with regard to the toxicity of the NF. The Panel concludes that the NF is safe under the proposed conditions of use.

Safety of freeze-dried mycelia of Antrodia camphorata 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 freeze-dried mycelia of Antrodia camphorata as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is produced by solid-state cultivation from tissue cultures derived from the fungus Antrodia camphorata. The applicant intends to market the NF in food supplements at a maximum dose of 990 mg per day. The target population is the general population. The NF mainly consists of carbohydrates, proteins and fats, and it contains numerous constituents, such as ß-glucans, antroquinonol and triterpenoids. Taking into account the composition of the NF and the proposed conditions of use, the consumption of the NF is not nutritionally disadvantageous. There are no concerns regarding genotoxicity of the NF. Based on a 90-day repeated dose toxicity study and a prenatal developmental toxicity study performed with the NF, the Panel derives a safe level of 16.5 mg/kg body weight per day. The Panel concludes that the NF, freeze-dried mycelia of Antrodia camphorata, is safe at the proposed use level for individuals aged 14 years and above.

Safety of oil from Schizochytrium sp. (strain ATCC 20889) for use in infant and follow-on formula 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 Schizochytrium sp. oil as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF which is the subject of the application is an oil rich in docosahexaenoic acid (DHA) that is produced by the microalgae Schizochytrium sp. (strain ATCC-20889). The applicant proposed to add the NF in infant formulae (IF) and follow-on formulae (FOF) at use levels in accordance with Regulation (EU) No 609/2013. The evidence provided by the applicant does not demonstrate to which species the strain Schizochytrium sp. ATCC 20889 belongs. As the source organism of the NF is not characterised at species level, no assessment for inclusion in the Qualified Presumption of Safety (QPS) list can be performed by EFSA. Marine biotoxins (including cyanotoxins) in the NF were below their limits of quantification. However, since it is unknown to which species the strain Schizochytrium sp. ATCC 20889 belongs, the concern that this strain has the potential to produce other toxins remains. No toxicological studies with the NF were provided by the applicant. Toxicological studies are available with DHA-rich algal oils produced from other strains of Schizochytrium sp. However, the Panel considers that those toxicological studies cannot be used to establish the safety of the oil produced by the strain which is under assessment in this application (Schizochytrium sp. ATCC 20889). Therefore, based on the information provided by the applicant, the Panel concludes that the safety of the NF has not been established.

Safety of oil from Schizochytrium limacinum (strain FCC-3204) for use in food supplements 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 Schizochytrium sp. oil as a novel food (NF) pursuant to Regulation (EU) 2015/2283. Schizochytrium sp. is a single-cell microalga. The strain FCC-3204, used by the applicant (Fermentalg), belongs to the species Schizochytrium limacinum. The NF, an oil rich in docosahexaenoic acid (DHA), is obtained from microalgae after enzymatic lysis. The applicant proposed to increase the use level of the NF as a food supplement, from 250 mg DHA/day (currently authorised for the general population, excluding pregnant and lactating women) to 3 g DHA/day for adults, excluding pregnant and lactating women. S. limacinum was attributed the qualified presumption of safety (QPS) status with the qualification 'for production purposes only'. Data provided by the applicant demonstrated the absence of viable cells in the NF. No toxicological studies were performed with the NF. However, based on the available toxicological data on oils derived from Schizochytrium sp., the QPS status of the source of the NF, the production process, the composition of the NF and the absence of viable cells in the NF, the Panel considers there are no concerns with regard to toxicity of the NF. The Panel considers that the data provided by the applicant are not sufficient to conclude on the safety of the NF at the proposed uses (3 g DHA/day as a food supplement) in adults. However, in 2012, the Panel concluded that supplemental intakes of DHA alone up to about 1 g/day do not raise safety concerns for the general population. The Panel concludes that the NF is safe for the use in food supplements at the maximum intake level of 1 g DHA/day for the target population (adults, excluding pregnant and lactating women).

Safety of oil from Schizochytrium limacinum (strain FCC-3204) for use in infant and follow-on formula 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 Schizochytrium sp. oil as a novel food (NF) pursuant to Regulation (EU) 2015/2283. Schizochytrium sp. is a single-cell microalga. The strain FCC- 3204, used by the applicant (Fermentalg), belongs to the species Schizochytrium limacinum. The NF, an oil rich in docosahexaenoic acid (DHA), is obtained from microalgae after enzymatic lysis. The applicant proposed to use the NF in infant formulae (IF) and follow-on formulae (FOF). The use level defined by the applicant was derived from Regulation (EU) 2016/127, which states the mandatory addition of DHA to IF and FOF at the level of 20-50 mg/100 kcal. The intake of DHA resulting from the use of the NF in IF and FOF is not expected to pose safety concerns. S. limacinum was attributed the qualified presumption of safety (QPS) status with the qualification 'for production purposes only'. Data provided by the applicant demonstrated the absence of viable cells in the NF. No toxicological studies were performed with the NF. However, based on the available toxicological data on oils derived from Schizochytrium sp., the QPS status of the source of the NF, the production process, the composition of the NF and the absence of viable cells in the NF, the Panel considers there are no concerns with regard to toxicity of the NF. The Panel concludes that the NF is safe under the proposed conditions of use.

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 betaine as a novel food pursuant to Regulation (EU) 2015/2283.

In 2017, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) concluded that betaine as a novel food (NF) is safe to be used at a maximum intake level of 6 mg/kg body weight per day in addition to the intake from the background diet. Following the present request from the European Commission, the EFSA NDA Panel was asked to deliver a scientific opinion on betaine by carrying out the assessment for the revised uses and use levels of betaine as proposed by the applicant. Thus, EFSA performed an intake assessment based on individual data from the EFSA Comprehensive European Food Consumption Database and the new proposed uses of the NF for the general population. The resulting ranges for the mean and high-level estimated intakes of betaine for the general population do not exceed the safe level of intake previously established. The Panel concludes that the NF, betaine, is safe under the new proposed conditions of use.

Safety of 2'-fucosyllactose/difucosyllactose mixture 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 2'-fucosyllactose/difucosyllactose (2'-FL/DFL) mixture as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is a powdered mixture mainly composed of two oligosaccharides, 2'-FL and DFL, which are produced together by fermentation with a genetically modified strain of Escherichia coli K12. The information provided on the manufacturing process, composition and specifications of the NF does not raise safety concerns. The applicant intends to add the NF in a variety of foods, including infant and follow-on formula, foods for infants and young children, foods for special medical purposes and food supplements. The target population is the general population except for food supplements, for which the target population is individuals above 1 year of age. Since the intake of 2'-FL and DFL from the NF at the proposed use levels is unlikely to exceed the intake level of naturally occurring 2'-FL and DFL in breastfed infants per kilogram body weight, the Panel concludes that the NF, a mixture of 2'-FL and DFL, is safe under the proposed conditions of use for the proposed target population.

Safety of xylo-oligosaccharides (XOS) 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 a mixture of xylo-oligosaccharides (XOS) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is obtained from corncobs (Zea mays subsp. mays) via enzyme-catalysed hydrolysis and subsequent purification. The main components of the NF, the oligosaccharides, are resistant to human digestive enzymes and are fermented by colonic bacteria. The intention is to add the NF to a variety of foods such as bakery and dairy products, fruit jelly, chocolates and soy-drinks. The information provided on composition, specifications, production process and stability of the NF, does not raise safety concerns. There were effects observed in the animal studies with the NF or with other XOS which were considered by the Panel to be expected from the intake of non-digestible carbohydrates. The Panel notes that the acute and transient gastrointestinal observed in human intervention studies with the NF or with other XOS have also been associated with the consumption of other non-digestible carbohydrates. The Panel concludes that the NF, a mixture of XOS, is safe under the proposed uses and use levels. The target population is the general population.

Safety of betaine 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 an opinion on betaine as a novel food (NF) pursuant to Regulation (EC) No 258/97. The information provided on the composition, the specifications, the batch-to-batch variability, stability and production process of the NF is sufficient and does not raise concerns about the safety of the NF. The NF is proposed to be used in foods intended to meet additional requirements for intense muscular effort with a maximum intake of 2.5 g/day of betaine for sports people above 10 years of age. Based on the lowest BMDL05, which was derived from a chronic toxicity study in rats in which a dose-related increase in platelet counts was observed, and the anticipated daily intake of the NF in the target population, the Margins of Exposure are 3.6 and 5, which are generally regarded as not sufficient. However, the total exposure to betaine from the diet (about 830 mg/day) is not known to be associated with adverse effects. Moreover, no adverse effects on platelet counts were noted in human intervention studies with exposure levels of 4 g/day of betaine for up to 6 months. A significant increase in total and low-density lipoprotein (LDL)-cholesterol concentrations was noted at intakes of 4 g/day of betaine in overweight subjects with metabolic syndrome but not in healthy subjects, nor at intakes of 3 g/day. Thus, considering 4 g/day of betaine as a reference point and applying an uncertainty factor of 10 to account for interindividual variability, an amount of 400 mg/day of betaine (i.e. 6 mg/kg body weight (bw) per day for adults) in addition to the background exposure is considered as safe. The Panel considers that the NF is safe to be used at maximum intake of 6 mg/kg bw per day in the target population.

Safety of hydroxytyrosol 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 an opinion on hydroxytyrosol, which is chemically synthesised, as a novel food (NF) pursuant to Regulation (EC) No 258/97. The information provided on the composition, specifications, batch-to-batch variability, stability and production process of the NF is sufficient and does not raise concerns about the safety of the NF. The applicant intends to add hydroxytyrosol to fish and vegetable oils up to 215 mg/kg and to margarines up to 175 mg/kg. The target group is the general population which excludes children under 36 months of age, pregnant women and breastfeeding women. Considering the no observed adverse effect level (NOAEL) of 50 mg/kg body weight per day from a subchronic oral toxicity study with the NF and the maximum anticipated daily intake for the NF, the margin of exposure (MoE) would result in 100 for children (3-9 years of age) and at least 200 for adolescents, adults (excluding pregnant and breastfeeding women) and elderly. Taking into account that the anticipated daily intake of the NF would be in the range of or even less than the exposure of hydroxytyrosol from the consumption of olive oils and olives, which has not been associated with adverse effects, and considering the similar kinetics of hydroxytyrosol in rats and humans, the Panel considers that the MoE for the NF at the intended uses and use levels is sufficient for the target population. The Panel concludes that the novel food, hydroxytyrosol, is safe under the proposed uses and use levels.

Safety of alginate-konjac-xanthan polysaccharide complex (PGX) 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 alginate-konjac-xanthan polysaccharide complex (PGX) as a novel food (NF) submitted pursuant to Regulation (EC) No 258/97. The NF is an off-white granular powder composed of three non-starch polysaccharides: konjac glucomannan, xanthan gum and sodium alginate. The information provided on the composition, the specifications, the batch-to-batch variability and the stability of the NF is sufficient and does not raise safety concerns. The production process is sufficiently described and does not raise concerns about the safety of the NF. The applicant intends to add the NF to a variety of foods as well as to market the NF in capsules. The recommended maximum daily intake of the NF from fortified foods and food supplements is 15 g. The target population proposed by the applicant is adults from 18 to 64 years of age. Considering the no observed adverse effect level of 1.8 g/kg body weight (bw) per day in a subchronic toxicity study with PGX and the highest mean and 95th percentile anticipated daily intake of NF from fortified foods, the margin of exposure (MoE) is 12 and 6, respectively, whereas the MoE for the NF from food supplements is 9. The Panel concludes that the safety of the novel food, PGX, for the intended uses and use levels as proposed by the applicant, has not been established.

Statement on the safety of EstroG-100™ 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 update its scientific opinion on the safety of EstroG-100™ as a novel food (NF) in the light of additional information submitted by the applicant. In its previous scientific opinion of 2016, the Panel concluded that EstroG-100™, which is a hot-water extract of a mixture of three herbal roots, is safe for the use in food supplements at the maximum intake level of 175 mg/day in post-menopausal women, which is lower than the maximum intake level proposed by the applicant (514 mg/day). The Panel reached its conclusions based on the effects of EstroG-100™ on liver and haematology as observed in several oral toxicity studies, the lack of information on liver and haematological parameters in human studies and the absence of chronic toxicity data. In view of the Panel's conclusion on the safety of EstroG-100™, the applicant has now provided additional information on haematological and liver parameters for the human intervention study with EstroG-100™ and historical control data related to the subchronic 90-day oral toxicity study with EstroG-100™. After assessing the additional information provided by the applicant, the Panel considers that the conclusion of the scientific opinion on the safety of EstroG-100™ does not need to be revised, and thus, the Panel reconfirms that the NF is safe for the use in food supplements at the maximum intake level of 175 mg/day in post-menopausal women.

Safety of synthetic N-acetyl-d-neuraminic acid 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 synthetic N-acetyl-d-neuraminic acid (NANA) as a novel food (NF) submitted pursuant to Regulation (EC) No 258/97. The information on the composition, the specifications, the batch-to-batch variability, stability and production process of the NF is sufficient and does not raise concerns about the safety of the NF. The NF is intended to be marketed as an ingredient in formulae and foods for infants and young children as well as an ingredient in a variety of foods and in food supplements for the general population. NANA is naturally present in human milk, in a bound and free form. The Margin of Exposure, which was based on the no-observed-adverse effect level (NOAEL) of 493 mg/kg body weight (bw) per day from a subchronic study and the anticipated daily intake of the NF, was considered to be sufficient for fortified foods for the general population and for food supplements for individuals above 10 years of age, as the anticipated daily intake was in the range of the exposure to free NANA from the consumption of early human milk, which is considered to be safe. The Panel concludes that the NF is safe when added to foods other than food supplements at the proposed uses and use levels for the general population; is safe in food supplements alone at the proposed uses and use levels for individuals above 10 years of age; is safe at the combined intake from fortified foods plus food supplements in individuals above 10 years of age; the safety of the NF is not established in food supplements alone at the proposed uses and use levels for individuals below 10 years of age.