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 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 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

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 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 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 β-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 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 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

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 Panelon 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 Panelconsiders 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 Panelconcludes 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

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