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 freeze‐dried mycelia of Antrodia camphorata as a novel food pursuant to regulation (EU) 2015/2283

[EN] 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 β-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 aboveS

Safety of freeze-dried mycelia of Antrodia camphorata as a novel food pursuant to regulation (EU) 2015/2283

Requestor: European Commission Question number: EFSA-Q-2019-00759 Correspondence: [email protected] reviewedPublisher PD

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 (TM) 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 (TM), 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 (TM) 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 (TM), the applicant has now provided additional information on haematological and liver parameters for the human intervention study with EstroG-100 (TM) and historical control data related to the subchronic 90-day oral toxicity study with EstroG-100 (TM). 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 (TM) 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. (C) 2017 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority

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. (C) 2018 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.Peer reviewe

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\u2010konjac\u2010xanthan polysaccharide complex (PGX) as a novel food pursuant to Regulation (EC) No\ua0258/97

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. (C) 2017 European Food Safety Authority

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.

Peer reviewe

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.

Peer reviewe

Safety of EstroG-100 (TM) 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 EstroG-100 (TM) as a novel food (NF) submitted pursuant to Regulation (EC) No 258/97 of the European Parliament and of the Council. The NF is EstroG-100 (TM), a hot-water extract of a mixture of three herbal roots (Cynanchum wilfordii Hemsley, Phlomis umbrosa Turcz. and Angelica gigas Nakai), which is concentrated and spray-dried. The information provided on the composition, specifications and stability of the NF is sufficient, and does not raise safety concerns. The applicant intends to use EstroG-100 (TM) in food supplements, with a proposed maximum intake level of 514 mg/day. The target population is post-menopausal women. The Panel considers that the information provided does not raise safety concerns as regards the genotoxicity of the NF. The Panel considers that the no-observed-adverse effect level (NOAEL) derived from the subchronic 90-day oral toxicity study with EstroG-100 (TM), which was supported by observations in other studies, is 500 mg/kg body weight (bw) per day. Taking into account the NOAEL and the proposed maximum intake level, the Panel considers that the margin of safety of 68 is not sufficient. Based on the absence of chronic toxicity data, increase in effects with exposure duration in toxicity studies, and the absence of investigations of liver parameters and haematology in human studies, the Panel applies the uncertainty factor of 200 to derive the maximum safe intake level for the NF. Thus, the Panel concludes that the NF, EstroG-100 (TM), is safe for the use in food supplements at the maximum intake level of 175 mg/day for an adult of 70 kg bw. (C) 2016 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.Peer reviewe