The European Union (EU) is committed to transitioning toward a circular economy model, with food waste being one of the areas to be targeted. To close the loop of food waste generated during food processing and discarded at the retail or consumption phases, research and innovation parties proposed to valorize agro-food by-products to produce novel foods and food improvement agents (food additives, food enzymes, and food flavorings). In the EU, the authorization of such novel foods and food improvement agents is governed by different regulatory frameworks. A centralized safety assessment by the European Food Safety Authority (EFSA) is the prerequisite for their authorization through the so-called Union Lists. Up to December 2023, EFSA published 45 scientific opinions on the safety of novel foods, food enzymes, and food additives derived from by-products of plant and animal origin. The current study illustrates examples of these by-products for the production of novel foods or food improvement agents and the data requirements behind their respective safety assessments conducted by EFSA. In this review, applications on novel foods, food enzymes, and food additives received by EFSA were screened and analyzed to find the common scientific requirements and differences in terms of the safety evaluation of such products. Various by-products (i.e., corncobs, coffee husks, spent grains of barley and rice, grape pomace, pumpkin peels, bovine whey, eggshells, shrimp heads, and animal organs or tissues) were described in the applications as being processed (extraction, physical treatments, and chemical and enzymatic reactions) to obtain novel foods and food improvement agents. The heterogeneity and complexity of these products emphasize the challenge of their safety assessment, depending on the characteristics of each product. However, as this study shows, the scientific requirements underpinning their safety do not differ substantially in the different regulated product areas considered, with similar information needed to assess their safety in terms of identity, production process, compositional characterization, proposed/intended uses and exposure assessment, toxicological information, and allergenicity data. Additional nutritional information and data on the history of use are required in the case of novel foods.
The food enzyme carboxypeptidase D (EC 3.4.16.6) is produced with the genetically modified Aspergillus oryzae strain NZYM-MK by Novozymes A/S. It is free from viable cells of the production organism and its DNA. The genetic modifications do not give rise to safety concerns. The food enzyme is intended to be used in five food manufacturing processes. Dietary exposure to the food enzyme-total organic solids (TOS) was estimated to be up to 0.908 mg TOS/kg body weight (bw) per day in European populations. Genotoxicity tests did not indicate a safety concern. The systemic toxicity was assessed by means of a repeated dose 90-day oral toxicity study in rats. The Panel identified a no observed adverse effect level of 2220 mg TOS/kg bw per day, the highest dose tested, which, when compared with the estimated dietary exposure, resulted in a margin of exposure of at least 2445. A search for the similarity of the amino acid sequence of the food enzyme to known allergens was made and two matches were found, one with a food allergen (wheat). The Panel considered that a risk of allergic reactions upon dietary exposure to this food enzyme, particularly in individuals sensitised to wheat, cannot be excluded, but will not exceed that of wheat consumption. Based on the data provided, the Panel concluded that this food enzyme does not give rise to safety concerns under the intended conditions of use.
The food enzyme sucrose phosphorylase (sucrose: phosphate α- d-glucosyltransferase; EC 2.4.1.7) is produced with the genetically modified Escherichia coli strain LE1B109-pPB129 by c-LEcta GmbH. The genetic modifications do not give rise to safety concerns. The food enzyme was free from viable cells of the production organism. It is intended to be used in combination with a cellobiose phosphorylase in the production of the specialty carbohydrate cellobiose. Since residual amounts of food enzyme-total organic solids are removed by the downstream purification steps, the Panel considered that toxicological studies other than assessment of allergenicity were unnecessary and a dietary exposure was not estimated. A search for the similarity of the amino acid sequence of the food enzyme to known allergens was made and no match was found. The Panel considered that the risk of allergic reactions upon dietary exposure cannot be excluded, but the likelihood is low. Based on the data provided, the Panel concluded that this food enzyme does not give rise to safety concerns under the intended conditions of use.
The food enzyme α-amylase (4-α-d-glucan glucanohydrolase; EC 3.2.1.1) is produced with the non-genetically modified microorganism Bacillus licheniformis strain AE-TA by Amano Enzyme Inc. The food enzyme is intended to be used in eight food manufacturing processes. Since residual amounts of food enzyme-total organic solids (TOS) are removed in two food manufacturing processes, dietary exposure was calculated only for the remaining six processes. It was estimated to be up to 0.056 mg TOS/kg body weight per day in European populations. The production strain of the food enzyme fulfils the requirements for the qualified presumption of safety approach to safety assessment. Consequently, in the absence of other concerns, the Panel considered that toxicological studies were not needed for the safety assessment of this food enzyme. A search for the similarity of the amino acid sequence of the food enzyme to known allergens was made and two matches with respiratory allergens were found. The Panel considered that the risk of allergic reactions upon dietary exposure to this food enzyme cannot be excluded (except for the production of distilled alcohol), but the likelihood is low. Based on the data provided, the Panel concluded that this food enzyme does not give rise to safety concerns under the intended conditions of use.
The food enzyme cellobiose phosphorylase (cellobiose: phosphate α-d-glucosyltransferase; EC 2.4.1.20) is produced with the genetically modified Escherichia coli strain LE1B109-pPB130 by c-LEcta GmbH. The genetic modifications do not give rise to safety concerns. The food enzyme is considered free from viable cells of the production organism and its DNA. It is intended to be used in combination with a sucrose phosphorylase in the production of the specialty carbohydrate cellobiose. Since residual amounts of total organic solids are removed by downstream purification steps, the Panel considered that toxicological studies other than assessment of allergenicity were unnecessary and a dietary exposure was not estimated. A search for similarity of the amino acid sequence of the food enzyme to known allergens was made and no match was found. The Panel considered that, under the intended conditions of use, the risk of allergic reactions upon dietary exposure cannot be excluded, but the likelihood is low. Based on the data provided, the Panel concluded that this food enzyme does not give rise to safety concerns under the intended conditions of use.
This assessment addresses a food enzyme preparation consisting of the immobilised non-viable cells of the non-genetically modified bacterium identified by the applicant (Samyang Corporation) as Microbacterium foliorum strain SYG27B. This strain produces the enzyme D-psicose 3-epimerase (EC 5.1.3.30). The food enzyme preparation is used for the isomerisation of fructose to produce the speciality carbohydrate D-allulose (synonym D-psicose). Since the hazard identification and characterisation could not be made and the identity of the production organism could not be established, the Panel was unable to complete the assessment of this food enzyme preparation containing D-psicose 3-epimerase.
The food enzyme mucorpepsin (EC 3.4.23.23) is produced with the non-genetically modified Rhizomucor miehei strain LP-N836 by Meito Sangyo Co., Ltd. The native enzyme can be chemically modified to produce a more thermolabile form. The food enzyme is free from viable cells of the production organism. It is intended to be used in the processing of dairy products for the production of cheese and fermented dairy products. Dietary exposure to the food enzyme-total organic solids (TOS) was estimated to be up to 0.108 mg TOS/kg body weight (bw) per day in European populations. Genotoxicity tests did not indicate a safety concern. The systemic toxicity was assessed by means of a repeated dose 90-day oral toxicity study in rats. The Panel identified a no observed adverse effect level of 95 mg TOS/kg bw per day, the mid-dose tested, which when compared with the estimated dietary exposure, resulted in a margin of exposure of at least 880. A search for the similarity of the amino acid sequence of the food enzyme to known allergens was made and four matches with respiratory allergens and one with a food allergen (mustard) were found. The Panel considered that the risk of allergic reactions upon dietary exposure to this food enzyme, particularly in individuals sensitised to mustard proteins, cannot be excluded. Based on the data provided, the Panel concluded that both the native and thermolabile forms of this food enzyme do not give rise to safety concerns under the intended conditions of use.
The food enzyme mucorpepsin (EC 3.4.23.23) is produced with the non-genetically modified Rhizomucor miehei strain M19-21 by Meito Sangyo Co., Ltd. The enzyme is chemically modified to produce a thermolabile form. The food enzyme was considered free from viable cells of the production organism. It is intended to be used in the processing of dairy products for the production of cheese and fermented dairy products. Based on the maximum use levels, dietary exposure was estimated to be up to 0.108 mg TOS/kg body weight (bw) per day in European populations. Genotoxicity tests did not indicate a safety concern. The systemic toxicity was assessed by means of a repeated dose 90-day oral toxicity study in rats. The Panel identified a no observed adverse effect level of 226 mg TOS/kg bw per day, the highest dose tested, which, when compared with the estimated dietary exposure, results in a margin of exposure of at least 2093. A search for the similarity of the amino acid sequence of the food enzyme to known allergens was made and four matches to respiratory allergens and one match to a food allergen (mustard) were found. The Panel considered that the risk of allergic reactions upon dietary exposure to this food enzyme, particularly in individuals sensitised to mustard proteins, cannot be excluded. Based on the data provided, the Panel concluded that this food enzyme does not give rise to safety concerns, under the intended conditions of use.
The food enzyme microbial collagenase (EC 3.4.24.3) is produced with the genetically modified Streptomyces violaceoruber strain pCol by Nagase (Europa) GmbH. The genetic modifications do not give rise to safety concerns. The food enzyme is free from viable cells of the production organism and its DNA. It is intended to be used in two food manufacturing processes: the production of modified meat and fish products and the production of protein hydrolysates from meat and fish proteins. The dietary exposure to the food enzyme-total organic solids (TOS) was estimated to be up to 1.098 mg TOS/kg body weight (bw) per day in European populations. Genotoxicity tests did not indicate a safety concern. The systemic toxicity was assessed by means of a repeated dose 90-day oral toxicity study in rats. The Panel identified a no observed adverse effect level of 940 mg TOS/kg bw per day, the highest dose tested, which, when compared with the estimated dietary exposure, resulted in a margin of exposure of at least 856. A search for the similarity of the amino acid sequence of the food enzyme to known allergens was made and no match was found. The Panel considered that the risk of allergic reactions by dietary exposure cannot be excluded, but the likelihood is low. Based on the data provided, the Panel concluded that this food enzyme does not give rise to safety concerns, under the intended conditions of use.
The food enzyme endo-1,4-ß-xylanase (4-ß-d-xylan xylanohydrolase, EC 3.2.1.8) is produced with the genetically modified Bacillus velezensis strain AR-112 by AB Enzymes GmbH. The genetic modifications do not give rise to safety concerns. The food enzyme is free from viable cells of the production organism and its DNA. It is intended to be used in baking processes. Dietary exposure to the food enzyme-total organic solids (TOS) was estimated to be up to 0.024 mg TOS/kg body weight (bw) per day in European populations. As the production strain B. velezensis strain AR-112 meets the requirements for the qualified presumption of safety (QPS) approach to safety assessment and no issue of concern arose from the production process, no toxicological data are required. A search for the similarity of the amino acid sequence of the food enzyme to known allergens was made and no match was found. The Panel considered that, under the intended conditions of use, the risk of allergic reactions upon dietary exposure cannot be excluded, but the likelihood is low. Based on the data provided, the Panel concluded that this food enzyme does not give rise to safety concerns under the intended conditions of use.
The food enzyme leucyl aminopeptidase (EC 3.4.11.1) is produced with the non-genetically modified Aspergillus sp. strain AE-MB by Amano Enzyme Inc. The food enzyme is considered free from viable cells of the production organism. It is intended to be used in five food manufacturing processes: processing of dairy products for the production of (1) flavouring preparations; processing of plant- and fungal-derived products for the production of (2) protein hydrolysates; processing of meat and fish products for the production of (3) protein hydrolysates, (4) modified meat and fish products and processing of (5) yeast and yeast products. Dietary exposure to the food enzyme-total organic solids (TOS) was estimated to be up to 2.273 mg TOS/kg body weight (bw) per day in European populations. Genotoxicity tests did not indicate a safety concern. The systemic toxicity was assessed by means of a repeated dose 90-day oral toxicity study in rats. The Panel identified a no observed adverse effect level of 183 mg TOS/kg bw per day. The calculated margin of exposure for each age group was 135 (infants), 81 (toddlers), 83 (children), 109 (adolescents), 160 (adults) and 184 (the elderly). A search for the similarity of the amino acid sequence of the food enzyme to known allergens was made and no matches were found. The Panel considered that the risk of allergic reactions by dietary exposure cannot be excluded, but the likelihood is low. The safety of the food enzyme could not be established given the derived margins of exposure. Therefore, the Panel concluded that this food enzyme could not be considered safe under the intended conditions of use.
The food enzyme phosphoinositide phospholipase C (1-phosphatidyl-1D-myo-inositol-4,5-bisphosphate inositoltrisphosphohydrolase EC 3.1.4.11.) is produced with the genetically modified Pseudomonas fluorescens strain PIC by DSM Food specialties B.V. The genetic modifications do not give rise to safety concerns. The food enzyme is free from viable cells of the production organism and its DNA. It is intended to be used in the processing of fats and oils for the production of refined edible fats and oils by degumming. Since residual amounts of the total organic solids are removed by the washing and purification steps applied during degumming, dietary exposure estimation and toxicity testing were considered unnecessary. A search for the similarity of the amino acid sequence of the food enzyme to known allergens was made and no matches were found. The Panel considered that the risk of allergic reactions by dietary exposure cannot be excluded, but the likelihood for this to occur is low. Based on the data provided, the Panel concluded that this food enzyme does not give rise to safety concerns under the intended conditions of use.
The food enzyme α-amylase (4-α-d-glucan glucanohydrolase; EC 3.2.1.1) is produced with the non-genetically modified Bacillus amyloliquefaciens strain NZYM-WR by Novozymes A/S. The production strain met the requirements for the qualified presumption of safety (QPS) approach. The food enzyme is intended to be used in nine food manufacturing processes: processing of cereals and other grains for the production of baked products, cereal-based products other than baked, glucose syrups and other starch hydrolysates, distilled alcohol and brewed products; production of refined and unrefined sugar, production of plant-based analogues of milk and milk products; processing of fruits and vegetables for the production of juices and fruit and vegetable products other than juices. Since residual amounts of total organic solids (TOS) are removed during two processes, a dietary exposure was calculated only for the remaining seven food manufacturing processes. Exposure was estimated to be up to 0.450 mg TOS/kg body weight per day in European populations. As the production strain qualified for the QPS approach and no issues of concern arose from the production process of the food enzyme, the Panel considered that toxicological studies were unnecessary. A search for the similarity of the amino acid sequence of the food enzyme to known allergens was made and one match with a respiratory allergen was found. The Panel considered that the risk of allergic reactions upon dietary exposure to this food enzyme cannot be excluded (except for distilled alcohol production), but the likelihood is low. Based on the data provided, the Panel concluded that this food enzyme does not give rise to safety concerns under the intended conditions of use.
The food enzyme α-amylase (1,4-α-d-glucan glucanohydrolase; EC 3.2.1.1) is produced with the genetically modified Bacillus licheniformis strain NZYM-AC by Novozymes A/S. The genetic modifications do not give rise to safety concerns and the production strain meets the requirements for the qualified presumption of safety (QPS) approach. The food enzyme was considered free from viable cells of the production organism and its DNA. It is intended to be used in seven food manufacturing processes: processing of cereals and other grains for the production of glucose syrups and other starch hydrolysates, cereal-based products other than baked, brewed products and distilled alcohol; processing of fruits and vegetables for the production of juices and products other than juices; production of refined and unrefined sugars. Since the residual amounts of total organic solids (TOS) are removed during two processes, dietary exposure was calculated only for the remaining five food manufacturing processes. It was estimated to be up to 0.167 mg TOS/kg body weight (bw) per day in European populations. Given the QPS status of the production strain and the lack of concerns resulting from the food enzyme manufacturing process, toxicological studies were not considered necessary. A search for similarity of the amino acid sequence of the food enzyme to known allergens was made and one match was found with a respiratory allergen. The Panel considered that the risk of allergic reactions by dietary exposure cannot be excluded (except for distilled alcohol production), but the likelihood is low. Based on the data provided, the Panel concluded that this food enzyme does not give rise to safety concerns, under the intended conditions of use.
The food enzyme bacillolysin (EC 3.4.24.28) is produced with the non-genetically modified Bacillus amyloliquefaciens strain HPN 131 by ENMEX SA de CV. The production strain qualifies for the qualified presumption of safety (QPS) approach to safety assessment. The food enzyme under assessment is intended to be used in seven food manufacturing processes: processing of cereals and other grains for the production of baked products, brewed products and distilled alcohol; processing of dairy products for the production of modified milk proteins; processing of meat and fish products for the production of protein hydrolysates; processing of plant- and fungal-derived products for the production of protein hydrolysates; processing of yeasts and yeast products. Since residual amounts of total organic solids (TOS) are not carried over to distilled alcohol, a dietary exposure was estimated only for the remaining six food manufacturing processes. Exposure was estimated to be up to 8.302 mg TOS/kg body weight (bw) per day in European populations. As the production strain qualifies for the QPS status and no issue of concern arose from the production process of the food enzyme, the Panel considered that no toxicological studies other than the assessment of allergenicity were necessary. A search for the similarity of the amino acid sequence of the food enzyme to known allergens was made and no matches were found. The Panel considered that the risk of allergic reactions by dietary exposure cannot be excluded (except for distilled alcohol production), but the likelihood is low. Based on the data provided, the Panel concluded that this food enzyme does not give rise to safety concerns under the intended conditions of use.
The food enzyme endo-polygalacturonase ((1â4)-α-d-galacturonan glycanohydrolase (endo-cleaving); EC 3.2.1.15)) is produced with the non-genetically modified Aspergillus tubingensis strain MUCL 55013 by Soufflet Biotechnologies. The food enzyme is free from viable cells of the production organism. It is intended to be used in 10 food manufacturing processes: processing of fruits and vegetables for the production of juices, other fruit and vegetable products, wine, distilled spirits from wine, alcoholic beverages other than grape wine; processing of plant-derived products for the production of refined and unrefined sugar, edible oils from plants, green coffee beans by demucilation, coffee extracts and tea and other herbal and fruit infusions. Since residual amounts of total organic solids (TOS) are removed in three processes, dietary exposure was calculated only for the remaining seven food manufacturing processes. Exposure was estimated to be up to 7.834 mg TOS/kg body weight (bw) per day in European populations. Genotoxicity tests did not indicate a safety concern. The systemic toxicity was assessed by a repeated dose 90-day oral toxicity study in rats. The Panel identified a no observed adverse effect level of 2,097 mg TOS/kg bw per day, the highest dose tested, resulting in a margin of exposure of at least 268. A search for the similarity of the amino acid sequence of the food enzyme to known allergens found 14 matches, one of which was to a food allergen. The Panel considered that the risk of allergic reactions upon dietary exposure to this food enzyme cannot be excluded, in particular for individuals sensitised to papaya, but that the risk will not exceed that of consumption of papaya. In addition, oral allergy reactions cannot be excluded in pollen-sensitised individuals. Based on the data provided, the Panel concluded that this food enzyme does not give rise to safety concerns, under the intended conditions of use.
The food enzyme bacillolysin (EC 3.4.24.28) is produced with the non-genetically modified Bacillus amyloliquefaciens strain AGS 430 by Kerry Ingredients & Flavours Ltd. The production strain qualifies for the qualified presumption of safety (QPS) approach to safety assessment. The food enzyme is intended to be used in 11 food manufacturing processes: processing of cereals and other grains for the production of baked products; cereal-based products other than baked; brewed products; starch and gluten fractions; distilled alcohol; processing of dairy products for the production of flavouring preparations and modified milk proteins; processing of meat and fish products for the production of protein hydrolysates; processing of plant- and fungal-derived products for the production of protein hydrolysates and plant-based analogues of milk and milk products; processing of yeast and yeast products. Since residual amounts of the total organic solids (TOS) are removed during two processes, dietary exposure was estimated only for the remaining nine food manufacturing processes. Exposure was estimated up to 3.482 mg TOS/kg body weight (bw) per day in European populations. As the production strain qualifies for the QPS approach and no issue of concern arose from the production process of the food enzyme, the Panel considered that no toxicological studies other than the assessment of allergenicity were necessary. A search for the similarity of the amino acid sequence of the food enzyme to known allergens was made and no match was found. The Panel considered that the risk of allergic reactions upon dietary exposure cannot be excluded (except for distilled alcohol production), but the likelihood is low. Based on the data provided, the Panel concluded that this food enzyme does not give rise to safety concerns under the intended conditions of use.
The food enzyme bacillolysin (EC 3.4.24.28) is produced with the non-genetically modified Bacillus amyloliquefaciens strain GNP by DSM Food Specialties B.V. The production strain qualifies for the qualified presumption of safety (QPS) approach to safety assessment. The food enzyme is intended to be used in nine food manufacturing processes: processing of cereals and other grains for the production of baked products, cereal-based products other than baked, brewed products and distilled alcohol; processing of dairy products for the production of flavouring preparation and modified milk proteins; processing of meat and fish products for the production of protein hydrolysates; processing of plant- and fungal-derived products for the production of protein hydrolysates and plant-based analogues of milk and milk products. Since the food enzyme-total organic solids (TOS) is not carried into distilled alcohols, dietary exposure was estimated only to the remaining eight food processes. Exposure was estimated to be up to 17.934 mg TOS/kg body weight per day in European populations. As the production strain qualifies for the QPS approach to safety assessment and no issue of concern arose from the production process, no toxicological studies other than the assessment of allergenicity were required. A search for the similarity of the amino acid sequence of the food enzyme to known allergens was made and no match was found. The Panel considered that the risk of allergic reactions upon dietary exposure cannot be excluded (except for distilled alcohol production), but the likelihood is low. Based on the data provided, the Panel concluded that this food enzyme does not give rise to safety concerns, under the intended conditions of use.
The food enzyme containing triacylglycerol lipase (triacylglycerol acylhydrolase; EC 3.1.1.3) is prepared from the pregastric tissues of calves, young goats and lambs by Caglificio Clerici SpA. The food enzyme is intended to be used in the production of cheese. As no concerns arose from the animal source of the food enzyme, from its manufacture and based on the history of safe use and consumption, the Panel considered that toxicological data were not required and no exposure assessment was necessary. A search for the similarity of the amino acid sequence of the food enzyme to known allergens was made and no match was found. The Panel considered that a risk of allergic reactions upon dietary exposure cannot be excluded, but the likelihood is low. Based on the data provided, the Panel concluded that this food enzyme does not give rise to safety concerns under the intended conditions of use.
The lipid-lowering effect of dry beans and their impact on lipid and cholesterol metabolism have been established. This study investigates the underlying mechanisms of this effect and explore how the structural integrity of processed beans influences their ability to modulate lipolysis using the INFOGEST static in vitro digestion model. Dietary fiber (DF) fractions were found to decrease lipolysis by increasing the digesta viscosity, leading to depletion-flocculation and/or coalescence of lipid droplets. Bean flours exhibited a more pronounced reduction in lipolysis compared to DF. Furthermore, different levels of bean structural integrity showed varying effects on modulating lipolysis, with medium-sized bean particles demonstrating a stronger reduction. Hydrothermal treatment compromised the ability of beans to modulate lipid digestion, while hydrostatic-pressure treatment (600 MPa/5min) enhanced the effect. These findings highlight that the lipid-lowering effect of beans is not solely attributed to DF but also to the overall bean matrix, which can be manipulated through processing techniques.
Phaseolus , Phaseolus/chemistry , Dietary Fiber/metabolism , Lipolysis , Lipids , Digestion
