Safety of the feed additive consisting of vitamin B2/riboflavin (produced by Bacillus subtilis KCCM 10445) for all animal species (Hubei Guangji Pharmaceutical Co. Ltd.).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the characterisation and safety of vitamin B2/riboflavin produced by fermentation with a genetically modified strain of Bacillus subtilis (KCCM 10445) as a nutritional additive in feed and water for drinking for all animal species. In 2021, the FEEDAP Panel issued an opinion on the safety and efficacy of vitamin B2 98% and vitamin B2 80% in the form of riboflavin produced by B. subtilis KCCM 10445. In that assessment, the Panel could not confirm the correspondence of the deposited strain under accession number KCCM 10445 with the strain used for production owing to discrepancies in the description of the genetic modification steps. Moreover, in the absence of data, no conclusions on the skin sensitisation potential of vitamin B2 98% and vitamin B2 80% nor on the possible risk by inhalation of vitamin B2 98% could be reached. For the present assessment, the applicant provided supplementary information to partially address the limitations identified in that assessment. Based on the results of a bioinformatic analysis between the strain deposited under accession number KCCM 10445 with the strain used for production under assessment, the Panel confirmed the correspondence between the two strains. As no new data have been submitted on the safety of the additives, the conclusions from the Panel remain that the use of vitamin B2/riboflavin produced by B. subtilis KCCM 10445 is safe for the target species, the consumer and the environment. Vitamin B2 80% is not hazardous by inhalation. In the absence of data, no conclusions on the possible risk by inhalation of vitamin B2 98% could be reached. Neither the vitamin B2 98% nor the vitamin B2 80% are irritant to skin or eyes. In the absence of data, no conclusions on the skin sensitisation potential of the additives could be reached.

Safety and efficacy of a feed additive consisting of concentrated liquid l-lysine, l-lysine monohydrochloride and concentrated liquid l-lysine monohydrochloride produced by Escherichia coliNITE BP-02917 for all animal species (Metex NoovistaGo).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of concentrated liquid l-lysine, l-lysine monohydrochloride and concentrated liquid l-lysine monohydrochloride produced by Escherichia coli NITE BP-02917 as nutritional and as sensory (flavouring compound) feed additives for all animal species. The production strain did not carry ■■■■■ antimicrobial resistance genes and no viable cells of the production strain were detected in the final products. ■■■■■ However, since no sequences of concern remained in the production strain, the potential presence of that DNA did not raise safety concerns. The use of the three forms of l-lysine produced by E. coli NITE BP-02917 in supplementing feed to compensate for l-lysine deficiency in feedingstuffs was safe for the target species. This conclusion would also cover the use as a sensory additive. The FEEDAP Panel identified risks of nutritional imbalances and hygienic concerns for amino acids when administered simultaneously in feed and in water for drinking. The use of the three forms of l-lysine produced by E. coli NITE BP-02917 in animal nutrition was considered safe for the consumers and for the environment. Concentrated liquid l-lysine, l-lysine HCl and concentrated liquid l-lysine HCl were not considered to have the potential to cause respiratory toxicity, or skin sensitisation. l-Lysine HCl and concentrated liquid l-lysine HCl were not considered skin and eye irritants. Concentrated liquid l-lysine, due to its high pH, might be corrosive for skin and eyes. The three forms were considered an efficacious source of the essential amino acid l-lysine for non-ruminant animal species. For the supplemental l-lysine to be as efficacious in ruminants as in non-ruminant species, it would require protection against degradation in the rumen. The three forms of the additive were also considered efficacious as feed flavouring compounds under the proposed conditions of use.

Safety and efficacy of a feed additive consisting of l-lysine monohydrochloride and l-lysine sulfate produced by fermentation with Corynebacterium glutamicumCGMCC 17927 for all animal species (Barentz Animal Nutrition B.V.).

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 l-lysine monohydrochloride and l-lysine sulfate produced by Corynebacterium glutamicum CGMCC 17927, when used as a nutritional additive in feed and water for drinking for all animal species. The active substance is l-lysine, and it was produced in two different forms: monohydrochloride (HCl) or sulfate salts. The production strain was genetically modified. Neither viable cells nor recombinant DNA of the production strain were detected in the final products. Therefore, the Panel concluded that the additives did not pose any safety concern regarding the production strain. The use of l-lysine HCl and l-lysine sulfate produced by the strain C. glutamicum CGMCC 17927 in supplementing feed to compensate for l-lysine deficiency in feedingstuffs was safe for the target species. The FEEDAP Panel identified risks of nutritional imbalances and hygienic concerns for amino acids when administered simultaneously in feed and in water for drinking. The use of both forms of l-lysine produced by fermentation using C. glutamicum CGMCC 17927 in animal nutrition was considered safe for the consumers and for the environment. Exposure of users through inhalation to l-lysine HCl and l-lysine sulfate produced with C. glutamicum CGMCC 17927 was considered very likely. In absence of data, the FEEDAP Panel could not conclude on the potential of both forms of the additive to be irritant for skin and eyes or to be dermal sensitisers. l-Lysine HCl and l-lysine sulfate were considered as efficacious sources of the essential amino acid l-lysine for non-ruminant animal species. For the supplemental l-lysine to be as efficacious in ruminants as in non-ruminant species, it would require protection against degradation in the rumen.

Safety and efficacy of a feed additive consisting of l-arginine (produced by Corynebacterium glutamicum CGMCC 20516) for all animal species (Eppen Europe SAS).

Following a request from the European Commission, the EFSA 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 the feed additive consisting of l-arginine produced by fermentation using a non-genetically modified strain of Corynebacterium glutamicum (CGMCC 20516). The additive is intended to be used in feed and water for drinking for all animal species and categories. The production strain was considered suitable for the qualified presumption of safety (QPS) approach to safety assessment. No viable cells of C. glutamicum CGMCC 20516 were detected in the final product. l-Arginine produced using C. glutamicum CGMCC 20516 is safe for the target species when supplemented in appropriate amounts to the diet according to the nutritional needs of the target species, for the consumer and for the environment. In the absence of data, the FEEDAP Panel could not conclude on the safety of l-arginine produced by C. glutamicum CGMCC 20516 for the users. The additive l-arginine produced by fermentation using C. glutamicum CGMCC 20516 is regarded as an efficacious source of the essential amino acid l-arginine for non-ruminant species. For the supplemental l-arginine to be as efficacious in ruminants as in non-ruminant species, it requires protection against degradation in the rumen.

Safety and efficacy of a feed additive consisting of l-lysine sulfate produced by Escherichia coli CGMCC 7.398 for all animal species (Kempex Holland B.V.).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of l-lysine sulfate produced by the genetically modified strain Escherichia coli CGMCC 7.398 as a nutritional feed additive for all animal species. Neither the production strain nor its recombinant DNA were detected in the final product. The additive does not pose any safety concerns associated with the production strain. The additive under assessment is considered safe for the target species. When using l-lysine sulfate, the background sulfur/sulfate content in the compound feed should be taken into account. l-lysine sulfate produced by E. coli CGMCC 7.398 is safe for the consumers and for the environment. In the absence of data, the FEEDAP Panel cannot conclude on the potential of the additive under assessment to be irritant to skin or eyes, or on its potential to be a dermal sensitiser. The endotoxin activity of the additive represents a risk by inhalation for users handling the additive. The additive l-lysine sulfate is considered as an efficacious source of the essential amino acid l-lysine for non-ruminant animal species. For the supplemental l-lysine to be as efficacious in ruminants as it is in non-ruminant species, this would require protection against degradation in the rumen.

Assessment of the feed additive consisting of potassium diformate for all animal species for the renewal of its authorisation (Addcon GmbH).

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 assessment of the application for renewal of authorisation of potassium diformate for all animal species. The additive was initially evaluated in 2004 and re-evaluated by the Panel in 2012, with the conclusion that the additive (i) was safe for the target species, the consumer and the environment when used under the proposed conditions; (ii) was an eye irritant and (iii) had the potential to increase the storage time of raw fish and fish by-products for feed use in a dose-dependent manner at low temperature. The FEEDAP Panel considered that the use of potassium diformate under the approved conditions of use remains safe for consumers and the environment, and that it is an eye irritant. Due to the absence of data, the FEEDAP Panel could not conclude on the potential of the additive to be a skin irritant or a respiratory or dermal sensitiser. Regarding the safety for the target species, the FEEDAP Panel considered that the mixture of different sources of potassium diformate remains safe for use in sows' feed under the approved conditions of use (12,000 mg/kg complete feed). However, based on a tolerance trial, the Panel concluded that the maximum safe level of potassium diformate in weaned piglets should be reduced to 6,000 mg/kg complete feed and the same conclusion was extended to pigs for fattening. Owing to the lack of information provided, the Panel could not conclude on the safety of the additive for species other than pigs under the approved conditions. The present application does not include a proposal for amending or supplementing the conditions of the original authorisation that would have an impact on the efficacy of the additive.

Safety and efficacy of a feed additive consisting of l-lysine sulfate produced by Corynebacterium glutamicum KCCM 80227 for all animal species (Daesang Europe BV).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of l-lysine sulfate produced by Corynebacterium glutamicum KCCM 80227 as a nutritional feed additive for all animal species. The FEEDAP Panel concluded that the production strain C. glutamicum KCCM 80227 qualifies for the qualified presumption of safety (QPS) approach to safety assessment and is not detected in the final product. l-Lysine sulfate produced using C. glutamicum KCCM 80227 does not pose any safety concern associated with the production strain. The additive under assessment is considered safe for the target species. When using l-lysine sulfate, the background sulfur/sulfate content in the compound feed should be taken into account. l-Lysine sulfate produced by C. glutamicum KCCM 80227 is safe for the consumers, users and for the environment. The additive l-lysine sulfate is considered as an efficacious source of the essential amino acid l-lysine for non-ruminant animal species. For the supplemental l-lysine to be as efficacious in ruminants as in non-ruminant species, it would require protection against degradation in the rumen.

Assessment of the feed additive consisting of copper chelate of hydroxy analogue of methionine for all animal species for the renewal of its authorisation (Novus Europe S.A./N.V.).

The Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the application for renewal of authorisation of copper chelate of hydroxy analogue of methionine (Mintrex®Cu) for all animal species. The FEEDAP Panel has delivered two opinions (in 2008 and 2009) on the safety and efficacy of the additive. The additive was authorised in 2010 as 'Copper chelate of hydroxy analogue of methionine' containing 18% copper, 79.5-81% (2-hydroxy-4-methylthio)butanoic acid (DL-methionine hydroxy analogue, HMTBa) and 1% mineral oil. Following some modifications in the manufacturing process, the additive does not contain mineral oil and the applicant proposes the following specifications: ≥ 16% copper and ≥ 78% HMTBa. The data provided indicate that the additive complies with the new specifications. No new evidence was found that would make the FEEDAP Panel reconsidering its previous conclusions on the safety for target species, consumers and environment. The applicant provided new studies on the effects of the additive on the respiratory tract and on skin and eyes. Data on the characterisation of the additive and the new studies on skin/eyes led the Panel to reconsider the safety for the user. Mintrex®Cu is considered as a skin and eye irritant and a skin sensitiser; the risk of respiratory sensitisation is considered low. The present application did not include a proposal for amending or supplementing the conditions of the original authorisation that would have an impact on the efficacy of the additive; therefore, there was no need for assessing the efficacy of the additive in the context of the renewal of the authorisation.

Safety and efficacy of an additive consisting of synthetic vitamin K1 (phytomenadione) for horses (JARAZ Enterprises GmbH & Co. KG).

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 a feed additive consisting of vitamin K1 (phytomenadione) produced by chemical synthesis when used as a nutritional additive in complementary feed of horses at a maximum supplemental level of 14 mg vitamin K1/horse per day. The use of vitamin K1 is safe when used as a feed additive for horses under the proposed conditions of use. The use of vitamin K1 in nutrition of horses under the proposed conditions of use is considered safe for the consumer and the environment. No exposure of users by inhalation is expected. The Panel cannot conclude on the potential of the additive to be a skin and eye irritant. Vitamin K1 is considered a moderate dermal sensitiser. Vitamin K1 is an effective source of vitamin K in horse nutrition. The Panel recommends that the specifications of the additive refer to the substance-related impurities listed in the most updated monograph of the European Pharmacopoeia.

Safety and efficacy of a feed additive consisting of chromium propionate (KemTRACE™ Chromium) for all growing poultry species (Kemin Europa NV).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of chromium propionate (KemTRACE™ Chromium; KemTRACE-Cr) as zootechnical feed additive for all growing poultry species. The EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) Panel was assigned to this mandate. Based on two tolerance studies submitted, the Panel concluded that the additive is safe for chickens for fattening at the maximum recommended supplementation level of 0.4 mg Cr/kg feed from KemTRACE-Cr, but a margin of safety cannot be established; this conclusion can be extended to chickens reared for laying/breeding, but cannot be extrapolated to other growing poultry species. The FEEDAP Panel considered that the use of KemTRACE-Cr in animal nutrition at the proposed conditions of use is safe for the consumer. No concerns for users following any inhalation exposure during the handling of the additive are expected; the additive was shown to be corrosive to the eyes but not irritant to skin or a skin sensitiser. The use of KemTRACE-Cr in animal nutrition according to the proposed conditions of use will not significantly alter the concentration in the receiving environmental compartments of concern; therefore, no safety concern is expected for the environment. Based on three efficacy studies, the FEEDAP Panel concluded that KemTRACE-Cr has the potential to be efficacious as a zootechnical additive in chickens for fattening at the supplementation level of 0.4 mg Cr/kg feed; this conclusion could be extended to chickens reared for laying and chickens reared for breeding, and extrapolated to other poultry species for fattening and reared for laying/breeding.

Safety and efficacy of the feed additives concentrated liquid l-lysine (base) and l-lysine monohydrochloride produced by Corynebacterium glutamicum KCCM 80183 for all animal species (CJ Europe GmbH).

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 concentrated liquid l-lysine (base) and l-lysine monohydrochloride (HCl) produced using Corynebacterium glutamicum KCCM 80183 when used as nutritional additives in feed and water for drinking for all animal species. The active substance is l-lysine. Concentrated liquid l-lysine (base) and l-Lysine HCl produced by the strain C. glutamicum KCCM 80183 do not pose any safety concern as regards the genetic modification of the production strain. The use of the additives under assessment in supplementing feed to compensate for l-lysine deficiency in feedingstuffs is safe for the target species. The FEEDAP Panel has concerns about the use of amino acids in water for drinking for hygienic reasons, and due to the risk of imbalances when administered simultaneously via feed. The use of both forms of l-lysine produced by fermentation using C. glutamicum KCCM 80183 in animal nutrition is considered safe for the consumers and for the environment. Concentrated liquid l-lysine (base) produced by C. glutamicum KCCM 80183 is considered hazardous by inhalation, not irritant to skin and eyes and it is not a skin sensitiser. l-Lysine HCl produced by C. glutamicum KCCM 80183 is considered hazardous by inhalation, it is not irritant to skin but mildly irritant to eyes and it is not a skin sensitiser. The additives under assessment are considered as efficacious sources of the essential amino acid l-lysine for non-ruminant animal species. For the supplemental l-lysine to be as efficacious in ruminants as in non-ruminant species, it would require protection against degradation in the rumen.

Safety of the feed additives consisting of l-lysine monohydrochloride and l-lysine sulfate produced by Corynebacterium glutamicum CCTCC M 2015595 for all animal species (Kempex Holland B. V.).

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 of l-lysine monohydrochloride and l-lysine sulfate produced using Corynebacterium glutamicum CCTCC M 2015595 for all animal species. In 2019, the FEEDAP Panel issued an opinion on the safety and efficacy of the products. In that assessment, the Panel could not conclude on the safety of the additives for the target species, the consumers and the environment due to the uncertainties regarding the possible genetic modification of the strain used to obtain the production strain C. glutamicum CCTCC M 2015595 and on the possible presence of viable cells and DNA of the production strain in the final products. Moreover, in the absence of data, the FEEDAP Panel could not conclude on the safety of the additives for the users. The applicant provided supplementary data to characterise the strain from which the production strain under assessment was obtained. However, uncertainties remain on its origin and history of modification, including whether it has been genetically modified. The production strain C. glutamicum CCTCC M 2015595 did not show the presence of acquired antimicrobial resistance genes nor of toxin and virulence factors genes. Moreover, as viable cells and DNA of the production strain were not detected in both final formulations, l-lysine HCl and l-lysine sulfate do not raise safety concerns as regards the production strain. The FEEDAP Panel concluded that l-lysine HCl and l-lysine sulfate produced by C. glutamicum CCTCC M 2015595 are safe for the target species, consumers and for the environment. No additional data have been provided on the safety of the additives for users. Therefore, the conclusions from the Panel remained that in the absence of data, no conclusions on the safety of the additives for the user can be drawn.

Safety and efficacy of a feed additive consisting of l-lysine monohydrochloride and l-lysine sulfate produced by Corynebacterium glutamicum CGMCC 14498 for all animal species (Kempex Holland BV).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of l-lysine monohydrochloride (l-lysine HCl) and l-lysine sulfate produced by Corynebacterium glutamicum (C. glutamicum) CGMCC 14498 as a nutritional feed additive for all animal species. The active substance is l-lysine and it is produced in two different forms (monohydrochloride or sulfate). The production strain C. glutamicum CGMCC 14498 and its recombinant DNA were not detected in the final products. The products l-lysine HCl and l-lysine sulfate do not pose any safety concern associated with the production strain. l-Lysine HCl and l-lysine sulfate produced by C. glutamicum CGMCC 14498 are considered safe for the target species. When using l-lysine sulfate, the background sulfur/sulfate content in the compound feed should be taken into account. l-Lysine HCl and l-lysine sulfate produced by C. glutamicum CGMCC 14498 are safe for the consumer and the environment. In the absence of data, the FEEDAP Panel cannot conclude on the potential of l-lysine HCl produced by the strain C. glutamicum CGMCC 14498 to be toxic by inhalation, and on the potential of l-lysine HCl and l-lysine sulfate produced by the above-mentioned strain to be irritant to skin or eyes, or on their potential to be dermal sensitisers. l-Lysine HCl and l-lysine sulfate produced by C. glutamicum CGMCC 14498 are considered efficacious sources of the essential amino acid l-lysine for non-ruminant animal species. For the supplemental l-lysine to be as efficacious in ruminants as in non-ruminant species, this would require protection against degradation in the rumen.

Assessment of the application for renewal of authorisation of manganese chelate of hydroxy analogue of methionine for all animal species.

The Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the application for renewal of authorisation of manganese chelate of hydroxy analogue of methionine (Mintrex®Mn) for all animal species. The FEEDAP Panel has delivered three opinions (in 2008, 2009 and 2010) on the safety and efficacy of the additive. The additive was authorised in 2010 as 'Manganese chelate of hydroxy analogue of methionine' containing 15.5-17 % manganese, 77-78 % (2-hydroxy-4-methylthio)butanoic acid (dl-Methionine Hydroxy Analogue, HMTBa) and maximum 1% mineral oil. Following some modifications in the manufacturing process the additive does not contain mineral oil and the applicant proposes the following specifications: ≥ 14 % manganese and ≥ 76 % HMTBa. The data provided indicate that the additive complies with the new specifications. No new evidence was found that would make the FEEDAP Panel reconsidering its previous conclusions on the safety for target species, consumers and environment. The applicant provided new studies on the effects of the additive on the respiratory tract and on skin and eyes. Data on the characterisation of the additive and the new studies on skin/eyes led the Panel to reconsider the safety for the user. Owing to the manganese and nickel content of Mintrex®Mn, the handling of the additive poses a risk to users by inhalation; the additive is not a skin or eye irritant but is considered as a skin sensitiser. The present application did not include a proposal for amending or supplementing the conditions of the original authorisation that would have an impact on the efficacy of the additive; therefore, there was no need for assessing the efficacy of the additive in the context of the renewal of the authorisation.

Safety and Efficacy of l-histidine monohydrochloride monohydrate produced by fermentation using Escherichia coli KCCM 80212 as a feed additive for all animal species.

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 l-histidine monohydrochloride (HCl) monohydrate produced by fermentation using Escherichia coli KCCM 80212 when used as a nutritional additive in feed for all animal species. The production strain is genetically modified. The production strain and its recombinant DNA were not detected in the final product. l-Histidine HCl monohydrate manufactured by fermentation using E. coli KCCM 80212 does not give rise to any safety concern regarding the genetic modification. The use of l-histidine HCl monohydrate produced by fermentation using E. coli KCCM 80212 is safe for the target species when used as a nutritional additive to supplement the diet in appropriate amounts to cover the requirements, depending on the species, the physiological state of the animal, the performance level, the environmental conditions, the background amino acid composition of the unsupplemented diet and the status of some essential trace elements such as copper and zinc. l-Histidine HCl monohydrate produced using E. coli KCCM 80212 supplemented at levels appropriate for the requirements of the target species is considered safe for the consumer. l-Histidine HCl monohydrate produced by E. coli KCCM 80212 is a skin sensitiser. There is a risk for persons handling the additive from the exposure to endotoxins by inhalation. The additive under assessment is not irritant to skin or eyes. The use of l-histidine HCl monohydrate produced using E. coli KCCM 80212 in animal nutrition is not expected to represent a risk to the environment. l-Histidine HCl monohydrate is considered an efficacious source of the essential amino acid l-histidine for non-ruminant animal species. For the supplemental l-histidine to be as efficacious in ruminants as in non-ruminant species, it would require protection against degradation in the rumen.