Safety and efficacy of a feed additive consisting of l‐valine produced using Corynebacterium glutamicumKCCM 80365 for all animal species (CJ Europe GmbH)

Following a request from the European Commission, the European Food Safety Authority (EFSA) was asked to deliver a scientific opinion on the safety and efficacy of l‐valine produced with a genetically modified strain of Corynebacterium glutamicum (KCCM 80365) when used as a nutritional additive in feed and water for drinking for all animal species and categories. l‐Valine manufactured by fermentation using C. glutamicum KCCM 80365 does not give rise to any safety concern regarding the genetic modifications of the production strain. No viable cells or DNA of the production strain were detected in the final product. The use of l‐valine produced with C. glutamicum KCCM 80365 in feed is safe for the target species when supplemented in appropriate amounts to the diet according to the nutritional needs of the species. The FEEDAP Panel has concerns on the use of l‐valine in water for drinking. The use of l‐valine produced by fermentation with C. glutamicum KCCM 80365 in animal nutrition is considered safe for the consumers and for the environment. l‐Valine produced with C. glutamicum KCCM 80365 is not irritant to skin and eyes, nor considered a skin sensitiser. The additive l‐valine is regarded as an effective source of the amino acid l‐valine for all non‐ruminant species. To be as efficacious in ruminants as in non‐ruminants, it should be protected from ruminal degradation.

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of the feed additive consisting of l‐threonine produced by fermentation with Escherichia coli CCTCC M 2024477 when used as a nutritional additive in feed and water for drinking for all animal species and categories. The production strain is genetically modified. None of the genetic modifications raised a safety concern. Viable cells or DNA of the production strain were not detected in the final product. The use of l‐threonine produced with E. coli CCTCC M 2024477 in feed is safe for the target species when supplemented in appropriate amounts to the diet according to their nutritional needs. The FEEDAP Panel has concerns on the use of amino acids in water for drinking. The use of l‐threonine (≥ 98.0%) produced with E. coli CCTCC M 2024477 in animal nutrition is considered safe for the consumers and the environment. Regarding the user safety, the FEEDAP Panel cannot conclude on the potential of the additive to be irritant to skin and/or eyes and to be a potential skin sensitiser. The FEEDAP Panel considers that the exposure of the users to bacterial endotoxins should be minimised. Any exposure to the additive is a risk. The additive is regarded as an effective source of the amino acid l‐threonine for all non‐ruminant species. To be as efficacious in ruminants as in non‐ruminants, it should be protected from ruminal degradation.

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of l-histidine and l-histidine monohydrochloride monohydrate produced with a genetically modified strain of Corynebacterium glutamicum (KCCM 80389) as nutritional and sensory feed additives for all animal species and categories. l-Histidine and l-histidine monohydrochloride monohydrate manufactured by fermentation with C. glutamicum KCCM 80389 do not give rise to any safety concern regarding the genetic modifications of the production strain. No viable cells or DNA of the production strain were detected in the final products. The FEEDAP Panel concluded that the use of l-histidine and l-histidine monohydrochloride monohydrate produced with C. glutamicum KCCM 80389 in feed raises no safety concerns for the target species when supplemented in appropriate amounts to the diet according to the nutritional needs of the species. The FEEDAP Panel had concerns on the use of l-histidine and l-histidine monohydrochloride monohydrate in water for drinking. The FEEDAP Panel concluded that the use of l-histidine and l-histidine monohydrochloride monohydrate produced by fermentation with C. glutamicum KCCM 80389 in animal nutrition are safe for the consumers of products from animals receiving the additive, and to the environment. Regarding the user safety, the additives are not considered irritant to skin or eyes and are not considered potential skin sensitisers. The additives were regarded as effective sources of the amino acid l-histidine for all non-ruminant species. To be as efficacious in ruminants as in non-ruminants, it should be protected from ruminal degradation.

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‐tryptophan produced by fermentation with a non‐genetically modified strain of Escherichia coli KCCM 10534 when used as a nutritional additive in feed and water for drinking for all animal species and categories. The production strain E. coli KCCM 10534 is safe for the production of l‐tryptophan and it was not detected in the final product. The use of l‐tryptophan produced using E. coli KCCM 10534 in supplementing feed to compensate for tryptophan deficiency in feedingstuffs is safe for non‐ruminant target species. There may be a risk for an increased production of toxic metabolites when unprotected tryptophan is used in ruminants. The FEEDAP Panel has concerns on the safety of the simultaneous oral administration of l‐tryptophan via water for drinking and feed due to possible amino acid imbalances. The use of l‐Tryptophan produced by E. coli KCCM 10534 in animal nutrition raises no safety concerns to consumers of animal products and to the environment. The additive under assessment is considered not toxic by inhalation, it is not a skin or eye irritant and is not a skin sensitiser. The endotoxin activity of the additive and its dusting potential indicate a risk by inhalation for the users. The product l‐tryptophan is regarded as an effective source of the amino acid l‐tryptophan for all non‐ruminant species. In order to be as efficacious in ruminants as in non‐ruminants, it should be protected from ruminal degradation.

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 zearalenone hydrolase (ZenA) produced by Escherichia coli DSM 32731 when used as a feed additive for all terrestrial animals. The production strain E. coli DSM 32731 is genetically modified and harbours a kanamycin resistance gene. No viable cells of the production strain were detected in the final product, but uncertainty remains on the presence of recombinant DNA in the final product. The ZenA contained in the additive is safe for all terrestrial animal species up to the maximum use levels of (in U/kg complete feed): 100 U/kg in chickens for fattening; 150 U/kg in laying hens, turkeys for fattening and rabbits; 200 U/kg in pigs; 250 U/kg in dairy cows; 400 U/kg in veal calf (milk replacer), cattle for fattening, sheep, goats, horses and cats; and 450 U/kg in dogs. Based on the ADME and toxicological data, the FEEDAP Panel considers that the use of the ZenA contained in the additive in animal nutrition is safe for the consumers. The endotoxin content in the additive poses a risk by inhalation for users handling the additive. The additive is not a skin/eye irritant nor a skin sensitiser. Due to its proteinaceous nature, the additive should be considered as a potential respiratory sensitiser. The ZenA contained in the additive and the resulting breakdown products of its enzymatic activity do not represent a safety concern for the environment. The production strain harbours an antimicrobial resistance gene and uncertainties remain on the possible presence of its recombinant DNA in the final product; therefore, the FEEDAP Panel cannot conclude on safety of the additive for the target species, the consumer, the user and the environment.

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‐tryptophan produced by fermentation with a genetically modified strain of Escherichia coli CGMCC 7.267 when used as a nutritional additive in feed and water for drinking for all animal species and categories. The production strain E. coli CGMCC 7.267 is safe for the production of l‐tryptophan. No viable cells or DNA of the production strain were detected in the additive under assessment. The use of l‐tryptophan produced using E. coli CGMCC 7.267 in supplementing feed to compensate for tryptophan deficiency in feedingstuffs is safe for non‐ruminant target species. However, excess doses would create amino acid imbalances with negative consequences on animal performance. The use of unprotected l‐tryptophan in feed poses safety concerns for ruminants. The use of l‐tryptophan produced by fermentation with E. coli CGMCC 7.267 in animal nutrition is considered safe for the consumers and for the environment. The endotoxin activity in the product and its dusting potential indicate an inhalation risk for the user. In the absence of data, the FEEDAP Panel cannot conclude on the potential of the additive to be irritant to skin and eyes or to be a skin sensitiser. The additive l‐tryptophan produced using E. coli CGMCC 7.267 is regarded as an effective source of the amino acid l‐tryptophan. In order to be as efficacious in ruminants as in non‐ruminants, it should be protected from ruminal degradation.

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 the feed additive consisting of l‐tryptophan produced by fermentation with Escherichia coliKCCM 80210 when used as a nutritional additive in feed for all animal species and categories. The production strain E. coliKCCM 80210 is safe for the production of l‐tryptophan and it was not detected in the final product. The Panel notes that two out of five batches of the additive do not comply with the minimum specification of 98% l‐tryptophan on a dry matter basis proposed by the applicant. The use of l‐tryptophan (≥ 98%) produced by E. coliKCCM 80210 in supplementing feed to compensate for l‐tryptophan deficiency in feedingstuffs is safe for non‐ruminant target species. There may be a risk for an increased production of toxic metabolites when unprotected l‐tryptophan is used in ruminants. The use of l‐tryptophan produced by E. coliKCCM 80210 in animal nutrition raises no safety concerns to consumers of animal products and to the environment. The additive under assessment is considered a mild eye irritant. The endotoxin activity of the additive and its dusting potential indicate a risk by inhalation for the users. The additive is not a skin irritant and is not a skin sensitiser. The additive l‐tryptophan is regarded as an effective source of the amino acid l‐tryptophan for all non‐ruminant species. In order to be as efficacious in ruminants as in non‐ruminants, it should be protected from ruminal degradation.

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‐threonine produced by fermentation when used as a nutritional additive in feed and water for drinking for all animal species and categories. The product under assessment is l‐threonine produced using a genetically modified strain of E. coli CGMCC 13325. The Panel notes that three out of five batches of the additive do not comply with the minimum specification of 98.5% l‐threonine on a dry matter basis proposed by the applicant. The production strain and its DNA were not detected in the final additive. Therefore, the final product does not give raise to any safety concern regarding the genetic modification of the production strain. The use of l‐threonine produced using E. coli CGMCC 13325 in supplementing feed to compensate for threonine deficiency in feedingstuffs is 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 l‐threonine produced by fermentation using E. coli CGMCC 13325 in animal nutrition is considered safe for the consumers and for the environment. There is a risk from the inhalation exposure to endotoxins for persons handling the additive. In the absence of data, the FEEDAP Panel cannot conclude on the potential of l‐threonine produced using E. coli CGMCC 13325 to be a skin or eye irritant or a skin sensitiser. The additive under assessment is regarded as an effective source of the amino acid l‐threonine for all non‐ruminant species. For the supplemental l‐threonine to be as efficacious in ruminants as in non‐ruminant species, it requires protection against degradation in the rumen.

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of l‐tryptophan produced with a genetically modified strain of Escherichia coli (CCTCC M 2024517) as a nutritional additive in feed and water for drinking for all animal species and categories. The l‐tryptophan produced by fermentation with E. coli CCTCC M 2024517 did not give rise to any safety concern regarding the genetic modifications of the production strain. No viable cells nor DNA of the production strain was detected in the final product. The use of l‐tryptophan produced with E. coli CCTCC M 2024517 in feed is safe for the target species when supplemented in appropriate amounts to the diet according to their nutritional needs. The FEEDAP Panel had concerns on the use of l‐tryptophan in water for drinking. The use of l‐tryptophan produced by fermentation with E. coli CCTCC M 2024517 in animal nutrition was considered safe for the consumers of products from animals receiving the additive and for the environment. The FEEDAP Panel could not conclude on the potential of the additive to be an irritant to skin and/or eyes and to be a potential skin sensitiser. The additive was regarded as an effective source of the amino acid l‐tryptophan for all non‐ruminant species. To be as efficacious in ruminants as in non‐ruminants, it should be protected from ruminal degradation.

The product L-threonine, technically pure, is an essential amino acid that contains by specification ≥ 98 % L-threonine. It is produced by a genetically modified Escherichia coli strain. Neither the production strain nor its recombinant DNA was detectable in the final product. The final product does not raise safety concerns with regard to the genetic modification. L-Threonine, technically pure, is considered safe for the target animals when used to meet the requirements. The toxicological studies, including mutagenicity tests, performed with the additive or other sources of L-threonine did not reveal any toxic effect. Since the composition of tissues and products of animal origin will not be changed by the use of L-threonine in animal nutrition, and considering the high purity of the product under assessment, no risks are expected for the consumer from the use of L-threonine, technically pure, as a feed additive. The product is not irritating to the skin or eyes and is not likely to be a skin sensitiser. Although there is a potential for user exposure by inhalation, there is no evidence of acute toxicity by the inhalation route. The use of the product as a feed additive does not represent a risk to the environment. L-Threonine, technically pure, is considered as an efficacious source of L-threonine for all animal species. Response in ruminants requires some degree of protection of threonine from ruminal degradation.

The additive riboflavin (80 %) is produced by fermentation of a genetically modified Bacillus subtilis strain. Neither the production strain nor its recombinant DNA was detected in the final product. Therefore, the final product does not give rise to any safety concern with regard to the genetic modification. The additive is safe for the target animals with a wide margin of safety provided that the current use levels for riboflavin are not exceeded. Setting a maximum content for riboflavin in complete feed is not considered necessary. Toxicological studies with the additive under assessment show that it has a low toxicity. The use of the additive in animal nutrition will not significantly alter the riboflavin content of food of animal origin. The FEEDAP Panel considers that the use of the additive in animal nutrition is not of safety concern for consumers. The FEEDAP Panel considers that the additive is an irritant to skin, eyes and the respiratory tract. It is unlikely to cause skin sensitisation. Workers might be exposed to a respirable dust when handling riboflavin, which should be regarded as being potentially harmful to their health. The use of the additive in animal nutrition does not pose a risk to the environment. The additive is regarded as an effective source of riboflavin in covering the animal's requirement when administered orally.

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‐tryptophan produced by fermentation with Escherichia coli CGMCC 11674 when used as a nutritional additive in feed and water for drinking for all animal species and categories. The production strain did not raise safety concerns. The FEEDAP Panel cannot conclude on the safety of l‐tryptophan produced by E. coli CGMCC 11674 for the target species and for the consumer due to the tryptophan‐related impurities such as 1,1’‐ethylidene‐bis‐l‐tryptophan (EBT). The FEEDAP Panel has concerns on the safety of the simultaneous oral administration of l‐tryptophan via water for drinking and feed. Using unprotected forms of tryptophan in ruminants can be a risk. The FEEDAP Panel cannot conclude on the dermal or ocular irritation and skin sensitisation of l‐tryptophan produced by E. coli CGMCC 11674. The additive poses a risk by inhalation from the exposure to endotoxins for people handling the additive. The use of l‐tryptophan produced by E. coli CGMCC 11674 in animal nutrition does not pose a risk to the environment. The additive under assessment is regarded as an effective source of the amino acid l‐tryptophan for all non‐ruminant species. If the product l‐tryptophan is intended for use in ruminants, it should be protected from ruminal degradation.

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of the feed additive consisting of l-threonine produced by fermentation with Escherichia coli CGMCC 7.455 when used as a nutritional additive in feed and water for drinking for all animal species and categories. The production strain is genetically modified. None of the introduced genetic modifications raised a safety concern. Viable cells of the production strain and its DNA were not detected in the final additive. Therefore, the final product does not give raise to any safety concern regarding the genetic modification of the production strain. The use of l-threonine (≥ 98.5%) produced with E. coli CGMCC 7.455 to supplement feed is safe for the target species. The Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) has concerns on the safety of the simultaneous oral administration of l-threonine via water for drinking and feed due to possible amino acid imbalances and hygienic reasons. The use of l-threonine produced with E. coli CGMCC 7.455 in animal nutrition raises no safety concerns to consumers of animal products and to the environment. In the absence of data, the FEEDAP Panel cannot conclude on the potential of the additive to be irritant to skin or eyes, or on its potential to be a dermal sensitiser. The endotoxin activity in the additive does not pose a risk for the user via inhalation. The additive l-threonine is regarded as an effective source of the amino acid l-threonine for all non-ruminant species. In order to be as efficacious in ruminants as in non-ruminants, it should be protected from ruminal degradation.

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 Corynebacterium glutamicum KCCM 80172 when used as a nutritional additive in feed and water for drinking 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 C. glutamicum KCCM 80172 does not give rise to any safety concern regarding the genetic modification. The use of l‐histidine HCl monohydrate produced by fermentation using C. glutamicum KCCM 80172 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 C. glutamicum KCCM 80172 supplemented at levels appropriate for the requirements of the target species is considered safe for the consumer. l‐Histidine HCl monohydrate produced using C. glutamicum KCCM 80172 is not irritant to skin, is a mildly irritant to eyes, and it is not a skin sensitiser. The additive does not pose a risk to users by inhalation. The use of l‐histidine HCl monohydrate produced by C. glutamicum KCCM 80172 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.

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of L‐arginine produced with a genetically modified strain of Escherichia coli (CCTCC M 20231961) as a nutritional feed additive for all animal species and categories. The EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concluded that the production strain E. coli CCTCC M 20231961 does not raise safety concerns. No viable cells or DNA of the production strain are detected in the final product. Therefore, the FEEDAP Panel concludes that the additive does not pose any safety concern regarding the production strain. The use of L‐arginine produced by fermentation with E. coli CCTCC M 20231961 in feed is safe for the target species when supplemented in appropriate amounts to the diet according to the nutritional needs of the target species. The FEEDAP Panel has concerns on the use of L‐arginine in water for drinking. The use of L‐arginine produced by fermentation with E. coli CCTCC M 20231961 in animal nutrition is considered safe for the consumers and for the environment. The FEEDAP Panel cannot conclude on the potential of the additive to be irritant to skin and/or eyes and to be a potential dermal sensitiser. The feed additive consisting of L‐arginine produced by fermentation with E. coli CCTCC M 20231961 is regarded as an efficacious source of the amino acid L‐arginine for all 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.