Safety and efficacy of a feed additive consisting of l‐tryptophan produced with Escherichia coliCCTCC M 2024517 for all animal species (Anhui Huaheng Biotechnology Co., Ltd.)

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‐isoleucine produced with Escherichia coli CCTCC M 20231916 as a nutritional feed additive for all animal species. The production strain E. coli CCTCC M 20231916 is genetically modified. No viable cells nor DNA of the production strain are detected in the final product. Therefore, the additive does not pose any safety concern regarding the production strain. The use of L‐isoleucine produced by fermentation with E. coli CCTCC M 20231916 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 about the use of L‐isoleucine in water for drinking. The use of L‐isoleucine produced by fermentation with E. coli CCTCC M 20231916 in animal nutrition is considered safe for consumers and the environment. As regards the safety for the user, 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 feed additive consisting of L‐isoleucine produced by fermentation with E. coli CCTCC M 20231916 is regarded as an effective source of the amino acid L‐isoleucine for all non‐ruminant species. For the supplemental L‐isoleucine 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, 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 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, 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.

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-arginine produced by fermentation with a genetically modified strain of Escherichia coli (CGMCC 7.401). The additive is intended to be used in feed and water for drinking for all animal species and categories. The genetic modifications introduced do not raise safety concerns. No viable cells or DNA of the production strain were detected in the final product. The EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concluded that the additive does not pose any safety concern with regard to the production strain. l-Arginine produced with E. coli CGMCC 7.401 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 amino acids in water for drinking for hygienic reasons, and due to the risk of imbalances when administered simultaneously via feed and water. The use of l-arginine produced with E. coli CGMCC 7.401 in animal nutrition is considered safe for the consumers and for the environment. The endotoxin activity of the additive does not represent a hazard for persons handling the additive. In the absence of data, the FEEDAP Panel cannot conclude on the potential of the additive to be irritant to skin and/or eyes, or to be a dermal or respiratory sensitiser. The additive l-arginine produced with E. coli CGMCC 7.401 is regarded as an efficacious source of the essential amino acid l-arginine for non-ruminant species. For supplemental l-arginine 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, 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 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, the FEEDAP Panel was asked to deliver a scientific opinion on the safety and efficacy of l‐methionine ≥ 98.5% or ≥ 90% produced by the combined activities of Corynebacterium glutamicum KCCM 80245 and Escherichia coli KCCM 80246) as nutritional additive for all animal species. The two production strains are genetically modified. l‐Methionine is intended to be used in feed or water for drinking for all animal species. Neither viable cells nor recombinant DNA of the production strains were detected in the final products. The additive does not pose any safety concern associated with the genetic modification of the production strains. The use of both products of l‐methionine produced by C. glutamicum KCCM 80245 and E. coli KCCM 80246 in supplementing feed to compensate for l‐methionine 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 products of l‐methionine produced by C. glutamicum KCCM 80245 and E. coli KCCM 80246 in animal nutrition is considered safe for the consumers and for the environment. The additive, in either product, is not an irritant to skin/eyes and not a dermal sensitiser and shows no toxicity by inhalation. Considering the respiratory exposure to endotoxins, l‐methionine ≥ 90% is a risk for the user. Both products of the additive produced by C. glutamicum KCCM 80245 and E. coli KCCM 80246 are considered as an efficacious source of the essential amino acid l‐methionine for non‐ruminant animal species. For the supplemental l‐methionine 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 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, EFSA was asked to deliver a scientific opinion on the safety and efficacy of l‐cystine produced with a genetically modified strain of Escherichia coli K‐12 (DSM 34232) as a sensory feed additive (functional group: flavouring compounds) for all animal species. The l‐cystine manufactured by fermentation with E. coli DSM 34232 did not give rise to any safety concern regarding the genetic modification of the production strain. No viable cells or DNA of the production strain were detected in the final product. The use of l‐cystine produced by fermentation with E. coli DSM 34232 in feed was considered safe for the target species when supplemented at concentrations up to 25 mg/kg complete feed. The FEEDAP Panel considered that the use of l‐cystine in animal nutrition is safe for the consumers of products from animals receiving the additive, and for the environment. Regarding user safety, the additive was not considered a skin and eye irritant, nor a skin sensitiser. As l‐cystine is used in food as a flavouring compound, it is expected that it can provide a similar function in feed and no further demonstration of efficacy is necessary.

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‐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.

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.

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of l‐lysine monohydrochloride produced by fermentation with a genetically modified strain of Corynebacterium glutamicum (CGMCC 7.453) as nutritional feed additive for all animal species. Neither viable cells nor recombinant DNA of the production strain were detected in the final product. Therefore, the FEEDAP Panel concluded that the additive does not pose any safety concern regarding the production strain. The FEEDAP Panel concluded that the use of l‐lysine HCl produced by fermentation with the strain C. glutamicum CGMCC 7.453 is safe for the target species when administered via feed. However, the FEEDAP Panel expressed concerns on the use of l‐lysine HCl in water for drinking. The Panel concluded that the use of l‐lysine HCl produced by fermentation with C. glutamicum CGMCC 7.453 in animal nutrition is considered safe for the consumers and for the environment. With regards user safety, the additive should be considered irritant to skin, eyes and the respiratory tract. Any exposure to the additive is a risk. l‐Lysine HCl is considered as 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.