Safety and efficacy of a feed additive consisting of l-valine produced with <i>Escherichia coli</i> CGMCC 22721 for all animal species (Eppen Europe SAS).
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Safety and efficacy of a feed additive consisting of l‐valine produced with Escherichia coli CGMCC 22721 for all animal species (Eppen Europe SAS)
Roberto Edoardo Villa, Giovanna Azimonti, Eleftherios Bonos, Henrik Christensen, Mojca Durjava, Birgit Dusemund, Ronette Gehring, Boet Glandorf, Maryline Kouba, Marta López‐Alonso, Francesca Marcon, Carlo Nebbia, Alena Pechová, Miguel Prieto‐Maradona, Ilen Röhe, Katerina Theodoridou, Lieve Herman, Montserrat Anguita, Nicole Bozzi Cionci, Elisa Pettenati, and Jordi Tarrés‐CallAbstract
Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of l‐valine produced by fermentation with a genetically modified strain of Escherichia coli (CGMCC 22721) as a nutritional additive for all animal species. 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 EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concludes that l‐valine produced using E. coli CGMCC 22721 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. The use of l‐valine produced using E. coli CGMCC 22721 in animal nutrition is considered safe for the consumers and for the environment. The FEEDAP Panel cannot conclude on the potential of l‐valine produced using E. coli CGMCC 22721 to irritant to the skin or eyes, a dermal or respiratory sensitiser due to the lack of data. The endotoxin activity of the additive does not represent a hazard for users handling the additive when exposed by inhalation. The additive l‐valine produced by fermentation using E. coli CGMCC 22721 is regarded as an efficacious source of the essential amino acid l‐valine for non‐ruminant nutrition. For the supplemental l‐valine to be as efficacious in ruminants as in non‐ruminant species, it requires protection against degradation in the rumen.
1. INTRODUCTION
1.1. Background and Terms of Reference
Regulation (EC) No 1831/2003 1 establishes the rules governing the Community authorisation of additives for use in animal nutrition. In particular, Article 4(1) of that Regulation lays down that any person seeking authorisation for a feed additive or for a new use of feed additive shall submit an application in accordance with Article 7.
The European Commission received a request from Eppen Europe SAS 2 for the authorisation of the additive consisting of l‐valine produced by fermentation with Escherichia coli CGMCC 22721, when used as a feed additive for all animal species (category: nutritional additives; functional group: amino acids, their salts or analogues).
According to Article 7(1) of Regulation (EC) No 1831/2003, the Commission forwarded the application to the European Food Safety Authority (EFSA) as an application under Article 4(1) (authorisation of a feed additive or new use of a feed additive). The dossier was received on 17 November 2023 and the general information and supporting documentation are available at https://open.efsa.europa.eu/questions/EFSA‐Q‐2023‐00739. The particulars and documents in support of the application were considered valid by EFSA as of 16 February 2023.
According to Article 8 of Regulation (EC) No 1831/2003, EFSA, after verifying the particulars and documents submitted by the applicant, shall undertake an assessment in order to determine whether the feed additive complies with the conditions laid down in Article 5. EFSA shall deliver an opinion on the safety for the target animals, consumer, user and the environment and on the efficacy of the feed additive consisting of l‐valine produced by fermentation with Escherichia coli CGMCC 22721, when used under the proposed conditions of use (see Section 3.1.6).
1.2. Additional information
The additive is a preparation containing l‐valine produced by fermentation with E.
coli CGMCC 22721, that is not authorised as a feed additive in the European Union.
The EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) issued a series of scientific opinions on the safety and efficacy of l‐valine produced by fermentation with different production strains, when used in feed for all animal species as a nutritional additive (functional group: amino acids, their salts and analogues).
l‐Valine produced by fermentation using different production strains is currently authorised for its use in all animal species as a nutritional additive (functional group: amino acids, their salts and analogues). 3
2. DATA AND METHODOLOGIES
2.1. Data
The present assessment is based on data submitted by the applicant in the form of a technical dossier
4
in support of the authorisation request for the use of l‐valine produced by fermentation with E.coli CGMCC 22721 as a feed additive.
The confidential version of the technical dossier was subject to a target consultation of the interested Member States from 19 February 2024 to 19 May 2024; the comments received were considered for the assessment.
In accordance with Article 38 of the Regulation (EC) No 178/2002 5 and taking into account the protection of confidential information and of personal data in accordance with Articles 39 to 39e of the same Regulation, and of the Decision of EFSA's Executive Director laying down practical arrangements concerning transparency and confidentiality, 6 a non‐confidential version of the dossier has been published on Open.EFSA.
According to Article 32c(2) of Regulation (EC) No 178/2002 and to the Decision of EFSA's Executive Director laying down the practical arrangements on pre‐submission phase and public consultations, EFSA carried out a public consultation on the non‐confidential version of the technical dossier from 17 July to 17 August 2024 for which no comments were received.
The FEEDAP Panel used the data provided by the applicant together with data from other sources, such as previous risk assessments by EFSA peer‐reviewed scientific papers, other scientific reports, to deliver the present output.
EFSA has verified the European Union Reference Laboratory (EURL) report as it relates to the methods used for the control of the l‐valine in animal feed. 7
2.2. Methodologies
The approach followed by the FEEDAP Panel to assess the safety and the efficacy of l‐valine produced by fermentation with E.coli CGMCC 22721 is in line with the principles laid down in Regulation (EC) No 429/2008
8
and the relevant guidance documents: Guidance on the assessment of the safety of feed additives for the consumer (EFSA FEEDAP Panel, 2017a), Guidance on the identity, characterisation and conditions of use of feed additives (EFSA FEEDAP Panel, 2017b), Guidance on the assessment of the safety of feed additives for the target species (EFSA FEEDAP Panel, 2017c), Guidance on the assessment of the efficacy of feed additives (EFSA FEEDAP Panel, 2018a), Guidance on the characterisation of microorganisms used as feed additives or as production organisms (EFSA FEEDAP Panel, 2018b), Guidance on the assessment of the safety of feed additives for the environment (EFSA FEEDAP Panel, 2019), EFSA statement on the requirements for whole genome sequence analysis of microorganisms intentionally used in the food chain (EFSA, 2024) and the Guidance on the assessment of the safety of feed additives for users (EFSA FEEDAP Panel, 2023).
3. ASSESSMENT
l‐Valine (≥ 98%) produced by fermentation with a genetically modified strain of E. coli (CGMCC 22721) is intended to be used as a nutritional feed additive (functional group: amino acids, their salts and analogues) in feed and water for drinking for all animal species.
3.1. Characterisation
3.1.1. Characterisation of the production organism
The production strain is a genetically modified derivative of E. coli K‐12 ■■■■■, deposited in the China General Microbiological Culture Collection Centre with accession number CGMCC 22721. 9
A ■■■■■ analysis ■■■■■ of the production strain confirmed its identity as an E. coli K‐12 derivative. 10 ■■■■■. E. coli K‐12 is well characterised, its safety (non‐pathogenicity) has been documented (Gorbach, 1978) and its ineffectiveness in colonising the human gut is reported (Smith, 1975).
■■■■■.
The susceptibility of the production strain to antimicrobials was tested using a broth microdilution method and including the data set of antimicrobials recommended by EFSA for Enterobacteriaceae (EFSA FEEDAP Panel, 2018b). 11 All minimum inhibitory concentration (MIC) values were below the cut‐off values and therefore, the strain is considered susceptible to all relevant antibiotics.
WGS data of the production strain, ■■■■■ was interrogated for the presence of antimicrobial resistance (AMR) genes ■■■■■. 12 ■■■■■ ■■■■■
The ■■■■■ production strain were also interrogated for the presence of toxin and virulence determinant genes ■■■■■ 13 ■■■■■. ■■■■■
Information related to the genetic modification 14
Description of the genetic modification
■■■■■.
■■■■■.
The following genetic modifications, aimed at increasing the production of l‐valine, were introduced to obtain the production strain E. coli CGMCC 22721:
- ■■■■■ ■■■■■
- ■■■■■ ■■■■■■■■■■
- ■■■■■ ■■■■■■■■■■
- ■■■■■ ■■■■■■■■■■.
The genetic modifications were performed ■■■■■. 15 ■■■■■ ■■■■■.
3.1.2. Manufacturing process
l‐Valine is produced by fermentation with E. coli CGMCC 22721 as a production strain. ■■■■■. 16
The applicant stated that no antibiotics are used during the manufacturing process. 17
3.1.3. Characterisation of the active substance/additive
l‐Valine (International Union of Pure and Applied Chemistry (IUPAC)) name: (2S)‐2‐amino‐3‐methylbutanoic acid; synonyms: α‐amino isovaleric acid, 2‐amino‐3‐methylbutyric acid, a compound identified by Chemical Abstracts Service (CAS) No 72‐18‐4 and European Inventory of Existing Commercial Chemical Substances (EINECS) No 200‐773‐6, has a molecular weight of 117.15 g/mol; the molecular formula is C5H11NO2 and its structural formula is given in Figure 1.
Molecular structure of l‐valine.
The additive is specified to contain ≥98% l‐valine on a dry matter (DM) basis and≤ 1.5% moisture.
The analysis of five batches showed an average of 100% valine (range 99.3%–102.3%) on DM. 18 Moisture was on average 0.04% (range 0%–0.1%).
The specific optical rotation measured in five batches ranged from +27.9 to +28.5°, which falls within the reference range (+26.5 to +29.0°) set in the European Pharmacopoeia (11th edition) (2023) and confirms the l‐enantiomer of valine. 19
Three batches of the additive were analysed for impurities. 20 Cadmium, lead, mercury and arsenic concentrations were below the limit of quantification (LOQ) of the analytical methods.
Polychlorinated dibenzo‐p‐dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and dioxin‐like polychlorinated biphenyls (DL‐PCBs) were analysed in three batches. 21 All values were below the corresponding limit of quantification (LOQ). The calculated upper bound (UB) was 0.14 ng WHO 2005‐TEQ/kg for the sum of PCDD/Fs, and 0.27 ng WHO 2005‐TEQ/kg the sum of PCDD/Fs and DL‐PCBs. The UB for the sum of non DL‐PCBs was 3 μg/kg (all values are expressed based on 88% dry matter). 22
The analysis of mycotoxins, including zearalenone, aflatoxins (not specified), ochratoxin A, fumonisins B1+B2+B3, deoxynivalenol and citrinin showed values below the limit of detection (LOD) of the analytical method, except for aflatoxins, which ranged from 0.3 to 0.9 μg/kg.
23
The FEEDAP Panel considers that the amounts of the detected impurities do not raise safety concerns.
Microbiological contamination was analysed in three batches of the additive. Enterobacteriaceae, Salmonella spp., filamentous fungi, yeasts and E.coli were absent in 25 g samples in all cases. The results were below the LOD of the respective methods.
24
The endotoxin activity of the additive was measured in three batches according to the European Pharmacopoeia and the results were below the LOQ of the analytical method (300 endotoxin units (EU)/g) in all three batches. 25
The presence of viable cells of the production strain was investigated in three batches of the additive, ■■■■■. 26 ■■■■■. No viable cells of the production strain were detected in any of the samples.
The presence of DNA of the production strain was tested in three batches of the additive ■■■■■. 27 ■■■■■. No DNA of the production strain was detected.
3.1.4. Physical properties of the additive
The additive appears as a light brown solid crystalline powder. 28 The bulk density of the additive measured in three batches ranged from 602 to 648 kg/m3. The solubility in water is about 50 g/L at 20°C.
The dusting potential of three batches of the additive was determined using the Stauber‐Heubach method and showed values ranging from 400 to 600 mg/m3. 29
3.1.5. Stability and homogeneity
The shelf life of the additive (three batches) was studied when stored at room temperature in sealed plastic bags protected from light for 6 months. No losses were observed at the end of the storage period. 30
The stability of the additive (three batches) in a vitamin‐mineral premixture for chickens for fattening 31 was studied when supplemented at 4% and stored at room temperature in closed plastic bags for 6 months. Losses at the end of the storage period ranged 4%–15%. 32
The stability of the additive (three batches) in complete feed for pigs (mash and pelleted forms, diet consisting of wheat and soybean meal) 33 was studied when supplemented at 0.2%. Pelleting temperature was 75–77°C. The pelleting process did not cause a loss in the concentration of the additive in feed. Samples were stored at room temperature in paper bags protected from light for 6 months. Losses at the end of the storage period ranged 2%–4% in the mash feed and 3%–5% in the pelleted feed. 34
The stability of the additive (three batches) in water for drinking was studied when supplemented at 0.2%. Samples were stored at 20°C (packaging not described) for 48 h. Losses at the end of the storage period ranged 0%–2.5%. 35
The capacity for homogeneous distribution of the additive in pelleted feed was studied in 10 subsamples. Total valine was analysed and subsequently the background concentration in the feed was subtracted. The coefficient of variation was 7%. 36
3.1.6. Conditions of use
l‐Valine is intended to be used in feeds and water for drinking to achieve an adequate amino acid profile and to meet the l‐valine requirements for all animal species. It can be added directly to complete feed, water, complementary feed or it can be supplemented via a premixture. No inclusion levels have been proposed, as the requirements, in quantitative terms, depend on the species, the physiological state of the animal, the performance level, the environmental conditions and the amino acid composition of the un‐supplemented diet.
3.2. Safety
3.2.1. Safety of the production microorganism
The parental strain is considered safe. The genetic modifications performed to obtain the production strain E. coli CGMCC 22721 have the purpose to increase the production of l‐valine. None of the introduced modifications raise a safety concern and the production strain does not carry acquired antimicrobial resistance genes. Moreover, the production strain and its DNA were not detected in the final additive. The final product does not give raise to any safety concern regarding the genetic modification of the production strain.
3.2.2. Safety for the target species, consumers and the environment
l‐Valine requirements of different animal species (non‐ruminant and ruminant), absorption and metabolic fate of l‐valine, and tolerance to l‐valine excess in the diet were described in previous opinions (EFSA FEEDAP Panel, 2013, 2014).
The additive is highly purified (contains > 98% l‐valine and< 1% unidentified material on DM basis) and the production strain and the manufacturing process do not raise safety concerns.
The use of the amino acid ‘per se’ will not raise safety concerns for the target animals provided it is supplemented in appropriate amounts to the diets with respect to the nutritional needs of the target species. The endotoxin activity was < 0.3 EU/mg. These values are compared with ca. 1000 EU/mg commonly found in feedingstuffs (Cort et al., 1990). Therefore, at the usual conditions of use of the additive in feed, the endotoxins added by the additive would be insignificant compared to the background in feed. Safety concerns from the additive could derive from the residues of the fermentation process/production strain remaining in the final product. As the production strain and the manufacturing process do not raise safety concerns, l‐valine produced by fermentation with E. coli CGMCC 22721 is safe for the target species when used to supplement the diet in appropriate amounts to satisfy the animal requirements. However, 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 (EFSA FEEDAP Panel, 2010).
The amino acid l‐valine will be incorporated into proteins of tissues and/or products of animal origin and any of its potential excess will be metabolised and excreted as urea/uric acid and carbon dioxide. Therefore, the composition of tissues and products of animal origin will not be affected by the use of l‐valine in animal nutrition, and its use would be of no concern for the consumers of animal tissues/products of animals fed with the additive.
The amino acid l‐valine is a physiological and natural component of the proteins of living organisms. When consumed, it will be absorbed and the non‐absorbed fraction will be incorporated into the intestinal microbial mass and excreted as such. The use of amino acids in water for drinking, when given in addition to complete diets with a well‐balanced amino acid profile, would disturb the nitrogen balance and increase nitrogen excretion via urine. The use of the additive in animal nutrition would not lead to any localised increase in the concentration of l‐valine or its metabolites in the environment.
3.2.3. Conclusions on the safety for the target species, consumers and the environment
l‐Valine produced by fermentation with E. coli CGMCC 22721 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.
The use of l‐valine produced by fermentation with E. coli CGMCC 22721 in animal nutrition is considered safe for the consumers and for the environment.
3.2.4. Safety for the user
No studies were submitted to support the safety of the additive for the user.
The additive under assessment is a powder and the highest dusting potential measured was 600 mg/m3. Therefore, exposure of users by inhalation is possible.
Users can suffer from occupational respiratory disease depending on the level of endotoxins in air and dust (Rylander et al., 1999; Thorn and Kerekes, 2001). The highest bacterial endotoxin activity analysed (three batches) was < 300 EU/g. Taking a concentration of 299 EU/g as worst‐case scenario, the exposure of persons handling the additive to endotoxins in the dust was calculated as described previously (EFSA FEEDAP Panel, 2022). The health based recommended threshold for the quantity of inhaled endotoxins per working day is 900 EU, derived from provisional occupational exposure limits given by the Dutch Expert Committee on Occupational Safety (DECOS) (Health Council of the Netherlands, 2010) and the UK Health and Safety Executive (HSE, 2013). Based upon the calculation of the potential endotoxin content in dust, the inhalation exposure is calculated as 100 EU per working day, indicating no risk of exposure by inhalation to endotoxins for persons handling the additive.
3.2.4.1. Conclusions on safety for the user
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 of the additive does not represent a hazard for users handling the additive when exposed by inhalation.
3.3. Efficacy
Efficacy studies are not required for amino acids that occur naturally in plant and animal proteins. The nutritional role of the amino acid l‐valine is well established in the scientific literature. The product l‐valine produced by fermentation with E. coli CGMCC 22721 is regarded as an efficacious source of the essential amino acid l‐valine for non‐ruminant nutrition. Ruminal degradation would reduce the delivery of the amino acid to the abomasum, and therefore measures to protect the additive from rumen degradation should be considered.
3.4. Post‐market monitoring
The FEEDAP Panel considers that there is no need for specific requirements for a post‐market monitoring plan other than those established in the Feed Hygiene Regulation 37 and Good Manufacturing Practice.
4. CONCLUSIONS
The production strain E. coli CGMCC 22721 is genetically modified. No viable cells or DNA were detected in the final additive. The final product does not raise safety concern regarding the genetic modification of the production strain.
l‐Valine produced by fermentation with E. coli CGMCC 22721 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‐valine produced by fermentation with E. coli CGMCC 22721 in animal nutrition is considered safe for the consumers and for the environment.
The FEEDAP Panel cannot conclude on the potential of l‐valine produced by fermentation with E.coli CGMCC 22721 to be irritant to the skin or eyes, a dermal or a respiratory sensitiser due to the lack of data.
The additive l‐valine produced by fermentation with E. coli CGMCC 22721 is regarded as an efficacious source of the essential amino acid l‐valine for non‐ruminant nutrition. For the supplemental l‐valine to be as efficacious in ruminants as in non‐ruminant species, it requires protection against degradation in the rumen.
ABBREVIATIONS
- ANI
- average nucleotide identity
- CAS
- Chemical Abstracts Service
- CFU
- colony‐forming unit
- DM
- dry matter
- DL‐PCBs
- dioxin‐like polychlorinated biphenyls
- EINECS
- European Inventory of Existing Chemical Substances
- EURL
- European Union Reference Laboratory
- FEEDAP
- EFSA Scientific Panel on Additives and Products or Substances used in Animal Feed
- IUPAC
- International Union of Pure and Applied Chemistry
- LOD
- limit of detection
- LOQ
- limit of quantification
- MIC
- minimum inhibitory concentration
- OECD
- Organisation for Economic Co‐operation and Development
- PCDDs
- Polychlorinated dibenzo‐p‐dioxins
- PCDFs
- polychlorinated dibenzofurans
- WGS
- whole genome sequence
- WHO
- World Health Organization
CONFLICT OF INTEREST
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PANEL MEMBERS
Roberto Edoardo Villa, Giovanna Azimonti, Eleftherios Bonos, Henrik Christensen, Mojca Durjava, Birgit Dusemund, Ronette Gehring, Boet Glandorf, Maryline Kouba, Marta López‐Alonso, Francesca Marcon, Carlo Nebbia, Alena Pechová, Miguel Prieto‐Maradona, Ilen Röhe, and Katerina Theodoridou.
LEGAL NOTICE
Relevant information or parts of this scientific output have been blackened in accordance with the confidentiality requests formulated by the applicant pending a decision thereon by EFSA. The full output has been shared with the European Commission, EU Member States (if applicable) and the applicant. The blackening may be subject to review once the decision on the confidentiality requests is adopted by EFSA and in case it rejects some of the confidentiality requests.
ACKNOWLEDGEMENTS
The Panel wishes to thank the following for the support provided to this scientific output (in alphabetical order of the last name): Jaume Galobart, Matteo Innocenti, Maria Vittoria Vettori and the experts of the Microbiology working group of the FEEDAP Panel.
Notes
EFSA FEEDAP Panel (EFSA Panel on Additives and Products or Substances used in Animal Feed) , Villa, R. E. , Azimonti, G. , Bonos, E. , Christensen, H. , Durjava, M. , Dusemund, B. , Gehring, R. , Glandorf, B. , Kouba, M. , López‐Alonso, M. , Marcon, F. , Nebbia, C. , Pechová, A. , Prieto‐Maradona, M. , Röhe, I. , Theodoridou, K. , Herman, L. , Anguita, M. , … Tarrés‐Call, J. (2024). Safety and efficacy of a feed additive consisting of l‐valine produced with Escherichia coli CGMCC 22721 for all animal species (Eppen Europe SAS). EFSA Journal, 22 (10), e9024. 10.2903/j.efsa.2024.9024 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Adopted: 18 September 2024
Amended: 26 October 2024
Correction Statement: EFSA urgently requested that this output be temporarily removed from Wiley Online Library on 11 October 2024. The output was republished on 26 October 2024 with post‐publication corrections supplied by EFSA.
Notes
1 Regulation (EC) No 1831/2003 of the European Parliament and of the council of 22 September 2003 on the additives for use in animal nutrition. OJ L 268, 18.10.2003, p. 29.
2 Eppen Europe SAS, 10 Rue de la Paix, 75002 Paris, France.
3 Commission Implementing regulation (EU) 2015/1114 of 9 July 2015 concerning the authorisation of l‐valine produced by Escherichia coli as feed additive for all animal species amending Regulation (EC) No 403/2009 and Implementing Regulations (EU) No 848/2014and (EU) 1236/2014. OJ L 182, 10.7.2015, p. 18. Commission Implementing Regulation (EU) 2019/1289 of 31 July 2019 concerning the authorisation of l‐valine produced by Corynebacterium glutamicum KCCM 11201P as a feed additive for all animal species. OJ L 203, 1.8.2019, p. 2. Commission Implementing Regulation (EU) 2020/1797 of 30 November 2020 concerning the authorisation of l‐valine produced by Escherichia coli KCCM 80159 as a feed additive for all animal species. OJ L 402, 1.12.2020, p. 36. Commission Implementing Regulation (EU) 2021/719 of 30 April 2021 concerning the authorisation of l‐valine produced by Corynebacterium glutamicum CGMCC 7.358 as a feed additive for all animal species. OJ L 151, 3.5.2021, p. 12. Commission Implementing Regulation (EU) 2021/2077 of 26 November 2021 concerning the authorisation of l‐valine produced by Corynebacterium glutamicum CGMCC 7.366 as a feed additive for all animal species. OJ L 426, 29.11.2021, p. 5. Commission Implementing Regulation (EU) 2022/1492 of 8 September 2022 concerning the authorisation of l‐valine produced by Escherichia coli CCTCC M2020321 as a feed additive for all animal species. OJ L 234, 9.9.2022, p. 14.
4 Dossier reference: FEED‐2023‐20070.
5 Regulation (EC) No 178/2002 of the European Parliament and of the Council of 28 January 2002 laying down the general principles and requirements of food law, establishing the European Food Safety Authority and laying down procedures in matters of food safety. OJ L 31, 1.2.2002, p. 1–48.
6 Decision available at: https://www.efsa.europa.eu/en/corporate‐pubs/transparency‐regulation‐practical‐arrangements.
7 Evaluation report received on 16/5/2024 and available on the EU Science Hub https://joint‐research‐centre.ec.europa.eu/eurl‐fa‐eurl‐feed‐additives/eurl‐fa‐authorisation/eurl‐fa‐evaluation‐reports_en.
8 Commission Regulation (EC) No 429/2008 of 25 April 2008 on detailed rules for the implementation of Regulation (EC) No 1831/2003 of the European Parliament and of the Council as regards the preparation and the presentation of applications and the assessment and the authorisation of feed additives. OJ L 133, 22.5.2008, p. 1.
9 2.2.1.2.a Certificate of Deposition CGMCC22721.
10 2.2.1.2.c Bioinformatic T1467R1481_2022.
11 2.2.2.2 MIC test T1467R1400_2022.
12 2.2.1.2.c Bioinformatic T1467R1481_2022.
13 2.2.1.2.c Bioinformatic T1467R1481_2022.
14 2.2.1.2.c Bioinformatic T1467R1481_2022 and 2.2.1.2.b Description genetic modifications valine E. coli CGMCC 22721.
15 2.2.1.2.b Description genetic modifications valine E. coli CGMCC 22721.
16 Other supporting document – 2.3.1.a Production flow chart and medium 20230927.
17 Other supporting document – 2.3.1.b C22721‐Statement of no use of antibiotics.
18 Study report – 2.1.3133790 Consolidated 240328. Analytical method stated to be in accordance with EU Regulation 152/2009, Appendix III, method G and F.
19 Certificate of analysis – 2.1.5.b CoAs Optical rotation (V1 – V5). Method of analysis in accordance to EP 2.2.7.
20 Study Report – 2.1.3133790 Consolidated 240328. LOQ in mg/kg was 0.01 for lead and arsenic, and 0.002 for mercury and cadmium.
21 Study Report – 2.1.4.a Dioxins PCBs.
22
Upper bound concentrations are calculated on the assumption that all values of the different congeners below the limit of quantification are equal to the limit of quantification. TEQ=toxic equivalency factors for PCDD/Fs and DL‐PCBs established by WHO in 2005 (van den Berg et al., 2006).
23 Study Report – 2.1.3133790 Consolidated 240328. LOD in μg/kg was 0.05 for aflatoxins, 2.8 for ochratoxin A, 15 for citrinin, 17 for zearalenone, 25 for fumonisins and 134 for deoxynivalenol.
24 Study Report – 2.1.3133790 Consolidated 240328. Section 2.6.3 indicates LOD of a single colony in 25 g samples for Enterobacteriaceae, Salmonella spp., filamentous fungi, yeasts and Escherichia coli.
25 Study Report – 2.1.4.d Endotoxin. Limit test (method A).
26 2.1.4.b Absence viable cells T1467R1437.1.
27 2.1.4.c Absence DNA T1467R1468.1_2022.
28 Other supporting document – 2.5.2 MSDS of L‐valine.
29 Study Report – 2.1.5.a Dust L‐valine (V3‐V5).
30 Study Report – 2.1.3 BtB impurities stability 133790.
31 Other supporting document – 2.4.1.a Premix 252 Broiler.
32 Study Report – 2.4.1.b Stability feed premix homogeneity 133791.
33 Other supporting document – 2.4.1c FEED Grower Commercial.
34 Study Report – 2.4.1.b Stability feed premix homogeneity 133791.
35 Study Report – 2.1.3 BtB impurities stability 133790.
36 Annex 2.4.1.b Stability feed premix homogeneity 133791.
37 Regulation (EC) No 183/2005 of the European Parliament and of the Council of 12 January 2005 laying down requirements for feed hygiene. OJ L 35, 8.2.2005, p. 1.
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