Abstract
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 l‐cysteine monohydrochloride monohydrate produced by fermentation using two genetically modified strains of Escherichia coli K12 (Escherichia coli KCCM 80180 and Escherichia coli KCCM 80181) as a flavouring additive for all animal species. No safety concerns are derived from the use of these strains as production strains of the additive. The FEEDAP Panel concludes that l‐cysteine hydrochloride monohydrate, produced by E.coli KCCM 80180 and KCCM 80181 at concentrations up to 25 mg/kg complete feed, is safe for the target species, for the consumer and for the environment. The product is proposed to be classified as respiratory irritant; however, exposure by inhalation is unlikely. l‐Cysteine hydrochloride monohydrate produced by E.coli KCCM 80180 and E.coli KCCM 80181 was shown to be a skin and eye irritant but not a skin sensitiser. Since l‐cysteine hydrochloride monohydrate is used in food as flavouring, it is to be expected that it can provide a similar function in feed and no further demonstration of efficacy is necessary when used at concentrations up to 25 mg/kg complete feed and the corresponding concentration in water.
Keywords: flavouring additive, l‐cysteine monohydrochloride monohydrate, Escherichia coli KCCM 80180, Escherichia coli KCCM 80181, feed additive
1. Introduction
1.1. Background and Terms of Reference
Regulation (EC) No 1831/20031 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 a feed additive shall submit an application in accordance with Article 7.
The European Commission received a request from CJ Europe GmbH2 for authorisation of the product l‐cysteine monohydrochloride monohydrate produced by fermentation with Escherichia coli KCCM 80180 and Escherichia coli KCCM 80181 when used as a feed additive for all animals(category: sensory additives; functional group: flavourings compounds).
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 particulars and documents in support of the application were considered valid by EFSA as of 19 October 2018.
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 product l‐cysteine monohydrochloride monohydrate produced by fermentation with E.coli KCCM 80180 and E.coli KCCM 80181, when used under the proposed conditions of use (see Section 3.1.2).
1.2. Additional information
l‐Cysteine hydrochloride monohydrate has been assessed by the EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) as a flavouring substance in pets only (EFSA FEEDAP Panel, 2013). The FEEDAP Panel also evaluated l‐cysteine hydrochloride monohydrate in an opinion on the safety and efficacy of the use of amino acids (chemical group 34) when used as flavourings for all animal species (EFSA FEEDAP Panel, 2014). In both opinions, the FEEDAP Panel did not conclude on l‐cysteine hydrochloride monohydrate produced by fermentation because no information on the production strains was submitted.
l‐Cysteine hydrochloride monohydrate has not been assessed for use as food flavour.
l‐Cysteine hydrochloride monohydrate is listed in the European Union Register of Feed Additives as feed flavourings.
l‐Cysteine hydrochloride monohydrate produced by chemical synthesis or protein hydrolysis instead of using production strains is currently authorised as a sensory additive for use in all animal species except cats and dogs in accordance with Regulation (EU) 2018/2493 and l‐cysteine hydrochloride monohydrate produced by hydrolysis of keratin from avian feathers is authorised in dogs and cats in accordance with Regulation (EU) 2015/2306.4
l‐Cysteine hydrochloride [17.032], but not its monohydrate form, is listed in the European Union (EU) database of flavouring substances.5
Cysteine hydrochloride monohydrate is described in the European Pharmacopoeia as Monograph (MG) 0895 (PhEur, 2010).
2. Data and methodologies
2.1. Data
The present assessment is based on data submitted by the applicant in the form of a technical dossier6 in support of the authorisation request for the use of l‐cysteine monohydrochloride monohydrate produced by fermentation with E.coli KCCM 80180 and E.coli KCCM 80181as a feed additive.
The FEEDAP Panel used the data provided by the applicant together with data from other sources, such as previous risk assessments by EFSA or other expert bodies, 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‐cysteine monohydrochloride monohydrate produced by fermentation with E.coli KCCM 80180 and E.coli KCCM 80181 in animal feed. The Executive Summary of the EURL report can be found in Annex A.7
2.2. Methodologies
The approach followed by the FEEDAP Panel to assess the safety and the efficacy of l‐cysteine monohydrochloride monohydrate produced by fermentation with E.coli KCCM 80180 and E.coli KCCM 80181 is in line with the principles laid down in Regulation (EC) No 429/20088 and the relevant guidance documents: Guidance on the identity, characterisation and conditions of use of feed additives (EFSA FEEDAP Panel, 2017a), Guidance on the assessment of the safety of feed additives for the target species (EFSA FEEDAP Panel, 2017b), Guidance on the assessment of the safety of feed additives for the consumer(EFSA FEEDAP Panel, 2017c), Guidance on studies concerning the safety of use of the additive for users/workers (EFSA FEEDAP Panel, 2012), Guidance on the characterisation of microorganisms used as feed additives or as production organisms (EFSA FEEDAP Panel, 2018), Guidance on the safety of feed additives for the environment (EFSA, 2008).
3. Assessment
The present opinion assesses the safety and efficacy of l‐cysteine monohydrochloride monohydrate produced by fermentation using E.coli KCCM 80180 and E.coli KCCM 80181 as a sensory additive (functional group: flavouring compounds) for all animal species. The proposed inclusion level of the additive is 25 mg/kg feed for all animal species in accordance with Commission Implementing Regulation (EU) 2018/249.3
3.1. Characterisation
3.1.1. Characterisation of the production organism
The additive is produced by two genetically modified strains of E. coli K12 which are deposited in the Korean Culture Collection of Microorganisms (KCCM) with accession numbers KCCM 80180 and KCCM 80181.■■■■■ The taxonomic identification of the production strains was confirmed by sequencing the 16S rRNA genes and comparing them to sequences from the GenBank database. The sequences showed 99% similarity with E. coli.■■■■■ The relationship of the production strains as E. coli K‐12 derivatives was established ■■■■■■■■■■
The susceptibility of the production strains to the antibiotics recommended by the FEEDAP Panel (EFSA FEEDAP Panel, 2018) was tested ■■■■■■■■■■■■■■■
3.1.1.1. Information relating to the genetically modified microorganism
Characteristics of the recipient or parental microorganism
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Characteristics of the donor organism
All the genes cloned in KCCM 80180 ■■■■■
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Description of the genetic modification process for E.coli KCCM80180
E.coli KCCM 80180 has several genetic modifications ■■■■■
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All genetic modifications of E. coli KCCM 80180 have been verified by genome analysis of the production strain.
Description of the genetic modification process for E.coli KCCM 80181
E.coli KCCM 80181 was genetically modified ■■■■■
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The absence of all antimicrobial resistance genes from the vectors transiently used during the genetic modification of the production strains E. coli KCCM 80180 and E. coli KCCM 80181, respectively, was demonstrated ■■■■■■■■■■
3.1.2. Manufacturing process
The two production strains E.coli KCCM 80180 and E.coli KCCM 80181 ■■■■■■■■■■■■■■■
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3.1.3. Characterisation of the additive
l‐Cysteine hydrochloride monohydrate (International Union of Pure and Applied Chemistry (IUPAC) name: (R)‐2‐Amino‐3‐mercaptopropionic acid hydrochloride monohydrate; synonym β‐Mercaptoalanine hydrochloride monohydrate) is a compound identified with the Chemical Abstracts Service (CAS) No 7048‐04‐6. It has a molecular mass of 175.6 g/mol. The molecular formula of l‐cysteine hydrochloride monohydrate is C3H7NO2S HCl H2O. The structural formula is given in Figure 1.
Figure 1.
Molecular structure of l‐cysteine hydrochloride monohydrate
The additive contains by specifications ≥ 98.5% l‐cysteine hydrochloride monohydrate and ≤ 12% water.18 The analysis of five batches showed an average value of l‐cysteine hydrochloride monohydrate of 99.23% (range 99.20–99.31%).19 Moisture average was 10.33% (range 10.28–10.38%).
Average cysteine content was 68.3% ‘as is’ (range 68.28–68.32), and average hydrochloride content was 20.5% (range 20.53–20.68). Other components analysed were sulphate 0.2% (in all batches), ammonium (detected in all five batches at 0.01%) and 0.13% free cystine.19 The sum of the identified material on ‘as is’ basis was 99.39%.
Analytical data on specific optical rotation of three batches of l‐cysteine hydrochloride monohydrate showed an average value of + 5.6° (range + 5.53° to + 5.59°), which is within the range described in the European Pharmacopoeia for this amino acid (5.5°–7.0°) and confirms the presence of the l‐enantiomer.20
3.1.3.1. Impurities
Three batches of the additive were analysed for impurities.21 Levels of heavy metals and arsenic were as follow: cadmium and lead were not quantifiable at the specific limit of detection (LOD),22 , 23 mercury = 0.06 mg/kg and arsenic not quantifiable at the LOD.24 Other metals were measured as impurities in the same three batches resulting in levels of chromium not quantifiable at the specific LOD,25 copper between 0.2 and 2.58 mg/kg, nickel between 0.2 and 1.41 mg/kg and zinc between < 0.2 and 1.16 mg/kg.
The same batches were analysed for dioxins (PCDD/F) and sum of PCDD/F and dioxin‐like PCBs and the average values were 0.16 ng TEQ‐WHO/kg and 0.30 ng TEQ‐WHO/kg, respectively (in all batches). In reference to the microbial contamination, three batches were analysed. Salmonella spp. was negative (enriching process). Total bacterial counts, E. coli, yeasts and filamentous fungi were < 103 colony‐forming units (CFU)/g.
Analytical data from three batches showed levels of aflatoxins < 0.1 μg/kg; the same batches were analysed for ochratoxin A, zearalenone and deoxynivalenol. In two out of three batches, these impurities were not detected; analytical data from the third batch showed levels of ochratoxin A < 1.0 μg/kg, zearalenone < 5.0 μg/kg and deoxynivalenol of < 100 μg/kg.26
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The presence of viable cells of the production strains was investigated in three batches of the additive analysed in triplicate.■■■■■■■■■■
The presence of recombinant DNA from the production strains was analysed in three batches of the final product.■■■■■■■■■■
3.1.3.2. Physicochemical characteristics
The additive is an off‐white crystalline powder, with a bulk density of 600–800 kg/m3,30 a pH (10% water solution) ranging from 0.8 to 1.2, and a solubility in water (at 25 °C) of 50 g/L.
The particle size distribution (three batches of the additive) was analysed ■■■■■31 The dusting potential of three batches of the final product (Stauber–Heubach method) ranged ■■■■■32
3.1.4. Stability and homogeneity
The shelf‐life of the additive (three batches) was studied when stored in sealed brown glass containers at 25°C for 12 months or 40 °C for 6 months. The losses of l‐cysteine detected at the end of the respective storage periods ranged from 0.5 to 0.8% at 25°C and from 0.1 to 0.8% at 40°C.33
The stability of the additive (three batches) was studied in water for drinking when used at a concentration of 0.05% (20 times the recommended dose in feed) and stored at 25 or 40°C for 48 h.34 Losses up to 5% and 33% were detected in samples stored at 25°C and 40°, respectively.
3.1.5. Physicochemical incompatibilities
No physicochemical incompatibilities in feed are expected with other additives, medicinal products or other feed materials.
3.1.6. Conditions of use
The applicant proposes the use of l‐cysteine hydrochloride monohydrate as a flavouring compound in feed or water for drinking for all animal species at a level of 25 mg/kg complete feed. The applicant also proposes the use of l‐cysteine hydrochloride monohydrate in water for drinking for all animal species, but no use level is proposed.
3.2. Safety
3.2.1. Safety of the genetic modification
The parental/recipient strain ■■■■■ is considered to be safe. The production strain KCCM 80180 contains ■■■■■ The production strain KCCM 80181 contains ■■■■■■■■■■ The two production strains are free of all antibiotic resistance genes used during the genetic modification processes. ■■■■■
3.2.2. Safety for the target species, consumer and environment
The additive is highly purified with < 1% unidentified material and no bacterial endotoxin activity was measured in the additive. Concerns from the use of the additive would not derive from l‐cysteine hydrochloride monohydrate, which is considered safe, but may arise from residues of the fermentation process/production strains remaining in the final product. Since the identity of the production strains has been established as E. coli K12 derivatives, they are susceptible to relevant antimicrobials used in human and veterinary medicine and no viable cells and their DNA of the production strains are in the final product and the proposed use level (25 mg/kg complete feed) is well below the requirements, the use of l‐cysteine hydrochloride monohydrate produced by E. coli KCCM 80180 and KCCM 80181 under the proposed conditions of use is considered safe for the target species. The FEEDAP Panel noted that the concentration proposed for use as sensory additives in feed falls well below normal intake levels in the target animals (e.g. soya bean meal, a common feed material, contains 1.5% cysteine (FAO, 2014)). Due to the risk of nutritional imbalances and hygienic reasons, associated with the use of amino acids via water for drinking, the FEEDAP Panel has concerns on the safety of the simultaneous oral administration of l‐cysteine hydrochloride monohydrate containing additives via feed and water for drinking.
The composition of edible tissues and products of animal origin will not be changed by the use of the additive; therefore, l‐cysteine hydrochloride monohydrate produced by E.coli KCCM 80180 and KCCM 80181 is safe for the consumer.
l‐Cysteine is a physiological and natural component of proteins in animals and plants. It is not excreted as such but as urea or uric acid, sulfate and CO2. The use of l‐cysteine in animal nutrition would not lead to any localised increase in its concentration in the environment. It is concluded that the use of this product as feed additive does not represent a risk to the environment.
The FEEDAP Panel concludes that the use of l‐cysteine hydrochloride monohydrate, produced by E.coli KCCM 80180 and KCCM 80181 under the proposed conditions of use, is safe for the target species, for the consumer and for the environment.
3.2.3. Safety for the user
3.2.3.1. Effects on the respiratory system
The pH of the additive (10% water solution) ranges from 0.8 to 1.2. The dusting potential of the additive, ■■■■■■■■■■■■■■■■■■■■ So the exposure of users via inhalation is unlikely.
A valid acute inhalation test in laboratory animals, performed according to OECD guideline 403 showed an LC50 greater than 5.14 mg/L in male and female rats.36
The applicant proposes to label the additive with the hazard statement H335 (may cause respiratory irritation)30 according to the Regulation (EC) No 1272/2008.37
3.2.3.2. Effects on the skin and eyes
The skin irritation potential of the additive was tested in a valid study38 performed according to OECD guideline 439. The results of the study indicate that the additive should be classified, according to the United Nations Globally Harmonized System of Classification and Labelling of Chemicals (UN GHS) as an UN GHS Category 2: ‘skin irritant’.30
The eye irritation potential of the additive was tested in a valid study39 performed according to OECD guideline 437. The results of the study indicate that the additive should be classified, according to the UN GHS as an UN GHS Category 1: ‘Serious eye damage’.30
In a valid dermal sensitisation study following OECD guideline 42940 (local lymph‐node assay), the additive did not show any skin sensitisation potential.
3.2.3.3. Conclusions on safety for the user
Although users’ exposure via inhalation is unlikely, the product is proposed to be classified as respiratory irritant due to its low pH when in solution.
l‐cysteine hydrochloride monohydrate produced by E.coli KCCM 80180 and E.coli KCCM 80181was shown to be a skin and eye irritant but not a dermal sensitiser.
3.3. Efficacy
Since l‐cysteine hydrochloride monohydrate is used in food as flavouring, it is to be expected that it can provide a similar function in feed and no further demonstration of efficacy is necessary when used feed and the corresponding concentration in water.
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 Regulation41 and Good Manufacturing Practice.
4. Conclusions
The additive is produced by two genetically modified strains of Escherichia coli K12 (E. coli KCCM 80180 and E. coli KCCM 80181). None of the genetic modifications of the production strains raise a safety concern. The two production strains are free of all antibiotic resistance genes used during the genetic modification processes. The production strain and its DNA were not detected in the final additive. No safety concerns are derived from the use of these strains as production strains of the additive.
The FEEDAP Panel concludes that the use of l‐cysteine hydrochloride monohydrate produced by E.coli KCCM 80180 and KCCM 80181 at concentrations up to 25 mg/kg complete feed, is safe for the target species, for the consumer and for the environment.
The product is proposed to be classified as respiratory irritant; however, exposure by inhalation is unlikely. l‐Cysteine hydrochloride monohydrate produced by E. coli KCCM 80180 and E. coli KCCM 80181 was shown to be a skin and eye irritant but not a skin sensitiser.
Since l‐cysteine hydrochloride monohydrate is used in food as flavourings, it is to be expected that it can provide a similar function in feed and no further demonstration of efficacy is necessary when used at concentrations up to 25 mg/kg complete feed and the corresponding concentration in water.
Documentation provided to EFSA/Chronology
| Date | Event |
|---|---|
| 25/06/2018 | Dossier received by EFSA |
| 09/07/2018 | Reception mandate from the European Commission |
| 19/10/2018 | Application validated by EFSA – Start of the scientific assessment |
| 19/01/2019 | Comments received from Member States |
| 11/02/2019 | Request of supplementary information to the applicant in line with Article 8(1)(2) of Regulation (EC) No 1831/2003 – Scientific assessment suspended. Issues: characterisation |
| 20/02/2019 | Reception of the Evaluation report of the European Union Reference Laboratory for Feed Additives |
| 22/03/2019 | Request of supplementary information addendum in line with Article 8(1)(2) of Regulation (EC) No 1831/2003 – Issues: characterisation |
| 28/06/2019 | Reception of supplementary information from the applicant ‐Scientific assessment re‐started |
| 6/09/2019 | Request of supplementary information to the applicant in line with Article 8(1)(2) of Regulation (EC) No 1831/2003 – Scientific assessment suspended. Issues: characterisation |
| 18/10/2019 | Reception of supplementary information from the applicant |
| 22/10/2019 | Clarification received by e‐mail – Scientific assessment re‐started |
| 10/01/2020 | Opinion adopted by the FEEDAP Panel by written procedure. End of the Scientific assessment |
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Annex A – Executive Summary of the Evaluation Report of the European Union Reference Laboratory for Feed Additives on the Method(s) of Analysis for l‐cysteine monohydrochloride monohydrate produced by fermentation with Escherichia coli KCCM 80180 and Escherichia coli KCCM 80181
1.
In the current application, authorisation is sought under Article 4(1) for l‐cysteine monohydrochloride monohydrate produced by fermentation with Escherichia coli KCCM 80180 and Escherichia coli KCCM 80181, under the category/functional groups 2(b) ‘sensory additives/flavouring compounds’ according to Annex I of Regulation (EC) No 1831/2003. Authorisation is sought for all animal species. According to the Applicant l‐cysteine monohydrochloride monohydrate has a minimum purity (mass fraction) of 98.5%. The feed additive is intended to be added directly into feedingstuffs or through premixtures and water for drinking. The Applicant proposed a maximum content of l‐cysteine monohydrochloride monohydrate in feedingstuffs of 25 mg/kg.
For the quantification of l‐cysteine monohydrochloride monohydrate in the feed additive the Applicant submitted an in‐house validated analytical method based on reversed phase high‐performance liquid chromatography coupled with ultraviolet detection (HPLC‐UV). While in the frame of the validation study satisfactory performance characteristics were derived, the Applicant did not present a verification study or any additional test performed by a second independent laboratory applying the above‐mentioned method.
However, in the frame of the stability studies, the Applicant presented experimental data obtained when analysing the feed additive with the VDLUFA method 4.11.6 designed for the analysis of lysine, methionine and threonine in feed additives and concentrated premixtures and based on ion exchange chromatography coupled with post‐column derivatisation and optical detection (IEC‐VIS/FD). The results presented are considered sufficient to demonstrate the suitability of the procedure for the determination of the amino acid in the feed additive. Furthermore, according to the experience of NRLs, the VDLUFA method and other ring trial validated methods designed for the analysis of amino acids and based on similar analytical procedure are fit‐for‐purpose. Hence, for official control, the EURL recommends this method (or equivalent) for the determination of l‐cysteine monohydrochloride monohydrate in the feed additive.
For the quantification of the l‐cysteine monohydrochloride monohydrate content in premixtures and feedingstuffs, the Applicant submitted the ring‐trial validated Community method (Commission Regulation (EC) No 152/2009) based on IEC‐VIS. This method, designed for the analysis of amino acids in premixtures and feedingstuffs, does not distinguish between the salts and the amino acid enantiomers. The Community method was further ring‐trial validated by 23 laboratories for the determination of total cyst(e)ine (sum of cysteine and cystine, peptide bound and free) in feed and resulted in the equivalent standard method EN ISO 13903:2005. While the Applicant proposed a maximum content of l‐cysteine HCl H2O in feedingstuffs of 25 mg/kg, a higher limit of quantification of 350 mg/kg feedingstuffs was derived for total cyst(e)ine. Therefore, the EURL is unable to recommend the Community method for the official control of this product in feedingstuffs when intended as flavouring feed additive. Nevertheless, based on the performance characteristics available, the EURL recommends for official control the ring‐trial validated Community method based on IEC‐VIS to quantify l‐cysteine monohydrochloride monohydrate in premixtures. Moreover exclusively the procedure for the determination of free amino acid applies.
The Applicant did not submit any method for the official control of l‐cysteine monohydrochloride monohydrate in water. However, in the frame of the stability studies, the Applicant presented experimental data obtained when analysing the amino acid with the above‐mentioned ring‐trial validated method VDLUFA – Method 4.11.6. The results presented are considered sufficient to demonstrate the suitability of the procedure for the analysis of l‐cysteine monohydrochloride monohydrate in water. Hence, for official control, the EURL recommends this method (or equivalent) for the determination l‐cysteine monohydrochloride monohydrate in water.
In the frame of the authorised ‘Chemical Defined flavouring Group 34 – amino acids’ (FAD‐2010‐0107), for the identification of l‐cysteine monohydrochloride monohydrate in the feed additive, the EURL positively evaluated the European Pharmacopeia 2.2.56 (2009) method for amino acids based on IEC coupled with post column derivatisation and photometric detection (visible – VIS). Furthermore, the EURL recommendation has been included in the corresponding authorising regulation. In order to foster the use of the same method for identical substances, the EURL recommends this European Pharmacopeia method for official control to identify l‐cysteine monohydrochloride monohydrate in the feed additive.
Further testing or validation of the methods to be performed through the consortium of National Reference Laboratories as specified by Article 10 (Commission Regulation (EC) No 378/2005), as last amended by Regulation (EU) 2015/1761) is not considered necessary.
Suggested citation: EFSA FEEDAP Panel (EFSA Panel on Additives and Products or Substances used in Animal Feed) , Bampidis V, Azimonti G, Bastos ML, Christensen H, Dusemund B, Kouba M, Kos Durjava M, López‐Alonso M, López Puente S, Marcon F, Mayo B, Pechová A, Petkova M, Ramos F, Sanz Y, Villa RE, Woutersen R, Glandorf B, Herman L, Maradona MP, Saarela M, Anguita M, Brozzi R, Galobart J, Gregoretti L, Innocenti M, López‐Gálvez G, Sofianidis K, Pettenati E and Vettori MV, 2020. Scientific Opinion on the safety and efficacy of l‐cysteine hydrochloride monohydrate produced by fermentation using Escherichia coli KCCM 80180 and Escherichia coli KCCM 80181 as a flavouring additive for all animal species. EFSA Journal 2020;18(2):6003, 14 pp. 10.2903/j.efsa.2020.6003
Requestor: European Commission
Question number: EFSA‐Q‐2018‐00552
Panel members: Giovanna Azimonti, Vasileios Bampidis, Maria de Lourdes Bastos, Henrik Christensen, Birgit Dusemund, Maryline Kouba, Mojca Kos Durjava, Marta López‐Alonso, Secundino López Puente, Francesca Marcon, Baltasar Mayo, Alena Pechová, Mariana Petkova, Fernando Ramos, Yolanda Sanz, Roberto Edoardo Villa and Ruud Woutersen.
Acknowledgements: The Panel wishes to thank the following for the support provided to this scientific output: Jaume Galobart, Manini Paola, Jordi Tarrés‐Call.
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 the European Commission. The full output has been shared with the European Commission, EU Member States and the applicant. The blackening will be subject to review once the decision on the confidentiality requests is adopted by the European Commission.
Adopted: 10 January 2020
Notes
Regulation (EC) No 1831/2003 of the European Parliament and of the Council of 22 September 2003 on additives for use in animal nutrition. OJ L 268, 18.10.2003, p. 29.
CJ Europe GmbH, Ober der Roeth, 4, 65824 – Schwalbach am Taunus, Germany.
Commission Implementing Regulation (EU) 2018/249 of 15 February 2018 concerning the authorisation of taurine, beta‐alanine, l‐alanine, l‐arginine, l‐aspartic acid, l‐histidine, d,l‐isoleucine, l‐leucine, l‐phenylalanine, l‐proline, d,l‐serine, l‐tyrosine, l‐methionine, l‐valine, l‐cysteine, glycine, monosodium glutamate and L‐glutamic acid as feed additives for all animal species and l‐cysteine hydrochloride monohydrate for all species except cats and dogs. OJ L 53, 23.2.2018, p. 134.
Commission Implementing Regulation (EU) 2015/2306 of 10 December 2015 concerning the authorisation of L‐cysteine hydrochloride monohydrate as a feed additive for cats and dogs. OJ L 326, 11.12.2015, p. 46.
Commission Implementing Regulation (EU) No 872/2012 of 1 October 2012 adopting the list of flavouring substances provided for by Regulation (EC) No 2232/96 of the European Parliament and of the Council, introducing it in Annex I to Regulation (EC) No 1334/2008 of the European Parliament and of the Council and repealing Commission Regulation (EC) No 1565/2000 and Commission Decision 1999/217/EC. OJ L 267, 2.10.2012, p. 1.
FEED dossier reference: FAD‐2018‐0042.
The full report is available on the EURL website: https://ec.europa.eu/jrc/en/eurl/feed-additives/evaluation-reports/fad-2018-0042.
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.
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Technical dossier/Section II/Annex II_1_01.
Technical dossier/Section II/Annex II_1_03.
Technical dossier/Section II/Annex II_1_02.
Technical dossier/Section II/Annex II_1_04.
LOD for Cd, < 0.2 mg/kg.
LOD for Pb, < 1 mg/kg.
LOD for As, < 1 mg/kg
LOD for Cr, < 0.2 mg/kg.
Technical dossier/Section II/Annex II_1_05.
Technical dossier/Supplementary information May 2019/Annex_SIN_4.
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Technical dossier/Section III/ Annex_III_3_01.
Technical dossier/Section II/Annex II_1_06.
Technical dossier/Section II/Annex II_1_07.
Technical dossier/Section II/Annex II_4_01.
Technical dossier/Section II/Annex II_4_03.
Technical dossier/Section II/Annex_III_3_03.
Technical dossier/Section III/Annex_III_3_04.
Regulation (EC) No 1272/2008 of the European Parliament and of the council of 16 December 2008 on classification, labelling and packaging of substances and mixtures, amending and repealing Directives 67/548/EEC and 1999/45/EC, and amending Regulation (EC) No 1907/2006, OJ L 353, 31.12.2008, p. 1.
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Technical dossier/Section III/ Annex_III_3_05.
Technical dossier/Section III/ Annex_III_3_07.
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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