Safety and efficacy of the feed additives l‐histidine and l‐histidine monohydrochloride monohydrate produced with Corynebacterium glutamicum KCCM 80389 for all animal species (CJ Europe GmbH)
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
TL;DR
This paper evaluates the safety and effectiveness of l-histidine additives made with a genetically modified bacteria for all animal species.
Contribution
The study confirms the safety of l-histidine additives for animals and consumers, but raises concerns about their use in drinking water.
Findings
The additives are safe for target species when used in appropriate amounts.
No viable cells or DNA from the production strain were found in the final products.
The additives are effective for non-ruminants but need protection for ruminants.
Abstract
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…
Genes, proteins, chemicals, diseases, species, mutations and cell lines named across the full text — each resolved to its canonical identifier and authoritative record.
Click any figure to enlarge with its caption.
FIGURE 1|
|
| |
|---|---|---|
|
| ||
|
| > 90 | > 72 |
|
| – | > 98 |
| Moisture (%) | < 1.5 | < 10 |
| Other amino acids (%) | < 1 | – |
|
| [5] | [5] |
|
| 93.14 (91.7–93.7) | 74.60 (73.2–75.8) |
| Chloride (%, DM) | < 0.04 | 17 |
| Moisture (%, as is) | 0.40 | 8.78 |
| Other amino acids (%, DM) | 0.698 (0.67–0.74) | < 0.05 |
|
| +12.90 to +13.04 [3] | +9.28 to +9.31 [3] |
|
| [3] | [3] |
| Lead (mg/kg) | 0.033–0.043 | < 0.015 |
| Mercury (mg/kg) | < 0.010 | < 0.010 |
| Cadmium (mg/kg) | < 0.010 | < 0.010 |
| Arsenic (mg/kg) | < 0.04 | < 0.04 |
| Antifoaming (%) | < 0.025 | < 0.025 |
| Dioxins and furans (upper bound) | ||
| PCDD/Fs (ng WHO2005‐TEQ/kg) | 0.057 | 0.057 |
| PCDD/Fs + PCBs (ng WHO2005‐TEQ/kg) | 0.12 | 0.12 |
| nDL‐PCBs (μg/kg) | 0.53 | 0.53 |
| Mycotoxins (μg/kg) | ||
| Aflatoxins B1, B2, G1, G2 | < 0.2 | < 0.2 |
| Ochratoxin A | < 0.5 | < 0.5 |
| Deoxynivalenol | < 10 | < 10 |
| Zearalenone | < 5.0 | < 5.0 |
| T‐2 Toxin | < 2.0 | < 2.0 |
| HT‐2 Toxin | < 2.0 | < 2.0 |
| Fumonisins B1, B2, B3 | < 50 | < 50 |
| Histamine (mg/kg) | 3.2–6.3 [5] | < 5 [5] |
|
| [3] | [3] |
|
| Not detected | Not detected |
|
| Not detected | Not detected |
|
| Not detected | Not detected |
| Yeast and moulds (CFU/g) | < 10 | < 10 |
|
|
| |
|---|---|---|
|
| ||
| Bulk density (kg/m3) | 609.3 | 817 |
| Solubility (g/L) | 43 | 45.6–419.3 |
| Dusting potential (Stauber–Heubach) (mg/m3) | 7177 | 1182 |
|
| ||
| 100 μm | 66.35 | 6.87 |
| 50 μm | 43.94 | 2.91 |
| 10 μm | 9.21 | 0.65 |
|
| ||
|
| ||
| 25°/60% RH – 6 months | 0–0.1 | 0.3–0.4 |
| 40°C/75% RH – 6 months | 0–0.6 | 0.1–0.2 |
|
| ||
| Vitamin‐mineral premix, 25°/60% RH – 6 months | 0–12.2 | 0–8.9 |
|
| ||
| Mash – 25°C/60% RH, 3 months | 0–11.4 | 0–6.5 |
| Pelleted – 25°C/60% RH, 3 months | 0–13.5 | 0–9.4 |
| Pelleting 70–75°C | 0–5.7 | 0–6.5 |
|
| 0 | 0 |
|
| ||
| Premixture (10 subsamples) | 3.89 | 4.01 |
| Broiler mash (10 subsamples) | 11.90 | 3.38 |
| Pelleted (10 subsamples) | 4.68 | 2.45 |
Peer Reviews
No public reviews on file for this paper yet. If you reviewed it on a platform where reviews are public (OpenReview, ICLR, NeurIPS, ICML), you can paste yours below so the community can read it here.
Videos
No videos yet. Explain this paper in a talk, walkthrough, or lecture? Add one.
Taxonomy
TopicsAgricultural safety and regulations · Effects and risks of endocrine disrupting chemicals · Pesticide Residue Analysis and Safety
INTRODUCTION
1
Background and Terms of Reference
1.1
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 feed additive shall submit an application in accordance with Article 7.
The European Commission received a request from CJ Europe GmbH for the authorisation of the additives l‐histidine and l‐histidine monohydrochloride monohydrate produced with Corynebacterium glutamicum KCCM 80389 when used as a feed additive for all animal species (category: nutritional additives; functional group: amino acids, their salts and analogues; and category: sensory additives; functional group: flavouring 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 dossier was received on 18 January 2024 and the general information and supporting documentation are available at https://open.efsa.europa.eu/questions/EFSA‐Q‐2024‐00031. The particulars and documents in support of the application were considered valid by EFSA as of 25 April 2024.
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 additives l‐histidine and l‐histidine monohydrochloride monohydrate produced with Corynebacterium glutamicum KCCM 80389, when used under the proposed conditions of use (see Section 3.1.4).
Additional information
1.2
The additives l‐histidine and l‐histidine monohydrochloride monohydrate produced with C. glutamicum KCCM 80389 have not been previously authorised as feed additives in the European Union (EU).2
l‐histidine and l‐histidine monohydrochloride monohydrate produced by chemical synthesis or protein hydrolysis or fermentation with production strains different from the one mentioned in the paragraph above are currently authorised in the EU.3
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‐histidine and l‐histidine monohydrochloride monohydrate produced by chemical synthesis or protein hydrolysis or fermentation using different production strains, when used as amino acid in feed for all animal species.4
DATA AND METHODOLOGIES
2
Data
2.1
The present assessment is based on data submitted by the applicant in the form of a technical dossier5 in support of the authorisation request for the use of l‐histidine and l‐histidine monohydrochloride monohydrate produced with C. glutamicum KCCM 80389 as a feed additives.
In accordance with Article 38 of the Regulation (EC) No 178/20026 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,7 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 8 May to 29 May 2025 for which no comments were received.
The confidential version of the technical dossier was subject to a target consultation of the interested Member States from 30 April 2024 to 30 July 2024 for which the received comments were considered for the assessment.
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, peer‐reviewed scientific papers, other scientific reports and experts' (elicitation) knowledge, 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‐histidine and l‐histidine monohydrochloride monohydrate in animal feed.8
Methodologies
2.2
The approach followed by the FEEDAP Panel to assess the safety and the efficacy of l‐histidine and l‐histidine monohydrochloride monohydrate produced with C. glutamicum KCCM 80389 is in line with the principles laid down in Regulation (EC) No 429/20089 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 characterisation of microorganisms used as feed additives or as production organisms (EFSA FEEDAP Panel, 2018), 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), Guidance on the assessment of the safety of feed additives for the users (EFSA FEEDAP Panel, 2023) and Guidance on the assessment of the efficacy of feed additives (EFSA FEEDAP Panel, 2024).
ASSESSMENT
3
l‐histidine and l‐histidine monohydrochloride monohydrate (≥ 90% and ≥ 98% on dry matter basis, respectively), produced by fermentation with a genetically modified strain of C. glutamicum KCCM 80389, are intended to be used as nutritional additives (functional group: amino acids, their salts and analogues) and as sensory additives (functional group: flavouring compounds) in feed and water for drinking for all animal species and categories.
Characterisation
3.1
Characterisation of the production microorganism
3.1.1
The production microorganism is a genetically modified strain of C. glutamicum that is deposited in the Korean Culture Collection of Microorganisms (KCCM) with accession number KCCM 80389.10
The taxonomic identification of the production strain was confirmed ■■■■■■■■■■ ■■■■■■■■■■ ■■■■■
The antimicrobial susceptibility of the production strain was tested ■■■■■■■■■■ ■■■■■ Therefore, the production strain is considered susceptible to all relevant antibiotics.
The WGS data of the production strain, was interrogated for the presence of antimicrobial resistance (AMR) genes ■■■■■ it can be concluded that no acquired AMR genes were identified, and the strain raises no concerns in that regard.14
Characterisation of the parental microorganism
The parental strain C. glutamicum ■■■■■15
Characteristics of the introduced genes
■■■■■
■■■■■
Description of the genetic modification
■■■■■
- ■■■■■
- ■■■■■
- ■■■■■
- ■■■■■
- ■■■■■
- ■■■■■
■■■■■16 ■■■■■17
■■■■■18 No concerns were identified.
Manufacturing process
3.1.2
l‐Histidine and l‐histidine monohydrochloride monohydrate are produced by fermentation with C. glutamicum KCCM 80389.19 The applicant provided information on the fermentation media and antifoaming reagent used. ■■■■■20
The applicant stated that no antimicrobial substances are used in the manufacturing process.21
Characterisation of the additives
3.1.3
The additives under assessment are l‐histidine and l‐histidine monohydrochloride monohydrate.
l‐Histidine (International Union of Pure and Applied Chemistry (IUPAC) name: (2S)‐2‐amino‐3‐(1H‐imidazol‐5‐yl) propanoic acid) is a compound identified with the Chemical Abstract Service (CAS) No 71‐00‐1, has a molecular weight of 155.15 g/mol and its chemical formula is C_6_H_9_N_3_O_2_. The additive l‐histidine is specified to contain l‐histidine ≥ 90% on dry matter basis, < 1.5% moisture and < 1.0% of other amino acids.22 The structural formula is given in Figure 1A.
l‐Histidine monohydrochloride monohydrate (IUPAC name (2S)‐2‐amino‐3‐(1H‐imidazol‐5‐yl) propanoic acid hydrate hydrochloride) is a compound identified with CAS number 5934‐29‐2 and has a molecular weight of 209.63 g/mol. The chemical formula is C_6_H_9_N_3_O_2_·HCl·H_2_O. l‐Histidine monohydrochloride monohydrate is specified to be ≥ 98% in the final product from which ≥ 72% is l‐histidine and < 10% moisture.23 The structural formula is given in Figure 1B.
Molecular structure of the additives.
The data provided by the applicant on the specifications,24 batch‐to‐batch variation25 and impurities26 are reported in Table 1, whereas the physical properties27 of the additives are reported in Table 2.
The data provided showed compliance of the two additives with the respective specifications set by the applicant. The total amount of identified material on a DM basis for l‐histidine and l‐histidine monohydrochloride monohydrate was > 98% and > 99%, respectively.
The FEEDAP Panel considers that the microbial contamination and the amounts of the detected impurities do not raise safety concerns.
The presence of viable cells of the production strain was investigated in three independent batches of each additive, l‐histidine and l‐histidine monohydrochloride monohydrate, in triplicate.28 ■■■■■) ■■■■■ Therefore, no viable cells of the production strain were detected in the additives.
The presence of DNA from the production strain C. glutamicum KCCM 80389 was investigated in three independent batches of each additive, l‐histidine and l‐histidine monohydrochloride monohydrate, in triplicate.29 ■■■■■ No DNA from the production strain was detected in the batches tested.
Conditions of use
3.1.4
The additives under assessment are intended to be used in feeds to achieve the adequate amino acid profile and meet the requirements on l‐histidine and l‐histidine monohydrochloride monohydrate for all animal species. They can be added directly to compound feed, through complementary feed or via premixtures and water for drinking. No inclusion levels are proposed, as the requirements in quantitative terms depend on the species, the physiological state of the animal, the performance level and the environmental conditions, as well as the water intake and the amino acid composition of the unsupplemented diet.
When used as feed flavouring, l‐histidine and l‐histidine monohydrochloride monohydrate are proposed to be used at a maximum recommended level of 25 mg/kg complete feed.30
Safety
3.2
Safety of the production microorganism
3.2.1
The production organism C. glutamicum KCCM 80389 is a genetically modified strain which was developed to increase the production of l‐histidine. The production strain belongs to a species, C. glutamicum, that qualifies for the qualified presumption of safety (QPS) approach to safety assessment when used for production purposes (EFSA BIOHAZ Panel, 2023). The taxonomic identification of the production strain was unequivocally established, KCCM 80389 does not carry acquired AMR genes and the genetic modification does not raise safety concerns. No viable cells nor DNA of the production strain were detected in the final products. Therefore, the FEEDAP Panel concludes that the additives do not pose any safety concerns regarding the genetically modified production strain.
Safety for the target species, consumers and the environment
3.2.2
The l‐histidine requirements of the target animal species and the safety of this amino acid in non‐ruminant and ruminant nutrition are well known by feed formulators and available in general publications on animal nutrition.
The additives are highly purified (> 98% l‐histidine and > 99% l‐histidine monohydrochloride monohydrate and about 2% unidentified material on a dry matter basis) and are produced by fermentation using a strain that is considered safe. Concerns on the use of the additive would not derive from the l‐histidine, which is considered safe, but may arise from residues of the fermentation process/production strain remaining in the final product.
The production strain qualifies for the QPS safety assessment approach; the genetic modifications performed are considered safe, and no viable cells nor DNA of the production strain were found in the final products. l‐Histidine produced with C. glutamicum KCCM 80389 is safe for the target species when used to supplement the diet in appropriate amounts to satisfy the animal requirements. However, due to the risk of nutritional imbalances and hygienic reasons associated to the use of amino acids via water for drinking (EFSA FEEDAP Panel, 2010), the FEEDAP Panel has concerns on the safety of the simultaneous oral administration of amino acid‐containing additives via feed and water for drinking.
The absorption and metabolic fate of l‐histidine in the organism are well known. The amino acid l‐histidine will be incorporated into proteins of tissues and/or products of animal origin and any of its potential excess will be metabolised and excreted. Therefore, the protein composition of tissues and products of animal origin will not be affected by using l‐histidine in animal nutrition. Therefore, the Panel considers that the use of the additive in animal nutrition is safe for the consumer.
Since the levels proposed for the use of l‐histidine as flavouring compound (25 mg/kg complete feed) are substantially lower than the animal requirements, the FEEDAP Panel considers that l‐histidine produced by fermentation with C. glutamicum KCCM 80389 is safe for the target species when used as a flavouring compound.
The amino acid l‐histidine is a physiological and natural component of animals and plants. It is not excreted as such, but as urea/uric acid, and carbon dioxide. The use of the product l‐histidine in animal nutrition would not lead to any localised increase in the concentration in the environment. The use of the additive 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. It is concluded that the use of the products, l‐histidine and l‐histidine monohydrochloride produced by fermentation with C. glutamicum KCCM 80389 as feed additives do not represent a risk to the environment.
Safety for the user
3.2.3
Based on the highest dusting potential measured value (see Section 3.1.3), the FEEDAP Panel considers that the exposure of users through inhalation is likely.
The acute inhalation toxicity of the additives was tested in studies performed according to OECD guideline (OECD 403, 2009, nose only exposure).31 The lethal concentration 50 (LC_50_) of l‐histidine and l‐histidine monohydrochloride monohydrate is more than 5 mg/L and 4.7 mg/L, respectively.
The skin irritation potential of l‐histidine and l‐histidine monohydrochloride monohydrate was tested in two studies performed according to OECD TG 439, which showed that the additives are not skin irritants (UN GHS No Category).32
The eye irritation potential of l‐histidine and l‐histidine monohydrochloride monohydrate was tested in two studies performed according to OECD TG 437, which showed that the additives are not eye irritants (UN GHS No Category).33
The skin sensitisation potential of l‐histidine and l‐histidine monohydrochloride monohydrate was tested in two studies performed according to OECD TG 429, which showed that the additives are not skin sensitisers (UN GHS No Category).34
Conclusions on the safety for the user
3.2.3.1
Based on the submitted studies, the additives l‐histidine and l‐histidine monohydrochloride monohydrate are not‐irritant to skin or eyes, and not skin sensitisers.
Efficacy
3.3
Efficacy studies are not required for amino acids that occur naturally in plant and animal proteins. The nutritional role of the amino acid l‐histidine is well established in the scientific literature. l‐Histidine and l‐histidine monohydrochloride monohydrate produced by fermentation using C. glutamicum KCCM 80389 are regarded as an efficacious source of the essential amino acid l‐histidine for non‐ruminant nutrition. Ruminal degradation would reduce the delivery of the amino acid to the abomasum, and protective measures should be considered.
As l‐histidine is used in food as flavouring compound, it is expected that it can provide a similar function in feed and no further demonstration of efficacy is necessary.
Post‐market monitoring
3.4
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 Regulation35 and Good Manufacturing Practice.
CONCLUSIONS
4
The production strain C. glutamicum KCCM 80389 does not raise safety concerns regarding the genetic modifications. No viable cells nor DNA of the production strain are detected in the final products. Therefore, the FEEDAP Panel concludes that the additives do not pose any safety concern regarding the production strain.
The use of l‐histidine and l‐histidine monohydrochloride monohydrate produced by fermentation with C. glutamicum KCCM 80389 in feed are 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‐histidine or l‐histidine monohydrochloride monohydrate via water for drinking.
The use of l‐histidine and l‐histidine monohydrochloride monohydrate produced by fermentation with C. glutamicum KCCM 80389 in animal nutrition is considered safe for the consumers and for the environment.
Regarding user safety, the l‐histidine and l‐histidine monohydrochloride produced by fermentation with C. glutamicum KCCM 80389 are not irritant to skin or eyes and are not skin sensitisers.
The feed additives consisting of l‐histidine and l‐histidine monohydrochloride monohydrate produced by fermentation with C. glutamicum KCCM 80389 are regarded as an effective source of the amino acid l‐histidine for all non‐ruminant species. In order to be as efficacious in ruminants as in non‐ruminants, it should be protected from ruminal degradation. As l‐histidine is used in food as flavouring compound, it is expected that it can provide a similar function in feed and no further demonstration of efficacy is necessary.
ABBREVIATIONSAMRantimicrobial resistanceCASChemical Abstract ServiceCFUcolony forming unitCVcoefficient of variationDMdry matterEINECSEuropean Inventory of Existing Chemical SubstancesEURLEuropean Union Reference LaboratoryFEEDAPEFSA Scientific Panel on Additives and Products or Substances used in Animal FeedLODlimit of detectionLOQlimit of quantificationMICminimum inhibitory concentrationnDL‐PCBnon‐dioxin‐like polychlorinated biphenylOECDOrganisation for Economic Co‐operation and DevelopmentPCBpolychlorinated biphenylPCDDpolychlorinated dibenzo‐p‐dioxinPCDFpolychlorinated dibenzofuranRHrelative humidityTEQtoxic equivalent factorWGSwhole genome sequenceWHOWorld Health Organization
REQUESTOR
European Commission
QUESTION NUMBER
EFSA‐Q‐2024‐00031
COPYRIGHT FOR NON‐EFSA CONTENT
EFSA may include images or other content for which it does not hold copyright. In such cases, EFSA indicates the copyright holder and users should seek permission to reproduce the content from the original source.
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.
The reference list from the paper itself. Each links out to its DOI / PubMed record.
- 1EFSA (European Food Safety Authority) . (2024). EFSA statement on the requirements for whole genome sequence analysis of microorganisms intentionally used in the food chain. EFSA Journal, 22(8), 8912. 10.2903/j.efsa.2024.8912 PMC 1131780639135845 · doi ↗ · pubmed ↗
- 2EFSA BIOHAZ Panel (EFSA Panel on Biological Hazards) , Koutsoumanis, K. , Allende, A. , Álvarez‐Ordóñez, A. , Bolton, D. , Bover‐Cid, S. , Chemaly, M. , De Cesare, A. , Hilbert, F. , Lindqvist, R. , Nauta, M. , Peixe, L. , Ru, G. , Simmons, M. , Skandamis, P. , Suffredini, E. , Cocconcelli, P. S. , Fernández Escámez, P. S. , Prieto Maradona, M. , … Herman, L. (2023). Scientific opinion on the update of the list of qualified presumption of safety (QPS) recommended microorganis · doi ↗
- 3EFSA FEEDAP Panel (EFSA Panel on Additives and Products or Substances used in Animal Feed) . (2010). Statement on the use of feed additives authorised/applied for use in feed when supplied via water. EFSA Journal, 8(12), 1956. 10.2903/j.efsa.2010.1956 · doi ↗
- 4EFSA FEEDAP Panel (EFSA Panel on Additives and Products or Substances used in Animal Feed) , Rychen, G. , Aquilina, G. , Azimonti, G. , Bampidis, V. , Bastos, M. L. , Bories, G. , Chesson, A. , Cocconcelli, P. S. , Flachowsky, G. , Gropp, J. , Kolar, B. , Kouba, M. , López‐Alonso, M. , López Puente, S. , Mantovani, A. , Mayo, B. , Ramos, F. , Saarela, M. , … Innocenti, M. L. (2017 a). Guidance on the assessment of the safety of feed additives for the consumer. EFSA Journal, 15 · doi ↗
- 5EFSA FEEDAP Panel (EFSA Panel on Additives and Products or Substances used in Animal Feed) , Rychen, G. , Aquilina, G. , Azimonti, G. , Bampidis, V. , Bastos, M. L. , Bories, G. , Chesson, A. , Cocconcelli, P. S. , Flachowsky, G. , Gropp, J. , Kolar, B. , Kouba, M. , López‐Alonso, M. , López Puente, S. , Mantovani, A. , Mayo, B. , Ramos, F. , Saarela, M. , … Innocenti, M. L. (2017 b). Guidance on the identity, characterisation and conditions of use of feed additives. EFSA Jour · doi ↗ · pubmed ↗
- 6EFSA FEEDAP Panel (EFSA Panel on Additives and Products or Substances used in Animal Feed) , Rychen, G. , Aquilina, G. , Azimonti, G. , Bampidis, V. , Bastos, M. L. , Bories, G. , Chesson, A. , Cocconcelli, P. S. , Flachowsky, G. , Gropp, J. , Kolar, B. , Kouba, M. , López‐Alonso, M. , López Puente, S. , Mantovani, A. , Mayo, B. , Ramos, F. , Saarela, M. , … Martino, L. (2017 c). Guidance on the assessment of the safety of feed additives for the target species. EFSA Journal, 1 · doi ↗ · pubmed ↗
- 7EFSA FEEDAP Panel (EFSA Panel on Additives and Products or Substances used in Animal Feed) , Rychen, G. , Aquilina, G. , Azimonti, G. , Bampidis, V. , Bastos, M. L. , Bories, G. , Chesson, A. , Cocconcelli, P. S. , Flachowsky, G. , Gropp, J. , Kolar, B. , Kouba, M. , López‐Alonso, M. , López Puente, S. , Mantovani, A. , Mayo, B. , Ramos, F. , Saarela, M. , … Galobart, J. (2018). Guidance on the characterisation of microorganisms used as feed additives or as production organis · doi ↗ · pubmed ↗
- 8EFSA FEEDAP Panel (EFSA Panel on Additives and Products or Substances used in Animal Feed) , Bampidis, V. , Bastos, M. , 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, R. E. , Woutersen, R. , Brock, T. , de Knecht, J. , … Azimonti, G. (2019). Guidance on the assessment of the safety of feed additives for the environment. EFSA Journal, 17(4), · doi ↗ · pubmed ↗