Assessment of the feed additive consisting of Saccharomyces cerevisiae NCYC R404 for dairy cows for the renewal of its authorisation (Volac International Ltd)

TL;DR

This paper assesses the safety of a yeast additive for dairy cows and concludes it remains safe for use.

Contribution

The paper confirms the continued safety of Saccharomyces cerevisiae NCYC R404 for dairy cows without new evidence to change prior conclusions.

Findings

The additive remains safe for target species, consumers, and the environment.

It is not irritant to eyes and skin but may be a potential sensitiser.

No new efficacy assessment is needed for renewal of authorisation.

Abstract

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the assessment of the application for renewal of the authorisation of Saccharomyces cerevisiae NCYC R404 as a zootechnical additive (functional group: gut flora stabilisers) for dairy cows. The applicant has provided evidence that the additive currently on the market complies with the existing conditions of authorisation. There was no new evidence that would lead the EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) to reconsider its previous conclusions on the safety of the product for the target species, consumers and the environment, for which the additive is considered to remain safe. Regarding user safety, the Panel reiterates its previous conclusions that the additive is not irritant to eyes and skin but should be considered a potential skin and respiratory sensitiser, and any exposure through skin and respiratory tract is considered a risk. There is no need for assessing the efficacy of the additive in the context of renewal of the authorisation.

Full text

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 14(1) of that Regulation lays down that an application for renewal shall be sent to the Commission at the latest 1 year before the expiry date of the authorisation.

The European Commission received a request from Volac International Ltd, represented in the EU by Volac Feeds Ltd.2 for the renewal of the authorisation of the additive consisting of Saccharomyces cerevisiae NCYC R404, when used as a feed additive for dairy cows (category: zootechnical additives; functional group: gut flora stabilisers).

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 14(1) (renewal of the authorisation). The dossier was received on 18 April 2024 and the general information and supporting documentation are available at https://open.efsa.europa.eu/questions/EFSA‐Q‐2024‐00260. The particulars and documents in support of the application were considered valid by EFSA as of 25 July 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 additive consisting of S. cerevisiae NCYC R404, when used under the proposed conditions of use (see Section 3.1.3).

Additional information

1.2

The additive is a preparation containing S. cerevisiae NCYC R404 and is currently authorised for use in feed for dairy cows (4b1871).3 EFSA issued two opinions on the safety and efficacy of this product when used in feed for dairy cows (EFSA FEEDAP Panel, 2009, 2014).

DATA AND METHODOLOGIES

2

Data

2.1

The present assessment is based on data submitted by the applicant in the form of a technical dossier4 in support of the authorisation request for the use of S. cerevisiae NCYC R404 as a feed additive.

In accordance with Article 38 of the Regulation (EC) No 178/20025 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 29 November 2024 to 20 December 2024 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 7 August 2024 to 7 November 2024; the comments received were considered for the assessment.

The European Union Reference Laboratory (EURL) considered that the conclusions and recommendations reached in the previous assessment regarding the methods used for the control of the S. cerevisiae NCYC R404 in animal feed are valid and applicable for the current application.7

Methodologies

2.2

The approach followed by the FEEDAP Panel to assess the safety and the efficacy of S. cerevisiae NCYC R404 is in line with the principles laid down in Regulation (EC) No 429/20088 and the relevant guidance documents: Guidance on the renewal of the authorisation of feed additives (EFSA FEEDAP Panel, 2021).

ASSESSMENT

3

The additive S. cerevisiae NCYC R404 is currently authorised as a zootechnical additive (functional group: gut flora stabilisers) for use in feed for dairy cows. The assessment regards the renewal of the authorisation.

Characterisation

3.1

Characterisation of the additive

3.1.1

The additive currently authorised is a solid preparation containing S. cerevisiae NCYC R404 at a minimum concentration of 1 × 10^10^ colony forming units (CFU)/g additive.

The applicant declared that the manufacturing process has not been modified since the previous application and no antimicrobials are used at any stage of the production process.9

The active agent is grown by fermentation and concentrated by centrifugation. Excipients are added and the resulting mixture is dried and milled. The final product contains about 1% dextrose, 1% sorbitan monostearate, used as stabiliser and 98% yeast cells.10 Sorbitan monostearate is authorised in the EU as food additive. Its safety is assessed in the Appendix A.

Analytical data to confirm the specifications regarding the minimum concentration of the active agent were provided for five batches of the additive, showing an average value of 1.32 × 10^10^ CFU/g (1.20–1.40 × 10^10^ CFU/g additive).11

Three batches of the additive were analysed for cadmium, lead, mercury, arsenic and fluoride levels. All the values were below limit of quantification (LOQ) of the analytical methods, except for cadmium (0.04–0.05 mg/kg).12

Polychlorinated dibenzo‐p‐dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and dioxin‐like polychlorinated biphenyls (DL‐PCBs) were analysed in three batches. The calculated upper bound (UB) concentrations for the sum of PCDD/Fs ranged between 0.0649 and 0.0654 ng WHO(2005)‐PCDD/F‐TEQ/kg, and between 0.101 and 0.102 ng WHO(2005)‐PCDD/F + PCB‐TEQ/kg for the sum of PCDD/Fs and DL‐PCBs. The calculated UB concentration for the sum of non DL‐PCBs was 0.354 μg/kg in all three batches (all values are expressed based on 88% dry matter).13

The analysis of mycotoxins, including aflatoxins (B1, G1, B2, G2), ochratoxin A, deoxynivalenol, T‐2 and HT‐2 toxins, diacetoxyscirpenol, fumonisins (B1 and B2), zearalenone, citrinin, cyclopiazonic acid, mycophenolic acid, penicillic acid, patulin and roquefortine C showed values below the limit of detection (LOD) of the analytical methods.14

The analysis of pesticides performed on one batch of the additive showed results below the LOQ of the analytical methods.15

Specifications were set by the applicant for coliforms (< 10 CFU/g), Enterobacteriaceae (< 10 CFU/g), Staphylococcus aureus (< 10 CFU/g) and moulds (< 1000 CFU/g). The analysis of three batches showed compliance with these specifications. Salmonella spp. and Escherichia coli were not detected in 25 g and 10 g of samples, respectively.16

The FEEDAP Panel considers that the microbial contamination and the amounts of the detected impurities do not raise safety concerns.

The average bulk density measured for five batches was 769 kg/m^3^.17 The dusting potential of three batches of the additive was determined using the Stauber‐Heubach method and showed values ranging from 0 to 6.25 mg/m^3^. The particle size distribution of the additive was analysed by laser‐diffraction method; the results showed that 0.02% of the particles were below 100 μm, 0.01% below 50 μm and 0.01% below 10 μm.18

Considering that no changes have been introduced in the manufacturing process and composition, the data on stability and homogeneity described in the previous opinion (EFSA FEEDAP Panel, 2014) are still valid.

The applicant provided new data on the shelf life of the additive (three batches) when stored at −18, 4, 10 and 20°C in sealed foil sachets for 4 months. Negligible losses (< 0.5 log) were observed at the end of the storage period for each condition.19

Characterisation of the active agent

3.1.2

The active agent was isolated from silage, and it is deposited in the National Collection of Yeast Cultures (NCYC) with the accession number R404.20 According to the applicant it has not been genetically modified.

The taxonomical identification was confirmed by a bioinformatic analysis of the whole genome sequence (WGS) data.21 This was based on a phylogenomic analysis (using 98 single‐copy orthogroups) on publicly available genomes of S. cerevisiae strains, including the reference strain S. cerevisiae S288C and the nomenclature type S. cerevisiae NRRL Y‐12632, and representatives of 10 other Saccharomyces species and of the Kazachstania, Naumovozyma and Torulaspora genera. The analysis showed that S. cerevisiae NCYC R404 clustered with S. cerevisiae strains, including the reference strain S. cerevisiae S288C and the nomenclature type S. cerevisiae NRRL Y‐12632.

The active agent was tested for antifungal susceptibility using a broth microdilution method.22 The minimum inhibitory concentration (MIC) values obtained for anidulafungin (0.12 mg/L), amphotericin B (0.5 mg/L), micafungin (0.12 mg/L), caspofungin (0.5 mg/L), 5‐flucytosine (< 0.06 mg/L), posaconazole (1 mg/L), voriconazole (0.12 mg/L), itraconazole (0.25 mg/L) and fluconazole (4 mg/L) were considered low.

Conditions of use

3.1.3

The additive is currently authorised for use in feed for dairy cows at a minimum inclusion level of 4.4 × 10^8^ CFU/kg complete feedingstuff. Under other provisions of the authorisation, it is specified that:

1. In the directions for use of the additive and premixture, indicate the storage conditions and stability to pelleting.
2. Recommended dose of the additive: 1 × 10^10^ CFU/head/day.
3. For safety: breathing and skin protection shall be used during handling.

The applicant did not request any change in the current conditions of the authorisation.23

Safety

3.2

In the previous opinion, the Panel concluded that following the qualified presumption of safety (QPS) approach to safety assessment, S. cerevisiae NCYC R404 is considered safe for target species, consumers and the environment (EFSA FEEDAP Panel, 2014). Regarding user safety, the Panel concluded that the additive was not irritant to the skin or eyes and was a skin sensitiser. Considering that the product had no dusting potential, exposure via the respiratory route was of no concern.

The applicant declared that no incidents or safety issues for the target species, consumers, user and the environment have been documented or reported regarding the additive since its first authorisation.24

In the context of the current application, the active agent was confirmed to belong to S. cerevisiae, a species suitable to the QPS approach (EFSA BIOHAZ Panel, 2023). Consequently, the conclusions already reached are still valid and the FEEDAP Panel considers that the strain S. cerevisiae NCYC R404 remains safe for target species, consumers and the environment.

Furthermore, in the current dossier the applicant performed a literature search in order to provide evidence that in the light of the current knowledge the additive remains safe under the approved conditions for target species, consumers, users and the environment.25 The search was conducted in Medline (OVID), Scopus, Web of Science, SciFinder, ProQuest and EBSCOhost Academic Search Premier covering the period from 2014 to 2024. None of the hits retrieved were further considered relevant for the safety assessment related to the additive.

The additive contains sorbitan monostearate used as stabiliser. Its safety at the proposed concentration of the additive was assessed and is reported in detail in Appendix A. The Panel concludes that sorbitan monostearate does not raise concerns for the safety for the target species, consumer and environment.

The Panel considers that the additive S. cerevisiae NCYC R404 remains safe for target species, consumer and environment.

Regarding the safety for the users, no new data have been provided. Based on the highest dusting potential measured value (6.25 mg/m^3^), the FEEDAP Panel considered that the exposure of users through inhalation is possible. The Panel reiterates its previous conclusions that the additive is not irritant to eye and skin. The additive consists of a microorganism, and therefore should be considered a potential skin and respiratory sensitiser, and any inhalation and dermal exposure is considered a risk.

Efficacy

3.3

The present application for renewal of the authorisation does not include a proposal for amending or supplementing the conditions of the original authorisation that would have an impact on the efficacy of the additive. Therefore, there is no need for assessing the efficacy of the additive in the context of the renewal of the authorisation.

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 Regulation26 and Good Manufacturing Practice.

CONCLUSIONS

4

The applicant has provided evidence that the additive currently on the market complies with the terms of the authorisation.

The Panel concludes that the additive S. cerevisiae NCYC R404 remains safe for dairy cows, consumers and the environment under the current approved conditions of the authorisation.

Regarding user safety, the additive is not irritant to skin or eyes, and it should be considered a potential skin and respiratory sensitiser, and any exposure through skin and respiratory tract is considered a risk.

There is no need for assessing the efficacy of the additive in the context of the renewal of the authorisation.

ABBREVIATIONSADIacceptable daily intakeANSEFSA Scientific Panel on Additives and Nutrient Sources added to FoodBWbody weightCFUcolony forming unitDL‐PCBsdioxin‐like polychlorinated biphenylsEURLEuropean Union Reference LaboratoryFEEDAPEFSA Scientific Panel on Additives and Products or Substances used in Animal FeedLODlimit of detectionLOQlimit of quantificationMICminimum inhibitory concentrationNCYCNational Collection of Yeast CulturesNOAELno observed adverse effect levelPCDDsPolychlorinated dibenzo‐p‐dioxinsPCDFspolychlorinated dibenzofuransQPSqualified presumption of safetyUBupper boundWGSwhole genome sequence

REQUESTOR

European Commission

QUESTION NUMBER

EFSA‐Q‐2024‐00260

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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.