Assessment of the feed additive consisting of endo‐1,4‐beta‐xylanase (produced with Trichoderma reesei MUCL 49755) and endo‐1,3(4)‐beta‐glucanase (produced with T. reesei MUCL 49754) (AveMix® XG 10) for pigs for fattening, minor porcine species for fattening and turkeys for fattening for the renewal of its authorisation (AVEVE BV)

TL;DR

This paper assesses the safety of a feed additive for fattening pigs and turkeys, confirming it is safe for animals, consumers, and the environment.

Contribution

The study confirms the safety of a modified feed additive formulation for use in animal feed.

Findings

Both forms of the additive remain safe for pigs, minor porcine species, and turkeys.

The additive is a respiratory and skin sensitiser but not irritating to skin and eyes.

No data were provided for one formulation, so its compliance could not be confirmed.

Abstract

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the assessment of the feed additive consisting of endo‐1,4‐beta‐xylanase (produced with Trichoderma reesei MUCL 49755) and endo‐1,3(4)‐beta‐glucanase (produced with T. reesei MUCL 49754) (AveMix® XG 10/AveMix® XG 10 L) for the renewal of its authorisation as zootechnical feed additive for pigs for fattening, minor porcine species for fattening and turkeys for fattening. The applicant declared a change in the carrier material used in AveMix® XG 10 from soybean meal to calcium carbonate + wheat flour or calcium carbonate + sepiolite. The applicant provided evidence that the additive Avemix® XG 10 with calcium carbonate + wheat flour and Avemix® XG 10 L comply with the conditions of the authorisation. The EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) noted that no data were submitted to support compliance of the formulation of Avemix® XG 10 with calcium carbonate + sepiolite with the conditions of the authorisation. The FEEDAP Panel concluded that both forms of the additive remain safe for pigs for fattening, minor porcine species for fattening and turkeys for fattening, consumers and the environment. Regarding the safety for the user, Avemix® XG 10 formulated with calcium carbonate + sepiolite and Avemix® XG 10 L are not irritant to skin and eyes. No conclusions on the irritation potential of Avemix® XG 10 formulated with calcium carbonate + wheat flour could be drawn. The additive in all its formulations is considered a respiratory and skin sensitiser. There was no need for assessing the efficacy of the additive in the context of the 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 AVEVE BV2 for renewal of the authorisation of the additive consisting of endo‐1,4‐beta‐xylanase (produced with Trichoderma reesei MUCL 49755) and endo‐1,3(4)‐beta‐glucanase (produced with T. reesei MUCL 49754) (AveMix® XG 10/ AveMix® XG 10 L), when used as a feed additive for pigs for fattening, minor porcine species for fattening and turkeys for fattening (category: zootechnical additives; functional group: digestibility enhancers).

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 15 November 2022 and the general information and supporting documentation are available at https://open.efsa.europa.eu/questions/EFSA‐Q‐2022‐00800. The particulars and documents in support of the application were considered valid by EFSA as of 7 September 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 endo‐1,4‐beta‐xylanase (produced with T. reesei MUCL 49755) and endo‐1,3(4)‐beta‐glucanase (produced with T. reesei MUCL 49754) (AveMix® XG 10), when used under the proposed conditions of use (see Section 3.1.2).

Additional information

1.2

The additive is a preparation containing endo‐1,4‐beta‐xylanase (produced with T. reesei MUCL 49755) and endo‐1,3(4)‐beta‐glucanase (produced with T. reesei MUCL 49754). The additive is currently authorised (4a9) for use in feed for chickens for fattening,3 weaned piglets,4 laying hens and minor poultry species for fattening and laying,5 pigs for fattening and minor porcine species for fattening and turkeys for fattening.6

EFSA issued several opinions on the safety and efficacy of the product (EFSA, 2009; EFSA FEEDAP Panel, 2010, 2011, 2012, 2013a, 2013b, 2020, 2024a, 2024b).

DATA AND METHODOLOGIES

2

Data

2.1

The present assessment is based on data submitted by the applicant in the form of a technical dossier7 in support of the authorisation request for the use of endo‐1,4‐beta‐xylanase (produced with T. reesei MUCL 49755) and endo‐1,3(4)‐beta‐glucanase (produced with T. reesei MUCL 49754) (AveMix® XG 10) as a feed additive.

In accordance with Article 38 of the Regulation (EC) No 178/20028 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,9 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 11 June to 2 July 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 September 2023 to 7 December 2023; the comments received 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 and other scientific reports, to deliver the present output.

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 endo‐1,4‐beta‐xylanase and endo‐1,3(4)‐beta‐glucanase in animal feed are valid and applicable for the current application.10

Methodologies

2.2

The approach followed by the FEEDAP Panel to assess the safety of endo‐1,4‐beta‐xylanase (produced with T. reesei MUCL 49755) and endo‐1,3(4)‐beta‐glucanase (produced with T. reesei MUCL 49754) (AveMix® XG 10) is in line with the principles laid down in Regulation (EC) No 429/200811 and the relevant guidance documents: Guidance on the renewal of the authorisation of feed additives (EFSA FEEDAP Panel, 2021).

ASSESSMENT

3

This assessment regards the renewal of the authorisation of the product that contains endo‐1,4‐β‐xylanase (EC 3.2.1.8; xylanase) produced with T. reesei MUCL 49755 and endo‐1,3(4)‐beta‐glucanase (EC 3.2.1.6; glucanase) produced with T. reesei MUCL 49754 as a feed additive for pigs for fattening, minor porcine species for fattening and turkeys for fattening.

Characterisation

3.1

Characterisation of the additive

3.1.1

The additive is available in powder and liquid formulations. It will be hereafter referred to with its trade name AveMix® XG 10 (powder)/AveMix® XG 10 L (liquid).

The additive is authorised at a minimum guaranteed activity of xylanase of 40,000 XU12/g and of glucanase of 9000 BGU13/g.

For AveMix® XG 10, the applicant declared a change in the carrier material from soybean meal to calcium carbonate + wheat flour or calcium carbonate + sepiolite.14 AveMix® XG 10 is now declared to contain 27–32% of the spray‐dried enzyme concentrate (which includes maltodextrin (resulting in 14–18% of the final product) and silica15 (resulting in ≤1% of the final product)) and 68–73% of carrier materials.16

AveMix® XG 10 L contains 77–82% of the liquid enzyme concentrate (which includes sucrose (resulting in 16–22% of the final product), sodium chloride (resulting in 3–4% of the final product), sodium benzoate (resulting in ≤ 1% of the final product), potassium sorbate (resulting in ≤1% of the final product)) and 18–23% of the carrier material (63% water and 37% sorbitol).17

The manufacturing process (including the characterisation of the production strains), composition, physico‐chemical properties, stability and homogeneity of the formulations of the additive were assessed in previous opinions (EFSA, 2009; EFSA FEEDAP Panel, 2024a, 2024b).

In its opinions from 2024, the Panel concluded that AveMix® XG 10 formulated with calcium carbonate + wheat flour as carrier and AveMix® XG 10 L complied with the conditions of the authorisation (EFSA FEEDAP Panel, 2024a, 2024b). The FEEDAP Panel also concluded that, due to the lack of data on the batch‐to‐batch variation, purity and physico‐chemical properties of AveMix® XG 10 formulated with calcium carbonate + sepiolite as carrier, this formulation of the additive could not be fully characterised.

In the context of the current assessment, the applicant did not submit new data except for the batch‐to‐batch variation of five recent batches of AveMix® XG 10 L which showed xylanase activity of 49,686 XU/g (range 47,465–52,635 XU/g) and glucanase of 9764 BGU/g (range 9100 to 10,265 BGU/g).18 These measured enzyme activities showed compliance with the specifications set in the authorisation. Therefore, the conclusions reached in 2024 (EFSA FEEDAP Panel, 2024a, 2024b) still apply.

Conditions of use

3.1.2

The additive is currently authorised as a zootechnical additive for use in feed for pigs for fattening, minor porcine species for fattening (other than Sus scrofa domesticus) and turkeys for fattening at a minimum recommended level of 4000 xylanase units and 900 glucanase units/kg complete feed.

The authorisation under other provisions foresees:

1. In the directions for use of the additive and premixture, indicate the storage conditions and stability to pelleting.
2. For use in feed rich in non‐starch polysaccharides (mainly betaglucans and arabinoxylans).
3. For safety: breathing protection, glasses and gloves shall be used during handling.

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

Safety

3.2

The safety of AveMix® XG 10 and AveMix® XG 10 L for the target species, consumers, users and the environment, including the safety of the production strains, has been evaluated in previous opinions (EFSA, 2009; EFSA FEEDAP Panel, 2013a, 2013b, 2024a, 2024b). The Panel concluded that the additive is safe for the target species assessed, and the use of the product as a feed additive would be of no concern for the consumers of products derived from animals fed with the additive, or for the environment. Regarding user safety, Avemix® XG 10 formulated with calcium carbonate + sepiolite as carrier and Avemix® XG 10 L are not irritant to skin and eyes. Due to the lack of data, no conclusions on the irritation potential of Avemix® XG 10 formulated with calcium carbonate + wheat flour can be drawn. Considering the proteinaceous nature of the active substances, Avemix® XG 10 (formulated either with calcium carbonate + sepiolite or with calcium carbonate + wheat flour as carrier) and Avemix® XG 10 L are considered respiratory and skin sensitisers.

For the present dossier, the applicant (i) states that no adverse events in any of the target animal species, consumers, users and environment have been reported since the first authorisation,19 and (ii) 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. The Panel assessed all these data.

Literature search

3.2.1

The applicant searched in a total of seven databases (Medline, Scopus, Web of Science, SciFinder, ProQuest, EBSCOHOST Academic Search Premier and Google Scholar).20 The search had no time limit (only manual search in Google Scholar covered the period 2012–2024) and the search terms and search strategy were provided. The main search terms regarded the additive, the active substances and the production strains. The different searches identified a total of 376 hits that, after eliminating duplicates, screening for title and abstract and applying the exclusion criteria, were reduced to one. This hit (Montagnon et al., 2022) was further excluded because it was an efficacy study not relevant for safety.

Safety aspects linked to the renewal of the authorisation

3.2.2

Based on the information provided by the applicant and the fact that the manufacturing and composition of AveMix® XG 10 L have not been substantially modified, the FEEDAP Panel concludes that there is no evidence to reconsider the conclusions reached in the previous opinions on the safety of AveMix® XG 10 L for pigs for fattening, minor porcine species for fattening and turkeys for fattening. Therefore, the Panel concludes that AveMix® XG 10 L remains safe under the approved conditions for these target species, consumers and the environment.

Avemix® XG 10 formulated with calcium carbonate + wheat flour as carrier has been characterised in terms of compliance with specifications and purity. The FEEDAP Panel considers that the inclusion of these new carriers would not impact the safety of the additive for target species, consumers and environment. Avemix® XG 10 formulated with calcium carbonate + sepiolite as carrier has not been characterised in terms of compliance with specifications and purity. However, the FEEDAP Panel considers that the inclusion of these new carriers which are feed materials or authorised feed additives would not impact the safety of the additive for target species, consumers and environment.

Avemix® XG 10 formulated with calcium carbonate + sepiolite as carrier and Avemix® XG 10 L are not irritant to skin and eyes. Due to the lack of data, no conclusions on the irritation potential of Avemix® XG 10 formulated with calcium carbonate + wheat flour can be drawn. Considering the proteinaceous nature of the active substances and the outcome of the dermal sensitisation, Avemix® XG 10 (formulated either with calcium carbonate + sepiolite or with calcium carbonate + wheat flour as carrier) and Avemix® XG 10 L are considered respiratory and skin sensitisers. Any 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 Regulation21 and good manufacturing practice.

CONCLUSIONS

4

The applicant provided evidence that the additive Avemix® XG 10 formulated with calcium carbonate + wheat flour and Avemix® XG 10 L comply with the conditions of the authorisation. The Panel notes that no data were submitted to support compliance of the formulation of Avemix® XG 10 formulated with calcium carbonate + sepiolite with the conditions of the authorisation.

The FEEDAP Panel concludes that the additive (powder and liquid forms) remains safe for the target species, consumers and the environment.

Regarding user safety, Avemix® XG 10 formulated with calcium carbonate + sepiolite as carrier and Avemix® XG 10 L are not irritant to skin and eyes. Due to the lack of data, no conclusions on the irritation potential of Avemix® XG 10 formulated with calcium carbonate + wheat flour can be drawn. The additive (all forms) is considered a respiratory and skin sensitiser and any exposure is considered a risk.

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

ABBREVIATIONSEURLEuropean Union Reference LaboratoryFEEDAPPanel on Additives and Products or Substances used in Animal Feed

CONFLICT OF INTEREST

If you wish to access the declaration of interests of any expert contributing to an EFSA scientific assessment, please contact interestmanagement@efsa.europa.eu.

REQUESTOR

European Commission

QUESTION NUMBER

EFSA‐Q‐2022‐00800

COPYRIGHT FOR NON‐EFSA CONTENT

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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