Assessment of the feed additive consisting of Lactiplantibacillus plantarum ATCC PTA‐6139 for all animal species for the renewal of its authorisation (Pioneer Hi‐Bred International, Inc.)

TL;DR

This paper assesses the safety of a feed additive for animals, finding it safe for use but noting potential risks for skin and respiratory sensitization.

Contribution

The paper provides a safety evaluation for the renewal of a feed additive's authorization.

Findings

The additive is safe for animals, consumers, and the environment.

It may cause skin and respiratory sensitization.

No data was available to assess eye irritation potential.

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 Lactiplantibacillus plantarum (formerly Lactobacillus plantarum) ATCC PTA‐6139 as a technological additive (functional group: silage additive) for all animal species. The applicant has provided evidence that the additive currently on the market complies with the existing conditions of authorisation. The EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concluded that the additive remains safe for all animal species, consumers and the environment. Regarding user safety, the Panel concluded that owing to the nature of the additive, Lactiplantibacillus plantarum ATCC PTA‐6139 should be considered a potential skin and respiratory sensitiser, and that any exposure through the skin and respiratory tract is considered a risk. The Panel could not conclude on the eye irritation potential of the additive due to the lack of data. There is 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 one year before the expiry date of the authorisation.

The European Commission received a request from Pioneer Hi‐Bred International, Inc. represented in the EU by Corteva Agriscience Belgium B.V.2 for the renewal of the authorisation of the additive consisting of Lactiplantibacillus plantarum ATCC PTA‐6139,3 when used as a feed additive for target species (category: technological additives; functional group: silage additives).

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 January 2022 and the general information and supporting documentation are available at https://open.efsa.europa.eu/questions/EFSA‐Q‐2022‐00022. The particulars and documents in support of the application were considered valid by EFSA as of 20 June 2022.

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 Lactiplantibacillus plantarum ATCC PTA‐6139, when used under the proposed conditions of use (see Section 3.1.3).

Additional information

1.2

The additive Lactiplantibacillus plantarum (formerly Lactobacillus plantarum) ATCC PTA‐6139 is currently authorised for use in feed for all animal species (1k20725).4 EFSA issued an opinion on the safety and efficacy of this product (EFSA FEEDAP Panel, 2012).

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 Lactiplantibacillus plantarum ATCC PTA‐6139 as a feed additive.

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.8

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,^2^ EFSA carried out a public consultation on the non‐confidential version of the application from 10 January 2023 to 31 January 2023 for which no comments were received.

In addition, the confidential version of the technical dossier was subject to a target consultation of the interested Member States from 17 June 2022 to 20 September 2022; 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 Lactiplantibacillus plantarum ATCC PTA‐6139 in animal feed are valid and applicable for the current application.9

Methodologies

2.2

The approach followed by the FEEDAP Panel to assess the safety and the efficacy of Lactiplantibacillus plantarum PTA‐6139 is in line with the principles laid down in Regulation (EC) No 429/200810 and the relevant guidance documents: Guidance on the renewal of the authorisation of feed additives (EFSA FEEDAP Panel, 2021).

ASSESSMENT

3

The additive Lactiplantibacillus plantarum ATCC PTA‐6139 is currently authorised as a technological additive (functional group: silage additives) for use in fresh material for all animal species. The present assessment regards the renewal of its authorisation.

Characterisation

3.1

Characterisation of the additive

3.1.1

The additive currently authorised is a preparation containing L. plantarum ATCC PTA‐6139 at a minimum concentration of 1 × 10^10^ colony forming units (CFU)/g of additive.

The applicant declared that no modifications to the manufacturing process and composition have been introduced since the previous application.11 The active agent is grown by fermentation and concentrated by either centrifugation or micro‐filtration. The cell concentrate is mixed with cryoprotectants (■■■■■) and the resulting product is freeze‐dried. The freeze‐dried cell concentrate may be standardised with carriers (maltodextrin or calcium carbonate) and anti‐caking agents (sodium aluminosilicate).12

Analytical data to confirm the specifications were provided for five batches of the additive showing an average of 6.62 × 10^11^ CFU/g additive (range 5.00–8.20 × 10^11^ CFU/g additive).13

No data on microbial contamination or impurities were made available for the additive under assessment as such, but only for premixtures containing the additive and other active agents, carriers and anti‐caking. The levels of coliforms, yeasts and filamentous fungi were all < 10 CFU/g. Salmonella spp. was not detected in 25 g of the samples. No data on Enterobacteriaceae concentration were provided.14 Mycotoxins (aflatoxins B1, B2, G1 and G2, deoxynivalenol, 3‐acetyl deoxynivalenol, fumonisins B1 and B2, ochratoxin A, T2‐toxin, HT‐2 toxin, zearalenone and α‐zearalenol), mercury, lead, cadmium and arsenic15 were below the limit of detection of the analytical methods.16 The microbial contamination and impurities in the premixtures analysed do not raise safety concerns. However, the FEEDAP Panel notes that the data on impurities regarding these premixtures may not represent the additive under assessment.

Since no changes were introduced in the manufacturing process or in the composition of the additive, the data on dusting potential, particle size distribution, bulk density and stability of the additive described in the previous opinion (EFSA FEEDAP Panel, 2012) are considered still valid. New data on dusting potential, particle size distribution, bulk density and stability were provided for a premixture containing L. plantarum ATCC PTA‐6139 in combination with other active agents.17 However, these data are not considered relevant for the current assessment.

Characterisation of the active agent

3.1.2

The active agent was originally isolated from high moisture maize and is deposited in the American Type Culture Collection (ATCC) under the deposition number ATCC PTA‐6139.18 It has not been genetically modified.

The taxonomical identification was confirmed by average nucleotide identity (ANI) calculation based on the whole genome sequence (WGS) using OrthoANI tool (version 0.93.1). The results of this analysis showed an ANI value of 98.95% with L. plantarum DSM 20174^T^.19

The bacterial strain was subjected to antimicrobial susceptibility testing using broth microdilution method and including the set of antimicrobials recommended by EFSA (EFSA FEEDAP Panel, 2018).20 All the minimum inhibitory concentration values were equal to or fell below the corresponding EFSA cut‐off values for L. plantarum/pentosus. Therefore, the strain is considered to be susceptible to all the relevant antimicrobials.

The WGS data of the strain were interrogated for the presence of antimicrobial resistance genes in the ResFinder and AMRFinderPlus databases.21 No hits of concern were identified exceeding the thresholds recommended by EFSA (EFSA, 2021).

Conditions of use

3.1.3

The additive is currently authorised for use as silage additive for all animal species. Under other provisions of the authorisation,22 it is specified that:

1. In the directions for use of the additive and premixture, indicate the storage temperature and storage life.
2. Minimum dose of the additive when used without combination with other microorganisms as silage additives: 2 × 10^7^ CFU/kg fresh material.
3. The additive shall be used in easy to ensile material.
4. For safety: It is recommended to use breathing protection and gloves during handling.

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

Safety

3.2

In its previous opinion, the FEEDAP Panel concluded that following the qualified presumption of safety (QPS) approach to safety assessment, L. plantarum ATCC PTA‐6139 is considered safe for target species, consumers and the environment (EFSA FEEDAP Panel, 2012). Regarding user safety, the Panel concluded that the additive may cause irritation to skin/eyes and should be considered a skin and respiratory sensitiser.

The applicant states that no adverse effects, including accidents, for target animals, consumers, users and the environment have been reported since the authorisation of the additive.24

In the context of the current application, the identity of a strain as Lactiplantibacillus plantarum was confirmed and evidence was provided that the strain does not show acquired antimicrobial determinants for antibiotics of human and veterinary importance, confirming the suitability of the QPS approach for safety assessment (EFSA BIOHAZ Panel, 2023). Consequently, the conclusions already reached are still valid and the Panel concludes that Lactiplantibacillus plantarum ATCC PTA‐6139 remains safe for the target species, consumers and the environment.

A literature search was performed to provide evidence that the additive remains safe under the approved conditions of use for the target species, consumers, users and the environment.25 The search was conducted in three databases (Web of Science Core Collection, CAB Abstracts and MEDLINE) using the Web of Science search engine by Clarivate Analytics. No limits regarding the language were included. A total of 110 hits were retrieved and after exclusion following the criteria, full‐text analysis and deduplication, a total of 22 publications were identified as relevant. None of the publications described safety concerns related to the use of Lactiplantibacillus plantarum ATCC PTA‐6139.

No specific data have been submitted on the effects of the additive on user safety. The applicant has submitted eye26 and skin27 irritation studies (according to OECD guidelines 404 and 438, respectively) which tested a premixture, containing the additive and other active agents, 50% maltodextrin and 5% of sodium aluminosilicate. The results showed no evidence of irritation, but the product tested does not allow to conclude on the additive under assessment.

Owing to the nature of the additive, the FEEDAP Panel concludes that the L. plantarum ATCC PTA‐6139 should be considered a potential skin and respiratory sensitiser, and any exposure through the skin and respiratory tract is considered a risk. In the absence of data, no conclusion can be reached on the eye irritation potential of the additive.

Conclusions on the safety

3.2.1

The FEEDAP Panel concludes that Lactiplantibacillus plantarum ATCC PTA‐6139 remains safe for the target species, consumers and the environment.

Considering the nature of the additive, the FEEDAP Panel concludes that the additive should be treated as a potential skin and respiratory sensitiser and any exposure through the skin and respiratory tract is considered a risk. The Panel cannot conclude on the eye irritation potential of the additive.

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.

CONCLUSIONS

4

The applicant has provided evidence that the additive currently on the market complies with the existing conditions of authorisation. However, no data on microbial contamination and impurities on the additive under assessment, necessary to fully characterise the additive, were provided.

The Panel concludes that Lactiplantibacillus plantarum ATCC PTA‐6139 remains safe for the target species, consumers and the environment.

Regarding user safety, the additive should be considered as a skin and respiratory sensitiser, and any exposure through skin and respiratory tract is considered a risk. No conclusions can be drawn on the eye irritancy potential of the additive.

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

ABBREVIATIONSCFUColony forming unitEURLEuropean Union Reference LaboratoryFEEDAPEFSA Scientific Panel on Additives and Products or Substances used in Animal FeedLODlimit of detectionMICminimum inhibitory concentration

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‐2022‐00022

PANEL MEMBERS

Vasileios Bampidis, Giovanna Azimonti, Maria de Lourdes Bastos, Henrik Christensen, Mojca Durjava, Birgit Dusemund, Maryline Kouba, Marta López‐Alonso, Secundino López Puente, Francesca Marcon, Baltasar Mayo, Alena Pechová, Mariana Petkova, Fernando Ramos, Roberto Edoardo Villa, and Ruud Woutersen.

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.

LEGAL NOTICE

Relevant information or parts of this scientific output have been blackened in accordance with EFSA's decision on the confidentiality requests that were submitted by the applicant. The full output has been shared with the European Commission, EU Member States` competent Authorities and the applicant.