Safety of a feed additive consisting of Duddingtonia flagrans NCIMB 30336 (BioWorma®) for all grazing animals (International Animal Health Products Pty Ltd)

TL;DR

This study confirms the safety of a feed additive made from Duddingtonia flagrans for various grazing animals.

Contribution

The study concludes the additive is safe for a broader range of grazing animals than previously assessed.

Findings

The additive is safe for grazing animals like pigs, rabbits, and horses.

Maximum safe levels exceed intake levels from recommended use.

Safety is supported by sub-chronic oral toxicity study results.

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 of a feed additive consisting of Duddingtonia flagrans NCIMB 30336 (BioWorma®) for all grazing animals other than dairy bovines, ovines and caprines (namely, grazing animals from the following species: pigs (all categories), rabbits (all categories), horses (all categories) and calves/kids of species in the family Cervidae (deer, etc.) and Camelidae (alpacas, etc)). The safety and efficacy of the additive have already been assessed previously; however, the FEEDAP Panel could not conclude on the safety of the additive for the grazing animals other than dairy bovines, ovines and caprines due to the limitations in the dataset provided. For the current assessment, the applicant referred to the sub‐chronic oral toxicity study provided in the previous application. The Panel considered that, since the microorganism is provided in the form of chlamydospores and is very unlikely to germinate during the gastrointestinal passage, the results from the sub‐chronic oral toxicity study can be used to support the safety of the additive for the target species. Based on the NOAEL derived from the sub‐chronic oral toxicity study, the maximum safe levels calculated are higher than the intake levels, resulting from the recommended use level for all the species. Therefore, the Panel concludes that the additive is safe for all grazing bovines, ovines, caprines, rabbits, horses, cervids, camelids and porcine species at the proposed conditions of use.

Tables

TABLE 1. Description of the additive.

Category of additive	Zootechnical additives
Functional group of additive	Other zootechnical additives
Description	Duddingtonia flagrans NCIMB 30336 (BioWorma®)
Target animal category	Grazing animals other than dairy bovines, ovines and caprines
Applicant	International Animal Health Products Pty Ltd., represented in the EU by GAB Consulting GmbH 1
Type of request	New opinion

TABLE 2. Proposed use levels and maximum safe concentration of Duddingtonia flagrans NCIMB 30336 in the feed of the major target species.*

Animal category	Proposed use level (chlamydospores/kg complete feed)	Safe concentration in feed (chlamydospores/kg complete feed)
Piglets	600,000	1,200,000
Pigs for fattening	720,000	1,440,000
Sows lactating	875,000	1,750,000
Veal calves	1,396,825	3,000,000
Cattle for fattening	1,320,000	2,640,000
Dairy cows	858,000	1,716,000
Sheep/goats	1,320,000	2,640,000
Horses	1,320,000	2,640,000
Rabbits	528,000	1,056,000

Full text

INTRODUCTION

1

Background and Terms of Reference as provided by the requestor

1.1

Regulation (EC) No 1831/2003 establishes the rules governing the Union authorisation of additives for use in animal nutrition; in particular, Article 9 defines the terms of the authorisation by the Commission. The applicant is seeking a Union authorisation of the feed additive described in Table 1.

On 14 November 2023, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) of the European Food Safety Authority (EFSA), in its opinion on the safety and efficacy of the product, could not conclude on the safety of the additive for grazing animals other than dairy bovines, ovines and caprines. The Commission gave the possibility to the applicant to submit supplementary information and data in order to complete the assessment and to allow a revision of the EFSA's opinion. The new data have been received on 28 May 2024.

In view of the above, the Commission asks EFSA to deliver a new opinion on Duddingtionia flagrans NCIMB 30336 (BioWorma®) as a feed additive for grazing animals other than dairy bovines, ovines and caprines based on the supplementary information and data submitted by the applicant, in accordance with Article 29(1)(a) of Regulation (EC) No 178/2002.

Additional information

1.2

The additive consisting of Duddingtonia flagrans NCIMB 30336 (BioWorma®) is currently authorised as a zootechnical additive (other zootechnical additives) for use in feed of dairy cows, dairy cows of minor bovine species, dairy sheep and dairy goats.2

The FEEDAP Panel has adopted two opinions on the safety and efficacy of the additive under assessment ( EFSA FEEDAP Panel, 2020, 2023).

DATA AND METHODOLOGIES

2

Data

2.1

The present assessment is based on data submitted by the applicant in the form of supplementary information3 to previous applications on the same product.4 The dossier was received on 19/6/2024 and the general information and supporting documentation are available on Open.EFSA at https://open.efsa.europa.eu/questions/EFSA‐Q‐2024‐00410.

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.

Methodologies

2.2

The approach followed by the FEEDAP Panel to assess the safety and the efficacy of D. flagrans NCIMB 30336 (BioWorma®) is in line with the principles laid down in Regulation (EC) No 429/20085 and the relevant guidance documents: Guidance on the assessment of the safety of feed additives for the target species (EFSA FEEDAP Panel, 2017).

ASSESSMENT

3

D. flagrans NCIMB 30336 (BioWorma®) is intended for use as a zootechnical feed additive (functional group: other zootechnical additives: reduction of the number of infective nematode larvae on pasture) to control pathogenic nematodes (eelworm) in the soil, with subsequent benefits for ruminants, horses and other grazing animals. D. flagrans (Dudd) Cooke belongs to a group of nematophagous fungi that physically entrap nematodes through a specialised adhesive hyphal net. The species is widely distributed in the environment and has been isolated from pasture soils in many countries worldwide. The additive is specified to contain a minimum of 5 × 10^5^ chlamydospores/g.

The additive is intended for use in all grazing animals of the following species: pigs (all categories), bovines (all categories), sheep (all categories), goats (all categories), rabbits (all categories), horses (all categories) and all other ruminant species: calves/kids of species in the family Cervidae (deer, etc.) and Camelidae (alpacas, etc) at a daily dose of 1.5 g additive per 25 kg body weight (bw) (equivalent to 60 mg/kg bw per day) to be incorporated directly in feed or via a premixture. This level approximates 3 × 10^4^ chlamydospores/kg body weight per day. No withdrawal period is proposed. The additive is currently authorised for use in the feed of dairy cows and dairy cows of minor bovines, dairy sheep and dairy goats.

The product has been characterised, and its safety and efficacy have been evaluated in previous opinions (EFSA FEEDAP Panel, 2020, 2023). Based on a tolerance trial in dairy cows, the FEEDAP Panel concluded that the additive is safe for grazing dairy bovines, ovines and caprines. However, due to the lack of data, the FEEDAP Panel could not establish the safety of the additive for other grazing species/categories. Additionally, the Panel concluded that the additive is safe for consumers and the environment. It was also concluded that the additive is not irritant to skin and eyes but is irritant to the respiratory tract and a respiratory sensitiser, but no conclusion could be drawn on its skin sensitisation potential. Finally, the FEEDAP Panel concluded that the additive reduces the number of parasitic nematodes on pasture to the benefit of grazing animals when used at the recommended application rate of 3 × 10^4^ chlamydospores/kg bw per day. Based on these opinions, the additive was authorised for use in dairy cows and dairy cows of minor bovines, dairy sheep and dairy goats.

The applicant has submitted additional data to support the safety for target species for which no conclusion was drawn.

Safety for the target species

3.1

The applicant did not submit any additional tolerance trial in the relevant target species in the current application but referred to the sub‐chronic oral toxicity study provided in the previous one (EFSA FEEDAP Panel, 2023).

The Panel considers that toxicological studies with oral administration in laboratory animals cannot be used to support the safety of target animals for additives consisting of viable microorganisms (EFSA FEEDAP Panel, 2017). In a previous opinion, based on data provided by the applicant, the FEEDAP Panel indicated that chlamydospores were shown in vitro not to germinate under anaerobic conditions or at temperatures above 37°C (EFSA FEEDAP Panel, 2020). Thus, since D. flagrans is provided in the form of chlamydospores, it was considered very unlikely to be metabolically active in the digestive tract of the target species. These data have also been provided in the current application6. Moreover, the applicant performed a literature search in order to provide further evidence of the lack of germination of the chlamydospores in the gastrointestinal tract of the relevant target species.7 The publications retrieved included in vitro and in vivo studies, reinforcing the lack of germination capacity under the temperature and oxygen ranges found in the gastrointestinal tract of the target species. One of the publications indicated that the spores require long times (about 36 h) under optimal conditions (25°C) to reach the maximum germination rate (about 55%) (Wang et al., 2019). This finding would suggest that the time passage through the gastrointestinal tract may also limit the germination potential of the chlamydospores in the gastrointestinal tract of the different target species. Taking all the data together, the FEEDAP Panel deems that it is very unlikely that the fungus in the form of chlamydospores will be able to germinate in the digestive tract of the target species in the scope of the application. Therefore, the Panel considers that the results from the sub‐chronic oral toxicity study in rats can be used to support the safety of the additive for the target species.

In the previous opinion (EFSA FEEDAP Panel, 2023), the Panel identified the highest dose tested in the 90‐day tox study as the no observed adverse effect level (NOAEL; 6 × 10^6^ chlamydospores/kg body weight per day). This NOAEL was used to calculate the maximum safe level for the different target species, following the procedure described in the Guidance on the safety for the target species (EFSA FEEDAP Panel, 2017); the results are shown in Table 2.

The maximum safe levels obtained are higher than the intake levels resulting from the recommended use level for all the species. Therefore, considering these data and the conclusion from the previous opinion on dairy bovines, ovines and caprines, the Panel concludes that the additive is safe for all grazing bovines, ovine, caprine, cervids, camelids, rabbits, horses and porcine species at the proposed conditions of use.

Post‐market monitoring

3.2

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 Regulation8 and Good Manufacturing Practice.

CONCLUSIONS

4

D. flagrans NCIMB 30336 (BioWorma®) is considered safe for all grazing bovines, ovine, caprine, cervids, camelids, rabbits, horses and porcine species at the proposed conditions of use.ABBREVIATIONSBWbody weightDMdry matterEURLEuropean Union Reference LaboratoryFEEDAPEFSA Scientific Panel on Additives and Products or Substances used in Animal FeedNOAELno observed adverse effect level

REQUESTOR

European Commission

QUESTION NUMBER

EFSA‐Q‐2024‐00410

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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.