The EFSA Journal (2005) 287, 1-9

Transcription

1 The EFSA Journal (2005) 287, 1-9 Opinion of the Scientific Panel on Additives and Products or Substances used in Animal Feed on the safety of the new granulate formulation of the enzyme preparation Grindazym GP, and its extension of use as feed additive for ducks (Question No EFSA-Q & -068) Adopted on 30 November 2005 SUMMARY The European Food Safety Authority (EFSA) received a request to deliver an opinion on the safety of a new granulate form of the enzyme preparation, Grindazym GP (enzyme E 1609), which is a preparation of endo-1,4-beta-xylanase and endo-1,4-beta-glucanase produced by Aspergillus niger for chickens for fattening, turkeys for fattening and piglets, for the consumer, the user, and the environment. EFSA was also requested to assess the safety of the existing enzyme preparation for the target species ducks for fattening. The safety of the product Grindazym GPL for ducks for fattening is demonstrated in a single study at approximately 15 times the intended use level, which showed no adverse effects over a period of 35 days. Considering also that Grindazym GP is already approved for chickens for fattening and turkeys for fattening, major species that are physiologically similar to ducks, the FEEDAP Panel concludes that the additive is safe for use in the feed of ducks for fattening. The data provided on composition, formulation and stability of the new granulate product demonstrate that it does not differ significantly in the content and source of the active ingredient, from the existing registered product Grindazym GP 15000, GPL or 15000MG. Since the new formulation does not alter the nature of the exposure compared with the existing product there is no reason to expect that it will present any novel safety issues for the target species, consumer, or the environment. In practice, re-formulation as a granulate may reduce the hazard for the user. FEEDAP Panel thus considers that the new formulation is acceptable for use as proposed. Keywords: Enzyme, granulate, new formulation, ducks, xylanase, beta-glucanase, tolerance test

2 Opinion on Grindazym GP 2/9 BACKGROUND Regulation (EC) No 1831/2003 establishes rules governing the Community authorisation of additives for animal nutrition and in particular defines the conditions that a substance/product should meet to be granted authorisation. This Regulation replaces Council Directive 70/524/EEC. The Regulation foresees transition procedures for handling applications submitted under the earlier directive in its Article 25. The applicant Danisco is seeking a change in the existing Community authorisation of its enzyme preparation with the trade name Grindazym GP as a feed additive for use for chickens for fattening, turkeys for fattening and piglets under the category "Enzyme" (Table 1). Table 1. Description of the product Product category: Trade name: Description: Target animal category: Applicant: Member State Rapporteur: Type of request: Enzyme Grindazym GP Preparation of endo-1,4-beta-xylanase and endo-1,4- beta-glucanase produced by Aspergillus niger (CBS ) (E 1609) Chickens for fattening, turkeys for fattening and piglets Danisco Denmark New granulate formulation This enzyme preparation is authorised for chickens for fattening, turkeys for fattening and piglets, as enzyme E1609 in coated, liquid and solid forms by Regulation (EC) No 1453/2004 (OJ L 269 of ). This enzyme preparation was evaluated by the former Scientific Committee of Animal Nutrition (SCAN). The applicant Danisco is also seeking provisional Community authorisation of its enzyme preparation with the trade name Grindazym GP, as a feed additive intended for use in ducks under the category "Enzyme" (Table 2). Table 2. Description of the product Product category: Trade name: Description: Target animal category: Applicant: Member State Rapporteur: Type of request: Enzyme Grindazym GP Preparation of endo-1,4-beta-xylanase and endo- 1,4-beta-glucanase produced by Aspergillus niger (CBS ) (E 1609) Ducks for fattening Danisco Denmark Provisional authorization In accordance with the above legislation, the Commission received an application, through Denmark, the Member State rapporteur chosen by the applicant, requesting a modification of the terms of the current authorization for the above described preparation under the conditions of use set out in Table 3, under Council Directive 70/524/EEC. Supporting data produced by the applicant were compiled in a dossier and accompanied that application. All Member States received the dossier, which was introduced at the Standing Committee on the Food Chain and Animal Health. This dossier was made available to the European Food Safety Authority.

3 Opinion on Grindazym GP 3/9 Table 3. Annex entry (in bold the proposed modifications) EC number Additive Chemical formula, description Species or category of animal Maximum age Minimum content Maximum content Units of activity per kg of complete feedingstuff Other provisions E 1609 Endo-1,4- betaxylanase EC Endo-1,4- betaglucanase EC Preparation of endo-1,4-betaxylanase and endo-1,4-betaglucanase produced by Aspergillus niger (CBS ) having minimum activities of: Granulated form: Endo-1,4-beta-xylanase: FXU 1 g -1 Endo-1,4-beta-glucanase: BGU 2 g -1 Chickens for fattening FXU 2025 BGU - 1. In the directions for use of the additive and premixture, indicate the storage temperature, storage life, and stability to pelleting. 2. Recommended dose per kg of complete feedingstuff: For use in compound feed rich in nonstarch polysaccharides (mainly arabinoxylans and beta-glucans), e.g. containing more than 35 % barley and 20 % wheat. 1 1 FXU is the amount of enzyme which liberates 0.15 micromoles of xylose from azurine-cross-linked xylan per minute at ph 5.0 and 40 C. 2 1 BGU is the amount of enzyme which liberates 0.15 micromoles of xylose from azurine-cross-linked beta-glucan per minute at ph 5.0 and 40 C.

4 Opinion on Grindazym GP 4/9 1. In the directions for use of the additive and premixture, indicate the storage temperature, storage life, and stability to pelleting. Turkeys for fattening FXU 2500 BGU - 2. Recommended dose per kg of complete feedingstuff: Piglets (weaned) For use in compound feed rich in nonstarch polysaccharides (mainly arabinoxylans and beta-glucans), e.g. containing more than 40 % wheat. 1. In the directions for use of the additive and premixture, indicate the storage temperature, storage life, and stability to pelleting. 2. Recommended dose per kg of complete feedingstuff: 3. For use in compound feed rich in nonstarch polysaccharides (mainly arabinoxylans and beta-glucans), e.g. containing more than 30 % wheat and 30 % barley. 4. For use in weaned piglets until approximately 35 kg

5 Opinion on Grindazym GP 5/9 E 1609 or 7 Endo-1,4- betaxylanase EC Endo-1,4- betaglucanase EC Preparation of endo-1,4-betaxylanase and endo-1,4-betaglucanase produced by Aspergillus niger (CBS ) having minimum activities of: Coated form: 3 g BGU g -1 Liquid form: 3 ml BGU ml -1 Granulate form: 3 g BGU g -1 ducks for fattening In the directions for use of the additive and premixture, indicate the storage temperature, storage life, and stability to pelleting. 2. Recommended dose per kg of complete feedingstuff: 3. For use in compound feed rich in nonstarch polysaccharides (mainly arabinoxylans and beta-glucans), e.g. containing more than 60 % wheat.

6 Opinion on Grindazym GP 6/9 TERMS OF REFERENCE In view of the above, the Commission asks the European Food Safety Authority to deliver an opinion on the safety of the new granulate form of the enzyme preparation of trade name Grindazym GP, enzyme E 1609, which is a preparation of endo-1,4-beta-xylanase and endo- 1,4-beta-glucanase produced by Aspergillus niger (CBS ), for the consumer, the user, the worker, for the target animal categories chickens for fattening, turkeys for fattening and piglets, and the environment, and the safety of this enzyme preparation for the target species ducks for fattening when used under the conditions set out in Table 3 above, and the taking into account the background and the information submitted by the applicant in the dossier. ASSESSMENT 1. Introduction This assessment relates to a preparation of endo-1,4-beta-xylanase and endo-1,4-betaglucanase produced by Aspergillus niger (CBS ). The product is identified by the trade name Grindazym GP and is available in three forms, dry product (Grindazym GP 15000), liquid product (Grindazym GPL 15000) and a microgranulate product (Grindazym 15000MG). The product is currently authorised for use in feed for chickens for fattening, turkeys for fattening, laying hens and piglets. Two separate applications have been received from the applicant. A submission for extension of the use of the existing product to ducks for fattening (a minor species) and an application for the approval of a new granulate formulation. These are evaluated separately below, first considering the extension of use and secondly the change in formulation. 2. Safety for ducks for fattening 2.1. Tolerance for ducks for fattening 160 day-old male Cherry Valley SM3 Heavy ducklings were randomly allocated to eight pens with 20 birds per pen. The pens were assigned to one of two treatment groups; either receiving control diet or diet containing Grindazym GPL15000 at 2505 mg kg -1 diet (approximately 15 times the normal use level). The Grindazym diet was analysed for enzyme activity and was found to be 92% of the intended activity. Table 4. Results of feeding diet containing 2505 mg kg -1 Grindazym GPL15000 to ducks for fattening for 35 days Control Grindazym Body weight gain (g) 0-35 days Feed Intake (g bird -1 ) Feed conversion Ratio Feeding the product to ducklings at a dietary level in excess of 15 times the normal use level shows no evidence of adverse effects on performance (Table 4) Conclusion on ducks for fattening Considering that this product is already approved for chickens for fattening and turkeys for fattening, major species that are physiologically similar to ducks, and taking into account the tolerance study provided, the FEEDAP Panel concludes that the additive is safe for use in the feed of ducks for fattening.

7 Opinion on Grindazym GP 7/9 3. New granulated form The current product is registered in 3 forms: Grindazym GP 15000, Grindazym GPL15000 and Grindazym GP 15000MG. Data is submitted to allow an additional granulated form to be marketed as Grindazym GP 15000G. Grindazym GP 15000G is a fine granular product with the following composition: Wheat carrier: 99% Enzyme protein: 0.5% (0.35% xylanase % beta-glucanase) Potassium sorbate: 0.03% Sodium benzoate: 0.06% The amount of wheat carrier added may vary by up to 10% due to variations in the yield of enzymes during the fermentation process. Any variation is compensated for in the standardisation process. Although the production site will differ from that for existing products the liquid enzyme used is described as consistent with that used in the other products and that described in the original submission Particle size distribution Particle size distribution studies In a particle size study conducted in an internal laboratory, three batches of enzyme were passed through sieves with varying size of aperture. The results for the three batches are summarised in the Table 5. Table 5. Particle size distribution (%) of three batches of Grindazym GP15000G Particle size (μm) Batch 1 Batch 2 Batch 3 > < Results indicated that a low proportion of the particles in the product were below the 212 μm threshold. Particle size study Three batches of Grindazym GP15000G were sent to an external laboratory for particle size studies. The aim of these studies was to determine the proportion of particles in the product that were <100 μm in diameter and thereby establish the inhalability of the product from a worker safety point of view. The results of the studies are summarised in Table 6. Table 6. Proportion of GRINDAZYM GP15000G with a particle size of < 100 μm Batch number Proportion of particles <100μm (%) GZG GZG GZG From the results of the three studies, the test material Grindazym GP15000G has been determined to be essentially non-inhalable.

8 Opinion on Grindazym GP 8/ Product and feed homogeneity Three separate batches of Grindazym GP15000G were tested for homogeneity, measuring both xylanase and ß-glucanase (Table 7). Table 7. Summary of Grindazym GP 15000G product homogeneity (n=3) Homogeneity (%CV) Batch number Xylanase Beta-glucanase GZG GZG GZG Mean value Three separate batches of Grindazym GP15000G were mixed into a feed mash to provide a minimum guaranteed 6 U kg -1 of xylanase activity as shown in Table 8. Table 8. Summary of homogeneity of xylanase activity of Grindazym GP 15000G in mash feed (U kg -1 ). (Guaranteed minimum xylanase activity 6 U kg -1 ) Sample Batch GZG01 Batch GZG02 Batch GZG Mean Std. Dev %CV Stability During storage for 24 months at 20ºC the xylanase activity (originally around U kg -1 ) of three batches declined to between 85 and 91% of the original value and ß-glucanase (originally around U kg -1 ) was between 75 and 82%. At 35ºC over the same period the activity of xylanase declined to between 72 and 75% of the original value and that of the ß-glucanase declined to 57-58% of original. Stability in feed was tested in a mash feed containing a minimum of 6 U g -1 of xylanase and 2.5 U g -1 of ß-glucanase. After six months storage at 20ºC the xylanase was between 72 and 91% of the original value and the ß-glucanase was % of the original value Conclusions regarding new granulated form Based upon the data provided by the applicant the new formulation is not significantly different from existing products in the content and source of the active ingredient. The homogeneity and stability of the product and the product mixed in feed has been adequately demonstrated to support the proposed use. The formulation does not alter the nature of user exposure compared with the existing products. The FEEDAP Panel considers that the formulation described as Grindazym GP15000G is acceptable as an additional form of the existing Grindazym GP15000 product range.

9 Opinion on Grindazym GP 9/9 CONCLUSIONS Considering that Grindazym GP is already approved for chickens for fattening and turkeys for fattening, major species that are physiologically similar to ducks, and taking into account the tolerance study provided, the FEEDAP Panel concludes that the additive is safe for use in the feed of ducks for fattening. In seeking the addition of a new granulated formulation (Grindazym GP 15000G) to the range of products containing this same enzyme combination the applicant has provided sufficient reassurance regarding product quality, stability and homogeneity for FEEDAP Panel to consider this formulation as acceptable. DOCUMENTATION PROVIDED TO EFSA 1. Supplementary dossier Grindazym TM GP 15000, Grindazym TM GPL and Grindazym TM GP MG. Application for provisional authorisation in ducks for fattening. September Submitted by Danisco Animal Nutrition. 2. Supplementary dossier Grindazym TM GP 15000G. Registration for new granulate product form. September Submitted by Danisco Animal Nutrition. PANEL MEMBERS Arturo Anadón, Margarita Arboix Arzo, Georges Bories, Paul Brantom, Joaquim Brufau de Barberà, Andrew Chesson, Pier Sandro Cocconcelli, Joop de Knecht, Noël Dierick, Gerhard Flachowsky, Anders Franklin, Jürgen Gropp, Ingrid Halle, Anne-Katrine Lundebye Haldorsen, Alberto Mantovani, Kimmo Peltonen, Guido Rychen, Pascal Sanders, Amadeu Soares, Pieter Wester and Wilhelm Windisch