EFSA Journal 2012;10(2):2575 SCIENTIFIC OPINION Scientific Opinion on the safety and efficacy of Natugrain Wheat TS (endo-1,4-beta-xylanase) as feed additive for chickens for fattening, chickens reared for laying, turkeys reared for breeding, minor avian species for fattening and reared for laying or breeding (including ducks) and ornamental birds 1 ABSTRACT EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) 2,3 European Food Safety Authority (EFSA), Parma, Italy The additive Natugrain Wheat TS is a preparation of endo-1,4-beta-xylanase (xylanase) produced by a genetically modified strain of Aspergillus niger. This product is authorised as a feed additive for chickens and turkeys for fattening and for ducks. The applicant requested for an extension of use of the additive to new poultry species and for a modification on the current authorisation in chickens for fattening and ducks. On the basis of the safety previously established for the major poultry species, Natugrain Wheat TS was considered safe for all avian species for fattening and reared for laying or breeding and ornamental birds at a maximum dose of 840 TXU per kg feed. Efficacy previously established in turkeys for fattening applies to turkeys reared for breeding (560 TXU/kg). The additional evidence provided on the efficacy of the additive in chickens for fattening confirmed 280 TXU per kg feed as a minimum effective dose and applies also to chickens reared for laying. The efficacy demonstrated for chickens for fattening was extrapolated to minor poultry species (for fattening, reared for breeding or reared for laying) and ornamental birds at the dose of 280 TXU per kg feed. European Food Safety Authority, 2012 KEY WORDS zootechnical additive, digestibility enhancer, endo-1,4-beta-xylanase, chickens, ducks, minor avian species, safety, efficacy 1 On request from the European Commission, Question No EFSA-Q-2011-00147, adopted on 2 February 2012. 2 Panel members: Gabriele Aquilina, Georges Bories, Andrew Chesson, Pier Sandro Cocconcelli, Joop de Knecht, Noël Albert Dierick, Mikolaj Antoni Gralak, Jürgen Gropp, Ingrid Halle, Christer Hogstrand, Reinhard Kroker, Lubomir Leng, Secundino López Puente, Anne-Katrine Lundebye Haldorsen, Alberto Mantovani, Giovanna Martelli, Miklós Mézes, Derek Renshaw, Maria Saarela, Kristen Sejrsen and Johannes Westendorf. Correspondence: FEEDAP@efsa.europa.eu 3 Acknowledgement: The Panel wishes to thank the members of the Working Group on Enzymes including Nuria Canibe, Friedrich Schöne and Piet Wester for the preparatory work of this scientific opinion. Suggested citation: EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP); Scientific Opinion on the safety and efficacy of Natugrain Wheat TS (endo-1,4-beta-xylanase) as feed additive for chickens for fattening, chickens reared for laying, turkeys reared for breeding, minor avian species for fattening and reared for laying and breeding (including ducks) and ornamental birds. EFSA Journal 2012;10(2):2575. [10 pp.] doi:10.2903/j.efsa.2012.2575. Available online: www.efsa.europa.eu/efsajournal European Food Safety Authority, 2012
SUMMARY 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 and efficacy of Natugrain Wheat TS (endo-1,4-beta-xylanase) as feed additive for avian species. The additive Natugrain Wheat TS is a preparation of endo-1,4-beta-xylanase (xylanase) produced by a genetically modified strain of Aspergillus niger. This product is authorised as a feed additive for chickens and turkeys for fattening and for ducks. EFSA issued opinions dealing with the safety and efficacy of the product for these species, including the assessment of the safety for the consumer, the user and the environment, as well as the safety aspects of the genetic modifications. On the basis of the safety established for the major poultry species, Natugrain Wheat TS was considered safe for all avian species for fattening and reared for laying or breeding and ornamental birds at a maximum dose of 840 TXU per kg feed. Efficacy previously established in turkeys for fattening applies to turkeys reared for breeding (560 TXU/kg). The additional evidence provided on the efficacy of the additive in chickens for fattening confirmed 280 TXU per kg feed as a minimum effective dose and applies also to chickens reared for laying. The efficacy demonstrated for chickens for fattening was extrapolated to minor poultry species (for fattening, reared for breeding or reared for laying) and ornamental birds at the dose of 280 TXU per kg feed. EFSA Journal 2012;10(2):2575 2
TABLE OF CONTENTS Abstract... 1 Summary... 2 Table of contents... 3 Background... 4 Terms of reference... 4 Assessment... 7 1. Introduction... 7 2. Conditions of use... 7 3. Evaluation of the analytical methods by the European Union Reference Laboratory (EURL)... 7 4. Safety for the target species... 7 5. Efficacy for the target species... 8 5.1. Efficacy for chickens for fattening... 8 5.2. Conclusions on the efficacy for the target species... 8 6. Post-market monitoring... 9 Conclusions... 9 Documentation provided to EFSA... 9 References... 9 EFSA Journal 2012;10(2):2575 3
BACKGROUND Regulation (EC) No 1831/2003 4 establishes the rules governing the Community authorisation of additives for use in animal nutrition. In particular, Article 4(1) of that Regulation lays down that any person seeking authorisation for a feed additive or for a new use of a feed additive shall submit an application in accordance with Article 7. Article 13(3) of that Regulation lays down that if the holder of an authorisation proposes changing the terms of the authorisation by submitting an application to the Commission, accompanied by the relevant data supporting the request for the change, the Authority shall transmit its opinion on the proposal to the Commission and the Member States. The European Commission received a request from the company BASF SE 5 for a modification of the terms of the authorisation and a new authorisation of the product Natugrain Wheat TS, endo-1,4- beta-xylanase, when used as a feed additive for chickens for fattening, chickens reared for laying, turkeys reared for breeding, turkeys for breeding purposes, minor avian species (including ducks) and ornamental birds (category: zootechnical additive; functional group: digestibility enhancer) under the conditions mentioned in Table 1. 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 4(1) (authorisation of a feed additive or new use of a feed additive) and under Article 13(3) (modification of the authorisation of a feed additive. EFSA received directly from the applicant the technical dossier in support of this application. 6 According to Article 8 of that Regulation, 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. The particulars and documents in support of the application were considered valid by EFSA as of 28 June 2011. The additive Natugrain Wheat TS is a preparation of endo-1,4-beta-xylanase produced by a genetically modified strain of Aspergillus niger (CBS 109.713). This product is currently authorised in the Community as feed additive for chickens for fattening, turkeys for fattening and ducks. 7,8 EFSA issued two opinions on the safety and efficacy of the product as feed additive for chickens for fattening including ducks (EFSA, 2005 and 2009) and another one regarding the safety and efficacy of the product as feed additive for turkeys for fattening (EFSA, 2007). The safety of the genetic modification of the strain has been evaluated by EFSA in 2005 and 2008. TERMS OF REFERENCE According to Article 8 of Regulation (EC) No 1831/2003, EFSA shall 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 animal(s), consumer, user and the environment and the efficacy of the product Natugrain Wheat TS (endo-1,4-beta-xylanase), when used under the conditions described in Table 1. 4 Regulation (EC) No 1831/2003 of the European Parliament and of the Council of 22 September 2003 on additives for use in animal nutrition. OJ L 268, 18.10.2003, p. 29. 5 BASF SE, G-ENL/R-LiHo 554, 67056 Ludwigshafen, Rhein, Germany. 6 EFSA Dossier reference: FAD-2011-0010. 7 Commission Regulation (EC) No 1380/2007 of 26 November 2007 concerning the authorisation of endo-1,4-beta-xylanase (Natugrain Wheat TS) as a feed additive. OJ L 309, 27.11.2007, p.21. 8 Commission Regulation (EC) No 1096/2009 of 16 November 2009 concerning the authorisation of an enzyme preparation of endo-1,4-beta-xylanase produced by Aspergillus niger (CBS 109.713) as a feed additive for chickens for fattening and the authorisation of a new use of this preparation as a feed additive for ducks (holder of authorisation BASF SE) and amending Regulation (EC) No 1458/2005. OJ L 301, 17.11.2009, p.3. EFSA Journal 2012;10(2):2575 4
Table 1: Description and conditions of use of the additive as proposed by the applicant Additive Registration number/ec No/No Category(ies) of additive Functional group(s) of additive Endo-1,4-ß-xylanase 4a62 4. Zootechnical additives (a) Digestibility enhancers Composition, description Endo- 1, 4-ß-xylanase EC 3.2.1.8 Description Chemical formula Preparation of endo-1,4-ßxylanase producted by Aspergillus niger (CBS 109.713) having a minimum activity of: Solid form: 5600 TXU/g Liquid form: 5600 TXU/g Purity criteria Method of analysis 1 TXU is the amount of enzyme which liberates 5 micromole of reducing sugars (xylose equivalents) from wheat arabinoxylan er minute at ph 3,5 and 55ºC Trade name Name of the holder of authorisation Natugrain Wheat TS BASF SE, 67056 Ludwigshafen, Germany Species or category of animal Chickens for fattening Chickens reared for laying Turkeys reared for breeding Minor avian species for fattening and reared for laying and breeding (including ducks) Ornamental birds Maximum Age - Conditions of use Minimum content Maximum content mg or Units of activity or CFU kg -1 of complete feedingstuffs (select what applicable) 280 TXU 280 TXU 560 TXU 280 TXU 280 TXU Withdrawal period - - Other provisions and additional requirements for the labelling EFSA Journal 2012;10(2):2575 5
Specific conditions or restrictions for use Specific conditions or restrictions for handling Post-market monitoring Specific conditions for use in complementary feedingstuffs 1. In the directions for use of the additive and premixture, indicate the storage temperature, storage life, and stability to pelleting. 2. For use in feed rich in non-starch polysaccharides (arabinoxylans), e. g. containing more than 40 % wheat (and/ or wheat by-products) and/ or triticale. 3. Recommended doses for kilogram of complete feedingstuffs: Chickens for fattening: 280-840 TXU; Chickens reared for laying: 280-840 TXU; Turkeys reared for breeding: 560-840 TXU Minor avian species for fattening and reared for laying and breeding: 280-840 TXU; Ornamental birds: 280-840 TXU For safety: breathing protection, glasses and gloves shall be used during handling. BASF has a general traceability system and a complaint procedure in place, including procedures for recalls. An emergency telephone number is printed on each label Not appropriate Marker residue Maximum Residue Limit (MRL) Species or category of animal Target tissue(s) or food products Maximum content in tissues Not appropriate - - - EFSA Journal 2012;10(2):2575 6
ASSESSMENT 1. Introduction Natugrain Wheat TS is an enzyme preparation of endo-1,4-beta-xylanase (xylanase, E.C. 3.2.1.8) produced by a genetically modified strain of Aspergillus niger (CBS 109.713) which is presented in two different formulations, liquid (Natugrain Wheat TS L) and solid (Natugrain Wheat TS), both ensuring a minimum activity 5600 TXU/g. The additive is currently authorised as feed additive for chickens, turkeys and ducks for fattening as a zootechnical additive (functional group: digestibility enhancers). The applicant is now requesting for an extension of use to chickens reared for laying, turkeys reared for breeding, minor poultry species and ornamental birds and a modification of the terms of the authorisation for chickens and ducks for fattening. 9 The safety and efficacy of this product, including the safety of the consequences of the genetic modification, and the detailed characterisation of the additive have been previously established (EFSA 2005, 2007, 2008 and 2009). Therefore, the present opinion is focused on the safety and efficacy of Natugrain Wheat TS/TS L as feed additive for the new target species/categories and on the new proposed dose of use for chickens and ducks for fattening (from 560 TXU/kg to 280 TXU/kg). 2. Conditions of use The additive is intended for use in feed for chickens for fattening or reared for laying, minor avian species for fattening and reared for laying or breeding (including ducks), and ornamental birds at a minimum recommended dose of 280 TXU/kg complete feed, and in feed for turkeys reared for breeding at a minimum recommended dose of 560 TXU/kg complete feed. In all cases the maximum dose is 840 TXU/kg complete feed. 3. Evaluation of the analytical methods by the European Union Reference Laboratory (EURL) The EURL considered that the conclusions and recommendations reached in the previous assessment are valid and applicable for the current application. 10 4. Safety for the target species The safety of the product was previously established in chickens for fattening and turkeys for fattening at a maximum dose of 840 TXU/kg feed (EFSA, 2007 and 2009). In the view of the FEEDAP Panel, safety previously established in chickens and turkeys for fattening (840 TXU/kg feed) applies to chickens reared for laying and turkeys reared for breeding. Given the margin of safety established for the major poultry species, these conclusions can be extended to include minor avian species for fattening and reared for laying or breeding (including ducks) and ornamental birds at the same dose. 9 The application was also made for turkeys for breeding purposes and laying minor avian species but during the assessment the applicant expressed its intention to withdraw the application for these species/categories-technical dossier/supplementary information/july 2011. 10 The full report is available on the EURL wesbite: http://irmm.jrc.ec.europa.eu/sitecollectiondocuments/finrep-fad- 2010-0034.pdf EFSA Journal 2012;10(2):2575 7
5. Efficacy for the target species 5.1. Efficacy for chickens for fattening The applicant is requesting to lower the dose in chickens and ducks (to be applied as well to minor fattening poultry species and ornamental birds). Four trials were provided, three of them were described in a previous EFSA opinion (2009): two trials provided evidence of efficacy at 280 TXU/kg (Table 2, trials 1 and 2) and one at 560 TXU/kg (not shown in the table). The applicant provided a new performance trial (duration: 35 days) (Table 2, trial 3). 11 A total of 160 day-old male chickens (Ross Strain) kept in floor pens in groups of eight, were distributed to two treatments each with 10 pens (replicates). The control group received the non-supplemented basal diets (starter and finisher) whereas the treatment group received the basal diets supplemented with Natugrain Wheat TS at a dose of 280 TXU/kg diet. The starter and finisher diets based on wheat and soybean meal were fed in pelleted form. The enzyme activity was confirmed by analysis: < 100 TXU/kg feed in the control group; 302 and 255 TXU/kg mean values- in the supplemented group for starter and grower pelleted feed, respectively. In pelleted supplemented diets there was about one quarter enzyme activity loss compared with the mash. Feed intake and body weight gain were measured and the feed to gain ratio was calculated. There were no death cases or culled birds during the experiment. The enzyme addition had no effect on total feed intake (3607 g/chicken in the control group vs 3514 g/chicken in the supplemented group) and final body weight (2100 vs 2141 g/chicken, respectively). The addition of Natugrain Wheat TS resulted in a significantly (P < 0.05) lower feed to gain ratio, from 1.73 (control) to 1.68 (with enzyme addition). Therefore, Natugrain Wheat TS at the dose of 280 TXU/kg diet has the potential to improve feed to gain ratio in chickens for fattening. Table 2: Effect of Natugrain Wheat TS in chickens for fattening Trial (sex) 1 12 ( / ) 2 13 ( / ) 3 14 ( ) Total number of animals (replicates/ treatment birds/replicate) 720 (12 20) 720 (12 20) 160 (10 8) Trial duration (days) 35 35 35 Basal diet wheat soybean meal wheat soybean meal rye wheat soybean meal rye Natugrain Wheat TS, (TXU /kg feed) 0 280 560 0 280 560 0 280 Body weight gain (g/day) 56.4 b 61.0 a 60.9 a 52.2 b 59.8 a 59.9 a 58.7 59.9 Feed/gain (kg/kg) 1.88 a 1.70 b 1.72 b 1.93 a 1.75 b 1.73 b Mortality (%) 7.1 2.1 4.6 6.7 2.5 2.9 1.73 a 0 1.68 b 0 a, b, Means within a column for a given trial not sharing a common superscript are significantly different (P < 0.05) 5.2. Conclusions on the efficacy for the target species Efficacy previously established in turkeys for fattening (EFSA, 2007) applies to turkeys reared for breeding (560 TXU/kg). 11 Technical dossier/section IV/Annexes 4.3.1.2 d1 to d4 12 Technical Dossier/Supplementary information August 2011/Annexes 2 and 3 13 Technical Dossier/Supplementary information August 2011/Annexes 4 and 5 14 Technical Dossier/Section IV/Annex 4.3.1.2 d1 EFSA Journal 2012;10(2):2575 8
The additional evidence provided on the efficacy of the additive in chickens for fattening confirms 280 TXU per kg feed as a minimum effective dose. This applies also to chickens reared for laying. Since the mode of action of the xylanase can be reasonably assumed to be the same in all poultry species the conclusions on efficacy for major poultry species can be extrapolated to include the minor poultry species (only for fattening, reared for breeding or reared for laying) and ornamental birds at the dose of 280 TXU per kg feed. 6. Post-market monitoring 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 Regulation 15 and Good Manufacturing Practice. CONCLUSIONS Natugrain Wheat TS is safe for all avian species for fattening and reared for laying or breeding and ornamental birds at a maximum dose of 840 TXU/kg feed. Efficacy previously established in turkeys for fattening applies to turkeys reared for breeding (560 TXU/kg). The additional evidence provided on the efficacy of the additive in chickens for fattening confirms 280 TXU per kg feed as a minimum effective dose. This applies also to chickens reared for laying. The efficacy demonstrated for chickens for fattening can be extrapolated to minor poultry species (for fattening, reared for breeding or reared for laying) and ornamental birds at the dose of 280 TXU per kg feed. DOCUMENTATION PROVIDED TO EFSA 1. Natugrain Wheat TS. February 2011. Submitted by BASF SE. 2. Natugrain Wheat TS. Supplementary information. August 2011. Submitted by BASF SE. 3. Natugrain Wheat TS. Supplementary information. December 2011. Submitted by BASF SE. 4. Letter from the European Union Reference Laboratory for Feed Additives on the Methods(s) on the evaluation for Natugrain Wheat TS. 5. Comments from Member States received through the ScienceNet. REFERENCES EFSA (European Food Safety Authority), 2005. Scientific Opinion of the Panel on Additives and Products or Substances used in Animal feed on a request from the Commission on the safety of the enzyme preparation Natugrain Wheat + for chickens for fattening. The EFSA Journal (2005), 198, 1-8. EFSA (European Food Safety Authority), 2007. Opinion of the Scientific Panel on Additives and Products or Substance used in Animal Feed on the safety and efficacy of the enzymatic preparation Natugrain Wheat TS (endo-1,4-beta-xylanase) as a feed additive for turkeys for fattening according to Regulation (EC) No 1831/2003. The EFSA Journal (2007), 474, 1-11. EFSA (European Food Safety Authority), 2008. Scientific Opinion of the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) and of the Panel on Genetically Modified Organisms (GMO) on a request from the European Commission on the safety and efficacy of Natugrain TS (endo-1,4-ß-xylanase and endo-1,4-ß-glucanase) as a feed additive for 15 Regulation (EC) No 183/2005 of the European Parliament and of the Council of 12 January 2005 laying down requirements for feed hygiene. OJ L 35, 8.2.2005, p. 1. EFSA Journal 2012;10(2):2575 9
piglets(weaned), chickens for fattening, laying hens, turkeys for fattening and ducks. The EFSA Journal (2008) 914, 1-19. EFSA (European Food Safety Authority), 2009. Scientific Opinion of the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) on a request from the European Commission on the safety and efficacy of Natugrain Wheat TS (endo-1,4-β-xylanase) as feed additive for chickens for fattening and ducks. The EFSA Journal (2009) 1155, 1-14. EFSA Journal 2012;10(2):2575 10