SCIENTIFIC OPINION Scientific Opinion on modification of the terms of authorisation of VevoVitall (Benzoic acid) as a feed additive for weaned piglets 1 EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) 2,3 European Food Safety Authority (EFSA), Parma, Italy ABSTRACT VevoVitall is a feed additive consisting of benzoic acid. It is currently authorised as zootechnical additive for weaned piglets and pigs for fattening. The applicant is now seeking for the modification of the terms of authorisation for weaned piglets, laid down in Commission Regulation (EC) No 1730/2006. The applicant proposes to modify the text of the Other provisions in the authorisation by deleting the sentences Complementary feedingstuffs for piglets may not contain more than 10000 mg/kg of benzoic acid and The additive shall be incorporated in compound feedingstuffs in form of a premixture and replacing them with Complementary feedingstuffs for piglets should be thoroughly mixed with other feed materials of the daily ration. Based on the similar coefficients of variation achieved for benzoic acid concentration after direct incorporation or incorporation via premixtures, the FEEDAP Panel concludes that there is no reason to restrict the inclusion of benzoic acid to compound feed via premixtures. In the view of the FEEDAP Panel, the restrictions on the use of the additive in complementary feed established for pigs for fattening by Commission Regulation (EC) No 1138/2007, are considered sufficient in respect to the narrow margin of safety of the compound and should be applied to weaned piglets. European Food Safety Authority, 2011 KEY WORDS zootechnical additive, other zootechnical additives, VevoVitall, benzoic acid, weaned piglets 1 On request from the European Commission, Question No EFSA-Q-2010-00881, adopted on 6 September 2011. 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 VevoVitall1B, including Guido Rychen, for the preparatory work on this scientific opinion. Suggested citation: EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP); Scientific Opinion on modification of the terms of authorisation of VevoVitall (Benzoic acid) as a feed additive for weaned piglets.. [9 pp.] doi:10.2903/j.efsa.2011.2358. Available online: www.efsa.europa.eu/efsajournal European Food Safety Authority, 2011
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 a modification to the terms of authorisation of VevoVitall (benzoic acid) as a feed additive for weaned piglets. The applicant proposes to modify the text of the Other provisions in the authorisation by deleting the sentences Complementary feedingstuffs for piglets may not contain more than 10000 mg/kg of benzoic acid and The additive shall be incorporated in compound feedingstuffs in form of a premixture and replacing them with Complementary feedingstuffs for piglets should be thoroughly mixed with other feed materials of the daily ration. Based on the similar coefficients of variation achieved for benzoic acid concentration after direct incorporation or incorporation via premixtures, the FEEDAP Panel concludes that there is no reason to restrict the inclusion of benzoic acid to compound feed via premixtures. In the view of the FEEDAP Panel, the restrictions on the use of the additive in complementary feed established for pigs for fattening by Commission Regulation (EC) No 1138/2007, are considered sufficient in respect to the narrow margin of safety of the compound and should be applied to weaned piglets. 2
TABLE OF CONTENTS Abstract... 1 Summary... 2 Table of contents... 3 Background... 4 Terms of reference... 4 Assessment... 6 1. Introduction... 6 1.1. Rationale for the proposal of modification... 6 1.2. Proposal of modifications and previous EFSA opinion... 6 2. Characterisation... 7 2.1. Homogeneity... 7 2.2. Evaluation of the analytical methods by the European Union Reference Laboratory (EURL) 7 Conclusions... 7 Documentation provided to EFSA... 8 References... 8 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 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 DSM Special Products 5 for the modification of the terms authorisation of the additive VevoVitall (benzoic acid, 4d 210). 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 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 17 May 2011. The additive VevoVitall (benzoic acid) consists of 99.9 % benzoic acid. The product is authorised in the EU for weaned piglets (until 14 December 2016)7, and for pigs for fattening (until 22 October 2017)8 at the maximum content of 5000 and 10000 mg/kg complete feedingstuffs, respectively. EFSA has issued two opinions on the safety and efficacy of VevoVitall, one for weaned piglets (EFSA, 2005) and one for pigs for fattening (EFSA, 2007). 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 VevoVitall consisting of 99.9 % benzoic acid when used under the conditions described in Table 1. 4 OJ L 268, 18.10.2003, p.29 5 DSM Special Products B.V. Mauritspark Mijnweg 1. 6167AC, Geleen. The Netherlands. 6 EFSA Dossier reference: FAD-2010-0029 7 OJ L 325, 24.11.2006, p.9 8 OJ L 256, 2.10.2007, p.8 4
Table 1: Description and conditions of use of the additive as proposed by the applicant Additive Benzoic acid (VevoVitall ) Registration number/ec No/No Category(-ies) of additive 4d 210 Zootechnical Functional group(s) of additive Other Composition, description Chemical formula Benzoic acid CAS 65-85-0 Description Purity criteria Benzoic acid 99.9 % Phthalic acid 100 mg/kg Polychlorinated Biphenyls 100 mg/kg Heavy metals 10 mg/kg Arsenic 2 mg/kg Method of analysis Reversed Phase HPLC coupled with UV detection Trade name Name of the holder of authorisation VevoVitall DSM Special Products Conditions of use Species or category of animal Maximum Age Minimum content Maximum content Withdrawal period mg/kg of complete feedingstuffs Piglet Up to 25 kg 5 000 5 000 - Other provisions and additional requirements for the labelling Specific conditions or restrictions for use Specific conditions or restrictions for handling Post-market monitoring Specific conditions for use in complementary feedingstuffs For user safety measures should be taken to minimize the production of breathable dust from this additive. Material safety data sheets (MSDS) available - Complementary feed containing benzoic acid may not be fed to piglets as such Complementary feedingstuffs for piglets should be thoroughly mixed with other feed materials of the daily ration Marker residue Maximum Residue Limit (MRL) Species or category of animal Target tissue(s) or food products Maximum content in tissues - - - - 5
ASSESSMENT 1. Introduction The product (VevoVitall ) is a feed additive (zootechnical; other zootechnical additives) consisting of 99.9 % benzoic acid. Its use in weaned piglets is authorised in the EU at dose of 5000 mg of active substance per kg complete feed (Commission Regulation (EC) No 1730/2006). 9 The applicant proposes a modification of the terms of the authorisation, to modify some terms under Other provisions of the authorisation. The following changes are expected by the applicant: - to delete the sentences Complementary feedingstuffs for piglets may not contain more than 10000 mg/kg of benzoic acid and The additive shall be incorporated in compound feedingstuffs in form of a premixture - to include Complementary feedingstuffs for piglets should be thoroughly mixed with other feed materials of the daily ration. The applicant aims to use the product either in premixtures, in complementary feed or directly in complete feed. 1.1. Rationale for the proposal of modification The applicant states that the inclusion rate of complementary feedingstuffs in the complete feed occurs in practice in the range of 1 to 30 % (most frequently in the range of 3 to 5 %). Therefore, in order to achieve the maximum concentration of 5000 mg VevoVitall /kg feed, the VevoVitall concentration in complementary feed would range from ca. 16000 to 500000 mg VevoVitall /kg complementary feed. Thus, to attain such a maximum concentration with the maximum authorised inclusion rate of 10000 mg VevoVitall /kg complementary feed would require a complementary feed inclusion into complete feed of more than 50 %, which is unlikely. On the other hand, the applicant states that the obligation to use the additive via a premixture restricts the possibility of the circulation of the additive to prepare the piglet feed. Moreover, the applicant argues that none of these provisions exist in the authorisation of Vevovitall for growing-finishing pigs (Regulation (EC) No 1138/2007). 10 1.2. Proposal of modifications and previous EFSA opinion In its previous assessment (EFSA, 2005), the FEEDAP Panel concluded that inclusion of 5000 ppm benzoic acid in complete feed for weaned piglets improves performance parameters (weight gain of feed/gain) in piglets up to 25 kg. A safety margin for the use of benzoic acid in piglets could not be determined but was less than a factor of two. Thus, the provision proposed by the applicant in the Register entry proposal (EFSA, 2005) In complementary feedingstuffs, the concentration of VevoVitall shall be calculated in order to achieve a concentration of 5000 mg kg -1 daily ration was found to be in agreement with the FEEDAP Panel conclusions. The two Other provisions given in Regulation (EC) No 1730/2006 and questioned by the applicant: Complementary feedingstuffs for piglets may not contain more than 10000 mg/kg of benzoic acid and The additive shall be incorporated in compound feedingstuffs in form of a premixture do not appear to be linked to the opinion of the FEEDAP Panel (EFSA, 2005). Indeed, as defined in Regulation (EC) No 767/2009, 11 complementary feedingstuffs have a high content of certain substances and are always used in combination with other feedingstuffs to form the daily ration. Therefore, complementary feedingstuffs may be incorporated at various levels in complete feed. Thus, it does not seem appropriate to limit the benzoic concentration in complementary feed to 10000 9 OJ L 325, 24.11.2006, p.9 10 OJ L 256, 2.10.2007, p.8 11 OJ L 229, 1.09.2009, p.1 6
mg/kg. On the contrary, it appears necessary to adapt the benzoic acid level in complementary feed in order to achieve a final dose of 5000 mg/kg in complete feed. The Other provisions indicating the need to incorporate the product in compound feed in form of a premixture does not fit with either with the opinion of the Panel, where it was considered that benzoic acid could be incorporated in complementary feed or in complete feedingstuffs. Since the applicant requests to use the additive directly in complete feedingstuffs and in complementary feedingstuffs at a higher level than the one currently authorised, new homogeneity trials have been provided. 2. Characterisation 2.1. Homogeneity Three homogeneity trials on piglet feed were performed (trial a, 12 trial b, 13 trial c 14 ) and are summarised in Table 2. All three trials studied the capacity of VevoVitall to homogeneously distribute in complete feed, at two inclusion rates, 5000 or 10000 mg/kg, while in two of them, VevoVitall was also included in a premixture at doses of 100000 (mineral premixture) and 150000 (limestone-based premixture) mg benzoic acid/kg premixture. The three studies report information collected across 17 feed batches implemented in various conditions (two feed manufacturers, three farms, one university, two countries). Table 2: Coefficients of variation (CV) of benzoic acid measured in feed samples (5000 mg/kg feed) after two different inclusion routes (premixture or directly in complete feed) Trials Trial a Trial b Trial a Trial b Trial c* Added via Directly added to feed Premixture Number of batches 6 1 6 1 3 Samples per batch 6 8 6 8 6 Min CV 2 % 2 % 2 % 2 % 4 % Max CV 6 % - 7 % - 8 % (*) Final concentration in feed: 10000 mg benzoic acid/kg feed Overall, the coefficients of variation (CV) of VevoVitall concentration in final feed ranged from 2 to 8 %. The CV appeared to be of the same magnitude when the product is included directly in feed or via premixture. These trials demonstrate that VevoVitall mixes homogenously in feed when the target level in feed ranges from 5000 (two trials, 14 batches) to 10000 (one trial, three batches) mg/kg. 2.2. Evaluation of the analytical methods by the European Union Reference Laboratory (EURL) EFSA has verified the EURL report as it relates to the methods used for the control of VevoVitall (benzoic acid) in animal feed. The Executive Summary of the EURL report can be found in the Appendix. CONCLUSIONS Based on the similar coefficients of variation achieved for benzoic acid concentration after direct incorporation or incorporation via premixtures, the FEEDAP Panel concludes that there is no reason to restrict the inclusion of benzoic acid to compound feed via premixtures. In the view of the FEEDAP Panel the restrictions on the use of the additive in complementary feed established for pigs for fattening by Commission Regulation (EC) No 1138/2007, are considered 12 Technical Dossier, Section II, Annex 2-9 13 Technical Dossier, Section II, Annex 2-10 14 Technical Dossier, Section II, Annex 2-11 7
sufficient in respect to the narrow margin of safety of the compound, and should be applied to weaned piglets. DOCUMENTATION PROVIDED TO EFSA 1. VevoVitall in piglet feed. April 2010. Submitted by DSM Special Products. 2. Evaluation report of the European Union Reference Laboratory for Feed Additives on the methods(s) of analysis for VevoVitall (Benzoic acid). REFERENCES EFSA (European Food Safety Authority), 2005. Opinion of the Scientific Panel on Additives and Products or Substances used in Animal Feed on the safety and efficacy of the product VevoVitall as a feed additive for weaned piglets in accordance with Regulation (EC) No 1831/2003 The EFSA Journal (2005) 290, 1-13. http://www.efsa.europa.eu/en/scdocs/doc/290.pdf EFSA (European Food Safety Authority), 2007. Opinion of the Scientific Panel on Additives and Products or Substances used in Animal Feed on the safety and efficacy of VevoVitall (benzoic acid) as feed additive for pigs for fattening. The EFSA Journal (2007) 457, 1-14. http://www.efsa.europa.eu/en/scdocs/scdoc/457.htm 8
APPENDIX Executive Summary of the Evaluation Report of the European Union Reference Laboratory for Feed Additives on the Method(s) of Analysis for VevoVitall (Benzoic acid) for weaned piglets In the current application authorisation is sought under article 13(3) for benzoic acid under the category of "zootechnical additives" functional group 4d (other zootechnical additives), according to the classification system of Annex I of Regulation (EC) No 1831/2003. The feed additive Vevo Vitall is currently authorised under Regulation (EC) No 1730/2006. According to the Applicant, the feed additive is a white powder of flaky consistency. The feed additive consists of benzoic acid, with minimum purity of 99.9 %. Specifically, authorisation is sought for the use of the feed additive for piglets (weaned). In contrast to the current authorisation where the feed additive has to be incorporated into the complete feeding stuff via a complementary feed, the feed additive is intended to be incorporated into premixtures and feedingstuffs. The Applicant suggested a minimum and maximum level of 5 g/kg feedingstuff, as set in the previous regulations. For the quantification of benzoic acid in feed additive the Applicant proposed the European Pharmacopoeia Monograph method based on acid/base titration with 0.1 M sodium hydroxide and phenol red as indicator. The EURL recommends for official control the internationally recognised European Pharmacopoeia method (Monograph 0066) to quantify benzoic acid in the feed additive. For the quantification of benzoic acid in premixtures and feedingstuff the Applicant proposed a method based on high performance liquid chromatography with UV detection (HPLC-UV) derived from ISO 9231:2008 (benzoic acid in milk and milk products). The Applicant provided validation and verification data demonstrating the applicability of the method and therefore extending the scope of the method to premixtures and feedingstuffs. Based on these acceptable method performance characteristics the EURL recommends for official control the Applicant's protocol based on ISO 9231:2008 to quantify benzoic acid content using HPLC-UV in the premixtures and feedingstuffs, within the concentration range covered by the experimental data. Further testing or validation of the methods to be performed through the consortium of National Reference Laboratories as specified by Article 10 (Commission Regulation (EC) No 378/2005) is not considered necessary. 9