SCIENTIFIC OPINION. EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) 2,3

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1 EFSA Journal 2015;13(7):4157 SCIENTIFIC OPINION Scientific Opinion on the safety and efficacy of VevoVitall (benzoic acid) as a feed additive for pigs for reproduction (gestating and lactating sows, boars and gilts) 1 EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) 2,3 ABSTRACT European Food Safety Authority (EFSA), Parma, Italy VevoVitall consists of 99.9 % benzoic acid. It is already authorised in the European Union as a zootechnical additive for weaned piglets and pigs for fattening. VevoVitall is intended to be used in pigs for reproduction to reduce the ph of their urine. The applicant initially linked this effect to the reduction of the ammonia emission from the target animal s manure and the control of urinary tract disorders in sows, but subsequently removed these claims from the scope of the application. In 2012, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) adopted an opinion on the safety and efficacy of VevoVitall as a feed additive for pigs for reproduction, covering gestating and lactating sows, boars and gilts. The Panel could not conclude on the safety of the additive for the target species or on its efficacy because of the lack of data provided by the applicant. The FEEDAP Panel considered the new information provided by the applicant on safety and efficacy, concluding that VevoVitall is safe for sows, gilts and boars at the highest proposed use level ( mg/kg complete feed), but no margin of safety could be established. VevoVitall at mg/kg has the potential to introduce a small reduction in urine ph in sows. No conclusion on the effects on urine ph could be drawn for boars and gilts. The FEEDAP Panel considers that an effect on urinary ph alone is of little practical or biological relevance unless it is demonstrated to be linked to a clear beneficial effect on animal production, performance, welfare or the environmental consequences of animal production. European Food Safety Authority, 2015 KEY WORDS zootechnical additive, VevoVitall, benzoic acid, pigs for reproduction, safety, efficacy 1 On request from the European Commission, Question No EFSA-Q , adopted on 16 June Panel members: Gabriele Aquilina, Vasileios Bampidis, Maria De Lourdes Bastos, Lucio Guido Costa, Gerhard Flachowsky, Mikolaj Antoni Gralak, Christer Hogstrand, Lubomir Leng, Secundino López-Puente, Giovanna Martelli, Baltasar Mayo, Fernando Ramos, Derek Renshaw, Guido Rychen, Maria Saarela, Kristen Sejrsen, Patrick Van Beelen, Robert John Wallace and Johannes Westendorf. Correspondence: FEEDAP@efsa.europa.eu 3 Acknowledgement: The Panel wishes to thank the members of the Working Group on Other Zootechnical Additives, including Andrew Chesson, for the preparatory work on this scientific opinion. Suggested citation: EFSA FEEDAP Panel (EFSA Panel on Additives and Products or Substances used in Animal Feed), Scientific Opinion on the safety and efficacy of VevoVitall (benzoic acid) as a feed additive for pigs for reproduction (gestating and lactating sows, boars and gilts). EFSA Journal 2015;13(7):4157, 7 pp. doi: /j.efsa Available online: European Food Safety Authority, 2015

2 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 VevoVitall (benzoic acid) as a feed additive for pigs for reproduction. VevoVitall consists of 99.9 % benzoic acid. The product is already authorised in the European Union as a zootechnical additive for piglets (weaned) and pigs for fattening. VevoVitall is intended to be used in pigs for reproduction to reduce the ph of their urine. The applicant initially linked this effect to the reduction of the ammonia emission from the target animal s manure and the control of urinary tract disorders in sows, but subsequently removed these claims from the scope of the application. In 2012, the FEEDAP Panel adopted an opinion on the safety and efficacy of VevoVitall as a feed additive for pigs for reproduction, covering gestating and lactating sows, boars and gilts. The FEEDAP Panel could not reach a conclusion regarding the safety of the additive for the target species or its efficacy as regards the reduction of the ammonia emission from the target animal s manure because of the lack of data provided by the applicant. The FEEDAP Panel considered the new information provided by the applicant with regard to the safety for the target species and the efficacy. VevoVitall is considered safe for sows at the highest proposed use level ( mg/kg), but no margin of safety could be established. Although the FEEDAP Panel had reservations about the relevance of safety studies in pigs for fattening for boars and gilts, with the new tolerance study provided in sows, safety at the maximum use level of mg/kg feed has now been established for weaned piglets, pigs for fattening and sows. Given that data is now available for weaned piglets, pigs for fattening and sows, the Panel considers that it is unlikely that this concentration would produce an adverse effect in boars and gilts. Therefore, the Panel concludes that VevoVitall is safe for gilts and boars at the highest proposed use level ( mg/kg complete feed). VevoVitall at the dose of mg/kg has the potential to introduce a small reduction in urine ph (approximately 0.4 units) in sows. In the absence of data, no conclusion on the effects on urine ph could be drawn for boars and gilts. The FEEDAP Panel considers that an effect on urinary ph alone is of little practical or biological relevance unless it is demonstrated to be linked to a clear beneficial effect on animal production, performance, welfare or on the environmental consequences of animal production. EFSA Journal 2015;13(7):4157 2

3 TABLE OF CONTENTS Abstract... 1 Summary... 2 Background as provided by the European Commission... 4 Terms of reference as provided by the European Commission... 4 Assessment Introduction Conditions of use Safety for the target species Conclusions on the safety for species Efficacy... 6 Conclusions... 6 Documentation provided to EFSA... 7 References... 7 EFSA Journal 2015;13(7):4157 3

4 BACKGROUND AS PROVIDED BY THE EUROPEAN COMMISSION Regulation (EC) No 1831/ establishes rules governing the Community authorisation of additives for animal nutrition and in particular, Article 9 defines the terms of the authorisation by the Commission. The applicant, DSM Nutritional Products, is seeking a Community authorisation of benzoic acid (VevoVitall ) for use in pigs for reproduction (gestating and lactating sows, boars and gilts), to be used as zootechnical additive (Table 1). Table 1: Description of the substance Category of additive Zootechnical additives Functional group of additive Other Trade name VevoVitall Description Benzoic acid Target animal category Pigs for reproduction (gestating and lactating sows, boars and gilts) Applicant DSM Nutritional Products Type of request Update opinion On 14th June 2012, the Panel on Additives and Products or Substances used in Animal Feed of the European Food Safety Authority ( Authority ), in its opinion on the safety and efficacy of the product, could not conclude on the safety and efficacy of the product because of the lack of data provided by the applicant. The Commission gave the possibility to the applicant to submit complementary information in order to complete the assessment on the safety and the efficacy to allow a revision of Authority s opinion. The Commission has now received an additional dossier from the applicant on benzoic acid (VevoVitall ) for use in pigs for reproduction (gestating and lactating sows, boars and gilts), with supplementary information, concerning the safety and efficacy studies of the additive. The data generated by the applicant and compiled in the above-mentioned supplementary report have been sent directly to the Authority by the applicant. TERMS OF REFERENCE AS PROVIDED BY THE EUROPEAN COMMISSION In view of the above, the Commission asks the Authority to deliver an updated opinion on the safety and efficacy of benzoic acid (VevoVitall ) for use in pigs for reproduction (gestating and lactating sows, boars and gilts) as zootechnical additive based on the additional data submitted by the applicant. 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, , p. 29. EFSA Journal 2015;13(7):4157 4

5 ASSESSMENT 1. Introduction VevoVitall consists of 99.9 % benzoic acid. The product is already authorised in the European Union as a zootechnical additive for piglets (weaned) and pigs for fattening. The Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) has previously delivered four opinions on the same product for weaned piglets (EFSA FEEDAP Panel, 2005, 2011), pigs for fattening (EFSA FEEDAP Panel, 2007) and pigs for reproduction (EFSA FEEDAP Panel, 2012). VevoVitall is intended to be used in pigs for reproduction to reduce the ph of their urine. The applicant initially linked this effect to the reduction of the ammonia emission from the target animal s manure and the control of urinary tract disorders in sows, but subsequently removed these claims from the scope of the application. In the previous application on the use of VevoVitall in pigs for reproduction covering gestating and lactating sows, boars and gilts the FEEDAP Panel could not reach a conclusion regarding the safety of the additive for the target species or its efficacy as regards the reduction of the ammonia emission from the target animal s manure (EFSA FEEDAP Panel, 2012). The applicant has now provided new information with regard to the safety for the target species and the efficacy, and this new information is the subject of this opinion Conditions of use VevoVitall is intended to be used in pigs for reproduction at a maximum level of mg/kg feed. The applicant recommends a use level of mg/kg feed. 3. Safety for the target species A tolerance study was performed to evaluate the tolerance of gestating and lactating sows to VevoVitall. 6 In total, 48 multiparous sows (Great Yorkshire Large White Dutch Landrace, 2nd to 6th parity) were used in this experiment. The experiment was conducted with sows in good health and with normal body condition at the beginning of the experiment. Sows were blocked based on parity, and individual feed intake was measured. Sows were transferred from the gestation unit to the farrowing rooms on approximately day 108 of gestation. Creep feed was supplied to the piglets from day 14 of lactation. No cross-fostering was applied. However, when the number of suckling piglets exceeded 14 viable piglets per litter, the surplus piglets were moved within three days after birth to a sow that was not used in the experiment. The experimental set-up was a completely randomised block design with four dietary treatments: supplementation of a basal diet with VevoVitall at 0, mg/kg, mg/kg (1 maximum recommended use level) or mg/kg (2 ). There were 12 replicates (sows) per treatment. The doses were confirmed by analysis. Experimental diets were provided from insemination until weaning. Body weight and back fat thickness were measured at the start of the experiment, on day 108 of gestation, at farrowing and at weaning. Feed intake was calculated as the difference between feed allowance and feed refusals from the start of the experiment until weaning. The numbers of total born, live born and stillborn piglets were recorded. Piglets were individually weighed at birth and at weaning. Furthermore, litter weight was determined on days 7, 14 and 21 of lactation. At weaning, blood samples were taken for measurement of haematological and biochemical parameters. 7 After weaning, sows were slaughtered and the stomachs were collected to determine the effect of VevoVitall on the prevalence of gastric ulcers. In metacarpal bone, calcium and phosphorus content was measured. Data were statistically 5 Supplementary Information Dossier (July 2014). 6 Supplementary Information Dossier (July 2014)/Appendix A. 7 Red blood cells, packed cell volume, mean corpuscular volume, haemoglobin, mean corpuscular haemoglobin, corpuscular haemoglobin concentration, white blood cells, aspartate aminotransferase, alanine aminotransferase, gammaglutamyltranspeptidase, alkaline phosphatase, calcium and phosphorus. EFSA Journal 2015;13(7):4157 5

6 evaluated with an analysis of variance, and a Tukey post-test was used to compare treatment means. Individual animals were used as the experimental unit. Dietary treatments did not have an effect on the feed intake of the sow during gestation (average: 2.84 kg/day) or lactation (average: 5.97 kg/day). However, the mean body weight at weaning of sows receiving VevoVitall at a dose of mg/kg (207.5 kg) was significantly lower (P = 0.002) than that of sows from the control or mg/kg groups (223.4 and kg, respectively). A similar effect was observed on back fat thickness at weaning. Sows from the mg/kg group had a reduced back fat thickness compared with that of the sows from the control and mg/kg groups (13.9, 15.5 and 15.9 mm for the , 0 and mg/kg groups, respectively, P = 0001). No effect of dietary treatment was observed in the number of piglets born, litter performance, haematology and blood chemistry parameters, prevalence and severity of gastric ulcers, or bone composition. The use of mg/kg VevoVitall did not affect any of the parameters evaluated Conclusions on the safety for the target species Based on a tolerance study in gestating and lactating sows, the FEEDAP Panel concludes that VevoVitall is safe for sows at the highest proposed use level ( mg/kg complete feed). However, no margin of safety can be established. Although the FEEDAP Panel had reservations about the relevance of safety studies in pigs for fattening for boars and gilts, with the new tolerance study provided in sows, safety at the maximum use level of mg/kg feed has now been established for weaned piglets, pigs for fattening and sows. Given that data is now available for weaned piglets, pigs for fattening and sows, the Panel considers that it is unlikely that this concentration would produce an adverse effect in boars and gilts. Therefore, the Panel concludes that VevoVitall is safe for gilts and boars at the highest proposed use level ( mg/kg complete feed). 4. Efficacy In the previous opinion (EFSA FEEDAP Panel, 2012), it was concluded that the concentration of mg VevoVitall /kg caused a statistically significant reduction in urine ph in all four studies. However this reduction was small and unlikely to affect ammonia emission from manure. The addition of mg/kg or above had a much greater impact on urinary ph in the two studies in which these levels were considered, but the consequences for ammonia emission could not be established. Consequently, the FEEDAP Panel is unable to conclude on the efficacy of VevoVitall in reducing ammonia emission from the manure of gestating and lactating sows. The FEEDAP Panel acknowledges that VevoVitall is able to reduce the ph of urine, as was concluded in the previous opinion. The concentration of mg VevoVitall /kg caused a small but statistically significant reduction in the four studies (from 0.25 to 0.61 ph units). The reduction in ph was greater (from 0.73 to 1.31 ph units) at mg/kg in the two studies where this dose was tested. However, the Panel considers that an effect on urinary ph alone is of little practical or biological relevance unless it can be linked to a clear beneficial effect on animal production, performance, welfare or the environmental consequences of animal production, as foreseen in Article 5(3) of Regulation (EC) No 1831/2003. Owing to the lack of data, and considering the different metabolism rate and physiological status as compared to pigs for fattening and lactating/gestating sows, no conclusion could be drawn as regards boars and gilts. CONCLUSIONS VevoVitall is considered safe for sows at the highest proposed use level ( mg/kg), but no margin of safety could be established. Although the FEEDAP Panel had reservations about the relevance of safety studies in pigs for fattening for boars and gilts, with the new tolerance study EFSA Journal 2015;13(7):4157 6

7 provided in sows safety at the maximum use level of mg/kg feed has now been established for weaned piglets, pigs for fattening and sows. Given that data is now available for weaned piglets, pigs for fattening and sows, the Panel considers that it is unlikely that this concentration would produce an adverse effect in boars and gilts. Therefore, the Panel concludes that VevoVitall is safe for gilts and boars at the highest proposed use level ( mg/kg complete feed). The FEEDAP Panel concludes that VevoVitall at the dose of mg/kg has the potential to introduce a small reduction in urine ph in sows. In the absence of data, no conclusion on the effects on urine ph could be drawn for boars and gilts. The FEEDAP Panel considers that an effect on urinary ph alone is of little practical or biological relevance unless it is demonstrated to be linked to a clear beneficial effect on animal production, performance, welfare or on the environmental consequences of animal production. DOCUMENTATION PROVIDED TO EFSA 1. Supplementary Information Dossier to demonstrate the safety and efficacy of VevoVitall (benzoic acid) for pigs for reproduction. July Submitted by DSM Nutritional Products. 2. Supplementary Information Dossier to demonstrate the safety and efficacy of VevoVitall (benzoic acid) for pigs for reproduction. Supplementary information. April Submitted by DSM Nutritional Products. REFERENCES EFSA (European Food Safety Authority), Opinion of the Scientific Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) 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, EFSA (European Food Safety Authority), Opinion of the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) on the safety and efficacy of VevoVitall (benzoic acid) as feed additive for pigs for fattening. The EFSA Journal 2007, 457, 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. EFSA Journal 2011;9(9):2358, 9 pp. doi: /j.efsa EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP), Scientific Opinion on the safety and efficacy of VevoVitall (benzoic acid) as feed additive for pigs for reproduction. EFSA Journal 2012;10(7):2775, 11 pp. doi: /j.efsa EFSA Journal 2015;13(7):4157 7