The additive (SBS) consists of sodium bisulphate without carrier materials. The applicants are seeking authorisation for SBS as a silage additive and for use as feed preservative for all animal species, as acidity regulator for pets and other non food-producing animals and as flavouring for pets. The FEEDAP Panel concluded that (i) there is no convincing evidence for the safety of SBS as preservative in all animal species at the recommended maximum concentration of 1% in complete feed, (ii) the use of SBS in pets and other non food-producing animals is safe up to a concentration of 0.5 % - this maximum safe concentration of SBS cannot be applied to all animal species because of the lack of data in food-producing animals, and (iii) 0.8 % SBS added to fresh ensiling forages is safe for all animal species, based on data from a study with dairy cows. The use of SBS in animal nutrition is safe for the consumer up to the highest recommended level in complete feed. Sodium bisulphate is irritant to skin, eye and the respiratory tract and should be considered as a potential skin sensitiser. The use of SBS in feed is not expected to pose an additional risk for the environment. SBS is considered efficacious as preservative for all animal species, as acidity regulator in feed for pets and other non foodproducing animals and as flavouring substance for pets, based on the fact that SBS is authorised for the same purpose in food and on the studies provided. The FEEDAP Panel concluded that SBS is not efficacious as silage additive at the concentrations tested. The FEEDAP Panel recommended setting a maximum content of 0.5 % for SBS if authorised as acidity regulator and flavouring substance for pets and other non food-producing animals. (C) European Food Safety Authority, 2011.

Following a request from the European Commission, the European Food Safety Authority (EFSA) was requested to deliver an opinion on the proposal made by the applicant for the modification of the withdrawal time for the existing additive Monteban (R) G100 from one to zero day.Monteban (R) G100 containing narasin is already authorised for use in chickens for fattening. The safety and efficacy of the product have already been assessed by the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) in a former opinion, establishing the ADI (0.005 mg narasin/kg bw) and a uniform MRL (0.05 mg narasin/kg for all (wet) tissues).Any eventual consequences of reducing the withdrawal time of Monteban r G100 from one to zero day would only concern consumer safety. Therefore, the former assessment of Monteban r G100 remains unchanged for the characterisation of the additive, its safety for the target animals, the user and the environment.A new marker residue study where the maximum content of narasin (70 mg/kg feed) has been administered was provided. The ratio of marker residue to total residue was calculated on that basis for a 0.25-day withdrawal.The FEEDAP Panel concluded that the request of the applicant to reduce the withdrawal time from one day to zero day for Monteban r G100 when fed to chickens for fattening at the maximum dose of 70 mg/kg feed could be accepted, considering that an experimental 0.25-day withdrawal reflects a zero-day withdrawal under field conditions.

Following a request from the European Commission, the European Food Safety Authority (EFSA) was asked to deliver a scientific opinion on the safety and efficacy of the product Biosprint (R) when used in feeds for horses at the minimum dose of 3.1 x 10(9) and a maximum of 6.0 x 10(9) CFU/kg of complete feedstuffs. The product is currently authorised for use in piglets, cattle for fattening, dairy cows and sows.Biosprint (R) consists of viable cells of Saccharomyces cerevisiae, which is considered by EFSA to be suitable for the QPS approach to safety assessment. As the identity of the active agent has been established, the use of Biosprint (R) can be presumed safe for horses, consumers and the environment.In the absence of data on skin and eye irritancy or skin sensitisation, Biosprint (R) should be considered as a potential irritant and sensitiser, and treated accordingly. Biosprint (R) S and Biosprint (R) G are unlikely to form respirable dust. Consequently, it is concluded that the inhalation exposure associated with the use of this product would be minimal.Three digestibility studies were provided in which Biosprint (R) used at the minimum recommended dose consistently increased apparent fibre digestion in adult horses.

Maxiban (R) G160 is a coccidiostat for chickens for fattening used at levels ranging from 40-50 mg narasin/kg plus 40-50 mg nicarbazin/kg complete feed. Maxiban (R) G160 is safe for chickens for fattening and effective in controlling coccidiosis. The metabolism and residue data for narasin and nicarbazin administered separately have already been described and assessed. Additional information concerning Maxiban (R) G160 indicates that the simultaneous administration of nicarbazin and narasin increases DNC-labelled nicarbazin derived total residues by 20 % (liver) to 50 % (muscle), whereas no modification is observed for HDP-labelled nicarbazin derived residues. There is no evidence resulting from the toxicological studies for any significant interaction between narasin and nicarbazin. The ADI for narasin is 0.005 mg/kg bw, derived from a NOAEL of 0.5 mg/kg bw in a one-year dog toxicity study and applying an uncertainty factor of 100. The ADI for DNC is 0.77 mg DNC/kg bw, based on a NOAEL of 154 mg DNC/kg bw in a two-year dog toxicity study and applying an uncertainty factor of 200. The following MRLs can be applied: 50 mu g narasin/kg liver, kidney, muscle and skin/fat; 15 mg DNC/kg liver, 6 mg DNC/kg kidney and 4 mg DNC/kg muscle and skin/fat. A zero-day withdrawal period is considered appropriate. Maxiban (R) G160 is a slight skin irritant, an eye irritant and a skin sensitiser. The inhalatory risk of users from narasin in Maxiban (R) G160 dust should be reduced by safety measures normally employed for handling dust-generating products. Maxiban (R) G160 would not pose a foreseeable risk for the soil compartment, groundwater or secondary poisoning. However, the risk for surface water could not be assessed.

Calsporin (R) is a microbial feed additive based on a single strain of Bacillus subtilis. The applicant is seeking authorisation for the use of the product with piglets at a proposed dose of 3 x 10(8) CFU/kg complete feedingstuff. The additive is currently authorised for use with chickens for fattening. The identity of the active agent was established in the previous application and belongs to a bacterial species whose safety EFSA considers can be assessed using the QPS approach. The strain is susceptible to antibiotics and evidence was previously provided to demonstrate a lack of toxigenic potential. Thus the product strain meets the qualifications attached to this group of bacilli, and the additive can be presumed safe for the target species, consumers and the wider environment. Five feeding trials are reported, each made with piglets given the additive at the proposed dose compared to matched groups fed the same diet without the additive. A significant improvement in feed to gain ratio and increase in final body weight and average daily gain in animals given the additive compared to control animals was seen in three trials. Consequently, Calsporin (R) can be considered as effective at the proposed dose.

Following a request from the European Commission, the European Food Safety Authority (EFSA) was asked to deliver an opinion on the safety of Finase (R) EC (6-phytase) for turkeys for fattening.Finase (R) EC is a feed additive with 6-phytase as its declared enzymatic activity and is produced by a genetically modified strain of Trichoderma reesei. The additive Finase (R) EC is presented in solid (Finase (R) EC 40 P) and liquid (Finase (R) EC 10 L) forms; the solid form ensures a minimum activity of 40000 PPU/g and the liquid form ensures a minimum of 10000 PPU/g. Finase (R) EC is intended to be used at a dose range of 250-1000 PPU/kg complete feed in turkeys for fattening or reared for breeding.In a previous opinion, it was not possible to conclude on the safety of the preparation when used in turkeys. The applicant has provided a new tolerance study with turkeys for fattening.Based on the results obtained from the tolerance study provided, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concludes that the 6-phytase contained in the product Finase (R) EC is safe at the maximum recommended dose of 1000 PPU/kg feed for turkeys for fattening. This conclusion can be extended to turkeys reared for breeding.

Koffogran (containing 25 % nicarbazin) is intended to be used as a coccidiostat for chickens for fattening up to an age of 28 days. Feeding 125 mg nicarbazin/kg feed was safe for chickens for fattening (margin of safety about 1.5) and effective in controlling coccidiosis. Ingested nicarbazin is rapidly split into its components 2-hydroxy4,6- dimethylpyrimidine (HDP) and 4,4'-dinitrocarbanilide (DNC). DNC is the marker residue, liver the target tissue. HDP-related residues are much lower than those derived from DNC. Nicarbazin is not genotoxic. In sub-chronic rat studies, no NOAEL could be derived for nicarbazin, but a NOAEL of 709 mg/kg bw/day was identified for DNC. Those differences may be related to the higher systemic exposure of rats to DNC when administered as nicarbazin instead of DNC alone. No major concern appeared in multigeneration reproduction studies in rats at 300 mg DNC + 100 mg HDP/kg bw/day and in developmental studies with rats and rabbits at 70 and 60 mg nicarbazin/kg bw, respectively. As the consumer is exposed to DNC rather than nicarbazin, an ADI was set for DNC with 0.77 mg/kg bw/day, derived from the NOAEL for elevated serum ALT in a two-year dog study (154 mg DNC/kg bw/day) applying a safety factor of 200. MRLs of 15, 6, 4 and 4 mg DNC/kg liver, kidney, muscle and skin/fat, respectively, were proposed. Applying those MRLs consumer exposure would not exceed 24 % of the ADI. A one-day withdrawal period was considered as adequate. Nicarbazin was not an irritant or sensitiser to skin, but a slight irritant to eyes. Inhalatory exposure of users to nicarbazin was negligibly small. No safety concern for the soil compartment, groundwater or by secondary poisoning was identified, the risk for surface water could however not be assessed.

Following a request from the European Commission, the European Food Safety Authority was asked to deliver technical advice on the guidelines to be followed for the submission of dossiers accompanying applications for authorisation of additives belonging to the functional group of substances for reduction of the contamination of feed by mycotoxins.Based on additional requirements identified for the assessment of additives falling into the functional group 'substances for reduction of the contamination of feed by mycotoxins', the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) derived a proposal for the modification of Annex III of Regulation (EC) No 429/2008.

Cylactin (R) is a product consisting of viable cells of Enterococcus faecium. The product strain was found to be resistant to kanamycin. A detailed study of the nature of kanamycin resistance demonstrated the absence of known acquired genes coding for aminoglycosides- modifying enzymes. Two genetic determinants, the aminoglycoside acetyltransferase gene aac(6')-li and the gene sfkmr, both intrinsic to E. faecium, were shown to contribute to the resistance to kanamycin. In the view of the FEEDAP Panel, the resistance of this strain of E. faecium is most likely to be caused by an unknown mechanism that potentiates the effect of the sfkmr gene, and not by acquisition of resistance genes, and thus is not a cause for concern. When used at 100 times the recommended level, Cylactin r did not show any adverse effect on performance or mortality of chickens for fattening. Therefore, the additive is safe for the target animals at the proposed conditions of use. E. faecium NCIMB 10415 is free of known enterococcal virulence factors. No other concerns for consumer safety were identified. Cylactin r is not a skin/mucosal irritant or skin sensitiser. As the product is formulated with a large particle size and the dusting potential is low, inhalation exposure of users will be minimal. Cylactin r is efficacious in chickens for fattening as demonstrated in three trials showing an increase in final body weight when diets were supplemented at or close to the minimum recommended dose (0.3 x 10(9) CFU/kg feed). Cylactin r is compatible with decoquinate, monensin, robenidine, diclazuril and semduramycin.

Following a request from the European Commission, the European Food Safety Authority (EFSA) was asked to deliver a scientific opinion on the safety for the target animals, consumer, user and for the environment and on the efficacy of a product based on a single strain of Pediococcus pentosaceus, when used as a technological additive intended to improve the ensiling process.The bacterial species P. pentosaceus is considered by EFSA to be suitable for the Qualified Presumption of Safety (QPS) approach. Therefore, it does not require any specific demonstration of safety other than confirming the absence of any determinants of resistance to antibiotics of human and veterinary clinical significance and the safety for the user. As the identity of the strain DSM 16244 has been established and no antibiotic resistance detected, the use of the strain in the production of silage is considered safe for livestock species, consumers of products from animals fed the treated silage and for the environment.The additive is not an irritant to skin or eyes. It should be considered as a potential sensitiser.Four studies with laboratory-scale silos are described, each lasting at least 90 days, made using grass forage of differing water-soluble carbohydrate content and representing material easy to ensile, moderately difficult to ensile and difficult to ensile. In each case, replicate silos containing treated forage were compared to identical silos containing the same untreated forage. The additive consistently showed the potential to improve the production of silage by a reduction of pH and increased preservation of dry matter.

Inflammatory bowel diseases, (IBD), are a group of chronic disorders of the gastro-intestinal tract, and include Crohn’s disease (CD) and Ulcerative Colitis (UC). The pathogenesis is not known, but involves at least in part a loss of tolerance towards the commensal colonic microbiota. In this thesis, we show in animal models of CD and UC that the colonic mucosal blood flow increased compared to healthy animals. This blood flow increase is due to an up regulation of endothelial nitric oxide synthase (NOS). Further, we show in the UC model that the thickness of the firmly adherent colonic mucus layer increased compared to healthy animals. This increase is due to an up regulation of inducible NOS in the epithelium. Both the blood flow and mucus thickness increase appear to be protective mechanisms. We demonstrate that the firmly adherent colonic mucus layer acts as a partial barrier towards luminal bacteria. In the UC model, this barrier is destroyed, causing increased bacterial translocation. The adhesion molecule P-selectin was up regulated in the UC model, leading to increased interactions between leukocytes and the endothelium, but also increased interactions between platelets and the endothelium. This indicates that not only leukocytes, but also platelets are involved in colonic inflammation. The addition of the probiotic bacterial strain Lactobacillus reuteri prevented disease by normalizing P-selectin levels and endothelial interactions with leukocytes and platelets. Lactobacillus reuteri also decreased bacterial translocation over the epithelium. In summary, this thesis highlights the importance of colonic barrier functions, and investigates the role of the microbiota in experimental IBD.

Following a request from the European Commission, the European Food Safety Authority was asked to deliver a scientific opinion on the safety and efficacy of sodium carbonate (soda ash) used as technological feed additive (functional group acidity regulator) for all animal species. It is an approved food additive without restrictions.On the basis of the existing use in food, the Panel on Additives and Products or Substances used in animal Feed (FEEDAP) concludes that sodium carbonate is safe for all animal species, the consumers and the users. At levels typically used in animal feed, sodium carbonate is not expected either to pose a risk for the environment.Sodium carbonate is a well-known component of many buffer solutions. However, the relevance of its buffering capacity in feed materials is not demonstrated.

Clinacox (R) 0.5% ( containing 0.5 % diclazuril) is intended to be used as a coccidiostat for chickens for fattening. Feeding 1 mg diclazuril/kg feed was safe for chickens for fattening (margin of safety of at least 25) and effective in controlling coccidiosis. Ingested diclazuril is absorbed and biotransformed to a limited extent, the parent compound being the main metabolite and marker substance. Diclazuril is not genotoxic or carcinogenic, and no major concern appeared in reproductive/developmental studies. The NOEL in a chronic mouse study was 2.9 mg/kg bw/day, yielding an ADI of 0.029 mg/kg bw. The maximum theoretical consumer exposure would be 13 % of the ADI when no withdrawal period is applied. MRLs are set at 1.5, 1.0, 0.5 and 0.5 mg/kg liver, kidney, muscle and skin/fat, respectively. No safety concern would arise for workers handling Clinacox r 0.5%. The use of Clinacox r 0.5% in chickens for fattening at the recommended dose does not pose a risk for the environment.

Following a request from the European Commission, the European Food Safety Authority (EFSA) was asked to deliver a scientific opinion on the safety and efficacy of the additive Bonvital for chickens for fattening. Bonvital is a preparation of Enterococcus faecium, containing a minimum of 1 x 1010 CFU/g. It is authorised for use in piglets and pigs for fattening, and in sows. The additive is intended to be used in diets for chickens for fattening at the minimum content of 0.5 x 10(9) and at the maximum content of 2.0 x 10(9) CFU/kg of complete feedingstuffs.A tolerance study was provided with chickens for fattening. Zootechnical performance was not adversely affected by the supplementation at 100 times the maximum recommended dose of Bonvital. Therefore, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concludes that the additive is safe for the target animals at the maximum recommended dose.Based on the efficacy studies provided, a significant improvement on body weight and/or feed to gain ratio was observed in three studies when Bonvital was added to feed at the minimum recommended dose. Therefore, the FEEDAP Panel concludes that there is evidence that Bonvital has the potential to be efficacious when fed to chickens for fattening at the minimum recommended dose.

Ronozyme (R) P/Bio-Feed (R) Phytase/ZY (R) Phytase is a 6-phytase produced by Aspergillus oryzae carrying a gene coding for phytase from Peniophora lycii. The safety of the genetic modification of the current production strain has been previously established by EFSA in 2004. The product is available in two forms: granulate and liquid, providing 5000 FYT/g and 20000 FYT/g, respectively. The liquid and solid forms of the additive are considered to be equivalent when used to deliver the same enzyme levels. Based on tolerance studies performed in chickens and turkeys for fattening, laying hens, ducks, piglets, pigs for fattening and sows, the FEEDAP Panel concludes that the additive is safe for those target species at the maximum proposed dose of 1000 FYT/kg complete feed. The FEEDAP Panel considers that these conclusions can be extended to all poultry (fattening and laying) and porcine species (growing and breeding) at the same maximum dose. The data previously assessed are considered to provide sufficient evidence that this product presents no risks for the consumer, user or the environment. The data provided allow drawing conclusions on the efficacy of the additive when supplemented to diets deficient in available P at the level of 250 FYT/kg complete feed for chickens and turkeys for fattening, 300 FYT/kg for laying hens, 500 FYT/kg for piglets and pigs for fattening and 750 FYT/kg for sows. These conclusions can be extended to the corresponding minor species.

Following a request from the European Commission, the European Food Safety Authority (EFSA) was asked to deliver a scientific opinion on the efficacy of Biosaf Sc 47 (Saccharomyces cerevisiae) for calves for rearing.In a previous opinion, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was not able to reach a conclusion on the efficacy of Biosaf Sc 47 for calves for rearing since only one study showed some positive effects on the performance of calves for rearing when fed diets supplemented with the additive.Three new studies were provided to support the efficacy of Biosaf Sc 47.In two of the studies, a significant increase in average daily gain and a reduction in feed to gain ratio were observed with the addition of Biosaf Sc 47 in the diets.The FEEDAP Panel concludes that two of the new studies, together with the study assessed in the previous opinion, provide evidence of the efficacy of Biosaf Sc 47 at the minimum recommended dose (1.5 x 10(9) CFU/kg complete feed) in calves for rearing.

The additive Quantum (TM) is an enzyme preparation containing 6-phytase produced by fermentation of a genetically modified strain of the yeast Pichia pastoris. The efficacy and safety of this product for chickens for fattening, laying hens, turkeys for fattening, ducks for fattening and piglets ( weaned) including the assessment of the safety for the consumer, the user and the environment, as well as the safety aspects of the genetic modification have already been previously assessed by EFSA. The applicant is now asking for a modification on the terms of authorisation of the feed additive when used in laying hens, by lowering the minimum recommended dose from 2000 FTU/kg to 250 FTU/kg. Two trials showed clear improvements in P retention when Quantum (TM) was supplemented at 125 FTU/kg and above, including a dose of 250 FTU/kg. Despite some weaknesses in the design of the experiment, data from a third trial is considered to support the dose-effect relationship seen in the other two trials. Therefore, the FEEDAP Panel concludes that there is evidence that the enzyme preparation Quantum (TM) is efficacious in laying hens at a minimum dose of 250 FTU/kg.

Following a request from the European Commission, the European Food Safety Authority (EFSA) was asked to deliver an opinion on the compatibility of microbial feed additive 035 based on Bacillus subtilis (DSM 17299) with the coccidiostats lasalocid sodium, maduramycin ammonium, monensin sodium, narasin, salinomycin sodium and semduramycin sodium. While the compatibility of Bacillus subtilis (DSM 17299) with lasalocid sodium has been established in a previous assessment of the product BioPlus 2B containing the same strain, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was unable to conclude on the compatibility with the rest of the coccidiostats. The applicant has now provided new data to support the compatibility of the product 035 with the coccidiostats mentioned above.Two studies have been provided, involving 560 and 600 chickens for a period of 34 and 28 days, respectively. The first trial was performed with the product BioPlus 2B, while the second one was done with 035. In both cases, the birds received a basal diet containing B. subtilis DSM 17299 at the recommended inclusion rate in the presence or absence of the coccidiostats monensin sodium, salinomycin sodium and semduramycin sodium (trial 1) or salinomycin sodium, narasin, monensin sodium and maduramycin ammonium (trial 2) at their maximum authorised levels. At the end of the experiments caecal samples were randomly collected and analysed for B. subtilis applying a heat treatment to distinguish between the vegetative cells and spores. No significant differences in the CFU counts were observed between the control and the treated groups in any of the two trials.The FEEDAP Panel concludes that the product 035 (B. subtilis DSM 17299) is compatible with lasalocid sodium, maduramycin ammonium, monensin sodium, narasin, salinomycin sodium and semduramycin sodium.

The safety and efficacy of Clinacox (R) 0.5%, containing 0.5 % diclazuril as active substance, at a use level of 1 mg (0.9-1.1 mg) similar in chickens for fattening, has recently been evaluated by the FEEDAP Panel. Since the guinea fowl is a physiologically similar minor species to the chicken for fattening, and 1 mg diclazuril was considered safe for chickens for fattening with a wide margin of safety, the same dose is considered safe for guinea fowl. Likewise, no specific metabolism and residue studies are required to establish the consumer safety. Consequently, the FEEDAP Panel proposes to apply the same MRLs for tissues (1.5, 1.0, 0.5 and 0.5 mg/kg liver, kidney, muscle and skin/fat, respectively) and the same zero-day withdrawal time for guinea fowl as those established in chickens for fattening. No safety concerns related to the user or the environment have been identified in the opinion on Clinacox (R) 0.5% in chickens for fattening, and the same applies to the use of the product in guinea fowl. Based on the uniform results of two studies with artificial Eimeria numidae and Eimeria grenieri infection indicating that these guinea fowl-specific strains are sensitive to diclazuril and considering the established efficacy of the additive at the proposed use level in the major species chickens for fattening, the FEEDAP Panel concludes that 1 mg diclazuril/kg feed is effective in controlling coccidiosis in guinea fowl.