The Degradome database: mammalian proteases and diseases of proteolysis

The degradome is defined as the complete set of proteases present in an organism. The recent availability of whole genomic sequences from multiple organisms has led us to predict the contents of the degradomes of several mammalian species. To ensure the fidelity of these predictions, our methods have included manual curation of individual sequences and, when necessary, direct cloning and sequencing experiments. The results of these studies in human, chimpanzee, mouse and rat have been incorporated into the Degradome database, which can be accessed through a web interface at http://degradome.uniovi.es. The annotations about each individual protease can be retrieved by browsing catalytic classes and families or by searching specific terms. This web site also provides detailed information about genetic diseases of proteolysis, a growing field of great importance for multiple users. Finally, the user can find additional information about protease structures, protease inhibitors, ancillary domains of proteases and differences between mammalian degradomes

Safety of the feed additive consisting of manganese chelates of lysine and glutamic acid for all animal species (Zinpro Animal Nutrition)

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 for target animals of manganese chelates of lysine and glutamic acid (Manganese-LG) as a nutritional feed additive for all animal species. The European Commission request followed an opinion of the FEEDAP Panel published in 2020; in that opinion, the FEEDAP Panel could conclude on the safety of the additive for chickens for fattening, but not for the rest of the target animals. The applicant submitted additional information to allow the FEEDAP Panel to complete its assessment; these additional data, comprising two tolerance studies (one with chickens for fattening and one with laying hens), were the subject of this opinion. The tolerance study in laying hens was not considered for the assessment since the housing conditions of the animals were not appropriate according to the relevant EU provisions. The results of the tolerance study in chickens for fattening showed that Manganese-LG at the highest level tested – 800 mg Mn/kg feed – is safe for these target animals. The FEEDAP Panel also considered a previous tolerance study in chickens for fattening. Taking all the evidence together the Panel concluded that Manganese-LG is safe for chickens for fattening at 150 mg Mn/kg feed, with a margin of safety of 5.5. This conclusion can be extrapolated to all animal species and categories provided that the maximum authorised levels in the EU for total manganese in feed are not exceeded

Assessment of the application for renewal of authorisation of GalliPro ® (Bacillus subtilis DSM 17299) for chickens for fattening

GalliPro \uae is the trade name for a feed additive based on viable cells of a strain of Bacillus subtilis intended for use as a zootechnical additive (gut flora stabiliser) in feed for chickens for fattening. The product is currently authorised for use in chickens for fattening. This opinion concerns the renewal of this authorisation. Bacillus subtilis is considered by EFSA to be suitable for the qualified presumption of safety (QPS) approach to establish the safety for the target species, consumers and the environment. The identity of the strain present in the additive was established and evidence was provided on the lack of toxigenic potential as well as acquired antibiotic resistance determinants to antibiotics of human and veterinary importance. Accordingly, this strain is presumed safe for the target species, consumers of products derived from animals fed the additive and the environment. Since no concerns are expected from other components of the additive, GalliPro \uae is considered safe for the target species, consumers and the environment. The applicant has provided evidence that the additive currently in the market complies with the existing conditions of authorisation. The FEEDAP Panel confirms its previous conclusions that GalliPro \uae is safe for the target species; consumers of products from animals fed the additive and the environment. GalliPro \uae should be considered a potential respiratory sensitiser. In the absence of data, the FEEDAP Panel cannot conclude on the potential of GalliPro \uae for skin and eyes irritancy and dermal sensitisation

Safety and efficacy of copper chelates of lysine and glutamic acid as a feed additive for all animal species

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of copper chelates of lysine and glutamic acid (Copper-LG) as a nutritional feed additive for all animal species. The EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concludes that, owing to safety considerations, Copper-LG should not be used in water for drinking. Copper-LG is safe for chickens for fattening; this conclusion can be extrapolated to all animal species and categories provided that the maximum authorised levels in the EU for total copper in feed are not exceeded. No increases in the copper content of animal tissues/products are expected from the use of Copper-LG in animal nutrition. There is no indication that the toxicity of Copper-LG is essentially different from that of inorganic divalent copper. The use of Copper-LG in animal nutrition is of no concern for consumer safety provided that the maximum authorised total copper in feed is respected. Owing to the copper and nickel content of Copper-LG, the handling of the additive, poses a risk to users by inhalation. The additive is considered as a skin and respiratory sensitiser; it is corrosive to the eye while it is non-irritant to skin. The additive is intended to be a substitute for other authorised copper additives and will not further increase the environmental burden of copper; therefore, the FEEDAP Panel considers that the use of the additive in animal nutrition would not pose an additional risk for the environment. Copper-LG is a bioavailable source of copper, comparable to the standard inorganic copper source, and therefore, the additive is efficacious in meeting the birds copper requirements; this conclusion can be extrapolated to all animal species/categories. The FEEDAP Panel posed a recommendation concerning the description of the additive

Safety and efficacy of Taminizer D (dimethylglycine sodium salt) as a feed additive for chickens for fattening

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of Taminizer D (dimethylglycine sodium salt) as a feed additive for chickens for fattening, based on a dossier submitted for the modification of the terms of authorisation of the additive. The product is authorised in the European Union for chickens for fattening at the maximum content of 1,000 mg/kg complete feedingstuffs. The applicant proposed the introduction of an additional manufacturing process, which introduces an impurity (dimethylamino-ethanol (DMAE)) in the additive at concentrations up to 0.09%. The EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) considered that the proposed modification would not substantially affect the previous assessment as related to the safety of the environment and the efficacy of the product. Since the safety of the active substance was established, the current assessment has dealt with the impurity DMAE. Considering the toxicological profile of DMAE, the estimated intake by the target animal and consumers, and making use of the Threshold of Toxicological Concern (TTC) approach, the Panel concluded that Taminizer D, manufactured by the DMAE route, is safe for both chickens for fattening and consumers, up to the maximum level of 1,000 mg/kg feed. The FEEDAP Panel extends its conclusions about Taminizer D produced by the original method to cover also Taminizer D produced by the new DMAE method. There is minimal risk to users from dust produced as a result of normal handling of the additive. Taminizer D is not irritant to skin but may be irritant to eyes; it is regarded as a potential skin sensitiser. The FEEDAP Panel recommended to set a specification for the DMAE content in the additive

Safety and efficacy of Biomin \uae DC-C as a zootechnical feed additive for weaned piglets

The additive (trade name Biomin \uae DC-C) is a blend of essential oils from oregano (Origanum vulgare L.) and from caraway seed (Carum carvi L.) and three individual compounds (carvacrol, methyl salicylate and l-menthol) encapsulated with a hydrogenated vegetable oil. The additive is intended for use in feed for weaned piglets at a minimum concentration of 75 mg/kg complete feed and a recommended maximum level of 125 mg/kg complete feed. A tolerance test in which piglets were exposed to feed containing up to an intended 1,250 mg additive/kg complete feed showed that additive is safe for piglets at the maximum recommended level with at least a sixfold margin of safety. The active components of the additive are not genotoxic and from the available residue study, based on the detection of five marker compounds, no measurable exposure of the consumers is foreseen; consequently, the use of the additive is considered safe for consumers of animal products. The FEEDAP Panel considered that exposure to users by inhalation is unlikely; in the absence of data, the Panel cannot conclude on the effects of Biomin \uae DC-C on skin and eyes. The use of the additive in animal production is not expected to pose a risk for the terrestrial or aquatic environments. Based on the results of three efficacy studies in which positive benefits were seen, the additive has a potential to improve the growth performance of weaned piglets at a minimum application rate of 75 mg/kg complete feed

Safety and efficacy of Biomin ® DC-C as a zootechnical feed additive for weaned piglets

The additive (trade name Biomin \uae DC-C) is a blend of essential oils from oregano (Origanum vulgare L.) and from caraway seed (Carum carvi L.) and three individual compounds (carvacrol, methyl salicylate and l-menthol) encapsulated with a hydrogenated vegetable oil. The additive is intended for use in feed for weaned piglets at a minimum concentration of 75 mg/kg complete feed and a recommended maximum level of 125 mg/kg complete feed. A tolerance test in which piglets were exposed to feed containing up to an intended 1,250 mg additive/kg complete feed showed that additive is safe for piglets at the maximum recommended level with at least a sixfold margin of safety. The active components of the additive are not genotoxic and from the available residue study, based on the detection of five marker compounds, no measurable exposure of the consumers is foreseen; consequently, the use of the additive is considered safe for consumers of animal products. The FEEDAP Panel considered that exposure to users by inhalation is unlikely; in the absence of data, the Panel cannot conclude on the effects of Biomin \uae DC-C on skin and eyes. The use of the additive in animal production is not expected to pose a risk for the terrestrial or aquatic environments. Based on the results of three efficacy studies in which positive benefits were seen, the additive has a potential to improve the growth performance of weaned piglets at a minimum application rate of 75 mg/kg complete feed

Safety and efficacy of Kelforce \uae (l-glutamic acid, N,N-diacetic acid, tetrasodium salt (GLDA-Na 4 )) as a feed additive for chickens for fattening

l-Glutamic acid, N,N-diacetic acid, tetrasodium salt (GLDA-Na 4 ) (Kelforce \uae ) is sought to be used as a zootechnical feed additive in chickens for fattening to improve the absorption of zinc from feed, reducing zinc emissions through manure and thus, affecting favourably the environment. The product has not been authorised in the European Union as a feed additive. Kelforce \uae is intended to be marketed as a liquid and solid formulation, containing 65 47% and 65 30% of GLDA-Na 4 , respectively. Kelforce \uae is safe for chickens for fattening at the maximum level of 1,000 mg GLDA-Na 4 /kg complete feed. Based on the toxicological profile of GLDA-Na 4 and the consumer exposure to GLDA-Na 4 and to nitrilotriacetic acid trisodium salt (NTA-Na 3 ; an impurity of the additive), the use of Kelforce \uae at the maximum proposed level in feed of chickens for fattening is of no concern for consumer safety. Due to its low inhalation toxicity, the exposure to GLDA-Na 4 is unlikely to pose a risk by inhalation. However, owing to the high-dusting potential of the solid formulation, a risk from such high level of dust, even if toxicologically inert, cannot be excluded. Kelforce \uae is not a skin/eye irritant or skin sensitiser. No risks for the terrestrial compartment were identified at the maximum use level of the additive. Risks for the aquatic compartment cannot be excluded based on the secondary effect of the additive on green algae. In the absence of data, the Panel cannot conclude on the safety for the sediment compartment or the possible ground water contamination. The risk of bioaccumulation and secondary poisoning caused by the additive is considered very low. Owing to the inconsistent and conflicting results from the studies assessed, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) cannot conclude on the efficacy of the additive. The Panel made a recommendation regarding the levels of formaldehyde and cyanide in the active substance

Assessment of the application for renewal of the authorisation of PHYZYME® XP 10000 TPT/L (6-phytase) as a feed additive for all avian species and all swine species

PHYZYME\uae XP 10000 TPT/L is a feed additive that contains 6-phytase produced by a genetically modified strain of Schizosaccharomyces pombe. The applicant requested for the renewal of the authorisation for PHYZYME\uae XP 10000 TPT and L to be used as a feed additive for avian species for fattening/laying, weaned piglets, pigs for fattening and sows and for an extension of use to avian species reared for laying/breeding, suckling piglets and minor porcine species. To support the request or the renewal of the authorisation, the applicant provided evidence that the additive in the market complies with the conditions of the authorisation. According to the information provided by the applicant, no new evidence has been identified that would make the FEEDAP Panel reconsider the previous conclusions regarding the safety for the target species, consumer, user and environment. The application for renewal of the authorisation did not include a proposal for amending the conditions of use in those species for which an authorisation exists that would have an impact on the efficacy of the additive. Therefore, there was no need for assessing the efficacy of the additive in the context of the renewal of the authorisation. Regarding the new species/categories, the Panel concluded that the additive is safe and has a potential to be efficacious in avian species reared for laying/breeding at 250 FTU/kg feed and for suckling piglets and minor porcine species at 500 FTU/kg feed

Safety and efficacy of Biomin\uae DC-P as a zootechnical feed additive for chickens for fattening, chickens reared for laying and minor avian species to the point of lay

The additive (trade name Biomin\uaeDC-P) is a blend of five individual compounds (carvacrol, thymol, d-carvone, methyl salicylate and l-menthol) encapsulated with a hydrogenated vegetable oil. The additive is intended for use in feed for various poultry species at a minimum concentration of 65 mg/kg complete feed and a recommended maximum level of 105 mg/kg complete feed. The results of a tolerance study show that Biomin\uae DC-P is safe for chickens for fattening at the maximum recommended application rate of 105 mg/kg complete feed; this conclusion is extended to include chickens reared for laying and extrapolated to minor poultry species The active components of a previously evaluated additive (Biomin\uaeDC-C) were shown to be not genotoxic; owing to the similarity on composition, this conclusion can be also applied to Biomin\uaeDC-P. Notwithstanding the uncertainties identified in the residue study, after applying a worst-case scenario to calculate potential exposure of consumers to menthol and carvone, and since that the components of the additive are considered safe for their use as food and feed flavourings, the FEEDAP Panel concludes that the use of the additive in animal nutrition is considered safe for consumers. The FEEDAP Panel considered that exposure of users by inhalation is unlikely, but cannot conclude on the effects of Biomin\uaeDC-P on skin and eyes. The use of Biomin\uaeDC-P is not expected to pose a risk for the environment. Biomin\uaeDC-P has a potential to increase the growth performance of chickens for fattening when incorporated into feed at a minimum application rate of 65 mg/kg complete feed; the conclusion can be extended to chickens reared for laying and extrapolated to minor poultry species reared up to the point of lay