Flavones isolated from Pseudognaphalium liebmannii with tracheal smooth muscle relaxant properties.

The inflorescences of Pseudognaphalium liebmannii are used as folk medicine to treat various respiratory diseases. In this work, we report the isolation of seven known flavones: 5-hydroxy-3,7-dimethoxyflavone 1, 5,8-dihydroxy-3,7-dimethoxyflavone 2, 5,7-dihydroxy-3,8-dimethoxyflavone 3 (gnaphaliin A), 3,5-dihydroxy-7,8-dimethoxyflavone 4 (gnaphaliin B), 3,5-dihydroxy-6,7,8-trimethoxyflavone 5, 3,5,7-trimethoxyflavone 6 and 3-O-methylquercetin 7. All these flavones except 1 and 6 showed a relaxant effect on guinea pig tracheal preparation with EC50 between 69.91 ± 15.32 and 118.72 ± 7.06 µM. Aminophylline (EC50 = 122.03 ± 7.05 µM) was used as a relaxant reference drug. The active flavones shifted the concentration-response curves of forskolin and nitroprusside leftward, and significantly reduced the EC50 values of these drugs. Furthermore, these flavones dose-dependently inhibited phosphodiesterase (PDE) in an in vitro assay. This reveals that the inflorescences of P. liebmannii contain several flavones with relaxant effect on airway smooth muscle and with PDEs inhibition that contribute to supporting the anti-asthmatic traditional use.

Assessment of the feed additive consisting of folic acid for all animal species for the renewal of its authorisation (Chr. Olesen A/S and DSM Nutritional Products Ltd).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the assessment of the application for the renewal of the authorisation of folic acid as a nutritional feed additive. The additive is authorised for use in feed and water for drinking for all animal species. The applicant provided evidence that the additive currently in the market complies with the existing conditions of authorisation and the production process has not been modified. The FEEDAP Panel considers that there is no evidence to revise the conclusions reached in the previous assessment for the safety for the terrestrial species, consumers and for the environment. The use of folic acid in aquatic animal species to cover their nutritional needs is considered safe. However, the Panel is not in a position to set a maximum safe level for all fish and crustacean species. Considering the narrow margin between the requirement and the tolerated levels seen in some aquatic animal species, the FEEDAP Panel considers that supplementation should not exceed the requirements of the different aquatic animal species. The additive is neither a skin irritant nor a dermal sensitiser. The exposure through inhalation is likely. Due to the lack of data, the FEEDAP Panel is not in the position to conclude on the potential of folic acid to be harmful to the respiratory system and irritant to eyes. The Panel retains that the previously made conclusion on the efficacy remains valid.

Safety and efficacy of a feed additive consisting of natrolite-phonolite obtained from volcanic rock from Kaiserstuhl for all animal species (Hans G. Hauri Mineralstoffwerk GmbH).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of natrolite-phonolite obtained from volcanic rock from Kaiserstuhl as a technological additive (functional group: anticaking) for all animal species. According to the conventional risk assessment, due to the lack of adequate data, the Panel is not in a position to conclude on the safety of the additive for the target species under the proposed conditions of use. However, from the tolerance studies in cattle for fattening and weaned piglets, effects observed in animal performance and blood clinical biochemistry suggest adverse effects on the animals supplemented with the additive. Based on current knowledge, there is no indication of substantial absorption of the components of the additive and, therefore, of concern for the consumer. The FEEDAP Panel is not in the position to conclude on the potential of the additive to be a skin and eye irritant. The additive is considered a respiratory and dermal sensitiser. In the absence of suitable data, the presence of small/nanoparticles cannot be excluded. As no suitable data in line with the requirements of the Guidance on risk assessment of nanomaterials were provided by the applicant, the potential risks associated with the presence of nanoparticles for the target species, the consumer and the user could not be assessed. Due to the lack of sufficient data, the Panel is not in a position to conclude on the efficacy of the additive.

Safety of 41 flavouring compounds providing a herbal flavour and belonging to different chemical groups for use as feed additives in all animal species (FEFANA asbl).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety of 41 compounds to provide a Herbal flavour and belonging to different chemical groups, when used as sensory additives in feed for all animal species. Fourteen out of the 41 compounds were tested in tolerance studies in chickens for fattening, piglets, cattle for fattening and Atlantic salmon. No adverse effects were observed in the tolerance studies at 10-fold the intended level. The Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concluded that the 14 tested compounds were safe for these species at the proposed use level and conclusions were extrapolated to all animal species. For the remaining 27 compounds, read-across from structurally similar compounds tested in tolerance trials and belonging to the same chemical group was applied. The FEEDAP Panel concluded that these 27 compounds were safe for all animal species at the proposed use level. No safety concern would arise for the consumer and the environment from the use of the 41 compounds up to the maximum proposed use level in feed.

Assessment of the safety of the feed additives acetic acid, calcium acetate and sodium diacetate for fish (FEFANA asbl).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety of acetic acid, calcium acetate and sodium diacetate as technological feed additives (preservatives) for salmonids/fish. The additives are already authorised for use for all animal species other than fish. In previous opinions, the FEEDAP Panel concluded that a maximum concentration of 2,500 mg acetic acid/kg complete feed (or 1,000 mg/L water for drinking) was safe for poultry, pigs and pet animals. Ruminants were considered to exhibit a higher tolerance. Due to lack of data for salmonids, the Panel could not conclude on the safety of acetic acid and its salts for fish. The applicant has provided supplementary information consisting in a tolerance study in Atlantic salmon (Salmo salar) and a literature search to support the safety of acetic acid in fish. Considering all the available information, the FEEDAP Panel concluded that acetic acid (and its salts by analogy) is considered safe for fish up to the maximum recommended supplementation level of 2,500 mg acetic acid/kg complete feed.

Safety and efficacy of a feed additive consisting of potassium ferrocyanide for all animal species (K + S KALI GmbH).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of potassium ferrocyanide as a technological feed additive, functional group anticaking agents, for all animal species. The additive potassium ferrocyanide is intended to be used in potassium chloride with a maximum content of 150 mg ferrocyanide anion/kg salt. The use of potassium ferrocyanide is safe, when added to potassium chloride at a maximum content of 150 mg ferrocyanide anions (anhydrous)/kg for: pigs for fattening and lactating sows, sheep, goats, salmon and dogs. In the absence of a margin of safety, the use of potassium chloride according to the proposed conditions of use is not considered to be safe for chickens for fattening, laying hens, turkeys, piglets, veal calf, cattle for fattening, dairy cows, horse, rabbit and cats. In the absence of information on the use of potassium chloride in the diets for any other animal species, no conclusion on a potentially safe level of potassium chloride, supplemented with 150 mg ferrocyanide/kg, can be made. The use of potassium ferrocyanide in animal nutrition is of no concern for consumer safety. The results of in vivo studies showed that potassium ferrocyanide is not irritant to skin and eye and is not a skin sensitiser. However, due to the presence of nickel, the additive should be considered as a respiratory and dermal sensitiser. The available data do not allow the FEEDAP Panel to conclude on the safety of the additive for the soil and the marine environment, while the use of the additive in land-based aquaculture according to the proposed conditions of use is considered of no concern. Potassium ferrocyanide is considered to be efficacious as an anticaking agent when included in potassium chloride at the proposed use levels.

Scientific opinion on the presence of DNA in the feed additives consisting of concentrated liquid l-lysine, l-lysine monohydrochloride and concentrated liquid l-lysine monohydrochloride produced by Escherichia coliNITE BP-02917 for all animal species (METEX NOOVISTAGO).

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 concentrated liquid l-lysine, l-lysine monohydrochloride and concentrated liquid l-lysine monohydrochloride produced by a genetically modified strain of Escherichia coli (NITE BP-02917) as nutritional and as sensory (flavouring compound) feed additives for all animal species. In 2022, the FEEDAP Panel issued an opinion on the safety and efficacy of these products. In that assessment, the FEEDAP Panel could not exclude the potential presence of recombinant DNA derived from the genetically modified production organism in the products. The applicant provided supplementary data to exclude the presence of recombinant DNA derived from the production organism in the final products. Based on the new data provided, the FEEDAP Panel concluded that no DNA of the production strain E. coli NITE BP-02917 was detected in concentrated liquid l-lysine, l-lysine monohydrochloride and concentrated liquid l-lysine monohydrochloride.

Safety and efficacy of feed additives consisting of sodium ferrocyanide and potassium ferrocyanide for all animal species (Eusalt a.i.s.b.l.).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of potassium and sodium ferrocyanide as technological feed additives for all animal species. The additives sodium- and potassium ferrocyanide are intended to be used in sodium chloride with a maximum content of 80 mg ferrocyanide anion (anhydrous)/kg salt. The FEEDAP Panel concluded that the use of sodium ferrocyanide and potassium ferrocyanide is safe, when added to sodium chloride at a maximum content of 80 mg ferrocyanide anion/kg for: turkey for fattening and laying hens and other laying/breeding birds; all porcine species and categories, all ruminant species and categories, rabbit, horse, salmonids and other minor fin fish, dogs and cats. In the absence of a margin of safety, the use of sodium and potassium chloride according to the proposed conditions of use is not considered to be safe for chickens for fattening and other poultry species for fattening or reared for laying/breeding other than turkeys. In the absence of information on the use of sodium chloride in the diets for any other animal species, no conclusion on a potentially safe level of sodium chloride, supplemented with 80 mg ferrocyanide anions (anhydrous)/kg, could be made. The use of sodium and potassium ferrocyanide in animal nutrition under the conditions of use proposed is of no concern for consumer safety. The results of in vivo studies showed that sodium and potassium ferrocyanide are not irritant to skin and eye and are not skin sensitisers. However, owing to the presence of nickel, sodium ferrocyanide, is considered a dermal and respiratory sensitiser. No conclusions could be reached on the safety of the user exposed via inhalation for potassium ferrocyanide. The use of sodium and potassium ferrocyanide as feed additives is considered safe for the environment. The additives are considered to be efficacious as anticaking agents in sodium chloride at the proposed use level.

Food supplement vitamins, minerals, amino-acids, fatty acids, phenolic and alkaloid-based substances: An overview of their interaction with drugs.

Food supplements are a widespread group of products ingested as a diet complement, whose consumption has recently skyrocketed due to the consumers' concern with their well-being. Among food supplements, vitamin- and mineral-based ones are the top sellers, and the demand of others, such as those containing polyphenols, is increasing. Owing to their alleged natural characteristics, consumers take the safety of food supplements for granted, and use them even when taking medicines. Thus, their potential interactions with drugs have been sparsely evaluated. This manuscript aims to bring forth an up-to-date overview of the most important knowledge involving the interactions between food supplements and drugs, relevant to be aware by nutritionists and other healthcare professionals. To this end, an extensive bibliographic review was conducted focusing on peer reviewed data from experimental in vivo evidence and clinical studies whenever major clinical interactions have been reported. Elder people and polymedicated or chronic patients are especially vulnerable to the therapeutic ineffectiveness and toxicity caused by these types of interactions. Drugs used to treat cardiovascular, autoimmune, nervous, and oncological diseases are commonly involved in important clinical interactions with food supplements, many with a narrow therapeutic margin.

Halophytes as source of bioactive phenolic compounds and their potential applications.

Halophytes are salt-tolerant plants that inhabit environments in which they are exposed to extreme stress, wherefore they exhibit conserved and divergent metabolic responses different from those of conventional plants. Thus, the synthesis and accumulation of metabolites, especially of those oxidative stress-related such as phenolic compounds, should be investigated. The potential of halophytes as a source of phenolics and their prospective industrial applications are evaluated based on a comprehensive review of the scientific literature on the phenolic compounds of more than forty halophytes and their biological activities. Additionally, an overview of the analytical methodologies adopted for phenolics determination in halophytes is provided. Finally, the prospective uses and beneficial effects of the phenolic preparations from these plants are discussed. Halophytes are complex matrices, exhibiting a wide variety of phenolics in their composition, wherefore the results can be greatly affected depending on the organ plant under analysis and the extraction methodology, especially the extraction solvent used. High-performance liquid chromatography, coupled with diode array detection (HPLC-DAD) or mass spectrometry (HPLC-MS), are the most used technique. Halophytes biosynthesize phenolics in concentrations that justify the remarkable antioxidant and antimicrobial activities shown, making them ideal sources of bioactive molecules to be employed in a multitude of sectors.

Safety of the feed additive consisting of vitamin B2/riboflavin (produced by Bacillus subtilis KCCM 10445) for all animal species (Hubei Guangji Pharmaceutical Co. Ltd.).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the characterisation and safety of vitamin B2/riboflavin produced by fermentation with a genetically modified strain of Bacillus subtilis (KCCM 10445) as a nutritional additive in feed and water for drinking for all animal species. In 2021, the FEEDAP Panel issued an opinion on the safety and efficacy of vitamin B2 98% and vitamin B2 80% in the form of riboflavin produced by B. subtilis KCCM 10445. In that assessment, the Panel could not confirm the correspondence of the deposited strain under accession number KCCM 10445 with the strain used for production owing to discrepancies in the description of the genetic modification steps. Moreover, in the absence of data, no conclusions on the skin sensitisation potential of vitamin B2 98% and vitamin B2 80% nor on the possible risk by inhalation of vitamin B2 98% could be reached. For the present assessment, the applicant provided supplementary information to partially address the limitations identified in that assessment. Based on the results of a bioinformatic analysis between the strain deposited under accession number KCCM 10445 with the strain used for production under assessment, the Panel confirmed the correspondence between the two strains. As no new data have been submitted on the safety of the additives, the conclusions from the Panel remain that the use of vitamin B2/riboflavin produced by B. subtilis KCCM 10445 is safe for the target species, the consumer and the environment. Vitamin B2 80% is not hazardous by inhalation. In the absence of data, no conclusions on the possible risk by inhalation of vitamin B2 98% could be reached. Neither the vitamin B2 98% nor the vitamin B2 80% are irritant to skin or eyes. In the absence of data, no conclusions on the skin sensitisation potential of the additives could be reached.

Safety and efficacy of a feed additive consisting of l-lysine monohydrochloride and l-lysine sulfate produced by fermentation with Corynebacterium glutamicumCGMCC 17927 for all animal species (Barentz Animal Nutrition B.V.).

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 l-lysine monohydrochloride and l-lysine sulfate produced by Corynebacterium glutamicum CGMCC 17927, when used as a nutritional additive in feed and water for drinking for all animal species. The active substance is l-lysine, and it was produced in two different forms: monohydrochloride (HCl) or sulfate salts. The production strain was genetically modified. Neither viable cells nor recombinant DNA of the production strain were detected in the final products. Therefore, the Panel concluded that the additives did not pose any safety concern regarding the production strain. The use of l-lysine HCl and l-lysine sulfate produced by the strain C. glutamicum CGMCC 17927 in supplementing feed to compensate for l-lysine deficiency in feedingstuffs was safe for the target species. The FEEDAP Panel identified risks of nutritional imbalances and hygienic concerns for amino acids when administered simultaneously in feed and in water for drinking. The use of both forms of l-lysine produced by fermentation using C. glutamicum CGMCC 17927 in animal nutrition was considered safe for the consumers and for the environment. Exposure of users through inhalation to l-lysine HCl and l-lysine sulfate produced with C. glutamicum CGMCC 17927 was considered very likely. In absence of data, the FEEDAP Panel could not conclude on the potential of both forms of the additive to be irritant for skin and eyes or to be dermal sensitisers. l-Lysine HCl and l-lysine sulfate were considered as efficacious sources of the essential amino acid l-lysine for non-ruminant animal species. For the supplemental l-lysine to be as efficacious in ruminants as in non-ruminant species, it would require protection against degradation in the rumen.

Safety and efficacy of a feed additive consisting of concentrated liquid l-lysine, l-lysine monohydrochloride and concentrated liquid l-lysine monohydrochloride produced by Escherichia coliNITE BP-02917 for all animal species (Metex NoovistaGo).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of concentrated liquid l-lysine, l-lysine monohydrochloride and concentrated liquid l-lysine monohydrochloride produced by Escherichia coli NITE BP-02917 as nutritional and as sensory (flavouring compound) feed additives for all animal species. The production strain did not carry ■■■■■ antimicrobial resistance genes and no viable cells of the production strain were detected in the final products. ■■■■■ However, since no sequences of concern remained in the production strain, the potential presence of that DNA did not raise safety concerns. The use of the three forms of l-lysine produced by E. coli NITE BP-02917 in supplementing feed to compensate for l-lysine deficiency in feedingstuffs was safe for the target species. This conclusion would also cover the use as a sensory additive. The FEEDAP Panel identified risks of nutritional imbalances and hygienic concerns for amino acids when administered simultaneously in feed and in water for drinking. The use of the three forms of l-lysine produced by E. coli NITE BP-02917 in animal nutrition was considered safe for the consumers and for the environment. Concentrated liquid l-lysine, l-lysine HCl and concentrated liquid l-lysine HCl were not considered to have the potential to cause respiratory toxicity, or skin sensitisation. l-Lysine HCl and concentrated liquid l-lysine HCl were not considered skin and eye irritants. Concentrated liquid l-lysine, due to its high pH, might be corrosive for skin and eyes. The three forms were considered an efficacious source of the essential amino acid l-lysine for non-ruminant animal species. For the supplemental l-lysine to be as efficacious in ruminants as in non-ruminant species, it would require protection against degradation in the rumen. The three forms of the additive were also considered efficacious as feed flavouring compounds under the proposed conditions of use.

Safety and efficacy of a feed additive consisting of l-arginine (produced by Corynebacterium glutamicum CGMCC 20516) for all animal species (Eppen Europe SAS).

Following a request from the European Commission, the EFSA 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 the feed additive consisting of l-arginine produced by fermentation using a non-genetically modified strain of Corynebacterium glutamicum (CGMCC 20516). The additive is intended to be used in feed and water for drinking for all animal species and categories. The production strain was considered suitable for the qualified presumption of safety (QPS) approach to safety assessment. No viable cells of C. glutamicum CGMCC 20516 were detected in the final product. l-Arginine produced using C. glutamicum CGMCC 20516 is safe for the target species when supplemented in appropriate amounts to the diet according to the nutritional needs of the target species, for the consumer and for the environment. In the absence of data, the FEEDAP Panel could not conclude on the safety of l-arginine produced by C. glutamicum CGMCC 20516 for the users. The additive l-arginine produced by fermentation using C. glutamicum CGMCC 20516 is regarded as an efficacious source of the essential amino acid l-arginine for non-ruminant species. For the supplemental l-arginine to be as efficacious in ruminants as in non-ruminant species, it requires protection against degradation in the rumen.

Ecotoxicological effects of untreated pig manure from diets with or without growth-promoting supplements on Eisenia andrei in subtropical soils.

This study aimed to evaluate the effects of untreated pig manure from diets incorporating growth-promoting supplements (antibiotics and Zn oxide) on the survival and reproduction of Eisenia andrei earthworms. The tested manures were obtained from four different groups of pigs fed with four different diets: CS, a diet based on corn and soymeal; TR, a diet based on corn, soymeal, and ground wheat (15%); CSa, a diet based on corn and soymeal + 100 ppm of doxycycline + 50 ppm of colistin + 2500 ppm of Zn oxide; and TRa, a diet based on corn, soymeal, and ground wheat (15%) + 100 ppm of doxycycline + 50 ppm of colistin + 2500 ppm of Zn oxide. The study used two soils representative of the Southern region of Brazil (Oxisol and Entisol). In general, there were no significant differences between the different manures tested in each soil. However, there were differences in the toxicity manure on E. andrei between the soils, and the magnitude of this effect was dependent on the applied dose. In Oxisol, LC50 values were higher than 80 m3 ha-1, and EC50 varied from 9 to 27 m3 ha-1. In Entisol, the LC50 values were below the lowest dose tested (< 25 m3 ha-1), and EC50 remained around 5 m3 ha-1. It may be possible that the effects observed were attributed to an excess of nitrogen, copper, and zinc, promoted by the addition of the untreated manure and how these factors interacted with soil type.

Safety and efficacy of a feed additive consisting of l-lysine sulfate produced by Escherichia coli CGMCC 7.398 for all animal species (Kempex Holland B.V.).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of l-lysine sulfate produced by the genetically modified strain Escherichia coli CGMCC 7.398 as a nutritional feed additive for all animal species. Neither the production strain nor its recombinant DNA were detected in the final product. The additive does not pose any safety concerns associated with the production strain. The additive under assessment is considered safe for the target species. When using l-lysine sulfate, the background sulfur/sulfate content in the compound feed should be taken into account. l-lysine sulfate produced by E. coli CGMCC 7.398 is safe for the consumers and for the environment. In the absence of data, the FEEDAP Panel cannot conclude on the potential of the additive under assessment to be irritant to skin or eyes, or on its potential to be a dermal sensitiser. The endotoxin activity of the additive represents a risk by inhalation for users handling the additive. The additive l-lysine sulfate is considered as an efficacious source of the essential amino acid l-lysine for non-ruminant animal species. For the supplemental l-lysine to be as efficacious in ruminants as it is in non-ruminant species, this would require protection against degradation in the rumen.

Assessment of the feed additive consisting of potassium diformate for all animal species for the renewal of its authorisation (Addcon GmbH).

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 assessment of the application for renewal of authorisation of potassium diformate for all animal species. The additive was initially evaluated in 2004 and re-evaluated by the Panel in 2012, with the conclusion that the additive (i) was safe for the target species, the consumer and the environment when used under the proposed conditions; (ii) was an eye irritant and (iii) had the potential to increase the storage time of raw fish and fish by-products for feed use in a dose-dependent manner at low temperature. The FEEDAP Panel considered that the use of potassium diformate under the approved conditions of use remains safe for consumers and the environment, and that it is an eye irritant. Due to the absence of data, the FEEDAP Panel could not conclude on the potential of the additive to be a skin irritant or a respiratory or dermal sensitiser. Regarding the safety for the target species, the FEEDAP Panel considered that the mixture of different sources of potassium diformate remains safe for use in sows' feed under the approved conditions of use (12,000 mg/kg complete feed). However, based on a tolerance trial, the Panel concluded that the maximum safe level of potassium diformate in weaned piglets should be reduced to 6,000 mg/kg complete feed and the same conclusion was extended to pigs for fattening. Owing to the lack of information provided, the Panel could not conclude on the safety of the additive for species other than pigs under the approved conditions. The present application does not include a proposal for amending or supplementing the conditions of the original authorisation that would have an impact on the efficacy of the additive.

Safety and efficacy of a feed additive consisting of l-lysine sulfate produced by Corynebacterium glutamicum KCCM 80227 for all animal species (Daesang Europe BV).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of l-lysine sulfate produced by Corynebacterium glutamicum KCCM 80227 as a nutritional feed additive for all animal species. The FEEDAP Panel concluded that the production strain C. glutamicum KCCM 80227 qualifies for the qualified presumption of safety (QPS) approach to safety assessment and is not detected in the final product. l-Lysine sulfate produced using C. glutamicum KCCM 80227 does not pose any safety concern associated with the production strain. The additive under assessment is considered safe for the target species. When using l-lysine sulfate, the background sulfur/sulfate content in the compound feed should be taken into account. l-Lysine sulfate produced by C. glutamicum KCCM 80227 is safe for the consumers, users and for the environment. The additive l-lysine sulfate is considered as an efficacious source of the essential amino acid l-lysine for non-ruminant animal species. For the supplemental l-lysine to be as efficacious in ruminants as in non-ruminant species, it would require protection against degradation in the rumen.

Assessment of the feed additive consisting of copper chelate of hydroxy analogue of methionine for all animal species for the renewal of its authorisation (Novus Europe S.A./N.V.).

The Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the application for renewal of authorisation of copper chelate of hydroxy analogue of methionine (Mintrex®Cu) for all animal species. The FEEDAP Panel has delivered two opinions (in 2008 and 2009) on the safety and efficacy of the additive. The additive was authorised in 2010 as 'Copper chelate of hydroxy analogue of methionine' containing 18% copper, 79.5-81% (2-hydroxy-4-methylthio)butanoic acid (DL-methionine hydroxy analogue, HMTBa) and 1% mineral oil. Following some modifications in the manufacturing process, the additive does not contain mineral oil and the applicant proposes the following specifications: ≥ 16% copper and ≥ 78% HMTBa. The data provided indicate that the additive complies with the new specifications. No new evidence was found that would make the FEEDAP Panel reconsidering its previous conclusions on the safety for target species, consumers and environment. The applicant provided new studies on the effects of the additive on the respiratory tract and on skin and eyes. Data on the characterisation of the additive and the new studies on skin/eyes led the Panel to reconsider the safety for the user. Mintrex®Cu is considered as a skin and eye irritant and a skin sensitiser; the risk of respiratory sensitisation is considered low. The present application did not include a proposal for amending or supplementing the conditions of the original authorisation 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.

Safety and efficacy of the feed additives concentrated liquid l-lysine (base) and l-lysine monohydrochloride produced by Corynebacterium glutamicum KCCM 80183 for all animal species (CJ Europe GmbH).

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 concentrated liquid l-lysine (base) and l-lysine monohydrochloride (HCl) produced using Corynebacterium glutamicum KCCM 80183 when used as nutritional additives in feed and water for drinking for all animal species. The active substance is l-lysine. Concentrated liquid l-lysine (base) and l-Lysine HCl produced by the strain C. glutamicum KCCM 80183 do not pose any safety concern as regards the genetic modification of the production strain. The use of the additives under assessment in supplementing feed to compensate for l-lysine deficiency in feedingstuffs is safe for the target species. The FEEDAP Panel has concerns about the use of amino acids in water for drinking for hygienic reasons, and due to the risk of imbalances when administered simultaneously via feed. The use of both forms of l-lysine produced by fermentation using C. glutamicum KCCM 80183 in animal nutrition is considered safe for the consumers and for the environment. Concentrated liquid l-lysine (base) produced by C. glutamicum KCCM 80183 is considered hazardous by inhalation, not irritant to skin and eyes and it is not a skin sensitiser. l-Lysine HCl produced by C. glutamicum KCCM 80183 is considered hazardous by inhalation, it is not irritant to skin but mildly irritant to eyes and it is not a skin sensitiser. The additives under assessment are considered as efficacious sources of the essential amino acid l-lysine for non-ruminant animal species. For the supplemental l-lysine to be as efficacious in ruminants as in non-ruminant species, it would require protection against degradation in the rumen.