Guidance on the assessment of the efficacy of feed additives.

This guidance document is intended to assist the applicant in preparing and presenting an application, as foreseen in Article 7.6 of Regulation (EC) No 1831/2003, for the authorisation of additives for use in animal nutrition. It specifically covers the assessment of the efficacy of feed additives.

Ultrasonic reactor set-ups and applications: A review.

Sonochemistry contributes to green science as it uses less hazardous solvents and methods to carry out a reaction. In this review, different reactor designs are discussed in detail providing the necessary knowledge for implementing various processes. The main characteristics of ultrasonic batch systems are their low cost and enhanced mixing; however, they still have immense drawbacks such as their scalability. Continuous flow reactors offer enhanced production yields as the limited cognition which governs the design of these sonoreactors, renders them unusable in industry. In addition, microstructured sonoreactors show improved heat and mass transfer phenomena due to their small size but suffer though from clogging. The optimisation of various conditions of regulations, such as temperature, frequency of ultrasound, intensity of irradiation, sonication time, pressure amplitude and reactor design, it is also discussed to maximise the production rates and yields of reactions taking place in sonoreactors. The optimisation of operating parameters and the selection of the reactor system must be considered to each application's requirements. A plethora of different applications that ultrasound waves can be implemented are in the biochemical and petrochemical engineering, the chemical synthesis of materials, the crystallisation of organic and inorganic substances, the wastewater treatment, the extraction processes and in medicine. Sonochemistry must overcome challenges that consider the scalability of processes and its embodiment into commercial applications, through extensive studies for understanding the designs and the development of computational tools to implement timesaving and efficient theoretical studies.

Safety and efficacy of a feed additive consisting of salinomycin sodium (Sacox®) for rabbits for fattening (Huvepharma N.V.).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of the coccidiostat salinomycin sodium (Sacox®) for rabbits for fattening. The EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concluded that the use of salinomycin sodium (SAL-Na) from Sacox® does not raise safety concerns for the target species, consumers, users and the environment with regard to the production strain. In the absence of adequate tolerance studies, the FEEDAP Panel could not conclude on the safety of SAL-Na from Sacox® for rabbits for fattening. The FEEDAP Panel concluded that the additive is safe for the consumer when it is used at the proposed maximum level of 25 mg SAL-Na/kg complete feed for rabbits and a withdrawal period of 1 day is respected. The following maximum residue limits (MRL) are proposed for the marker residue compound salinomycin (SAL): 0.2 and 0.03 mg SAL/kg for liver and kidney, respectively. The additive is not irritant to skin and eyes but should be considered a potential dermal and respiratory sensitiser. A risk for inhalation toxicity could not be excluded. The use of the SAL-Na from Sacox® in feed for rabbits for fattening up to the highest proposed level will not pose a risk for the terrestrial and aquatic compartment and ground water. The risk of secondary poisoning can be excluded for worm-eating birds and mammals, while it cannot be excluded for fish-eating birds and mammals. The FEEDAP Panel concludes that SAL-Na from Sacox® at the minimum concentration of 20 mg SAL-Na/kg complete feed has the potential to control coccidiosis in rabbits for fattening. Development of resistance to SAL-Na of field Eimeria spp. strains isolated from rabbits for fattening should be monitored.

Safety and efficacy of a feed additive consisting of vitamin B12 (cyanocobalamin) produced by fermentation with Ensifer adhaerens CGMCC 21299 for all animal species (NHU Europe GmbH).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of vitamin B12 (cyanocobalamin) produced by fermentation with a non-genetically modified strain of Ensifer adhaerens (CGMCC 21299), when used as a nutritional additive for all animal species. No viable cells or DNA of the production strain were detected in the additive. Therefore, cyanocobalamin produced by fermentation with E. adhaerens CGMCC 21299 does not raise safety concerns as regards to the production strain. The Panel on Additives and Products or Substances used in Animal Feed concluded that cyanocobalamin produced by fermentation with E. adhaerens CGMCC 21299 is considered safe for all animal species, for the consumers and the environment. Due to the presence of nickel, the additive is considered a skin and respiratory sensitiser. Inhalation and dermal exposure are considered a risk. Due to the lack of data, the Panel could not conclude on the potential of the additive to be an eye irritant. Cyanocobalamin produced by fermentation with E. adhaerens CGMCC 21299 is effective in meeting animal's nutritional requirements when administered via feed.

Modification of the terms of authorisation regarding the maximum inclusion level of a feed additive consisting of 4-hydroxy-2,5-dimethylfuran-3(2H)-one for cats and dogs (V. MANE FILS).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the proposed modification of the terms of the authorisation regarding the maximum inclusion level of a feed additive consisting of 4-hydroxy-2,5-dimethylfuran-3(2H)-one for cats and dogs. 4-Hydroxy-2,5-dimethylfuran-3(2H)-one is currently authorised for use as a sensory additive (functional group: flavouring compounds) for cats and dogs at a recommended maximum content of 5 mg/kg complete feed. The applicant is requesting a modification of the authorisation to increase the recommended maximum content of the additive up to 25 mg/kg complete feed for cats and dogs. Based on the toxicological data available, the FEEDAP Panel concludes that 4-hydroxy-2,5-dimethylfuran-3(2H)-one is safe for dogs at 25 mg/kg feed and for cats at 18 mg/kg feed. The additive is irritant to skin, eyes and to the respiratory tract and is a skin sensitiser. No further demonstration of efficacy is necessary.

Safety and efficacy of a feed additive consisting of monensin sodium (Coxidin®) for chickens for fattening, chickens reared for laying, turkeys for fattening and turkeys reared for breeding (Huvepharma N.V.).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of monensin sodium (Coxidin®) as a coccidiostat for chickens for fattening, chickens reared for laying, turkeys for fattening and turkeys reared for breeding. The additive currently on the market complies with the existing conditions of authorisation. The FEEDAP Panel concluded that Coxidin® remains safe for turkeys for fattening (up to 16 weeks) and extends this conclusion to turkeys reared for breeding (up to 16 weeks). The Panel was not in the position to confirm that the current maximum authorised level of 125 mg monensin sodium/kg complete feed remains safe for chickens for fattening and chickens reared for laying. The use of monensin sodium from Coxidin® at the corresponding maximum authorised/proposed use levels in the target species is safe for the consumer. The existing maximum residue levels (MRLs) for poultry tissues ensure consumer safety. No withdrawal time is necessary. Both formulations of Coxidin® pose a risk by inhalation. The formulation with wheat bran as a carrier was neither irritant to the skin nor a skin sensitiser but it was irritant to the eyes. In the absence of data, no conclusions could be made on the potential of the formulation containing calcium carbonate to be irritant to skin and eyes and to be a skin sensitiser. The use of monensin sodium from Coxidin® in complete feed for the target species poses no risk for the terrestrial compartments and for sediment. No risk for groundwater is expected. For chickens for fattening the risk for aquatic compartment cannot be excluded, but no risks are expected for the other animal categories. There is no risk of secondary poisoning. Coxidin® is efficacious in controlling coccidiosis at a level of 100 mg/kg complete feed for chickens for fattening and at 60 mg/kg complete feed for turkeys for fattening. These conclusions are extended to chickens reared for laying and turkeys reared for breeding. The Panel noted that there are signs of development of resistance of Eimeria spp. to monensin sodium.

Safety and efficacy of a feed additive consisting of narasin (Monteban® G100) for chickens for fattening (Elanco GmbH).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of the coccidiostat narasin (Monteban® G100) for chickens for fattening. In a previous opinion, uncertainties remained on the identification and characterisation of the non-genetically modified production strain of the active substance narasin. The Panel could not conclude either on the safety of Monteban® G100 for chickens for fattening or on the efficacy of the additive at the minimum applied concentration. The FEEDAP Panel excluded risks for environment but the risk for sediment compartment could not be assessed. The applicant provided supplementary information to cover the data gaps and substituted the narasin production strain from Streptomyces spp. NRRL 8092 to Streptomyces spp. NRRL B-67771. The information submitted to taxonomically identify the production strain did not allow to assign it to any described microbial species. Based on the information provided, the Panel concluded that the use of Monteban® G100 did not raise safety concerns as regards the production strain for the target animal, consumer, user and environment. The Panel concluded that 70 mg narasin/kg complete feed was safe for chickens for fattening with a margin of safety of 1.4; narasin from Monteban® G100 was unlikely to increase shedding of Salmonella Enteritidis, Salmonella Typhimurium and Campylobacter jejuni. Narasin, when used in chickens for fattening at 70 mg/kg feed, was not expected to pose a risk to the aquatic compartment and to sediment, while a risk for the terrestrial compartment could not be excluded. No risk for groundwater was expected, nor for secondary poisoning via the terrestrial food chain, but the risk of secondary poisoning via the aquatic food chain could not be excluded. The Panel concluded that 60 mg narasin/kg feed was efficacious in controlling coccidiosis in chickens for fattening.

Guidance for the assessment of detoxification processes in feed.

This statement provides scientific guidance on the information needed to support the risk assessment of the detoxification processes applied to products intended for animal feed in line with the acceptability criteria of the Commission Regulation (EU) 2015/786.

Efficacy of Availa®Cr (chromium chelate of dl-methionine) as a feed additive for dairy cows (Zinpro Animal Nutrition (Europe), Inc).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the efficacy of Availa®Cr (active compound: chromium chelate of dl-methionine) as a feed additive for dairy cows. In a previous opinion, the FEEDAP Panel concluded that Availa®Cr at a maximum recommended use level of 0.5 mg Cr(III) (8 mg Cr from Availa®Cr/cow per day) was safe for dairy cows and the consumers. Additionally, the FEEDAP Panel considered that the additives posed a risk to the user by inhalation, it was not irritant to skin and eyes, and it should be considered a skin sensitiser. The Panel could not conclude on the efficacy of the additive at the proposed conditions of use. Since the new information provided in the current application is lacking sufficient evidence, the FEEDAP Panel is still not in the position to conclude on the efficacy of chromium dl-methionine from Availa®Cr.

Safety and efficacy of a feed additive consisting of benzoic acid (Kalama® Animal Feed Grade Benzoic acid) for weaned piglets and pigs for fattening (Emerald Kalama Chemical, B.V).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of benzoic acid (Kalama®) as a zootechnical feed additive for weaned piglets at a level of 5000 mg/kg complete feed and for pigs for fattening at a minimum content of 5000 mg/kg and a maximum content of 10,000 mg/kg complete feed. The FEEDAP Panel concluded that benzoic acid is safe for weaned piglets at 5000 mg/kg complete feed and for pigs for fattening at 10,000 mg/kg complete feed. The Panel considered the use of benzoic acid under the proposed conditions of use to be of no concern for consumer safety and the environment. Benzoic acid poses a risk by inhalation, it is irritant to skin and corrosive to eyes, but no conclusions can be drawn on dermal sensitisation. The additive, benzoic acid, is efficacious as a zootechnical feed additive for weaned piglets and for pigs for fattening at the proposed conditions of use.

Formic Acid Decomposition Using Palladium-Zinc Preformed Colloidal Nanoparticles Supported on Carbon Nanofibre in Batch and Continuous Flow Reactors: Experimental and Computational Fluid Dynamics Modelling Studies.

The need to replace conventional fuels with renewable sources is a great challenge for the science community. H2 is a promising alternative due to its high energy density and availability. H2 generation from formic acid (FA) decomposition occurred in a batch and a packed-bed flow reactor, in mild conditions, using a 2% Pd6Zn4/HHT (high heated treated) catalyst synthesised via the sol-immobilisation method. Experimental and theoretical studies took place, and the results showed that in the batch system, the conversion was enhanced with increasing reaction temperature, while in the continuous flow system, the conversion was found to decrease due to the deactivation of the catalyst resulting from the generation of the poisoning CO. Computational fluid dynamics (CFD) studies were developed to predict the conversion profiles, which demonstrated great validation with the experimental results. The model can accurately predict the decomposition of FA as well as the deactivation that occurs in the continuous flow system. Of significance was the performance of the packed-bed flow reactor, which showed improved FA conversion in comparison to the batch reactor, potentially leading to the utilisation of continuous flow systems for future fuel cell applications for on-site H2 production.

Safety and efficacy of a feed additive consisting of phenylcapsaicin (aXiphen) for chickens for fattening (aXichem AB).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of phenylcapsaicin (aXiphen®) as a zootechnical additive (functional group: physiological condition stabilisers) in feed for chickens for fattening. The additive under assessment, phenylcapsaicin, is safe for chickens for fattening up to the maximum proposed use level of 15 mg/kg complete feed. A margin of safety could not be established. Phenylcapsaicin is not genotoxic. The reference point for phenylcapsaicin derived from a 90-day repeated dose oral toxicity study in rats is 37.2 mg/kg body weight (bw) per day, the lowest of the model averaged BMDL20 values for alanine aminotransferase increase in plasma. The metabolic similarity in the laboratory animals and the target species was not demonstrated and the identity of the marker residue could not be established. In the absence of such data, the safety for the consumers could not be evaluated. The inhalation exposure of phenylcapsaicin (as liquid) for the user was considered unlikely. The FEEDAP Panel considered the additive irritant to the eyes but not to the skin and it is not a dermal sensitiser. In the absence of appropriate data, the environmental risk assessment for phenylcapsaicin could not be performed. It is unlikely that phenylcapsaicin bioaccumulates in the environment and the risk of secondary poisoning is considered low. The FEEDAP Panel could not conclude on the efficacy of the additive in chickens for fattening at the proposed conditions of use.

Assessment of the feed additive consisting of orthophosphoric acid for all animal species for the renewal of its authorisation (Prayon S.A.; Chemische Fabrik Budenheim KG; BK Giulini 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 application for renewal of orthophosphoric acid as a technological additive (functional group: preservatives) for all animal species. The applicant has provided evidence that the additive currently on the market complies with the existing conditions of authorisation. There is no evidence that would lead the FEEDAP Panel to reconsider its previous conclusions. Thus, the Panel concluded that the additive remains safe for all animal species provided that the optimal Ca:P ratio is maintained. Additionally, the FEEDAP Panel concluded that orthophosphoric acid remains safe for the consumer and the environment under the authorised conditions of use. Regarding the user safety, orthophosphoric acid is corrosive to the skin and eyes and should be considered as hazardous to the respiratory tract. There is no need for assessing the efficacy of the additive in the context of the renewal of the authorisation.

Recent progress on sonochemical production for the synthesis of efficient photocatalysts and the impact of reactor design.

Sonochemical-assisted synthesis has flourished recently for the design of photocatalysts. The main power used is ultrasound that allows the nanomaterials shape and size modification and control. This review highlights the effect in formation mechanism by ultrasound application and the most common photocatalysts that were prepared via sonochemical techniques. Moreover, the challenge for the suitable reactor design for the synthesis of materials or for their photocatalytic evaluation is discussed since the most prominent reactor systems, batch, and continuous flow, has both advantages and drawbacks. This work summarises the significance of sonochemical synthesis for photocatalytic materials as a green technology that needs to be further investigated for the preparation of new materials and the scale up of developed reactor systems to meet industrial needs.

Effects of oxygen functionalities on hydrous hydrazine decomposition over carbonaceous materials.

Metal-free heterogeneous catalysis is promising in the context of H2 generation. Therefore, establishing structure-activity relationships is a crucial issue to improve the development of more efficient catalysts. Herein, to evaluate the reactivity of the oxygen functionalities in carbonaceous materials, commercial functionalized pyrolytically stripped carbon nanofibers (CNFs) were used as catalysts in the liquid-phase hydrous hydrazine decomposition process and its activity was compared to that of a pristine CNF material. Different oxygenated groups were inserted by treating CNFs with hydrogen peroxide for 1 h (O1-H2O2) and HNO3 for 1 h (O1-HNO3) and 6 h (O6-HNO3). An increase in activity was observed as a function of the oxidizing agent strength (HNO3 > H2O2) and the functionalization time (6 h > 1 h). A thorough characterization of the catalysts demonstrated that the activity could be directly correlated with the oxygen content (O6-HNO3 > O1-HNO3 > O1-H2O2 > CNFs) and pointed out the active sites for the reaction at carbon-oxygen double bond groups (CO and COOH). Systematic DFT calculations supported rationalization of the experimental kinetic trends with respect to each oxygen group (CO, C-O-C, C-OH and COOH).

Computational Studies on Microreactors for the Decomposition of Formic Acid for Hydrogen Production Using Heterogeneous Catalysts.

Sustainable alternatives to conventional fuels have emerged recently, focusing on a hydrogen-based economy. The idea of using hydrogen (H2) as an energy carrier is very promising due to its zero-emission properties. The present study investigates the formic acid (FA) decomposition for H2 generation using a commercial 5 wt.% Pd/C catalyst. Three different 2D microreactor configurations (packed bed, single membrane, and double membrane) were studied using computational fluid dynamics (CFD). Parameters such as temperature, porosity, concentration, and flow rate of reactant were investigated. The packed bed configuration resulted in high conversions, but due to catalyst poisoning by carbon monoxide (CO), the catalytic activity decreased with time. For the single and double membrane microreactors, the same trends were observed, but the double membrane microreactor showed superior performance compared with the other configurations. Conversions higher than 80% were achieved, and even though deactivation decreased the conversion after 1 h of reaction, the selective removal of CO from the system with the use of membranes lead to an increase in the conversion afterwards. These results prove that the incorporation of membranes in the system for the separation of CO is improving the efficiency of the microreactor.

Safety and efficacy of a feed additive consisting of monensin sodium (Elancoban® G200) for chickens for fattening, chickens reared for laying and turkeys (Elanco GmbH).

Following a request from the European Commission, EFSA was asked to deliver a new scientific opinion on the coccidiostat monensin sodium (Elancoban® G200) when used as a feed additive for chickens for fattening and turkeys. Based on the new data provided, the Panel updates its previous conclusions as follows: monensin sodium is produced by fermentation by a non-genetically modified strain of Streptomyces sp. NRRL B-67924. Genome analysis suggests the production strain may belong to a new species within the genus Streptomyces. The production strain and its DNA were not detected in the final additive. The product is free of antimicrobial activity other than monensin. The FEEDAP Panel cannot conclude on the safety of monensin sodium from Elancoban® G200 in feed for chickens for fattening and chickens reared for laying at the proposed maximum use level due to a dose-related reduction of the final body weight. The toxicological profile of monensin sodium was evaluated in studies made with the product obtained from the parental strain ATCC 15413. Based on a comparison of the genomes of the two strains, the FEEDAP Panel concludes that toxicological equivalence has been established, thus the conclusions already drawn on Elancoban® G200 are valid for the product obtained with the new production strain concluding that the additive is safe for the consumer and the environment; the production strain does not represent an additional risk when safety for the user is considered. Monensin sodium from Elancoban® G200 is safe for turkeys up to 16 weeks of age at the concentration of 100 mg monensin sodium/kg feed and has the potential to control coccidiosis at the minimum concentration of 60 mg/kg complete feed.

Efficacy of a feed additive consisting of Bacillus velezensisNITE BP-01844 (BA-KING®) for chickens for fattening, chickens reared for laying, turkeys for fattening, turkeys reared for breeding and all avian species for fattening, or rearing to slaughter or point of lay including non-food producing species (Toa Biopharma Co., Ltd.).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the efficacy of BA-KING® Bacillus velezensis as a zootechnical feed additive to be used as a gut flora stabiliser for chickens for fattening, chickens reared for laying, turkeys for fattening, turkeys reared for breeding and all avian species for fattening or rearing to slaughter or point of lay including non-food producing species. The product under assessment is based on viable spores of a strain identified as B. velezensis, which is considered suitable for the qualified presumption of safety (QPS) approach to safety assessment. In a previous opinion, the FEEDAP Panel concluded that BA-KING® was safe for the target species, consumers of products derived from animals fed the additive and the environment. Additionally, the additive was not irritant to skin but potentially irritant to eyes and respiratory sensitiser. The Panel could not conclude on the efficacy of the additive for the target species at the proposed conditions of use. In the current application, two additional efficacy trials in chickens for fattening were provided. The results showed an improvement in the performance parameters of chickens when supplemented with BA-KING® at 2.0 × 108 CFU/kg complete feed relative to a control group. Considering the previously submitted studies and the newly submitted studies in chickens for fattening, the Panel concluded that BA-KING®, supplemented at 2.0 × 108 CFU/kg complete feed, has the potential to be efficacious in all avian species for fattening or reared for laying/breeding and non-food-producing avian species at the same physiological stage.

Safety and efficacy of a feed additive consisting of Saccharomyces cerevisiae DBVPG 48 SF (BioCell®) for horses, pigs and ruminants (Mazzoleni S.p.A.).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of Saccharomyces cerevisiae DBVPG 48 SF (BioCell®) as a zootechnical feed additive for horses, pigs and ruminants. The product, manufactured in three formulations (microsphere, micropellet and powder), is intended for use in complete feed at a minimum inclusion level of 3 × 109 CFU/kg complete feed for horses, 4 × 108 CFU/kg complete feed for dairy cows and minor dairy species, 4 × 109 CFU/kg complete feed for calves, cattle for fattening, minor growing and fattening ruminants, piglets and pigs for fattening and minor porcine species and 6 × 109 CFU/kg complete feed for sows and minor porcine species for reproduction. Saccharomyces cerevisiae is considered by EFSA to be suitable for the qualified presumption of safety approach to safety assessment. The identity of the strain was conclusively established and, therefore, the use of the additive in animal nutrition is considered safe for the target species, the consumer and the environment. The additive, in any formulation, is not irritant to the eyes and skin but should be considered a respiratory sensitiser. The Panel cannot conclude on the skin sensitisation potential of the additive. The Panel concluded that the additive has the potential to be efficacious at the proposed conditions of use for horses, dairy ruminants and all pigs. However, the Panel was not in the position to conclude on the efficacy of the additive for calves, and neither for cattle for fattening, minor growing and fattening ruminants.

Safety and efficacy of a feed additive consisting of halofuginone hydrobromide (STENOROL®) for chickens for fattening and turkeys for fattening/reared for breeding (Huvepharma N.V.).

Following a request from the European Commission, EFSA was asked to deliver a new scientific opinion on the coccidiostat halofuginone hydrobromide (STENOROL®) when used as a feed additive for chickens for fattening and turkeys for fattening/reared for breeding. The Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concludes that the safety for turkeys for fattening established in its previous opinion can be extended to turkeys for breeding up to 12 weeks of age. Based on the new data provided on the safety for consumer, environment and efficacy, the Panel updates its previous conclusions as follows: halofuginone hydrobromide is not genotoxic. Applying an uncertainty factor of 100 to the lowest no observed adverse effect level (NOAEL) of 0.03 mg/kg body weight (bw) per day, an acceptable daily intake (ADI) of 0.3 µg halofuginone/kg bw is established. The chronic exposure of consumers to residues of halofuginone would amount to 6-19% of the ADI after 3 days of withdrawal. Therefore, the Panel considers that the additive is safe for the consumer of tissues obtained from chickens for fattening and turkeys for fattening fed the additive at a maximum level of 3 mg/kg complete feed at a 3-day withdrawal time. For control purposes, the Panel recommends the setting of the following maximum residue limits (MRLs): liver, 50 µg/kg; kidney, 40 µg/kg; muscle, 3 µg/kg; skin/fat, 10 µg/kg wet tissue. Based on an updated environmental risk assessment, no concern for groundwater is expected. Halofuginone is unlikely to bioaccumulate and the risk of secondary poisoning is not likely to occur. No safety concerns are expected for terrestrial and aquatic environments. The additive has the potential to control coccidiosis in chickens for fattening and turkeys for fattening/reared for breeding up to 12 weeks of age at a minimum level of 2 mg/kg complete feed.