Scientific Opinion on the safety and efficacy of Urea for ruminants

Urea supplementation to feed for ruminants provides non-protein nitrogen for microbial protein synthesis in the rumen and thus in part replaces other dietary protein sources. Urea supplementation of feed for ruminants at doses up to 1 % of complete feed DM (corresponding to 0.3 g/kg bw/day) is considered safe when given to animals with a well adapted ruminal microbiota and fed diets rich in easily digestible carbohydrates. Based on the metabolic fate of urea in ruminants, the use of urea in ruminant nutrition does not raise any concern for consumers\u2019 safety. Urea is considered to be non irritant to skin and eyes and its topical use suggests that it is not a dermal sensitiser. The risk of exposure by inhalation would be low. The substitution of protein by urea in well balanced feed for ruminants would not result in an increased environmental nitrogen load. Urea is an effective source of non-protein nitrogen substituting for dietary protein in ruminants

Safety and efficacy of a feed additive consisting of a dry grape extract (Nor-Grape® α) for all avian species (Nor-Feed S.A.S.)

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of a feed additive consisting of a dry grape extract (Nor-Grape® α) as a zootechnical feed additive, functional group physiological condition stabilisers - increase antioxidant defences, for all avian species. The additive is already authorised for use as a feed flavouring for all animal species, except dogs. The FEEDAP Panel concluded that the additive is safe for all avian species. The use of the additive in animal nutrition is of no concern for consumer safety. Based on the data submitted, the FEEDAP Panel could not conclude on the potential of the additive to be a skin or eye irritant or a dermal or respiratory sensitiser. However, the Panel considered that exposure through inhalation is likely. The use of the feed additive is considered safe for the environment. The Panel was unable to conclude on the potential of the additive to be efficacious under the proposed conditions of use

Safety of 27 flavouring compounds providing a milky-vanilla 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 27 compounds to provide a milky-vanilla flavour belonging to different chemical groups, when used as sensory additives in feed for all animal species. Fifteen of the 27 compounds were tested in tolerance studies in chickens for fattening, piglets and cattle for fattening. 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 15 tested compounds were safe for these species at the proposed use level and conclusions were extrapolated to all animal species. For the remaining 12 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 12 compounds were safe for all animal species at the proposed use level. No safety concern would arise for the consumer from the use of the 27 compounds up to the highest levels considered safe for target animals. No new data were submitted on the safety for the user that would allow the FEEDAP Panel to change its previous conclusion for 5-methylhept-2-en-4-one [07.139], 5-methylfurfural [13.001] and 4-phenylbut-3-en-2-one [07.024]. The concentrations considered safe for the target species are unlikely to have detrimental effects on the environment for all the compounds

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

Safety and efficacy of an essential oil from Elettaria cardamomum (L.) Maton when used as a sensory additive in feed for all animal species

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 an essential oil from the seeds of Elettaria cardamomum (L.) Maton when used as a sensory additive for all animal species. Characterisation of the essential oil identified 37 components accounting for > 99% of its composition, with terpineol acetate (> 35%) and 1,8-cineole (> 20%) being the most prevalent compounds. In the absence of toxicological data of the feed additive itself, a component-based approach was applied to assess the safety of the essential oil as a mixture. Based on structural and metabolic similarity, the components of cardamom oil were allocated to seven assessment groups. Assuming the absence of toxicologically relevant interactions among components, dose addition was applied within each assessment group by calculating the combined margin of exposure as a basis for risk characterisation. The FEEDAP Panel concluded that the additive under assessment is safe at the proposed use level of 5 mg/kg in feed for all animal species. A concentration of 5 mg/L water for drinking is considered safe for all animal species. The use of cardamom essential oil in animal feed is considered safe for the consumer. In the absence of studies, the Panel cannot conclude on the safety for the users when handling the additive. The use of the essential oil under assessment in animal production is not expected to pose a risk for the environment. Since the seeds of E. cardamomum and their preparations are recognised to flavour food and their function in feed would be essentially the same, no further demonstration of efficacy is considered necessary. The Panel made a recommendation to limit the content of methyleugenol in the oil

Safety and efficacy of an essential oil of Origanum vulgare ssp. hirtum (Link) leetsw. for all poultry species

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 an essential oil of Origanum vulgare ssp. hirtum (Link) leetsw. for all poultry species. The essential oil under assessment obtained is specified to contain carvacrol and thymol (7%). The remaining 30% of the composition remains uncharacterised. In the absence of these data, the FEEDAP Panel was unable to make a risk assessment of the additive for the target species, the consumer and the user. Use in animal production of the essential oil extracted from O. vulgare ssp. hirtum (Link) leetsw. is not expected to pose a risk for the environment. Since oregano and its extracts are universally recognised to flavour food and their function in feed would be essentially the same as that in food, no further demonstration of efficacy is considered necessary

Bifidobacterium longum CECT 7347 Modulates Immune Responses in a Gliadin-Induced Enteropathy Animal Model

Coeliac disease (CD) is an autoimmune disorder triggered by gluten proteins (gliadin) that involves innate and adaptive immunity. In this study, we hypothesise that the administration of Bifidobacterium longum CECT 7347, previously selected for reducing gliadin immunotoxic effects in vitro, could exert protective effects in an animal model of gliadin-induced enteropathy. The effects of this bacterium were evaluated in newborn rats fed gliadin alone or sensitised with interferon (IFN)-γ and fed gliadin. Jejunal tissue sections were collected for histological, NFκB mRNA expression and cytokine production analyses. Leukocyte populations and T-cell subsets were analysed in peripheral blood samples. The possible translocation of the bacterium to different organs was determined by plate counting and the composition of the colonic microbiota was quantified by real-time PCR. Feeding gliadin alone reduced enterocyte height and peripheral CD4+ cells, but increased CD4+/Foxp3+ T and CD8+ cells, while the simultaneous administration of B. longum CECT 7347 exerted opposite effects. Animals sensitised with IFN-γ and fed gliadin showed high cellular infiltration, reduced villi width and enterocyte height. Sensitised animals also exhibited increased NFκB mRNA expression and TNF-α production in tissue sections. B. longum CECT 7347 administration increased NFκB expression and IL-10, but reduced TNF-α, production in the enteropathy model. In sensitised gliadin-fed animals, CD4+, CD4+/Foxp3+ and CD8+ T cells increased, whereas the administration of B. longum CECT 7347 reduced CD4+ and CD4+/Foxp3+ cell populations and increased CD8+ T cell populations. The bifidobacterial strain administered represented between 75–95% of the total bifidobacteria isolated from all treated groups, and translocation to organs was not detected. These findings indicate that B. longum attenuates the production of inflammatory cytokines and the CD4+ T-cell mediated immune response in an animal model of gliadin-induced enteropathy

Discrete populations of isotype-switched memory B lymphocytes are maintained in murine spleen and bone marrow

At present, it is not clear how memory B lymphocytes are maintained over time, and whether only as circulating cells or also residing in particular tissues. Here we describe distinct populations of isotype-switched memory B lymphocytes (Bsm) of murine spleen and bone marrow, identified according to individual transcriptional signature and B cell receptor repertoire. A population of marginal zone-like cells is located exclusively in the spleen, while a population of quiescent Bsm is found only in the bone marrow. Three further resident populations, present in spleen and bone marrow, represent transitional and follicular B cells and B1 cells, respectively. A population representing 10-20% of spleen and bone marrow memory B cells is the only one qualifying as circulating. In the bone marrow, all cells individually dock onto VCAM1+ stromal cells and, reminiscent of resident memory T and plasma cells, are void of activation, proliferation and mobility

Macrophages and Fc-receptor interactions contribute to the antitumour activities of the anti-CD40 antibody SGN-40

SGN-40 is a therapeutic antibody targeting CD40, which induces potent anti-lymphoma activities via direct apoptotic signalling cells and by cell-mediated cytotoxicity. Here we show antibody-dependent cellular phagocytosis (ADCP) by macrophages to contribute significantly to the therapeutic activities and that the antitumour effects of SGN-40 depend on Fc interactions