Showing papers by "Christer Hogstrand published in 2013"

A mechanism for epithelial–mesenchymal transition and anoikis resistance in breast cancer triggered by zinc channel ZIP6 and STAT3 (signal transducer and activator of transcription 3)

Abstract: Genes involved in normal developmental processes attract attention as mediators of tumour progression as they facilitate migration of tumour cells. EMT (epithelial–mesenchymal transition), an essential part of embryonic development, tissue remodelling and wound repair, is crucial for tumour metastasis. Previously, zinc transporter ZIP6 [SLC39A6; solute carrier family 39 (zinc transporter), member 6; also known as LIV-1) was linked to EMT in zebrafish gastrulation through a STAT3 (signal transducer and activator of transcription 3) mechanism, resulting in nuclear localization of transcription factor Snail. In the present study, we show that zinc transporter ZIP6 is transcriptionally induced by STAT3 and unprecedented among zinc transporters, and is activated by N-terminal cleavage which triggers ZIP6 plasma membrane location and zinc influx. This zinc influx inactivates GSK-3β (glycogen synthase kinase 3β), either indirectly or directly via Akt or GSK-3β respectively, resulting in activation of Snail, which remains in the nucleus and acts as a transcriptional repressor of E-cadherin (epithelial cadherin), CDH1, causing cell rounding and detachment. This was mirrored by ZIP6-transfected cells which underwent EMT, detached from monolayers and exhibited resistance to anoikis by their ability to continue proliferating even after detachment. Our results indicate a causative role for ZIP6 in cell motility and migration, providing ZIP6 as a new target for prediction of clinical cancer spread and also suggesting a ZIP6-dependent mechanism of tumour metastasis.

Scientific Opinion on the safety and efficacy of L-cysteine hydrochloride monohydrate as a flavouring additive for pets

Abstract: L-Cysteine is a non-essential amino acid produced by hydrolysis of natural keratin (typically from duck feathers). In the absence of information on bacterial fermentation, the FEEDAP Panel cannot conclude on this way of manufacturing. The addition of L-cysteine to the food of cats and dogs is safe if the balance between cysteine and methionine in the complete diet is maintained. Owing to the unknown total content of free Lcysteine in the final diet, it cannot be assessed whether or not the addition of L-cysteine as a feed flavouring would disrupt this balance. In the absence of data, the FEEDAP Panel considers it prudent to assume that exposure of the skin, eyes and mucous membranes poses a risk to users. As L-cysteine is intended for use in pets, assessment of the safety for the environment is not needed. It is not clear if the use of L-cysteine, applied as described by the applicant, is the same as that for human food and, therefore, efficacy cannot be assumed and has not been demonstrated. The FEEDAP Panel made a recommendation regarding the specification of the additive. © European Food Safety Authority, 2013

Scientific Opinion on the safety and efficacy of iodine compounds (E2) as feed additives for all animal species: calcium iodate anhydrous, based on a dossier submitted by Calibre Europe SPRL/BVBA

Abstract: Calcium iodate anhydrous is considered a safe source of iodine for all animal species/categories when used up to the currently authorised maximum content of total iodine in complete feed, with the exception of horses and dogs, for which maximum tolerated levels are 3 and 4 mg I/kg complete feed, respectively. The limited data available on iodine tolerance in cats support a provisional tolerated level of 5 mg I/kg complete feed. Exposure of consumers was calculated in two scenarios applying the currently authorised maximum iodine contents in feed and reduced contents. The iodine content of food of animal origin, if produced taking account of the currently authorised maximum content of iodine in feed, would represent a substantial risk to high consumers. The risk would originate primarily from the consumption of milk and to a minor extent from eggs. The UL for adults (600 μg/day) and for toddlers (200 μg/day) would be exceeded by a factor of 2 and 4, respectively. If the authorised maximum iodine concentrations in feed for dairy cows and laying hens were reduced to 2 and 3 mg I/kg feed, respectively, the exposure of adult consumers would be below the UL. However, iodine intake in highconsuming toddlers would remain above the UL (1.6-fold). Calcium iodate is considered as irritant to the eye, skin and respiratory tract, and a dermal sensitiser. The exposure by inhalation should be avoided. The use of calcium iodate in animal nutrition is not expected to pose a risk to the environment. Calcium iodate is efficacious to meet animal iodine requirements. The FEEDAP Panel recommends that the maximum iodine contents in complete feed be reduced as follows: dairy cows and minor dairy ruminants, 2 mg I/kg; laying hens, 3 mg I/kg; horses, 3 mg I/kg; dogs, 4 mg I/kg; cats, 5 mg I/kg. © European Food Safety Authority, 2013

Scientific Opinion on the safety and efficacy of Bacillus amyloliquefaciens (NCIMB 30229) as a silage feed additive for all species

Abstract: A strain of Bacillus amyloliquefaciens is intended to be added to forages to promote the ensiling process (technological additive, functional group: silage additive). The identity of the strain and its susceptibility to relevant antibiotics has been established. However, the strain produces cyclic lipopeptides which possess potent surfactant activity, known to be involved in food intoxication. Although the strain is intended for use only in the production of silage, as a spore former it will survive the ensiling process and be ingested by target animals. The spores will also survive passage through the gastrointestinal tract of animals and be a potential source of contamination of food of animal origin and of the environment. The greatest risk would be to those handling the product on farm following oral, dermal and respiratory exposure. Consequently, the FEEDAP Panel concludes that use of the strain in the production of silage presents a hazard to consumers, users and the environment, and potentially also to the target animals. A total of three laboratory experiments with laboratory-scale silos, each lasting at least 90 days, were carried out using samples of forage of differing dry matter and water-soluble carbohydrate content. In each case, replicate silos containing treated forage were compared with identical silos containing the same but untreated forage. The potential of the additive to improve aerobic stability of silages at the proposed dose of 5.0 107 CFU/kg fresh materials was not convincingly demonstrated.

Scientific Opinion on the safety and efficacy of vitamin A (retinyl acetate, retinyl palmitate and retinyl propionate) as a feed additive for all animal species and categories

Abstract: Vitamin A is essential for vision, growth differentiation and proliferation of a wide range of epithelial tissues, bone growth, reproduction and embryonic development. The tolerance data for the target species do not indicate a concern for animal safety considering the maximum values set in the European Union regulation for food producing animals and pets. All consumer exposure calculations demonstrated that liver is the only food of animal origin for which consumption poses a risk to adult consumers. This risk could be considerably reduced, but not eliminated, if the new levels proposed by EFSA for a reduction in the maximum vitamin A content of feedingstuffs were respected. The proposal for a maximum content of vitamin A in complete feed or milk replacers or a maximum daily intake for the target species and categories of target species is presented in this opinion. However, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) notes that the availability of an additional route of administration of vitamin A (e.g. water for drinking) would increase the risk for the consumer. Retinyl esters are irritants to skin and potential skin sensitisers. Data on respiratory toxicity and the levels of exposure of workers that would cause systemic or respiratory toxicity are not available. However, it is likely that workers will be exposed to inhalation by handling certain formulations. The use of vitamin A in animal nutrition up to the maximum contents authorised does not pose a risk to the environment. Retinyl esters are regarded as effective sources of vitamin A.

Scientific Opinion on the safety and efficacy of Miya-Gold (Clostridium butyricum) for chickens for fattening, chickens reared for laying and minor avian species

Abstract: Miya-Gold is an additive containing viable spores of a single strain of Clostridium butyricum as the active agent. It is presently authorised for use in diets for weaned piglets, minor weaned porcine species, chickens for fattening and minor avian species for fattening. The applicant is now seeking to reduce the minimum authorised dose from 5 x 108 CFU/kg feed to 2.5 x 108 CFU/kg feed when used with chickens for fattening and all minor avian species (except laying birds) and to extend this authorisation to chickens reared for laying. The safety for the consumers, users of the product and the environment has been previously assessed by EFSA and found that it did not raise concerns. In a previous opinion the FEEDAP Panel concluded that the additive is safe for chickens for fattening when used at the then recommended dose. The Panel considers that this conclusion can be extended to chickens reared for laying. This conclusion can be taken to apply to the revised dose for all of species under application. The data from three trials made with chickens for fattening confirmed the effectiveness of the additive when used at the currently authorised dose of 5 x 108 CFU/kg feed. Effects with the reduced dose of 2.5 x 108 CFU/kg feed were less clear and showed significantly positive results in only two of the five trials in which this dose was tested. However, a meta-analysis made by pooling results from the five trials showed significant gains in final body weight and improved feed conversion indicating that the additive had some potential to improve performance of chickens for fattening at the lower dose. This conclusion can be extended to chickens reared for laying and extrapolated to minor avian species (other than those used for laying).

Scientific opinion on the characterisation of zinc compound ‘Zinc chelate of amino acids, hydrate (Availa®Zinc)’ as a feed additive for all animal species

Abstract: The opinion newly describes the characterisation and identity of the hydrolysed zinc-containing raw product used for formulation of the additive, and replaces the section ‘Characterisation and identity’ of the previous opinion on ‘Zinc chelate of amino acids hydrate, based on a dossier submitted by Zinpro Animal Nutrition Inc.’ published by the European Food Safety Authority (EFSA) in 2012. The conclusions on the safety and efficacy of the additive, as well as recommendations, of the previous EFSA opinion remain unchanged. A further recommendation concerning the monitoring of raw material by the applicant was added. © European Food Safety Authority, 2013

Immobilization of Shewanella oneidensis MR-1 in diffusive gradients in thin films for determining metal bioavailability

Abstract: Assessing metal bioavailability in soil is important in modelling the effects of metal toxicity on the surrounding ecosystem. Current methods based on diffusive gradient thin films (DGTs) and Gel-Integrated Microelectrode are limited in their availability and sensitivity. To address this, S. oneidensis, an anaerobic iron reducing bacterium, was incorporated into a thin layer of agarose to replace the polyacrylamide gel that is normally present in DGT to form biologically mobilizing DGT (BMDGT). Viability analysis revealed that 16-35% of the cells remained viable within the BMDGTs depending on the culturing conditions over a 20 h period with/without metals. Deployment of BMDGTs in standardized metal solutions showed significant differences to cell free BMDGTs when cells grown in Luria Broth (LB) were incorporated into BMDGTs and deployed under anaerobic conditions. Deployment of these BMDGTs in hematite revealed no significant differences between BMDGTs and BMDGTs containing heat killed cells. Whether heat killed cells retain the ability to affect bioavailability is uncertain. This is the first study to investigate how a microorganism that was incorporated into a DGT device such as the metal reducing bacteria, S. oneidensis, may affect the mobility of metals.

Scientific opinion on the safety and efficacy of manganese compounds (E5) as feed additives for all species: manganous oxide and manganous sulphate monohydrate, based on a dossier submitted by Eramet & Comilog Chemicals S.A.

Abstract: Manganese, an essential trace element, functions as an enzyme activator and is a constituent of several enzymes. Primary signs of manganese deficiency are impaired growth, skeletal abnormalities, depressed reproductive function, ataxia of the newborn and faults in lipid and carbohydrate metabolism. Manganous oxide and manganous sulphate monohydrate are safe sources of manganese for all animal species/categories, provided that the current maximum total contents of manganese authorised in feed are respected. Generally, dietary manganese does not appear to cause any adverse health effects in the population and has not proven to be a risk at the usual intake levels. Manganese intake resulting from the consumption of tissues and products of animal origin is low and not of concern for the safety of consumers, including more sensitive subgroups such as infants and elderly people. It is concluded that the use of manganous oxide and manganous sulphate monohydrate in animal nutrition is of no concern for the safety of consumers, provided that the current maximum total contents of manganese authorised in feed are respected. The handling of manganous oxide and manganous sulphate monohydrate poses a risk to users upon inhalation exposure. The additive manganous oxide should be considered as a potential skin and eye irritant and as a dermal sensitiser. Manganous sulphate monohydrate is not irritating to skin but it is an eye irritant; it is likely not a dermal sensitiser. The use of manganous oxide and manganous sulphate monohydrate in animal nutrition for all animal species is not of concern for the environment, provided that the current maximum total contents of manganese authorised in feed are respected. Manganous oxide and manganous sulphate monohydrate are efficacious sources of manganese in meeting animals’ requirements. 1 On request from the European Commission, Question No EFSA-Q-2012-00438, adopted on 9 October 2013. 2 Panel members: Gabriele Aquilina, Vasileios Bampidis, Maria De Lourdes Bastos, Lucio Guido Costa, Gerhard Flachowsky, Mikolaj Antoni Gralak, Christer Hogstrand, Lubomir Leng, Secundino Lopez-Puente, Giovanna Martelli, Baltasar Mayo, Fernando Ramos, Derek Renshaw, Guido Rychen, Maria Saarela, Kristen Sejrsen, Patrick Van Beelen, Robert John Wallace and Johannes Westendorf. Correspondence: FEEDAP@efsa.europa.eu 3 Acknowledgement: The Panel wishes to thank the members of the Working Group on Trace Elements, including Noel Albert Dierick, Jurgen Gropp and Alberto Mantovani, for the preparatory work on this scientific opinion. 4 This scientific opinion has been amended following the adoption of the decision of the Commission on confidentiality claims submitted by the applicant, in accordance with Article 8(6) and Article 18 of Regulation (EC) No 1831/2003. The modified sections are indicated in the text. 5 An editorial amendment was carried out that does not materially affect the contents or outcome of this Scientific Opinion, under the section on the environmental safety. To avoid confusion, the previous version has been removed from the EFSA Journal, but is available on request, as is a version showing all the changes made. Previous revision: 19 March 2015, publication of full opinion. Suggested citation: EFSA FEEDAP Panel (EFSA Panel on Additives and Products or Substances used in Animal Feed), 2013. Scientific Opinion on the safety and efficacy of manganese compounds (E5) as feed additives for all species: manganous oxide and manganous sulphate monohydrate, based on a dossier submitted by Eramet & Comilog Chemicals S.A. EFSA Journal 2013;11(10):3435, 28 pp. doi:10.2903/j.efsa.2013.3435 Available online: www.efsa.europa.eu/efsajournal Manganous oxide and manganous sulphate monohydrate for all species EFSA Journal 2013;11(10):3435 2 © European Food Safety Authority, 2013

Scientific Opinion on the safety and efficacy of Enterococcus faecium (CNCM I-3236) as a silage additive for all species

Abstract: Enterococcus faecium is a technological additive intended to improve the ensiling process at a proposed dose of 1 x 108 CFU/kg fresh material. The strain does not contain marker genes typical of hospital-associated isolates responsible for clinical infections and is susceptible to clinically relevant antibiotics. It is not expected that the use of E. faecium at the dose proposed would substantially increase the exposure to this species of animals given silage as part of their rations Therefore, the FEEDAP Panel considers that use of this strain in the preparation of silage is safe for the target animals. Since the strain does not belong to the hospital-associated clade and does not express resistance to the antibiotics tested, use of this strain in animal nutrition is not expected to raise concerns for consumers of animal products. The material safety data sheet proposed indicates that preparations containing the strain may cause irritation upon contact with skin and eyes. The dustiness of the preparation tested indicated a potential for users to be exposed via inhalation. Given the proteinaceous nature of the active agent, the additive should be considered to have the potential to be a skin/respiratory sensitiser and treated accordingly. The use of the strain under the conditions proposed is considered safe for the environment. Studies with laboratory-scale silos are described made using three samples of mixed forage of differing water-soluble carbohydrate content and representing material easy, moderately difficult and difficult to ensile. In each case, replicate silos containing treated forage were compared to identical silos containing the same but untreated forage. Because of the very limited responses to treatment in two of the three forage samples tested, the FEEDAP Panel is unable to conclude on the benefit of using the strain of E. faecium as a silage additive for all forage species.