Suchergebnisse

Progressive expansion of nanomaterials in our everyday life raises concerns about their safety for human health. Although kidneys are the primary organs of xenobiotic elimination, little attention has been paid to the kidneys in terms of nanotoxicological studies up to now. Here we investigate the cytotoxic and genotoxic potential of four solid-core uncoated inorganic nanoparticles (TiO2NPs, SiO2NPs, Fe3O4NPs and AuNPs) using the human renal proximal tubule epithelial TH1 cells. To mimic the in vivo conditions more realistic, TH1 cells were exposed in vitro to inorganic NPs under static as well as dynamic conditions for 3 h and 24 h. The medium throughput alkaline comet assay (12 minigels per slide) was employed to evaluate the impact of these NPs on genome integrity and their capacity to produce oxidative lesions to DNA. The accumulation and localization of studied inorganic NPs inside the cells was monitored by transmission electron microscopy (TEM) and the efficacy of internalization of particular NPs was determined by atomic absorption spectroscopy (AAS) and inductively coupled plasma mass spectrometry (ICP-MS). From all the tested NPs, only Fe3O4NPs induced a slight cytotoxicity in TH1 cells exposed to high concentrations (>700 μg/ml) for 24 h. On the other hand, the inorganic NPs did not increase significantly the level of DNA strand breaks or oxidative DNA damage regardless of the treatment mode (static vs. dynamic conditions). Interestingly, substantial differences were observed in the internalized amount of inorganic NPs in TH1 cells exposed to equivalent (2.2 μg/ml) concentration. Fe3O4NPs were most efficiently taken up while the lowest quantity of particles was determined in TiO2NPs-treated cells. As the particle size and shape of individual inorganic NPs in culture medium was nearly identical, it is reasonable to suppose that the chemical composition may contribute to the differences in the efficacy of NPs uptake. ; This article was created by the realization of the H2020 project HISENTS No. 685817, COST Action CA15132, VEGA grant 2/0056/17, project "Center of excellence of environmental health", ITMS No. 26240120033, based on the support of operational Research and development program financed from the European Regional Development Fund; and the EEA projectSK0020. Filip Razga received support within the SASPRO Programme (Project No. 0057/01/02) co-funded by the European Union and the Slovak Academy of Sciences. ; Peer reviewed

Despite the obvious advantages of gold nanoparticles for biomedical applications, controversial and incomplete toxicological data hamper their widespread use. Here, we present the results from an in vivo toxicity study using gold nanoparticles coated with polyethylene glycol (PEG-AuNPs). The pharmacokinetics and biodistribution of PEG-AuNPs were examined in the rat's liver, lung, spleen, and kidney after a single i.v. injection (0.7 mg/kg) at different time intervals. PEG-AuNPs had a relatively long blood circulation time and accumulated primarily in the liver and spleen, where they remained for up to 28 days after administration. Increased cytoplasmic vacuolation in hepatocytes 24 h and 7 days after PEG-AuNPs exposure and apoptotic-like cells in white splenic pulp 24 h after administration has been detected, however, 28 days post-exposure were no longer observed. In contrast, at this time point, we identified significant changes in lipid metabolism, altered levels of liver injury markers, and elevated monocyte count, but without marked biological relevance. In blood cells, no DNA damage was present in any of the studied time intervals, with the exception of DNA breakage transiently detected in primary kidney cells 4 h post-injection. Our results indicate that the tissue accumulation of PEG-AuNPs might result in late toxic effects. ; This paper is supported by European Union's Horizon 2020 research and innovation program under grant agreement No. 857381, project VISION (Strategies to strengthen scientific excellence and innovation capacity for early diagnosis of gastrointestinal cancers), project HISENTS No. 685817, VEGA grants 2/0055/20, 2/0121/21.

Abstract
The food enzyme triacylglycerol lipase (triacylglycerol acylhydrolase, EC 3.1.1.3) is produced with the genetically modified Aspergillus oryzae strain NZYM‐AL by Novozymes A/S. A safety evaluation of this food enzyme was made previously, in which EFSA concluded that, under the intended conditions of use, this food enzyme did not give rise to safety concerns. Due to the implementation of a new methodology to estimate the dietary exposure to food enzymes in 2016, the European Commission requested EFSA to revise the exposure assessment of this food enzyme by using this new methodology. In this assessment, EFSA realigned the intended uses of this food enzyme to four food manufacturing processes. The dietary exposure was calculated to be up to 0.089 mg TOS/kg body weight (bw) per day in European populations. When combined with the no observed adverse effect level previously reported (49.1 mg TOS/kg bw per day, the lowest dose tested), the Panel derived a margin of exposure of at least 552. Based on the revised exposure estimate, the margin of exposure calculated thereof and the previous evaluation, the Panel concluded that this food enzyme does not give rise to safety concerns under the intended conditions of use.

Abstract
The food enzyme endo‐1,4‐β‐xylanase (4‐β‐d‐xylan xylanohydrolase, EC 3.2.1.8) is produced with the genetically modified Bacillus subtilis strain LMG S‐24584 by Puratos NV. In a previous opinion, the Panel noted the presence of recombinant DNA in all food enzyme batches tested. As a follow‐up, the applicant changed the manufacturing process of the food enzyme and provided new data. The genetic modifications do not give rise to safety concerns and the production strain fulfils the requirements for the QPS approach to safety assessment. The food enzyme is free from viable cells of the production organism and its DNA. It is intended to be used in the processing of cereals and other grains for the production of baked products. Dietary exposure is estimated to be up to 0.010 mg TOS/kg body weight per day in European populations. As no concerns arising from the microbial source and its genetic modifications or from the manufacturing process have been identified, the Panel considered that toxicological tests were not needed for the assessment of this food enzyme. A search for the homology of the amino acid sequence of the food enzyme to known allergens was made and no match was found. The Panel considered that the risk of allergic reactions upon dietary exposure cannot be excluded, but the likelihood is low. Based on the data provided, the Panel concluded that this food enzyme does not give rise to safety concerns, under the intended conditions of use.

Abstract
The food enzyme thrombin (EC 3.4.21.5) is produced from cattle and pig's blood by Sonac. A safety evaluation of this food enzyme was made previously, in which EFSA concluded that, under the intended conditions of use, this food enzyme did not give rise to safety concerns. Due to the implementation of a new methodology to estimate the dietary exposure to food enzymes in 2016, the European Commission requested EFSA to revise the exposure assessment of this food enzyme by using this new methodology. In this assessment, EFSA realigned the intended uses of this food enzyme to the processing of meat and fish products for the production of modified meat and fish products. The dietary exposure was calculated to be below 0.0001 mg total organic solids/kg body weight (bw) per day in European populations. The intake of prothrombin (the precursor of thrombin) from animal blood in the diet of European population is also below 0.0001 mg/kg bw per day. Based on the origin of the food enzyme from edible parts of animals, the previous evaluation of the manufacturing process and the compositional data, and the comparable exposure estimation between the use of the food enzyme and its source, the Panel concluded that the food enzyme thrombin derived from cattle (bovine) and pig's blood does not give rise to safety concerns under the intended conditions of use.

Abstract
The food enzyme has four declared activities: endo‐polygalacturonase ((1–4)‐α‐d‐galacturonan glycanohydrolase (endo‐cleaving); EC 3.2.1.15), pectinesterase (pectin pectylhydrolase; EC 3.1.1.11), pectin lyase ((1–4)‐6‐O‐methyl‐α‐d‐galacturonan lyase; EC 4.2.2.10) and non‐reducing end α‐l‐arabinofuranosidase (α‐l‐arabinofuranoside non‐reducing end α‐l‐arabinofuranosidase; EC 3.2.1.55). It is produced with the non‐genetically modified Aspergillus niger strain PEC by DSM Food Specialties B.V. A safety evaluation of this food enzyme was made previously, in which EFSA concluded that this food enzyme did not give rise to safety concerns when used in three food manufacturing processes. Subsequently, the applicant has requested to extend its use to include four additional processes. In this assessment, EFSA updated the safety evaluation of this food enzyme when used in a total of seven food manufacturing processes. As the food enzyme–total organic solids (TOS) are removed from the final foods in one food manufacturing process, the dietary exposure to the food enzyme–TOS was estimated only for the remaining six processes. The dietary exposure was calculated to be up to 0.612 mg TOS/kg body weight (bw) per day in European populations. When combined with the no observed adverse effect level previously reported (204 mg TOS/kg bw per day, the highest dose tested), the Panel derived a margin of exposure of at least 333. Based on the previous evaluation, the assessment of the new data and the revised margin of exposure, the Panel concluded that this food enzyme does not give rise to safety concerns under the revised intended conditions of use.

Abstract
The food enzyme α‐amylase (4‐α‐d‐glucan glucanohydrolase i.e. EC 3.2.1.1) is produced with the non‐genetically modified Cellulosimicrobium funkei strain AE‐AMT by Amano Enzyme Inc. A safety evaluation of this food enzyme was made previously, in which EFSA concluded that the food enzyme did not give rise to safety concerns when used in seven food manufacturing processes. Subsequently, the applicant has requested to extend its use to include three additional processes. In this assessment, EFSA updated the safety evaluation of this food enzyme when used in a total of ten food manufacturing processes. As the food enzyme‐total organic solids (TOS) are removed from the final foods in one food manufacturing process, the dietary exposure to the food enzyme‐TOS was estimated only for the remaining nine processes. The dietary exposure was calculated to be up to 0.049 mg TOS/kg body weight (bw) per day in European populations. When combined with the no observed adverse effect level previously reported (230 mg TOS/kg bw per day, the highest dose tested), the Panel derived a margin of exposure of at least 4694. Based on the data provided for the previous evaluation and the revised margin of exposure in the present evaluation, the Panel concluded that this food enzyme does not give rise to safety concerns under the intended conditions of use.

Abstract
The food enzyme containing endo‐polygalacturonase and β‐glucosidase (EC 3.2.1.15 and EC 3.2.1.21) is produced with the non‐genetically modified Aspergillus tubingensis strain ARO by DSM Food Specialties B.V. The food enzyme was free from viable cells of the production organism. It is intended to be used in five food manufacturing processes. Dietary exposure was estimated to be up to 0.609 mg total organic solids (TOS)/kg body weight per day in European populations. Genotoxicity tests did not indicate a safety concern. The systemic toxicity was assessed by means of a repeated dose 90‐day oral toxicity study in rats. The Panel identified a no observed adverse effect level of 2217 mg TOS/kg bw per day, the highest dose tested, resulting in a margin of exposure of at least 3640. A search for the homology of the amino acid sequence of the food enzymes to known allergens was made and four matches with food allergens and 22 matches with respiratory allergens were found. Known sources of food allergens were used in the food enzyme manufacturing process. The Panel considered that the risk of allergic reactions upon dietary exposure cannot be excluded. Based on the data provided, the Panel concluded that this food enzyme does not give rise to safety concerns, under the intended conditions of use.

Abstract
The food enzyme glucan 1,4‐α‐maltohydrolase (4‐α‐d‐glucan α‐maltohydrolase; EC 3.2.1.133) is produced with the genetically modified Saccharomyces cerevisiae strain LALL‐MA+ by Danstar Ferment AG. The genetic modifications do not give rise to safety concerns. The food enzyme is free from viable cells of the production organism and its DNA. It is intended to be used in the processing of cereals and other grains for production of baked products. Dietary exposure was estimated to be up to 0.014 mg TOS/kg body weight per day in European populations. Given the QPS status of the production strain and the absence of concerns resulting from the food enzyme manufacturing process, toxicity tests were considered unnecessary by the Panel. A search for the identity of the amino acid sequence of the food enzyme to known allergens was made and four matches were found, three with respiratory allergens and one with an allergen from mosquito (injected). The Panel considered that the risk of allergic reactions upon dietary exposure cannot be excluded, but the likelihood is low. Based on the data provided, the Panel concluded that this food enzyme does not give rise to safety concerns, under the intended conditions of use.

Abstract
The food enzyme β‐galactosidase (β‐d‐galactoside galactohydrolase; EC 3.2.1.23) is produced with the genetically modified Bacillus licheniformis strain DSM 34099 by Kerry Group Services International, Ltd. (KGSI). The genetic modifications do not give rise to safety concerns. The food enzyme is free from viable cells of the production organism and its DNA. The production strain met the requirements for the qualified presumption of safety (QPS) approach. The food enzyme is intended to be used in two food manufacturing processes. Dietary exposure was estimated to be up to 7.263 mg total organic solids/kg body weight per day in European populations. Given the QPS status of the production strain and the absence of concerns resulting from the food enzyme manufacturing process, toxicity tests, other than an assessment of allergenicity, were considered unnecessary by the Panel. A search for the identity of the amino acid sequence of the food enzyme to known allergens was made and one match with a food allergen from kiwi fruit was found. The Panel considered that a risk of allergic reactions upon dietary exposure to this food enzyme, particularly in individuals sensitised to kiwi fruit, cannot be excluded. Based on the data provided, the Panel concluded that this food enzyme does not give rise to safety concerns, under the intended conditions of use.

Abstract
The food enzyme glucan‐1,4‐α‐glucosidase (4‐α‐d‐glucan glucohydrolase; EC 3.2.1.3) is produced with the non‐genetically modified Aspergillus niger strain DP‐Azh100 by Genencor International B.V. It was considered free from viable cells of the production organism. The food enzyme is intended to be used in four food manufacturing processes. Since residual amounts of total organic solids (TOS) are removed in two processes, dietary exposure was calculated only for the two remaining processes. It was estimated to be up to 1.390 mg TOS/kg body weight (bw) per day in European populations. Genotoxicity tests did not indicate a safety concern. The systemic toxicity was assessed by means of a repeated dose 90‐day oral toxicity study in rats. The Panel identified a no observed adverse effect level at the highest dose tested of 1000 mg TOS/kg bw per day, which when compared with the estimated dietary exposure, resulted in a margin of exposure of at least 719. A search for the homology of the amino acid sequence of the food enzyme to known allergens was made and one match to a respiratory allergen was found. Known sources of food allergens were used in the food enzyme manufacturing process. The Panel considered that the risk of allergic reactions upon dietary exposure to this food enzyme cannot be excluded, but the likelihood is low. Based on the data provided, the Panel concluded that this food enzyme does not give rise to safety concerns, under the intended conditions of use.