TY - JOUR A1 - Sieg, H. A1 - Braeuning, C. A1 - Kunz, B. M. A1 - Daher, H. A1 - Kästner, C. A1 - Krause, B.-C. A1 - Meyer, T. A1 - Jalili, P. A1 - Kogeveen, K. A1 - Böhmert, L. A1 - Lichtenstein, D. A1 - Burel, A. A1 - Chevance, S. A1 - Jungnickel, H. A1 - Tentschert, J. A1 - Laux, P. A1 - Braeuning, A. A1 - Gauffre, F. A1 - Fessard, V. A1 - Meijer, J. A1 - Estrela-Lopis, I. A1 - Thünemann, Andreas A1 - Luch, A. A1 - Lampen, A. T1 - Uptake and molecular impact of aluminum-containing nanomaterials on human intestinal caco-2 cells N2 - Aluminum (Al) is one of the most common elements in the earth crust and increasingly used in food, consumer products and packaging. Its hazard potential for humans is still not completely understood. Besides the metallic form, Al also exists as mineral, including the insoluble oxide, and in soluble ionic forms. Representatives of these three species, namely a metallic and an oxidic species of Al-containing nanoparticles and soluble aluminum chloride, were applied to human intestinal cell lines as models for the intestinal barrier. We characterized physicochemical particle parameters, protein corona composition, ion release and cellular uptake. Different in vitro assays were performed to determine potential effects and molecular modes of Action related to the individual chemical species. For a deeper insight into signaling processes, microarray transcriptome analyses followed by bioinformatic data analysis were employed. The particulate Al species showed different solubility in biological media. Metallic Al nanoparticles released more ions than Al2O3 nanoparticles, while AlCl3 showed a mixture of dissolved and agglomerated particulate entities in biological media. The protein corona composition differed between both nanoparticle species. Cellular uptake, investigated in transwell experiments, occurred predominantly in particulate form, whereas ionic Al was not taken up by intestinal cell lines. Transcellular transport was not observed. None of the Al species showed cytotoxic effects up to 200 mg Al/mL. The transcriptome analysis indicated mainly effects on oxidative stress pathways, xenobiotic metabolism and metal homeostasis. We have shown for the first time that intestinal cellular uptake of Al occurs preferably in the particle form, while toxicological effects appear to be ion-related. KW - Small-angle x-ray scattering KW - SAXS KW - Nanopatricle PY - 2018 DO - https://doi.org/10.1080/17435390.2018.1504999 SN - 1743-5390 VL - 12 IS - 9 SP - 992 EP - 1013 PB - Taylor & Francis AN - OPUS4-47432 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Laux, P. A1 - Tentschert, J. A1 - Riebeling, Ch. A1 - Braeuning, A. A1 - Creutzenberg, O. A1 - Epp, A. A1 - Fessard, V. A1 - Haas, K.-H. A1 - Haase, A. A1 - Hund-Rinke, K. A1 - Jakubowski, Norbert A1 - Kearns, P. A1 - Lampen, A. A1 - Rauscher, H. A1 - Schoonjans, R. A1 - Störmer, A. A1 - Thielmann, A. A1 - Mühle, U. A1 - Luch, A. T1 - Nanomaterials: certain aspects of application, risk assessment and risk communication N2 - Development and market introduction of new nanomaterials trigger the need for an adequate risk assessment of such products alongside suitable risk communication measures. Current application of classical and new nanomaterials is analyzed in context of regulatory requirements and standardization for chemicals, food and consumer products. The challenges of nanomaterial characterization as the main bottleneck of risk assessment and regulation are presented. In some areas, e.g., quantification of nanomaterials within complex matrices, the establishment and adaptation of analytical techniques such as laser ablation inductively coupled plasma mass spectrometry and others are potentially suited to meet the requirements. As an example, we here provide an approach for the reliable characterization of human exposure to nanomaterials resulting from food packaging. Furthermore, results of nanomaterial toxicity and ecotoxicity testing are discussed, with concluding key criteria such as solubility and fiber rigidity as important parameters to be considered in material development and regulation. Although an analysis of the public opinion has revealed a distinguished rating depending on the particular field of application, a rather positive perception of nanotechnology could be ascertained for the German public in general. An improvement of material characterization in both toxicological testing as well as end-product control was concluded as being the main obstacle to ensure not only safe use of materials, but also wide acceptance of this and any novel technology in the general public. KW - Nanomaterials KW - Toxicity KW - Ecotoxicity KW - Standardization KW - Exposure PY - 2018 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-441096 DO - https://doi.org/10.1007/s00204-017-2144-1 VL - 92 IS - 1 SP - 121 EP - 141 PB - Springer AN - OPUS4-44109 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Sieg, H. A1 - Kästner, Claudia A1 - Krause, B. A1 - Meyer, T. A1 - Burel, A. A1 - Böhmert, L. A1 - Lichtenstein, D. A1 - Jungnickel, H. A1 - Tentschert, J. A1 - Laux, P. A1 - Braeuning, A. A1 - Estreal-Lopis, I. A1 - Gauffre, F. A1 - Fessard, V. A1 - Meijer, J. A1 - Luch, A. A1 - Thünemann, Andreas A1 - Lampen, A. T1 - Impact of an artificial digestion procedure on aluminum-containing nanomaterials N2 - Aluminum has gathered toxicological Attention based on relevant human exposure and its suspected hazardous potential. Nanoparticles from food supplements or Food contact materials may reach the human gastrointestinal tract. Here, we monitored the physicochemical fate of aluminum containing nanoparticles and aluminum ions when passaging an in vitro model of the human gastrointestinal tract. Smallangle X-ray scattering (SAXS), transmission electron microscopy (TEM), ion beam microscopy (IBM), secondary ion beam mass spectrometry (TOF-SIMS), and inductively coupled plasma mass spectrometry (ICP-MS) in the singleparticle mode were employed to characterize two aluminumcontaining nanomaterials with different particle core materials (Al0, γAl2O3) and soluble AlCl3. Particle size and shape remained unchanged in saliva, whereas strong Agglomeration of both aluminum nanoparticle species was observed at low pH in gastric fluid together with an increased ion release. The levels of free aluminum ions decreased in intestinal fluid and the particles deagglomerated, thus liberating primary particles again. Dissolution of nanoparticles was limited and substantial changes of their shape and size were not detected. The amounts of particle-associated phosphorus, chlorine, potassium, and calcium increased in intestinal fluid, as compared to nanoparticles in standard dispersion. Interestingly, nanoparticles were found in the intestinal fluid after addition of ionic aluminum. We provide a comprehensive characterization of the fate of aluminum nanoparticles in simulated gastrointestinal fluids, demonstrating that orally ingested nanoparticles probably reach the intestinal epithelium. The balance between dissolution and de novo complex formation should be considered when evaluating nanotoxicological experiments. KW - Small-angle X-ray scattering KW - SAXS KW - Nanoparticle PY - 2017 DO - https://doi.org/10.1021/acs.langmuir.7b02729 SN - 1520-5827 SN - 0743-7463 VL - 33 IS - 40 SP - 10726 EP - 10735 PB - Americal Chemical Society AN - OPUS4-42438 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Krause, B. A1 - Meyer, T. A1 - Sieg, H. A1 - Kästner, Claudia A1 - Reichardt, P. A1 - Tentschert, J. A1 - Jungnickel, H. A1 - Estrela-Lopis, I. A1 - Burel, A. A1 - Chevance, S. A1 - Gauffre, F. A1 - Jalili, P. A1 - Meijer, J. A1 - Böhmert, L. A1 - Braeuning, A. A1 - Thünemann, Andreas A1 - Emmerling, Franziska A1 - Fessard, V. A1 - Laux, P. A1 - Lampen, A. A1 - Luch, A. T1 - Characterization of aluminum, aluminum oxide and titanium dioxide nanomaterials using a combination of methods for particle surface and size analysis N2 - The application of appropriate analytical techniques is essential for nanomaterial (NM) characterization. In this study, we compared different analytical techniques for NM analysis. Regarding possible adverse health effects, ionic and particulate NM effects have to be taken into account. As NMs behave quite differently in physiological media, special attention was paid to techniques which are able to determine the biosolubility and complexation behavior of NMs. Representative NMs of similar size were selected: aluminum (Al0) and aluminum oxide (Al2O3), to compare the behavior of metal and metal oxides. In addition, titanium dioxide (TiO2) was investigated. Characterization techniques such as dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA) were evaluated with respect to their suitability for fast characterization of nanoparticle dispersions regarding a particle's hydrodynamic diameter and size distribution. By application of inductively coupled plasma mass spectrometry in the single particle mode (SP-ICP-MS), individual nanoparticles were quantified and characterized regarding their size. SP-ICP-MS measurements were correlated with the information gained using other characterization techniques, i.e. transmission electron microscopy (TEM) and small angle X-ray scattering (SAXS). The particle surface as an important descriptor of NMs was analyzed by X-ray diffraction (XRD). NM impurities and their co-localization with biomolecules were determined by ion beam microscopy (IBM) and confocal Raman microscopy (CRM). We conclude advantages and disadvantages of the different techniques applied and suggest options for their complementation. Thus, this paper may serve as a practical guide to particle characterization techniques. KW - Small-angle X-ray scattering KW - SAXS PY - 2018 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-447057 DO - https://doi.org/10.1039/C8RA00205C SN - 2046-2069 VL - 8 IS - 26 SP - 14377 EP - 14388 PB - The Royal Society of Chemistry AN - OPUS4-44705 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Sieg, H. A1 - Krause, B.-C. A1 - Kästner, Claudia A1 - Böhmert, L. A1 - Lichtenstein, D. A1 - Tentschert, J. A1 - Jungnickel, H. A1 - Laux, P. A1 - Braeuning, A. A1 - Fessard, V. A1 - Thünemann, Andreas A1 - Luch, A. A1 - Lampen, A. T1 - Cellular Effects of In Vitro-Digested Aluminum Nanomaterials on Human Intestinal Cells N2 - Aluminum (Al) can be taken up from food, packaging, or the environment and thus reaches the human gastrointestinal tract. Its toxic potential after oral uptake is still discussed. The fate of different solid and ionic Al species during the passage through the digestive tract is the focus of this research, as well as the cellular effects caused by these different Al species. The present study combines the physicochemical processing of three recently studied Al species (metallic Al0, mineral Al2O3, and soluble AlCl3) in artificial digestion fluids with in vitro cell systems for the human intestinal barrier. Inductively coupled plasma mass spectrometry (ICP-MS) and small-angle X-ray scattering (SAXS) methods were used to characterize the Al species in the artificial digestion fluids and in cell culture medium for proliferating and differentiated intestinal Caco-2 cells. Cytotoxicity testing and cellular impedance measurements were applied to address the effects of digested Al species on cell viability and cell proliferation. Microarray-based transcriptome analyses and quantitative real-time PCR were conducted to obtain a deeper insight into cellular mechanisms of action and generated indications for cellular oxidative stress and an influence on xenobiotic metabolism, connected with alterations in associated signaling pathways. These cellular responses, which were predominantly caused by formerly ionic Al species and only at very high concentrations, were not impacted by artificial digestion. A two-directional conversion of Al between ionic species and solid particles occurred throughout all segments of the gastrointestinal tract, as evidenced by the presence of nanoscaled particles. Nevertheless, this presence did not increase the toxicity of the respective Al species. KW - SAXS KW - Small-angle X-ray scattering KW - Nanoparticle PY - 2020 DO - https://doi.org/10.1021/acsanm.9b02354 VL - 3 IS - 3 SP - 2246 EP - 2256 PB - American Chemical Society AN - OPUS4-50632 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Juling, S. A1 - Böhmert, L. A1 - Lichtenstein, D. A1 - Oberemm, A. A1 - Creutzenberg, O. A1 - Thünemann, Andreas A1 - Braeuning, A. A1 - Lampen, A. T1 - Comparative proteomic analysis of hepatic effects induced by nanosilver, silver ions and nanoparticle coating in rats N2 - The presence of nano-scaled particles in food and food-related products has drawn attention to the oral uptake of nanoparticles and their interactions with biological systems. In the present study, we used a toxicoproteomics approach to allow for the untargeted experimental identification and comparative analysis of cellular Responses in rat liver after repeated-dose treatment with silver nanoparticles, ions, and the coating matrix used for particle stabilization. The proteomic analysis revealed treatment-related effects caused by exposure to silver in particulate and ionic form. Both silver species induced similar patterns of signaling and metabolic alterations. Silver-induced cellular alterations comprised, amongst others, proteins involved in metal homeostasis, oxidative stress response, and energy metabolism. However, we discovered that secondary nano-scaled structures were formed from ionic silver. Furthermore, also the coating matrix alone gave rise to the formation of nano-scaled particles. The present data confirm, complement, and extend previous knowledge on silver toxicity in rodent liver by providing a comprehensive proteomic data set. The observation of secondary particle formation from nonparticle controls underlines the difficulties in separating particle-, ion-, and matrix coating-related effects in biological systems. Awareness of this issue will support proper evaluation of nanotoxicology-related data in the future. KW - Silver nanoparticles KW - Small-angle X-ray scattering KW - SAXS PY - 2018 DO - https://doi.org/10.1016/j.fct.2018.01.056 SN - 0278-6915 SN - 1873-6351 VL - 113 SP - 255 EP - 266 PB - Elsevier AN - OPUS4-44563 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Juling, S. A1 - Niedzwiecka, A. A1 - Böhmert, L. A1 - Lichtenstein, D. A1 - Selve, S. A1 - Braeuning, A. A1 - Thünemann, Andreas A1 - Krause, E. A1 - Lampen, A. T1 - Protein Corona Analysis of Silver Nanoparticles Links to Their Cellular Effects N2 - The breadth of applications of nanoparticles and the access to food-associated consumer products containing nanosized materials lead to oral human exposure to such particles. In biological fluids nanoparticles dynamically interact with biomolecules and form a protein corona. Knowledge about the protein corona is of great interest for understanding the molecular effects of particles as well as their fate inside the human body. We used a mass spectrometry-based toxicoproteomics approach to elucidate mechanisms of toxicity of silver nanoparticles and to comprehensively characterize the protein corona formed around silver nanoparticles in Caco-2 human intestinal epithelial cells. Results were compared with respect to the cellular function of proteins either affected by exposure to nanoparticles or present in the protein corona. A transcriptomic data set was included in the analyses in order to obtain a combined multiomics view of nanoparticle-affected cellular processes. A relationship between corona proteins and the proteomic or transcriptomic responses was revealed, showing that differentially regulated proteins or transcripts were engaged in the same cellular signaling pathways. Protein corona analyses of nanoparticles in cells might therefore help in obtaining information about the molecular consequences of nanoparticle treatment. KW - Silver nanoparticles KW - Protein KW - Small-angle X-ray scattering KW - SAXS PY - 2017 DO - https://doi.org/10.1021/acs.jproteome.7b00412 SN - 1535-3893 SN - 1535-3907 VL - 16 IS - 11 SP - 4020 EP - 4034 PB - Americal Chemical Society AN - OPUS4-42688 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Oberemm, A. A1 - Hansen, Ulf A1 - Böhmert, L. A1 - Meckert, C. A1 - Braeuning, A. A1 - Thünemann, Andreas A1 - Lampen, A. T1 - Proteomic responses of human intestinal Caco-2 cells exposed to silver nanoparticles and ionic silver N2 - Even although quite a number of studies have been performed so far to demonstrate nanoparticle-specific effects of substances in living systems, clear evidence of these effects is still under debate. The present study was designed as a comparative proteomic analysis of human intestinal cells exposed to a commercial silver nanoparticle reference material and ions from AgNO3. A two-dimensional gel electrophoresis/MALDI mass spectrometry (MS)-based proteomic analysis was conducted after 24-h incubation of differentiated Caco-2 cells with non-cytotoxic and low cytotoxic silver concentrations (2.5 and 25 µg ml−1 nanosilver, 0.5 and 5 µg ml−1 AgNO3). Out of an overall number of 316 protein spots differentially expressed at a fold change of ≥ 1.4 or ≤ −1.4 in all treatments, 169 proteins could be identified. In total, 231 spots were specifically deregulated in particle-treated groups compared with 41 spots, which were limited to AgNO3-treatments. Forty-four spots (14 %) were commonly deregulated by both types of treatment. A considerable fraction of the proteins differentially expressed after treatment with nanoparticles is related to protein folding, synthesis or modification of proteins as well as cellular assembly and organization. Overlays of networks obtained for particulate and ionic treatments showed matches, indicating common mechanisms of combined particle and ionic silver exposure and exclusive ionic silver treatment. However, proteomic responses of Caco-2 cells treated with higher concentrations of silver species also showed some differences, for example regarding proteins related to fatty acid and energy metabolism, suggesting an induction of also some different molecular mechanisms for particle exposure and ionic treatment. KW - Nanoparticle KW - Nanosilver KW - Silver PY - 2016 DO - https://doi.org/10.1002/jat.3231 SN - 1099-1263 VL - 36 SP - 404 EP - 413 PB - Wiley CY - Chichester AN - OPUS4-35301 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Voss, L. A1 - Hsiao, I-L. A1 - Ebisch, Maximilian A1 - Vidmar, J. A1 - Dreiack, N. A1 - Böhmert, L. A1 - Stock, V. A1 - Braeuning, A. A1 - Loeschner, K. A1 - Laux, P. A1 - Thünemann, Andreas A1 - Lampen, A. A1 - Sieg, H. T1 - The presence of iron oxide nanoparticles in the food pigment E172 N2 - Iron oxides used as food colorants are listed in the European Union with the number E172. However, there are no specifications concerning the fraction of nanoparticles in these pigments. Here, seven E172 products were thoroughly characterized. Samples of all colors were analyzed with a Broad spectrum of methods to assess their physico-chemical properties. Small-Angle X-ray Scattering (SAXS), Dynamic Light Scattering (DLS), Transmission Electron Microscopy (TEM), zeta-potential, Inductively Coupled Plasma-Mass Spectrometry (ICP-MS), X-ray diffraction (XRD), Brunauer-Emmett-Teller analysis (BET), Asymmetric Flow Field-Flow Fractionation (AF4) and in vitro cell viability measurements were used. Nanoparticles were detected in all E172 samples by TEM or SAXS measurements. Quantitative results from both methods were comparable. Five pigments were evaluated by TEM, of which four had a size median below 100 nm, while SAXS showed a size median below 100 nm for six evaluated pigments. Therefore, consumers May be exposed to iron oxide nanoparticles through the consumption of food pigments. KW - SAXS KW - Small-angle X-ray scattering KW - Nanoparticle PY - 2020 DO - https://doi.org/10.1016/j.foodchem.2020.127000 VL - 327 SP - 127000 PB - Elsevier Ltd. AN - OPUS4-50810 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - GEN A1 - Voss, L. A1 - Saloga, Patrick E. J. A1 - Stock, V. A1 - Böhmert, L. A1 - Braeuning, A. A1 - Thünemann, Andreas A1 - Lampen, A. A1 - Sieg, H. T1 - Correction to "Environmental impact of ZnO nanoparticles evaluated by in vitro simulated digestion" N2 - This is a corrigendum to the original article "Environmental impact of ZnO nanoparticles evaluated by in vitro simulated digestion" that was published in the journal "ACS Applied Nano Materials", vol. 3 (2020), no. 1, pp. 724-733. PY - 2020 DO - https://doi.org/10.1021/acsanm.0c01054 VL - 3 IS - 5 SP - 4914 EP - 4914 PB - American Chemical Society CY - Washington, D.C., USA AN - OPUS4-50812 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Lichtenstein, D. A1 - Meyer, T. A1 - Böhmert, L. A1 - Juling, S. A1 - Fahrenson, C. A1 - Selve, S. A1 - Thünemann, Andreas A1 - Meijer, J. A1 - Estrela-Lopis, I. A1 - Braeuning, A. A1 - Lampen, A. T1 - Dosimetric quantification of coating-related uptake of silver nanoparticles N2 - The elucidation of mechanisms underlying the cellular uptake of nanoparticles (NPs) is an important topic in nanotoxicological research. Most studies dealing with silver NP uptake provide only qualitative data about internalization efficiency and do not consider NP-specific dosimetry. Therefore, we performed a comprehensive comparison of the cellular uptake of differently coated silver NPs of comparable size in different human intestinal Caco-2 cell-derived models to cover also the influence of the intestinal mucus barrier and uptake-specialized M-cells. We used a combination of the Transwell system, transmission electron microscopy, atomic absorption spectroscopy, and ion beam microscopy techniques. The computational in vitro sedimentation, diffusion, and dosimetry (ISDD) model was used to determine the effective dose of the particles in vitro based on their individual physicochemical characteristics. Data indicate that silver NPs with a similar size and shape show coating-dependent differences in their uptake into Caco-2 cells. The internalization of silver NPs was enhanced in uptake-specialized M-cells while the mucus did not provide a substantial barrier for NP internalization. ISDD modeling revealed a fivefold underestimation of dose–response relationships of NPs in in vitro assays. In summary, the present study provides dosimetry-adjusted quantitative data about the influence of NP coating materials in cellular uptake into human intestinal cells. Underestimation of particle effects in vitro might be prevented by using dosimetry models and by considering cell models with greater proximity to the in vivo situation, such as the M-cell model. KW - Silver nanoparticles KW - Small-angle X-ray scattering KW - Saxs PY - 2017 DO - https://doi.org/10.1021/acs.langmuir.7b01851 SN - 0743-7463 VL - 33 IS - 45 SP - 13087 EP - 13097 PB - Americal Chemical Society AN - OPUS4-42875 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER -