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ABSTRACT: Although researchers have intentionally produced and used nanomaterials for more than a century, nanotechnology has made its mark in most areas of daily life in the past 20 years. Now thousands of products contain nanoparticles, nanofibers, or nanostructured parts. Because some chemical products have caused severe problems to human health and to the environment, we should consider the overall biological and toxicological effects of nanomaterials as we decide whether to use them in various products. We should also reflect on the mechanisms for making these decisions, which may greatly influence the development, production, and use of such products. The preselection of appropriate materials during the early product design state should allow industry and applied researchers to mitigate the risks of these new materials. However, currently the human and ecological risks of the applied nanomaterials during their life cycle are unknown. A large set of physicochemical characteristics can determine the potential human and environmental exposure to and hazards from nanomaterials. Thus, researchers will need many years to gather and analyze all the data to perform a comprehensive risk assessment for engineered nanomaterials and to develop a sound decision making process. The ideal risk assessment approach would include cost-effective screening processes to target resources toward the risks of greatest concern. The outcome of the risk assessment is only as good as the quality of the data used. Unfortunately, the actual review process of most journals that publish on nanotoxicology focuses on "mechanistic studies and results" rather than a toxicologically relevant outcome. For example, journals often do not include studies that show no effect as worthy of publication ("no-effect-studies" dilemma), which can lead to misleading interpretations of toxicological data for hazard identification. However, even with insufficient data sets, researchers can produce a preliminary comparable risk assessment ("approximate" risk assessment). Researchers have already performed risk-based evaluations of nanomaterials grounded on the comparison of exposure concentrations with no-effect levels (as required for chemical risk assessment), examining generic nanomaterials such as "nano-TiO(2)" but not specific forms or modifications. Even though these data sets on hazard and exposure are incomplete, they already provide the basis to illustrate the current state of knowledge and uncertainties. Therefore industry and applied researchers can calculate the probability that an adverse effect might occur and begin to balance the benefits and potential risks of an innovation. Based on the increasing numbers of nanotoxicology publications and funding programs, this Account reviews the decision support approaches that already exist to safely implement engineered nanomaterials during an early phase of innovation.
Accounts of Chemical Research 10/2012; · 21.64 Impact Factor
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ABSTRACT: BACKGROUND: Increasing concern has been expressed regarding the potential adverse health effects that may be associated with human exposure to inhaled multi-walled carbon nanotubes (MWCNTs). Thus it is imperative that an understanding as to the underlying mechanisms and the identification of the key factors involved in adverse effects are gained. In the alveoli, MWCNTs first interact with the pulmonary surfactant. At this interface, proteins and lipids of the pulmonary surfactant bind to MWCNTs, affecting their surface characteristics. Aim of the present study was to investigate if the pre-coating of MWCNTs with pulmonary surfactant has an influence on potential adverse effects, upon both (i) human monocyte derived macrophages (MDM) monocultures, and (ii) a sophisticated in vitro model of the human epithelial airway barrier. Both in vitro systems were exposed to MWCNTs either pre-coated with a porcine pulmonary surfactant (Curosurf) or not. The effect of MWCNTs surface charge was also investigated in terms of amino (NH2) and carboxyl (COOH) surface modifications. RESULTS: Pre-coating of MWCNTs with Curosurf affects their oxidative potential by increasing the reactive oxygen species levels and decreasing intracellular glutathione depletion in MDM as well as decreases the release of Tumour necrosis factor alpha (TNF-alpha). In addition, an induction of apoptosis was observed after exposure to Curosurf pre-coated MWCNTs. In triple cell-co cultures the release of Interleukin-8 (IL-8) was increased after exposure to Curosurf pre-coated MWCNTs. Effects of the MWCNTs functionalizations were minor in both MDM and triple cell co-cultures. CONCLUSIONS: The present study clearly indicates that the pre-coating of MWCNTs with pulmonary surfactant more than the functionalization of the tubes is a key factor in determining their ability to cause oxidative stress, cytokine/chemokine release and apoptosis. Thus the coating of nano-objects with pulmonary surfactant should be considered for future lung in vitro risk assessment studies.
Particle and Fibre Toxicology 05/2012; 9(1):17. · 7.25 Impact Factor
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Environmental Science & Technology 08/2011; · 4.80 Impact Factor
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ABSTRACT: New properties of engineered nanomaterials raise great expectations for industrial, scientific as well as medical applications. At the same time concerns among consumers regarding the safety aspects of this new technology emerge. Furthermore, among the multitude of published studies, a considerable number do not reveal reliable data. Thus, standardized, validated, reliable, robust, reproducible and intelligent testing strategies are urgently needed that address nanomaterial toxicity. This article discusses the reliability of currently used in vitro toxicity assays. It covers major problems, pitfalls and challenges of assay performance and validation. We recommend a series of different controls to improve the experimental quality and, thus, also the reliability and reproducibility of current in vitro systems. These recommendations consequently applied in the future will increase the safe and sustainable use of nanotechnology.
Nanomedicine 07/2011; 6(5):837-47. · 5.05 Impact Factor
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ABSTRACT: The increasing consumption of products containing nanomaterials that can be currently observed and forecasts of new developments and applications fan the fear of individuals and organizations regarding new risks to health. Considering experiences gained from previous technology developments, such fears are not completely unfounded. But are they really justified? And is it justified, moreover, to speak of "nanotoxicology" as a new discipline? This Review seeks to cast light on the phenomena that may occur as nanoobjects interact with cells, tissues, and organisms. Furthermore, we will demonstrate that the many data made available on the biological effects of nanomaterials do not always come from studies that can be considered reliable. We will point out the aspect of reliability with specific examples from the literature and will not address specific (nano)materials. In particular, inadequate methods will be described together with recommendations how to avoid this in the future, thereby contributing to a sustainable improvement of the available data.
Angewandte Chemie International Edition 02/2011; 50(6):1260-78. · 13.45 Impact Factor
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ABSTRACT: The close resemblance of carbon nanotubes to asbestos fibers regarding their high aspect ratio, biopersistence and reactivity increases public concerns on the widespread use of these materials. The purpose of this study was not only to address the acute adverse effects of industrially produced multiwalled carbon nanotubes (MWCNTs) on human lung and immune cells in vitro but also to further understand if their accumulation and biopersistence leads to long-term consequences or induces adaptive changes in these cells. In contrast to asbestos fibers, pristine MWCNTs did not induce overt cell death in A549 lung epithelial cells and Jurkat T lymphocytes after acute exposure to high doses of this material (up to 30 μg/ml). Nevertheless, very high levels of reactive oxygen species (ROS) and decreased metabolic activity were observed which might affect long-term viability of these cells. However, the continuous presence of low amounts of MWCNTs (0.5 μg/ml) for 6 months did not have major adverse long-term effects although large amounts of nanotubes accumulated at least in A549 cells. Moreover, MWCNTs did not appear to induce adaptive mechanisms against particle stress in long-term treated A549 cells. Our study demonstrates that despite the high potential for ROS formation, pristine MWCNTs can accumulate and persist within cells without having major long-term consequences or inducing adaptive mechanisms.
Toxicology Letters 02/2011; 200(3):176-86. · 3.23 Impact Factor
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ABSTRACT: Nanosilver is one nanomaterial that is currently under a lot of scrutiny. Much of the discussion is based on the assumption that nanosilver is something new that has not been seen until recently and that the advances in nanotechnology opened completely new application areas for silver. However, we show in this analysis that nanosilver in the form of colloidal silver has been used for more than 100 years and has been registered as a biocidal material in the United States since 1954. Fifty-three percent of the EPA-registered biocidal silver products likely contain nanosilver. Most of these nanosilver applications are silver-impregnated water filters, algicides, and antimicrobial additives that do not claim to contain nanoparticles. Many human health standards for silver are based on an analysis of argyria occurrence (discoloration of the skin, a cosmetic condition) from the 1930s and include studies that considered nanosilver materials. The environmental standards on the other hand are based on ionic silver and may need to be re-evaluated based on recent findings that most silver in the environment, regardless of the original silver form, is present in the form of small clusters or nanoparticles. The implications of this analysis for policy of nanosilver is that it would be a mistake for regulators to ignore the accumulated knowledge of our scientific and regulatory heritage in a bid to declare nanosilver materials as new chemicals, with unknown properties and automatically harmful simply on the basis of a change in nomenclature to the term "nano".
Environmental Science & Technology 01/2011; · 4.80 Impact Factor
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ABSTRACT: Humans have been exposed to fine and ultrafine particles throughout their history. Since the Industrial Revolution, sources, doses, and types of nanoparticles have changed dramatically. In the last decade, the rapidly developing field of nanotechnology has led to an increase of engineered nanoparticles with novel physical and chemical properties. Regardless of whether this exposure is unintended or not, a careful assessment of possible adverse effects is needed. A large number of projects have been carried out to assess the consequences of combustion-derived or engineered nanoparticle exposure on human health. In recent years there has been a growing concern about the possible health influence of exposure to air pollutants during pregnancy, hence an implicit concern about potential risk for nanoparticle exposure in utero. Previous work has not addressed the question of whether nanoparticles may cross the placenta.
In this study we investigated whether particles can cross the placental barrier and affect the fetus.
We used the ex vivo human placental perfusion model to investigate whether nanoparticles can cross this barrier and whether this process is size dependent. Fluorescently labeled polystyrene beads with diameters of 50, 80, 240, and 500 nm were chosen as model particles.
We showed that fluorescent polystyrene particles with diameter up to 240 nm were taken up by the placenta and were able to cross the placental barrier without affecting the viability of the placental explant.
The findings suggest that nanomaterials have the potential for transplacental transfer and underscore the need for further nanotoxicologic studies on this important organ system.
Environmental Health Perspectives 03/2010; 118(3):432-6. · 7.04 Impact Factor
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ABSTRACT: During production and processing of multi-walled carbon nanotubes (MWCNTs), they may be inhaled and may enter the pulmonary circulation. It is essential that interactions with involved body fluids like the pulmonary surfactant, the blood and others are investigated, particularly as these interactions could lead to coating of the tubes and may affect their chemical and physical characteristics. The aim of this study was to characterize the possible coatings of different functionalized MWCNTs in a cell free environment.
To simulate the first contact in the lung, the tubes were coated with pulmonary surfactant and subsequently bound lipids were characterized. The further coating in the blood circulation was simulated by incubating the tubes in blood plasma. MWCNTs were amino (NH2)- and carboxyl (-COOH)-modified, in order to investigate the influence on the bound lipid and protein patterns. It was shown that surfactant lipids bind unspecifically to different functionalized MWCNTs, in contrast to the blood plasma proteins which showed characteristic binding patterns. Patterns of bound surfactant lipids were altered after a subsequent incubation in blood plasma. In addition, it was found that bound plasma protein patterns were altered when MWCNTs were previously coated with pulmonary surfactant.
A pulmonary surfactant coating and the functionalization of MWCNTs have both the potential to alter the MWCNTs blood plasma protein coating and to determine their properties and behaviour in biological systems.
Journal of Nanobiotechnology 01/2010; 8:31. · 5.09 Impact Factor
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ABSTRACT: This study has evaluated the effects of three industrially relevant multi-walled carbon nanotubes (MWNTs) on human Jurkat T cells and compared them to those of crocidolite asbestos. No overt acute toxicity was observed for all MWNTs tested although signs of oxidative stress were evident. MWNTs did not activate resting Jurkat cells and only slightly stimulated the release of the cytokine interleukin-2 (IL-2) in activated cells. Similar to MWNTs, crocidolite had little toxic effects on Jurkat cells but neither induced the formation of reactive oxygen species nor changes in IL-2 signaling. These findings suggest that, in contrast to many other cell types, T cells are relatively resistant to stress induced by high-aspect ratio particles.
11/2009; 3(4):319-338.
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ABSTRACT: Nanoparticulate materials and, among them, carbon nanotubes (CNTs) are new types of material that are generating high expectations owing to their unique physical, chemical and optical properties. Owing to the predictably increasing production of various types of CNTs and other nanoparticle-containing products, it is expected that environmental and public exposure to engineered nanoparticles will also increase in parallel. If and how far CNTs are able to affect health is, at present, discussed controversially. In this article, we summarize how CNTs are produced and processed to identify critical parameters, which have to be included in the toxicological assessment. A special effort is made to address the adverse effects of CNTs on cell physiology. Furthermore, we report on CNTs in medical applications and we discuss two selected examples of prospective applications of CNTs in nanomedicine, which have realistic chances of achieving ready-to-market products in just a few years.
Nanomedicine 02/2009; 4(1):57-63. · 5.05 Impact Factor
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ABSTRACT: Elevated concentrations of particulate matter in the environmental atmosphere constitute a potential risk to human health. In vitro cell-based assays are therefore necessary to evaluate the toxicological potential of inhaled particulate emissions. In this study, the exposure of a co-culture cell model at the air-liquid interface was used to evaluate the dose-dependent biological effects of a test aerosol. The CULTEX system was used to expose human cells to an environmentally-relevant aerosol, generated from fly ash collected in a commercial municipal waste incinerator and resuspended in filtered air. Human bronchial epithelial cells, BEAS-2B, co-cultured with differentiated THP-1 macrophages growing on Transwell inserts, were employed in the bioassay. Analyses of cell viability, interleukin-8 (IL-8) release, intracellular glutathione, and haeme oxygenase-1 enzyme expression were performed. Transportation of the cells and exposure to humidified filtered air or the test aerosol, at 100 ml/min for 1 to 6 hours, were well tolerated by the cells and had no effect on their viability. Levels of IL-8 release and haeme oxygenase-1 expression were elevated by exposure to fly ash aerosol as a function of time, but not by exposure to clean air. For IL-8 release, a dose-dependent effect was demonstrated with the assumption that the deposited mass of the particles correlated with exposure time. Exposure to the test aerosol did not affect the intracellular glutathione concentration. This in vitro approach simulates particle deposition in the human lung more realistically than does submerged exposure, and it preserves the inherent properties of the particles. It shows promise for use to detect particulate emissions which are potentially detrimental to human health.
Alternatives to laboratory animals: ATLA 08/2008; 36(3):285-98. · 1.58 Impact Factor
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ABSTRACT: Efficient drug delivery is essential for many therapeutic applications. Some cell-penetrating peptides, peptide mimetics, and peptoids express transport function that, however, lack in most cases specific intracellular destination. In this study, carrier-peptoids with either amino or guanidinium side chains, were investigated with regard to their cellular uptake, toxicity, and intracellular localization. Transport specifically to the cytosol or to the nuclei was observed, thus providing a powerful tool for targeted drug delivery.
Journal of Medicinal Chemistry 03/2008; 51(3):376-9. · 5.25 Impact Factor
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ABSTRACT: The aim of this study is to analyse the toxicological potential of fine and ultrafine particles from industrial combustion
processes using a biotest. This biotest is performed by near-realistic exposure of cultivated lung cells at the air-liquid
interface and analysing the biological responses. Important steps in this work are to develop the exposure system for the
use at industrial particle sources, to provide reproducible deposition conditions for submicron particles and to validate
the exposure protocol for the bioassay. The presented technique maintains the viability of the cells but is sensitive for
inflammatory effects. Exposure experiments with the ultrafine fraction of fly ash from a municipal waste incinerator have
shown an increased release of IL-8 as a function of exposure time and dose. The presented exposure method and the lung specific
bioassay seem to be an appropriate model to simulate the inhalation of particulate air pollution and to screen the biological
effects of particulate emissions from different sources.
Keywords: Aerosol, bioassay, PM10, toxicity, ultrafine particles
12/2007: pages 402-414;
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09/2007; , ISBN: 9783527610419
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ABSTRACT: Poly-brominated flame retardants are ecotoxicologically relevant chemicals that can show high persistency in environmental samples and bioaccumulation in marine and fresh water animals. One of the most widely used compound is tetrabromobisphenol A (TBBPA). Until today, the toxicological data are rather fragmentary. Our studies on acute and sub-acute toxic effects with established cell lines demonstrate that TBBPA interferes with cellular signaling pathways. Cell viability is significantly reduced in a time- and concentration-dependent manner. The observed EC50 for rat kidney cells (NRK) was 52 microM (27 mg/l), 168 microM (90 mg/l) for A549 human lung cells, and 200 microM (108 mg/l) for Cal-62 human thyroid cells, respectively. The comparison of TBBPA with the non-brominated substance bisphenol A (BPA) clearly demonstrates that only the brominated compound exerts these effects on proliferation and cell viability. Cell cycle regulation was influenced considerably in Cal-62 cells, showing an explicit G2/M arrest in the cell cycle at TBBPA concentrations higher than 75 microM. Cellular signaling pathways directly connected to these affected parameters, e.g. the mitogen activated protein kinase (MAPK) cascades, are partly influenced in a cell specific and dose dependent manner. The extracellular-signal regulated kinase (ERK) is deactivated in NRK and A549 cells and activated in Cal-62 cells with increasing TBBPA concentrations.
Chemosphere 05/2007; 67(9):S405-11. · 3.21 Impact Factor
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ABSTRACT: The platinum group elements (PGE) Pt, Pd and Rh are increasingly emitted into the environment by automobile catalytic converters. Whereas the biological availability of PGE to plants and animals has been demonstrated, only few studies concentrate on the influence of PGE on a cellular level. The effects of Pt, Pd and Rh compared with Cd, Ni and Cr on cell viability and oxidative stress response using soluble metal salts were studied in the human bronchial epithelial cell line BEAS-2B. Whilst Rh(III) showed little influence, both Pt(II) and Pt(IV) as well as Pd(II) had significant effects on cell viability at levels comparable to Cd(II) and Cr(VI). Arranging metal species in order of increasing toxicity as determined by LC50 yields: Rh(III)=1.2 mmol/L<Ni(II)=0.8 mmol/L<Pt(II)=Pd(II)=0.4 mmol/L<Pt(IV)=0.05 mmol/L<Cr(VI)=0.02 mmol/L<Cd(II)=0.005 mmol/L. ROS induction can be used as a biomarker for oxidative cell stress. The maximum relative increase in ROS production for Pt(IV) (1134%) was more than twice as high as for Cr(VI) (560%), with Pt(II) still resulting in an increase of 238%. These findings underline the strong effects of PGE on cell metabolism and emphasize the need for further studies of their toxic properties.
Environment International 05/2007; 33(3):385-90. · 5.30 Impact Factor
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ABSTRACT: Metal oxides may hold, as nanosized particles, a toxic potential to human health and the environment that is not present in the bulk material. Due to the high surface-to-volume ratio, small amounts can lead to strong oxidative damage within biological systems, impairing cellularfunctions as a consequence of their high surface reactivity. We report here on a new nanosized V203 material that has a needle-like structure with diameters of less than 30 nm and variable lengths. The potentiated toxicity of nanoscale vanadium oxide (V203) compared to bulk material is demonstrated here in human endo- and epithelial lung cells, and might be due to the higher catalytic surface of the particles. Reduction in cell viability is almost ten times stronger and starts with lowest concentrations of "nanoscaled" material (10 microg/mL). Vanadium oxide leads to an induction of heme oxygenase 1 (HO-1) in a dose dependent manner in ECV304 cells whereas a reduction in protein levels can be observed for the epithelial cells (A549). Lipid peroxidation can be observed also for "nanoscaled" vanadium oxide to a much stronger extent in macrophages (RAW cells) than for bulk material. The observed effects can not only be explained by oxidation from V2O3 to V2O5 as there are significant differences between the novel nano vanadium and all used bulk materials (V203 and V205). It appears rather to be a nanoeffect of a high surface reactivity, here coupled with a yet unknown toxicity potentiating effect of a technically important catalyst.
Environmental Science and Technology 02/2007; 41(1):331-6. · 5.23 Impact Factor
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ABSTRACT: Today nanosciences are experiencing massive investment worldwide although research on toxicological aspects of these nano-sized particles has just begun and to date, no clear guidelines exist to quantify the effects. In the present study, we focus on carbon nanotubes (CNTs), which represent one of the most widely investigated carbon nanoparticles. The present data indicate that CNTs are able to cross the cell membrane of rat macrophages (NR8383) and, therefore, might have an influence on cell physiology and function. NR8383 and human A549 lung cells were incubated with commercial single-walled (NT-1) and multi-walled (NT-2, NT-3) CNTs, carbon black and quartz as reference particles as well as an acid-treated single-walled CNT preparation (SWCNT a.t.) with reduced metal catalyst content. We did not observe any acute toxicity on cell viability (WST-1, PI-staining) upon incubation with all CNT products. None of the CNTs induced the inflammatory mediators NO, TNF-alpha and IL-8. A rising tendency of TNF-alpha release from LPS-primed cells due to CNT treatment could be observed. We detected however, a dose- and time-dependent increase of intracellular reactive oxygen species and a decrease of the mitochondrial membrane potential with the commercial CNTs in both cell types after particle treatment whereas incubation with the purified CNTs (SWCNT a.t.) had no effect. This leads us to the conclusion that metal traces associated with the commercial nanotubes are responsible for the biological effects.
Toxicology Letters 02/2007; 168(1):58-74. · 3.23 Impact Factor
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International Aerosol ConferenceInternational Aerosol Conference, St. Paul; 01/2006
