Elke Dopp

University Hospital Essen, Essen, North Rhine-Westphalia, Germany

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Publications (70)209.83 Total impact

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    ABSTRACT: Pharmaceuticals and their metabolites enter the hydrological cycle mainly through hospital effluents and private households. They were detected in surface and ground water in concentrations to μg/L and even after the water treatment process in drinking water. To gain biologically and chemically save conditions in aquatic systems, as required by the EU Water Framework Directive, advanced oxidation processes (AOP: ozone, UV/H2O2) are the only conceivable possibility to remove these persistent organic substances from waste water. However, water treatment plants are not designed for the complete mineralization of these substances, so that oxidation by-products occur, whose chemical and toxicological properties are often unknown. Therefore, it is necessary to complement the oxidative processes by toxicological analyses. In this study, different UV-oxidation systems with and without H2O2 were tested to optimize the elimination of pharmaceuticals, and replenished with toxicological investigations of untreated and oxidatively treated samples. The substances carbamazepine, metoprolol, amidotrizoic acid, diclofenac, and sulfamethoxazole were used as lead compounds. They were studied separately and as a substance mixture to investigate combination effects (conc. 100 mg/L). The UV-systems differed in their capacities (1, 250, 1000 L), flow rates (0.03, 1.5, 20 m³/h), UV-outputs (15 W, 80 W or 2 kW, 2x4 kW) and wavelengths (254, 185 & 254, 200-400 nm). Different matrices (waste water, ultrapure water) were used to detect possible matrix effects of real samples. Samples were taken before and after the oxidative treatment and spiked with each substance or the prepared mixture. The degradation rates of the substances were analyzed and quantified using an API 3000 and a Q Trap 3200 with LC-MS/MS. The comparison revealed that higher emission energies and a broad spectrum lower the degradation rate for those substances. The additional use of H2O2 enhanced the degradation significantly, especially in waste water samples where the degradation of stable substances by UV-radiation is limited through interfering substances. To test the samples (system: 0.03 m³/h, 15 W, 254 nm) for cyto- and genotoxicity (MTT Assay, Alkaline Comet Assay) Chinese Hamster Ovary cells were exposed to 10 μg/L of the sample for 24 hours. Generally, samples treated only with UV showed no toxic effects. Toxic results occurred for samples with the substance mixture that were treated with UV+H2O2, indicating that combination effects lead to the formation of toxic by-products. Nevertheless, the most effective system mentioned above might lead to different, non-toxic by-products, and shows that AOP are a promising technique to enhance the pharmaceutical reduction during waste water treatment.
    DBP 2014 (Disinfection by-products in drinking water), Mülheim an der Ruhr, Germany; 10/2014
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    ABSTRACT: In case problematic organic substances, like pharmaceuticals and personal care products, cannot be eliminated during wastewater treatment, they can reach surface waters and harm the environment and have adverse effects on human health already at low concentrations of the substance. The amount of micropollutants in surface waters is steadily growing [1]. Micropollutants occur in surface water samples at concentrations in the pico-, nano- or micromolar range, thus, there is a need of as sensitive biological test systems as possible to detect toxic effects. Different genotoxicity tests are available and have been already implemented, therein the micronucleus assay proposed by the German Umweltbundesamt in 2003 [2] and the umu-test for mutagenicity testing required by the waste water guideline [3]. In this study four genotoxicity tests with different endpoints were compared for their sensitivity to detect effects induced by different chemical substances that are commonly used as positive controls in toxicity tests, and surface water samples (original and concentrated). The Micronucleus assay (MN) was used to measure the potential to induce chromosome aberrations, while the Alkaline Comet Assay detects DNA strand breaks; the p53 Calux® measures the activity of the p53 tumor suppressor gene and the umu-test the activity of the umuC gene. The tested chemicals were N-Ethyl-N-Nitrosourea (ENU), 4-Nitroquinoline 1-oxide (4-NQO), Mitomycin C and 2-Aminoanthracene (2-AA). Neither cyto- nor genotoxic effects of original surface water samples were detected with the tested methods. The study revealed that only the receptor based p53 Calux® was able to detect genotoxic effects in 2.8x and 4x concentrated water samples [4]. Furthermore, in testing the chemical substances the p53 Calux® and umu-test show the lowest detectable effect concentrations (< 0.5 µg/mL) compared to the Comet Assay and the MN. Therefore, we conclude that of the tested systems the p53 Calux® is the most sensitive test to detect effects of micropollutants in surface water samples.
    8th BioDetectors Conference, Torino, Italy; 09/2014
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    ABSTRACT: Arsenic, a common poison, is known to react with sulfide in vivo, forming thioarsenates. The acute toxicity of the inorganic thioarsenates is currently unknown. Our experiments showed that a fourfold sulfide excess reduced acute arsenite cytotoxicity in human hepatocytes (HepG2) and urothelial cells (UROtsa) significantly, but had little effect on arsenate toxicity. Speciation analysis showed immediate formation of thioarsenates (up to 73 % of total arsenic) in case of arsenite, but no speciation changes for arsenate. Testing acute toxicity of mono- and trithioarsenate individually, both thioarsenates were found to be more toxic than their structural analogue arsenate, but less toxic than arsenite. Toxicity increased with the number of thio groups. The amount of cellular arsenic uptake after 24 h corresponded to the order of toxicity of the four compounds tested. The dominant to almost exclusive intracellular arsenic species was arsenite. The results imply that thiolation is a detoxification process for arsenite in sulfidic milieus. The mechanism could either be that thioarsenates regulate the amount of free arsenite available for cellular uptake without entering the cells themselves, or, based on their chemical similarity to arsenate, they could be taken up by similar transporters and reduced rapidly intracellularly to arsenite.
    Environmental Science and Pollution Research 05/2014; 21(17). DOI:10.1007/s11356-014-2950-4 · 2.76 Impact Factor
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    ABSTRACT: Thousands of organic micropollutants and their transformation products occur in water. Although often present at low concentrations, individual compounds contribute to mixture effects. Cell-based bioassays that target health-relevant biological endpoints may therefore complement chemical analysis for water quality assessment. The objective of this study was to evaluate cell-based bioassays for their suitability to benchmark water quality and to assess efficacy of water treatment processes. The selected bioassays cover relevant steps in the toxicity pathways including induction of xenobiotic metabolism, specific and reactive modes of toxic action, activation of adaptive stress response pathways and system responses. Twenty laboratories applied 103 unique in vitro bioassays to a common set of 10 water samples collected in Australia, including wastewater treatment plant effluent, two types of recycled water (reverse osmosis and ozonation/activated carbon filtration), stormwater, surface water, and drinking water. Sixty-five bioassays (63%) showed positive results in at least one sample, typically in wastewater treatment plant effluent, and only five (5%) were positive in the control (ultrapure water). Each water type had a characteristic bioanalytical profile with particular groups of toxicity pathways either consistently responsive or not responsive across test systems. The most responsive health-relevant endpoints were related to xenobiotic metabolism (pregnane X and aryl hydrocarbon receptors), hormone-mediated modes of action (mainly related to the estrogen, glucocorticoid, and antiandrogen activities), reactive modes of action (genotoxicity) and adaptive stress response pathway (oxidative stress response). This study has demonstrated that selected cell-based bioassays are suitable to benchmark water quality and it is recommended to use a purpose-tailored panel of bioassays for routine monitoring.
    Environmental Science & Technology 12/2013; DOI:10.1021/es403899t · 5.48 Impact Factor
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    ABSTRACT: The entry of pharmaceuticals into the water cycle from sewage treatment plants is of growing concern because environmental effects are evident at trace levels. Ozonation, UV- and UV/H2O2-treatment were tested as an additional step in waste water treatment because they have been proven to be effective in eliminating aqueous organic contaminants. The pharmaceuticals carbamazepine, ciprofloxacin, diclofenac, metoprolol and sulfamethoxazole as well as the personal care products galaxolide and tonalide were investigated in terms of degradation efficiency and by-product formation in consideration of toxic effects. The substances were largely removed from treatment plant effluent by ozonation, UV- and UV/H2O2-treatment. Transformation products were detected in all tested treatment processes. Accompanying analysis showed no genotoxic, cytotoxic or estrogenic potential for the investigated compounds after oxidative treatment of real waste waters. The results indicate that by-product formation from ozonation and advanced oxidation processes does not have any negative environmental impact.
    Water Science & Technology 11/2013; 68(9):1976-83. DOI:10.2166/wst.2013.452 · 1.21 Impact Factor
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    ABSTRACT: Natural and synthetic fibres and particles are being introduced into the workplace and environment daily. Comparative analyses of the induced signalling pathways are essential in order to understand the potential hazards of these particles. To identify the molecular characteristics of particles and fibres, we selected crocidolite and chrysotile asbestos as representatives for fibered dust and titanium dioxide (TiO2) (100-200 nm), zirconium dioxide (ZrO2) (50-100 nm) and hematite (Fe2O3) (20 nm) as representatives for bio-persistent granular dust. SV-40 virus-transformed human bronchial epithelial cells (BEAS-2B) were exposed to well-defined fibres and particles. RT2 Profiler™ PCR Array Human Stress & Toxicity PathwayFinder was used to compare the relative mRNA expression of 84 genes. A detailed characterization of the dust samples used in this study was accomplished to ensure comparability to other studies. Investigation of mRNA expression of 84 signalling molecules attributed to pathways such as DNA damage and repair; oxidative/metabolic stress; growth arrest and senescence; inflammation, proliferation and carcinogenesis; and heat shock and apoptosis revealed that crocidolite and chrysotile asbestos induced mRNA expression of pathway molecules involved in proliferation and carcinogenesis, as well as inflammation. Titanium dioxide, zirconium dioxide and hematite mainly induced pathway molecules responsible for oxidative/metabolic stress and inflammation. Our findings suggest that the hazards of fibered dust mainly include the induction of direct toxicity by altering signalling pathways such as carcinogenesis and proliferation, while granular dust shows indirect toxicity by altering signalling pathways involved in inflammatory processes. PCR arrays, therefore, may be a helpful tool to estimate the hazard risk of new materials.
    Molecular Medicine Reports 10/2013; 9(1). DOI:10.3892/mmr.2013.1765 · 1.48 Impact Factor
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    ABSTRACT: The fate in wastewater treatment of gadolinium chelates used in increasing amounts as contrast agents in magnetic resonance imaging recently got into the focus of research. Oxidative processes, in particular the application of ozone, are currently discussed or even implemented for advanced wastewater treatment. However, reactions of the gadolinium chelates with ozone are not yet characterized. In this study, therefore, rate constants with ozone were determined for the three commonly used chelates Gd DTPA, Gd DTPA BMA and Gd BT DO3A, which were 4.8 ± 0.88, 46 ± 2.5 and 24 ± 1.5 M(-1) s(-1), respectively. These low rate constants indicate that a direct reaction with ozone in wastewater is negligible. However, application of ozone in wastewater leads to substantial yields of (•)OH. Different methods have been applied and compared for determination of k(•OH + Gd chelate). From rate constants determined by pulse radiolysis experiments (k((•)OH + Gd DTPA) = 2.6 ± 0.2 × 10(9) M(-1) s(-1), k((•)OH + Gd DTPA BMA) = 1.9 ± 0.7 × 10(9) M(-1) s(-1), k((•)OH + Gd BT DO3A) = 4.3 ± 0.2 × 10(9) M(-1) s(-1)), it is concluded, that a reaction in wastewater via (•)OH radicals is feasible. Toxicity has been tested for the transformation products mixture of both reactions. Cytotoxicity (MTT test) and genotoxicity (micronuclei assay) were not detectable.
    Environmental Science & Technology 07/2013; 47(17). DOI:10.1021/es402219u · 5.48 Impact Factor
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    ABSTRACT: UROtsa is an authentic, immortalized human urothelial cell line that is used to study the effects of metals and other toxic substances, mostly in the context of bladder cancer carcinogenesis. Unusual properties on the molecular level of a provided UROtsa cell line stock prompted us to verify its identity. UROtsa cell line stocks from different sources were tested on several molecular levels and compared with other cell lines. MicroRNA and mRNA expression was determined by Real-Time PCR. Chromosome numbers were checked and PCR of different regions of the large T-antigen was performed. DNA methylation of RARB, PGR, RASSF1, CDH1, FHIT, ESR1, C1QTNF6, PTGS2, SOCS3, MGMT, and LINE1 was analyzed by pyrosequencing and compared with results from the cell lines RT4, T24, HeLa, BEAS-2B, and HepG2. Finally, short tandem repeat (STR) profiling was applied. All tested UROtsa cell line stocks lacked large T-antigen. STR analysis unequivocally identified our main UROtsa stock as the bladder cancer cell line T24, which was different from two authentic UROtsa stocks that served as controls. Analysis of DNA methylation patterns and RNA expression confirmed their differences. Methylation pattern and mRNA expression of the contaminating T24 cell line showed moderate changes even after long-term culture of up to 56 weeks, whereas miRNAs and chromosome numbers varied markedly. It is important to check the identity of cell lines, especially those that are not distributed by major cell banks. However, for some cell lines STR profiles are not available. Therefore, new cell lines should either be submitted to cell banks or at least their STR profile determined and published as part of their initial characterization. Our results should help to improve the identification of UROtsa and other cells on different molecular levels and provide information on the use of urothelial cells for long-term experiments.
    PLoS ONE 01/2013; 8(5):e64139. DOI:10.1371/journal.pone.0064139 · 3.53 Impact Factor
  • PLoS ONE 01/2013; 8:e64139. · 3.53 Impact Factor
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    ABSTRACT: The specific properties of nanoscale particles, large surface-to-mass ratios and highly reactive surfaces, have increased their commercial application in many fields. However, the same properties are also important for the interaction and bioaccumulation of the nonbiodegradable nanoscale particles in a biological system and are a cause for concern. Hematite (α-Fe(2)O(3)), being a mineral form of Fe(III) oxide, is one of the most used iron oxides besides magnetite. The aim of our study was the characterization and comparison of biophysical reactivity and toxicological effects of α-Fe(2)O(3) nano- (d < 100 nm) and microscale (d < 5 μm) particles in human lung cells. Our study demonstrates that the surface reactivity of nanoscale α-Fe(2)O(3) differs from that of microscale particles with respect to the state of agglomeration, radical formation potential, and cellular toxicity. The presence of proteins in culture medium and agglomeration were found to affect the catalytic properties of the hematite nano- and microscale particles. Both the nano- and microscale α-Fe(2)O(3) particles were actively taken up by human lung cells in vitro, although they were not found in the nuclei and mitochondria. Significant genotoxic effects were only found at very high particle concentrations (> 50 μg/ml). The nanoscale particles were slightly more potent in causing cyto- and genotoxicity as compared with their microscale counterparts. Both types of particles induced intracellular generation of reactive oxygen species. This study underlines that α-Fe(2)O(3) nanoscale particles trigger different toxicological reaction pathways than microscale particles. However, the immediate environment of the particles (biomolecules, physiological properties of medium) modulates their toxicity on the basis of agglomeration rather than their actual size.
    Toxicological Sciences 03/2012; 126(1-126(1)):173-82. · 4.48 Impact Factor
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    ABSTRACT: The specific properties of nanoscale particles, large surface-to-mass ratios and highly reactive surfaces, have increased their commercial application in many fields. However, the same properties are also important for the interaction and bioaccumulation of the nonbiodegradable nanoscale particles in a biological system and are a cause for concern. Hematite (α-Fe₂O₃), being a mineral form of Fe(III) oxide, is one of the most used iron oxides besides magnetite. The aim of our study was the characterization and comparison of biophysical reactivity and toxicological effects of α-Fe₂O₃ nano- (d < 100 nm) and microscale (d < 5 μm) particles in human lung cells. Our study demonstrates that the surface reactivity of nanoscale α-Fe₂O₃ differs from that of microscale particles with respect to the state of agglomeration, radical formation potential, and cellular toxicity. The presence of proteins in culture medium and agglomeration were found to affect the catalytic properties of the hematite nano- and microscale particles. Both the nano- and microscale α-Fe₂O₃ particles were actively taken up by human lung cells in vitro, although they were not found in the nuclei and mitochondria. Significant genotoxic effects were only found at very high particle concentrations (> 50 μg/ml). The nanoscale particles were slightly more potent in causing cyto- and genotoxicity as compared with their microscale counterparts. Both types of particles induced intracellular generation of reactive oxygen species. This study underlines that α-Fe₂O₃ nanoscale particles trigger different toxicological reaction pathways than microscale particles. However, the immediate environment of the particles (biomolecules, physiological properties of medium) modulates their toxicity on the basis of agglomeration rather than their actual size.
    Toxicological Sciences 03/2012; 126(1):173-82. DOI:10.1093/toxsci/kfs014 · 4.48 Impact Factor
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    ABSTRACT: Triclosan is an antimicrobial agent widely used in many household and personal care products. Widespread use of this compound has led to the elevated concentrations of triclosan in wastewater, wastewater treatment plants and receiving waters. In this study removal of triclosan by aqueous ozone was investigated and the degradation products formed during ozonation of an aqueous solution of triclosan were analyzed by GC-MS and HPLC-MS/MS. The following transformation products have been identified: 2,4-dichlorophenol, chloro-catecol, mono-hydroxy-triclosan and di-hydroxy-triclosan during treatment process. Cytotoxicity and genotoxicity of pure triclosan and 2,4-dichlorophenol have been investigated and the results showed reduced genotoxic effects after ozonation, though the respective chlorophenol is harmful to aquatic organisms.
    Water Research 02/2012; 46(7):2247-56. DOI:10.1016/j.watres.2012.01.039 · 5.32 Impact Factor
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    Bladder Cancer - From Basic Science to Robotic Surgery, 02/2012; , ISBN: 978-953-307-839-7
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    Journal of Toxicology 01/2012; 2012:358484. DOI:10.1155/2012/358484
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    ABSTRACT: In contrast to the temporary administration of arsenic in cancer therapy (e.g. in the form of arsenic trioxide), chronic exposure to low doses can cause bladder cancer and other cancers. Especially the trivalent arsenic species MMA(III) (monomethylarsonous acid) and DMA(III) (dimethylarsinous acid) are known to be highly toxic. In the present study we analysed the soluble, intracellular biotransformation products of MMA(III) in methylating HepG2 (hepatocytes) and non-methylating UROtsa cells (urothelial cells) after various times of exposure. As most of the intracellulararsenic is bound to cellular structures and proteins the soluble arsenicmetabolites can hardly be speciated and even less quantified. Using an improved isolation procedure and HPLC-ICP/MS, we investigated the time-resolved biotransformation of MMA(III) and detected and quantified MMA(V) (monomethylarsonic acid) as an oxidation product of MMA(III) and, to a minor degree, DMA(V) (dimethylarsenic acid) as a methylation and oxidation product of MMA(III) in the lysates of HepG2 cells. In contrast, only MMA(V) but no DMA(V) was detected in the lysates of UROtsa cells. We conclude from our study that MMA(III) is taken up by HepG2 and UROtsa cells and immediately oxidized to MMA(V). Only in HepG2 cellsMMA(V) is finally methylated to DMA(V) over time. The new method might help to advance the analysis of metabolic pathways of arsenic in mammalian cells.
    Journal of Analytical Atomic Spectrometry 12/2011; 26(12):2396-2403. DOI:10.1039/C1JA10150A · 3.40 Impact Factor
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    ABSTRACT: The reaction of the fragrance compounds 4,6,6,7,8,8-hexamethyl-1,3,4,7-tetrahydrocyclopenta[g]isochromene (HHCB), 1-(3,5,5,6,8,8-hexamethyl-6,7-dihydronaphthalen-2-yl)ethanone (AHTN), 1-tert-butyl-3,5-dimethyl-2,4,6-trinitrobenzene (musk xylene/MX), 1-(4-tert-butyl-2,6-dimethyl-3,5-dinitrophenyl)ethanone (musk ketone/MK), and 1-(2,3,8,8-tetramethyl-1,3,4,5,6,7-hexahydronaphthalen-2-yl)ethanone (OTNE) with ozone in tap water as well as waste water treatment plant (WWTP) effluents is described. Several transformation products are characterized by means of gas chromatography coupled to mass spectrometry. One transformation product (HHCB-Lactone) was confirmed by means of a true standard. Musk xylene and musk ketone do not react with ozone under the conditions used in this study. AHTN and HHCB reacted slowly to a multitude of transformation products, while OTNE reacted quickly to several stable transformation products. The reaction constants and half lives are used to predict removal efficiencies for full scale reactors.
    Chemosphere 09/2011; 85(9):1481-6. DOI:10.1016/j.chemosphere.2011.08.043 · 3.50 Impact Factor
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    ABSTRACT: Copper plumbing materials can be the source of copper ions in drinking water supplies. The aim of the current study was to investigate the influence of copper ions on the viability and cytotoxicity of the potential pathogen Pseudomonas aeruginosa that presents a health hazard when occurring in building plumbing systems. In batch experiments, exposure of P. aeruginosa (10(6)cells/mL) for 24h at 20°C to copper-containing drinking water from domestic plumbing systems resulted in a loss of culturability, while total cell numbers determined microscopically did not decrease. Addition of the chelator diethyldithiocarbamate (DDTC) to copper-containing water prevented the loss of culturability. When suspended in deionized water with added copper sulfate (10 μM), the culturability of P. aeruginosa decreased by more than 6 log units, while total cell counts, the concentration of cells with intact cytoplasmic membranes, determined with the LIVE/DEAD BacLight kit, and the number of cells with intact 16S ribosomal RNA, determined by fluorescent in situ hybridization, remained unchanged. When the chelator DDTC was added to copper-stressed bacteria, complete restoration of culturability was observed to occur within 14 d. Copper-stressed bacteria were not cytotoxic towards Chinese hamster ovary (CHO-9) cells, while untreated and resuscitated bacteria caused an almost complete decrease of the concentration of viable CHO-9 cells within 24 h. Thus, copper ions in concentrations relevant to drinking water in plumbing systems seem to induce a viable but non-culturable (VBNC) state in P. aeruginosa accompanied by a loss of culturability and cytotoxicity, and VBNC cells can regain both culturability and cytotoxicity, when copper stress is abolished.
    International journal of hygiene and environmental health 07/2011; 214(6):485-92. DOI:10.1016/j.ijheh.2011.06.004 · 2.64 Impact Factor
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    ABSTRACT: The biochemical transformation of mercury, tin, arsenic and bismuth through formation of volatile alkylated species performs a fundamental role in determining the environmental processing of these elements. While the toxicity of inorganic forms of most of these compounds are well documented (e.g., arsenic, mercury) and some of them are of relatively low toxicity (e.g., tin, bismuth), the more lipid-soluble organometals can be highly toxic. In the present study we investigated the cyto- and genotoxicity of five volatile metal(loid) compounds: trimethylbismuth, dimethylarsenic iodide, trimethylarsine, tetramethyltin, and dimethylmercury. As far as we know, this is the first study investigating the toxicity of volatile metal(loid) compounds in vitro. Our results showed that dimethylmercury was most toxic to all three used cell lines (CHO-9 cells, CaCo, Hep-G2) followed by dimethylarsenic iodide. Tetramethyltin was the least toxic compound; however, the toxicity was also dependend upon the cell type. Human colon cells (CaCo) were most susceptible to the toxicity of the volatile compounds compared to the other cell lines. We conclude from our study that volatile metal(loid) compounds can be toxic to mammalian cells already at very low concentrations but the toxicity depends upon the metal(loid) species and the exposed cell type.
    Journal of Toxicology 01/2011; 2011:503576. DOI:10.1155/2011/503576
  • Arbeitsmedizin Sozialmedizin Umweltmedizin 01/2011; 46(3):189.

Publication Stats

1k Citations
209.83 Total Impact Points

Institutions

  • 2004–2013
    • University Hospital Essen
      • Institute of Hygiene and Occupational Medicine
      Essen, North Rhine-Westphalia, Germany
  • 2002–2013
    • University of Duisburg-Essen
      • • Group of Instrumental Analytical Chemistry
      • • Biofilm Centre
      Essen, North Rhine-Westphalia, Germany
  • 1995–2002
    • University of Rostock
      Rostock, Mecklenburg-Vorpommern, Germany