741 research outputs found
Dialogvs Qvi Inter S. T. Danielem Eschervm, Scholæ Latinæ Orphantrophei Inspectorem Fidelissimvm, Beate Ipsis Kal. Decembris MDCCXIX. Defvnctvm, Solemniter Prid. Non. Decembr. Inhvmatvm Et Servatorem Meritissimvm Habitvs Fingitvr Ab Ordinis I. Latini Discipvlis
No full textTrauerschrift auf Daniel Escher, +01.12.1719Autopsie nach Exemplar der ULB Sachsen-AnhaltVorlageform des Erscheinungsvermerks: Halae Magdeb., Litteris Stephani Orbani, Acad. Typogr
Beate Sigriddaughter’s Story of Sigrid
No full textdeath of childNorth VancouverteachingWorld War II1910’sEurop
In vitro bioassay for reactive toxicity towards proteins implemented for water quality monitoring
No full textReactive organic chemicals comprise a large number of compounds with a variety of reactive moieties. While most assays for reactive toxicity focus on DNA damage, reactivity towards proteins can also lead to irreparable damage, but reactivity towards proteins is typically not included in any test battery for water quality assessment. Glutathione (GSH) is a small tripeptide whose cysteine moiety can serve as a model for nucleophilic sites on proteins. GSH is also an important indicator of detoxification processes and the redox status of cells and due to its protective role, depletion of GSH ultimately leads to adverse effects. A bioassay based on genetically modified Escherichia coli strains was used to quantify the specific reactivity towards the protein-like biological nucelophile GSH. The significance of GSH for detoxification was assessed by comparing the growth inhibition induced by reference chemicals or water samples in a GSH-deficient strain to its fully functional parent strain. The GSH deficient strain showed the same sensitivity as the GSH proficient strain to non-reactive and DNA damaging chemicals, but was more sensitive to chemicals that attack cysteine in proteins. The difference in effect concentrations for 50% inhibition of growth assessed as biomass increase (EC50) between the two strains indicates the relevance of GSH conjugation as a detoxification step as well as direct reactivity with cysteine-containing proteins. Seven reference compounds serving as positive and negative controls were investigated. The E. coli strain that lacks GSH was four times more sensitive towards the positive control Sea-Nine, while negative controls benzo[ a] pyrene, 2-aminoanthracene, phenol, t-butylhydroquinone, methyl methane sulfonate and 4-nitroquinoline oxide showed equal effect concentrations in both strains. Water samples collected across an indirect potable reuse scheme representing the complete water cycle from sewage to drinking water in South East Queensland, Australia were used to evaluate the applicability of the E. coli assay for reactive toxicity in water samples. While the EC50 values of the GSH+ strain showed similar trends as in other biological endpoints over the various treatment chains, the specific response indicative of protein damage was only observed in samples that had undergone chlorination as a disinfection process. High natural organic matter or other matrix components disturbed the bioassay so much that we recommend it for future routine testing only in tertiary treated water or drinking water
Application of a reporter gene assay indicative of the oxidative stress response pathway for water quality assessment
No full textBioanalytical Tools in Water Quality Assessment
No full textThe first edition of Bioanalytical Tools in Water Quality Assessment was released in 2012. The field has exploded since and the second edition updates and reviews the application of bioanalytical tools for water quality assessment including surveillance monitoring. The book focuses on applications to water quality assessment ranging from wastewater to drinking water, including recycled water, as well as treatment processes and advanced water treatment. Emerging applications for other environmental matrices are also included. Bioanalytical Tools in Water Quality Assessment, Second Edition, not only demonstrates applications but also fills in the background knowledge in toxicology/ecotoxicology needed to appreciate these applications. Each chapter summarises fundamental material in a targeted way so that information can be applied to better understand the use of bioanalytical tools in water quality assessment. The book can be used by lecturers teaching academic and professional courses and also by risk assessors, regulators, experts, consultants, researchers and managers working in the water sector. It can also be a reference manual for environmental engineers, analytical chemists and toxicologists. Detailed descriptions of dose-response assessment, data reporting, mixture modelling and quality assurance/quality control are complemented by a series of online resources and tools to apply some of the principles and data methods explained in this book. This supplementary information is available at www.ufz.de/bioanalytical-tools
Der Deutsche Kalibrierdienst (DKD): Eine Erfolgsgeschichte geht weiter
No full textPTB-Mitteilungen. Band 129 (2019), Heft 3. ISSN 0030-834XDer Deutsche Kalibrierdienst (DKD): Eine Erfolgsgeschichte geht weiter - Peter Ulbig - 03
Die Fachausschüsse im Deutschen Kalibrierdienst - 09
40 Jahre Deutscher Kalibrierdienst - 15
Begrüßung - Joachim Ullrich - 17
Grußwort - Ole Janssen - 19
Alle Macht den Konstanten - Jens Simon, Imke Frischmuth - 23
Aufbruch in das Kalibrierwesen der Zukunft – von der Forschung in die Praxis - Peter Ulbig - 27
Zusammenarbeit PTB und DAkkS – Erfolgsgarantie für das deutsche Kalibrierwesen - Stephan Finke - 31
Der Beitrag der Kalibration zur digitalen Produktion - Ulrich Kaiser - 37
Grußwort der Deutschen Gesellschaft für Qualität (DGQ) - Beate Kulessa - 41
Die Entwicklung von der Bestätigung als erstes DKD-Kalibrierlabor zur heutigen DAkkS-Akkreditierung - Lioba Stenner - 43
24 Jahre Zusammenarbeit und Wünsche für die Zukunft - Lars Ahrendt - 49
Internationale Spitzenleistungen sind kein Zufall – SPEKTRA sagt Danke - Holger Nicklich - 51
Kalibrieren von Strommessgeräten für DC-Ströme bis 2000 A - Marcus Escher - 54
Referenzsysteme für Messgrößen in der Laboratoriumsmedizin - Gerhard Schumann - 57
Impressionen - 6
Effect-based trigger values for mixtures of chemicals in surface water detected with in vitro bioassays
No full textEffect-based trigger (EBT) values for in vitro bioassays are important for surface water quality monitoring because they define the threshold between acceptable and poor water quality. EBTs have been derived for highly specific bioassays, such as hormone-receptor activation in reporter gene bioassays, by reading across from existing chemical guideline values. This read-across method is not easily applicable to bioassays indicative of adaptive stress responses, which are triggered by many different chemicals, and activation of nuclear receptors for xenobiotic metabolism, to which many chemicals bind with rather low specificity. We propose an alternative approach to define the EBT from the distribution of specificity ratios of all active chemicals. Specificity ratios are the ratio between the predicted baseline toxicity of a chemical in a given bioassay and its measured specific endpoint. Unlike many previous read-across methods to derive EBTs, the proposed method accounts for mixture effects and includes all chemicals, not only high-potency chemicals. The EBTs were derived from a cytotoxicity EBT that was defined as equivalent to 1% of cytotoxicity in a native surface water sample. The cytotoxicity EBT was scaled by the median of the log-normal distribution of specificity ratios to derive the EBT for effects specific for each bioassay. We illustrate the new approach using the example of the AREc32 assay indicative of the oxidative stress response and two nuclear receptor assays targeting the peroxisome proliferator activated receptor PPAR⃞ and the arylhydrocarbon receptor AhR. The EBTs were less conservative than previously proposed but were able to differentiate untreated and insufficiently treated wastewater from wastewater treatment plant effluent with secondary or tertiary treatment and surface water.No Full Tex
Effect-based human biomonitoring of complex chemical mixtures using high-throughput target screening and in vitro bioassays
No full textHuman biomonitoring is a valuable tool for investigating and understanding the human chemical exposome and its association to human health. Current approaches are mainly focusing on a small subset of already well-studied chemicals and neglect the fact that humans are exposed to a diverse set of complex chemical mixtures. This thesis introduced the concept of effect-based human biomonitoring (EB-HBM), which combines chemical exposure assessment, cell-based in vitro bioassays and in silico models to assess the composition and effects of human-relevant complex chemical mixtures. The developed and optimized models and methods were demonstrated with a case study on neurotoxic mixture effects of chemicals extracted from the blood of 624 pregnant women from a German cohort study. Chemical mixtures were extracted by a holistic two-step extraction method. Over 1,000 chemicals in this large number of samples could be analyzed with a new workflow for automated analysis and quantification. Effect drivers were identified by mixture experiments and modeling. The mixture toxicity concept of concentration addition turned out to valid for predicting the effects of the recreated real-life mixtures. The use of high-throughput target screening combined with cell-based bioassays bears great potential to improve human biomonitoring and provide a novel approach to include mixtures in epidemiological studies
Toxic Effects and Exposure of Per- and Polyfluoroalkyl Substances in Cell-based Bioassays
No full textPer- and polyfluoroalkyl substance (PFAS) are man-made chemicals that are widely used in commercial, industrial and military products. PFAS are ubiquitously found in environmental media and organisms including human beings due to their persistence and bioaccumulation potential. Many studies have shown the correlation of PFAS exposure and diseases. There are more than 14,000 PFAS chemicals in the CompTox Chemicals Dashboard but only fraction of them have toxicological information. Cell-based high-throughput screening (HTS) bioassays may inform risk assessment of large numbers of PFAS provided that quantitative in vitro to in vivo extrapolation (QIVIVE) can be developed. Challenges of QIVIVE lie in the predictive accuracy of the bioavailability of PFAS, species difference, as well as the specificity of cellular responses that may lead to potential adverse outcomes.
This thesis aimed to evaluate the toxic effects and exposure of PFAS in cell-based bioassays to facilitate the use of in vitro bioassay data for risk assessment. The first objective was to measure in vitro exposure and determine the binding constants to plasma proteins of different species. The bioavailability of PFAS can be presented as the free concentrations (Cfree) in bioassays and plasma. PFAS bound to proteins and lipids usually result in lower Cfree compared to their nominal (i.e. dosed) concentrations (Cnom). Solid-phase microextraction (SPME) combined with liquid chromatography mass spectrometry (LCMS) was used to measure the Cfree of PFAS among biomaterials, including bioassay media, cell homogenates and blood plasmas. The binding constants were derived from different binding models. Binding isotherms of 16 PFAS with human and trout (fish) plasmas were compared. Anionic PFAS showed higher binding affinities to human plasma in the low concentration ranges compared to the trout plasma, because there were more proteins in human plasma, which led to very strong and specific binding of PFAS with proteins. Partitioning of PFAS to plasma was also predicted correctly by mass balance models (MBMs) that were parameterized with the protein-water and lipid-water binding constants (chemical characteristics) as well as the protein and lipid contents of the plasma (species characteristics). The second objective was to inform risk assessment with a simple form of QIVIVE, which is the ratio of in vivo human plasma concentrations (Cplasma) and in vitro cell-based effect concentrations (EC), either based on nominal or free concentrations. The Cfree can be measured experimentally or predicted by validated MBMs. Cnom,plasma of PFAS were collected from literature and Cfree,plasma were predicted by the MBMs parameterized with plasma binding constants. A cell-based reporter gene assays targeting peroxisome proliferator-activated receptor gamma (PPARγ) was selected to measure the effect concentrations ECnom or ECfree of PFAS, because PPARs have been shown to be specific targets of PFAS. QIVIVEfree ratios, which are the ratios between freely dissolved concentration of PFAS in blood and their ECfree, of some hydrophobic PFAS were up to 1000 times lower than their corresponding QIVIVEnom ratios. This was caused by a strong affinity to proteins and human plasma contained 50 times more proteins than in the bioassay medium, leading highly specific binding at low PFAS concentrations in human plasma, contrasted by nonspecific partitioning to proteins at high concentrations that were required to trigger an effect in bioassays. The proteins and lipids in plasma may act as reservoirs of PFAS in human bodies that pose a risk of chronic exposure. The case study using PPARγ is a demonstration of the importance of using Cfree for the QIVIVE ratios, but for a comprehensive risk assessment, a large set of specific responsive in vitro cell-based bioassays needs to be applied. The third objective was to identify the specific from nonspecific effects among different cell-based HTS bioassays, where baseline toxicity can be a reference. Baseline toxicity is the minimal toxicity that is caused by nonspecific accumulation of chemicals in the cellular membranes. Exceedance of the critical membrane burden leads to cell death. Separate baseline toxicity prediction models were developed for anionic PFAS and neutral chemicals, which were used to define the specificity of cell response of 30 PFAS on six target effects (activation of PPARγ, aryl hydrocarbon receptor, oxidative stress response, and neurotoxicity in own experiments, and literature data for activation of several PPARs and the estrogen receptor). HFPO-DA showed high specificity for PPARs, while the majority of PFAS acted as baseline toxicants. This implicates a heightened need for the risk assessment of PFAS mixtures, because nonspecific effects, i.e., baseline toxicity, behave concentration-additive in mixtures.
In brief, QIVIVE is suggested to consider the bioavailability using Cfree. It will not always be necessary to measure Cfree of PFAS but existing data of plasma concentration and bioassay effect based on Cnom can be converted to Cfree by using MBMs. The differences of plasma binding can be predicted by amounts of proteins and lipids in plasmas, which is influenced by many factors not only between species but also between individuals, and also depends on the concentration range because specific binding at low concentrations is very strong while nonspecific binding at higher concentration has lower binding constants. The baseline toxicity prediction model may be able to re-evaluate the specificity of existing bioassay results, as well as provide a testing strategy in future studies. The identification of high specificity of targets may advance the development of adverse outcome pathways related to single PFAS, which may also be applied for PFAS mixtures. The combined assessment in vitro cellular responses of PFAS and organism exposure levels (e.g. human and fish plasma) can facilitate the comprehensive human and environmental risk assessment of PFAS in the near future
- …
