Auflistung nach Autor:in "Kühnen, Ute"

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Auf dem Weg zur harmonisierten Bewertung - Literatur Ringtest
(2021) Kühnen, Ute; Konradi, Sabine; von der Ohe, Peter C.; Gräff, Thomas
Environmental Implications of Nanosilver
(2014) Völker, Doris; Hohndorf, Lars; Koch, Wolfgang; Kühnen, Ute; Schlich, Karsten; Hunde-Rinke, Kerstin
Environmental risk assessment of veterinary medicines
(2013) Deutschland. Umweltbundesamt; Kühnen, Ute; Ebert, Ina; Berkner, Silvia; Simon, Markus; Herrchen, Monika; Förster, Bernard; Graf, Nadin; Römbke, Jörg
Environmental effects of veterinary medicines are assessed according to the guidelines of the European Medicines Agency (EMA) and the VICH GL 38 (ECOTOXICITY PHASE II). According to the guideline a terrestrial plant test in phase II is required because residues of pharmaceuticals release with dung and manure from treated animals on agriculture land. The terrestrial plant test is conducted using thestandardisedtest protocol OECD 208 (Seedling Emergence and Seedling Growth Test).
The current regulations take into account only the parent compound and not transformation products and NER (Non Extractable Residues). That might result in incorrect estimation of risk in case of substances applied on agricultural soils with manure. For these substances the German Federal Environmental Agency (UBA) has thus initiated a research project to develop a special terrestrial plant test with a more realistic exposure scenario. In order to evaluate the potential phytotoxicity of transformation products and NER the test substance is applied in manure and stored over a defined period prior to testing. After storing this mixture is tested in a standard terrestrial plant test according to OECD 208. The approach is currently developed with different plant species, different manures and storing periods by two research partners:Fraunhofer IME Schmallenberg and ECT Oekotoxikologie GmbH Flörsheim. The poster presents the regulatory background of this special plant testing approach and first results of the research project.
Quelle: ©Ute Kühnen
Heart rate as an early warning parameter and proxy for subsequent mortality in Danio rerio embryos exposed to ionisable substances
(2022) Schweizer, Mona; Gräff, Thomas; Kühnen, Ute; von der Ohe, Peter C.
Environmental risk assessments of organic chemicals usually do not consider pH as a key factor. Hence, most substances are tested at a single pH only, which may underestimate the toxicity of ionisable substances with a pKa in the range of 4-10. Thus, the ability to consider the pH-dependent toxicity would be crucial for a more realistic assessment. Moreover, there is a tendency in acute toxicity tests to focus on mortality only, while little attention is paid to sublethal endpoints. We used Danio rerio embryos exposed to ten ionisable substances (the acids diclofenac, ibuprofen, naproxen and triclosan and the bases citalopram, fluoxetine, metoprolol, propranolol, tramadol and tetracaine) at four external pH levels, investigating the endpoints mortality (LC50) and heart rate (EC20). Dose-response curves were fitted with an ensemble-model to determine the true uncertainty and variation around the mean endpoints. The ensemble considers eight (heart rate) or twelve (mortality) individual models for binominal and Poisson distributed data, respectively, selected based on the Akaike Information Criterion (AIC). In case of equally good models, the mean endpoint of all models in the ensemble was calculated, resulting in more robust ECx estimates with lower 'standard errors' as compared to randomly selected individual models. We detected a high correlation between mortality (LC50) at 96 hpf and reduced heart rate (EC20) at 48 hpf for all compounds and all external pH levels (r = 0.98). Moreover, the observed pH-dependent effects were strongly associated with log D and thus, likely driven by differences in uptake (toxicokinetic) rather than internal (toxicodynamic) processes. Prospectively, the a priori consideration of pH-dependent effects of ionisable substances might make testing at different pH levels redundant, while the endpoint of mortality might even be replaced by a reliable sublethal proxy that would reduce the exposure, accelerating the evaluation process. © 2021 The Authors
Kombinationswirkungen von Umweltchemikalien am beispiel von Azolen
(2015) Kühnen, Ute; Gildemeister, Daniela
LogD-based modelling and "Delta"logD as a proxy for pH-dependent action of ionizable chemicals reveal the relevance of both neutral and ionic species for fish embryotoxicity and possess great potential for practical application in the regulation of chemicals
(2023) Köhler, Heinz R.; Gräff, Thomas; Schweizer, Mona; Maletzki, Dirk; Kühnen, Ute; von der Ohe, Peter C.
Depending on the ambient pH, ionizable substances are present in varying proportions in their neutral or charged form. The extent to which these two chemical species contribute to the pH-dependant toxicity of ionizable chemicals and whether intracellular ion trapping has a decisive influence in this context is controversially discussed. Against this background, we determined the acute toxicity of 24 ionizable substances at up to 4 different pH values on the embryonic development of the zebrafish, Danio rerio, and supplemented this dataset with additional data from the literature. The LC50 for some substances (diclofenac, propranolol, fluoxetine) differed by a factor of even >103 between pH5 and pH9. To simulate the toxicity of 12 acids and 12 bases, six models to calculate a pH-dependant logD value as a proxy for the uptake of potentially toxic molecules were created based on different premises for the trans-membrane passage and toxic action of neutral and ionic species, and their abilities to explain the real LC50 data set were assessed. Using this approach, we were able to show that both neutral and charged species are almost certainly taken up into cells according to their logD-based distribution, and that both species exert toxicity. Since two of the models that assume all intracellular molecules to be neutral overestimated the real toxicity, it must be concluded, that the toxic effect of a single charged intracellularly present molecule is, on the average, lower than that of a single neutral molecule. Furthermore, it was possible to attribute differences in toxicity at different pH values for these 24 ionizable substances to the respective deltas in logD at these pH levels with high accuracy, enabling particularly a full logD-based model on the basis of logPow as a membrane passage descriptor to be used for predicting potential toxicities in worst-case scenarios from existing experimental studies, as stipulated in the process of registration of chemicals and the definition of Environmental Quality Standards (EQS). © 2023 The Author(s).
Prospective environmental risk assessment of mixtures in wastewater
(2018) Coors, Anja; Vollmar, Pia; Sacher, Frank; Hassold, Enken; Polleichtner, Christian; Gildemeister, Daniela; Kühnen, Ute
The aquatic environment is continually exposed to a complex mixture of chemicals, whereby effluents of wastewater treatment plants (WWTPs) are one key source. The aim of the present study was to investigate whether environmental risk assessments (ERAs) addressing individual substances are sufficiently protective for such coincidental mixtures. Based on a literature review of chemicals reported to occur in municipal WWTP effluents and mode-of-action considerations, four different types of mixtures were composed containing human pharmaceuticals, pesticides, and chemicals regulated under REACH. The experimentally determined chronic aquatic toxicity of these mixtures towards primary producers and the invertebrate Daphnia magna could be adequately predicted by the concept of concentration addition, with up to 5-fold overestimation and less than 3-fold underestimation of mixture toxicity. Effluents of a municipal WWTP had no impact on the predictability of mixture toxicity and showed no adverse effects on the test organisms. Predictive ERAs for the individual mixture components based on here derived predicted no effect concentrations (PNECs) and median measured concentrations in WWTP effluents (MCeff) indicated no unacceptable risk for any of the individual chemicals, while MCeff/PNEC summation indicated a possible risk for multi-component mixtures. However, a refined mixture assessment based on the sum of toxic units at species level indicated no unacceptable risks, and allowed for a safety margin of more than factor 10, not taking into account any dilution of WWTP effluents by surface waters. Individual substances, namely climbazole, fenofibric acid and fluoxetine, were dominating the risks of the investigated mixtures, while added risk due to the mixture was found to be low with the risk quotient being increased by less than factor 2. Yet, uncertainty remains regarding chronic mixture toxicity in fish, which was not included in the present study. The number and identity of substances composing environmental mixtures such as WWTP effluents is typically unknown. Therefore, a mixture assessment factor is discussed as an option for a prospective ERA of mixtures of unknown composition. © 2018 Elsevier Ltd. All rights reserved.
Results of extended plant tests using more realistic exposure scenarios for improving environmental risk assessment of veterinary pharmaceuticals
(2016) Richter, Elisabeth; Berkner, Silvia; Ebert, Ina; Förster, Bernhard; Graf, Nadine; Herrchen, Monika; Kühnen, Ute; Römbke, Jörg; Simon, Markus
Sauer ist nicht immer lustig
(2022) Kühnen, Ute; Gräff, Thomas; Maletzki, Dirk; von der Ohe, Peter C.
The comet assay with standard aquatic test organisms as an alternative test system for environmental risk assessment of human pharmaceuticals
(2022) Jafari, Marwin; Vogt, Maria; Eilebrecht, Elke; Brückner, Jasmin; Kühnen, Ute; Westphal-Settele, Kathi
Umweltrisikobewertung von Human- und Tierarzneimitteln
(2022) Kühnen, Ute