Simon Schwarz

Monitoring Primary Effects of Pharmaceuticals in the Aquatic Environment with Mode of Action-Specific in Vitro Biotests

Environment with Mode of Action-Specific in Vitro Biotests Rita Triebskorn,*,†,‡ Kristin Berg, Ina Ebert, Manfred Frey, Dirk Jungmann, Jörg Oehlmann, Matthias Oetken, Frank Sacher, Marco Scheurer, Hannah Schmieg,† Simon Schwarz,† and Heinz-R. Köhler† †Animal Physiological Ecology, University of Tübingen, Auf der Morgenstelle 5, D-72076 Tübingen, Germany ‡Steinbeis Transfer Center for Ecotoxicology and Ecophysiology, Blumenstr. 13, D-72108 Rottenburg, Germany GWT-Technical University Dresden, Blasewitzer Str. 43, D-01307 Dresden, Germany Federal Environment Agency, Wörlitzer Platz 1, D-06844 Dessau-Roßlau, Germany Steinbeis Innovation Center Cell Culture Technology, Schulzenstr. 4, D-68259 Mannheim, Germany Aquatic Ecotoxicology, University of Frankfurt am Main, Max-von-Laue-Str. 13, D-60438 Frankfurt, Germany DVGW Water Technology Center, Karlsruher Str. 84, D-76139 Karlsruhe, Germany

Impact of the NSAID diclofenac on survival, development, behaviour and health of embryonic and juvenile stages of brown trout, Salmo trutta f. fario

The NSAID diclofenac is controversially discussed with respect to its environmental relevance. Since further information is need to assess whether diclofenac should be included as substance of priority in the EU water framework directive, we investigated the impact of this analgesic on the embryonic development of brown trout (Salmo trutta f. fario) from fertilized egg until the end of sac-fry stage and studied effects in juvenile fish six months post hatch. Embryos were exposed to five test concentrations (0.1, 0.5, 1, 10, 100μg/L) over 127days at 7°C. None of the treatments affected mortality, hatching, development or heart rate. Six months old juveniles exposed to five concentrations (0.1, 1, 10, 100, 200μg/L) over 25days at 7°C, however, showed increased mortality, reaching significance at 100μg/L. Furthermore, a significantly higher proportion of juvenile animals bore injuries at concentrations higher 10μg/L. Neither the levels of the stress protein Hsp70, nor the amount of lipid peroxides was affected by any of the treatments. Histological analyses of gill, liver and kidney revealed visible tissue reactions in fish from all experimental groups. Histological responses in livers of diclofenac-exposed fish outstripped the status of laboratory control fish, particularly when exposed to the two highest concentrations. Chemical analyses of fish muscle tissue revealed concentration-dependent uptake of DCF into the animal, but no relevant bioconcentration. Our study supports earlier findings indicating a lower sensitivity of trout early life stages compared to older individuals, suggesting that studies for risk assessment of diclofenac should predominantly focus on later life stages. Furthermore, fish mortality was found to increase with rising diclofenac concentrations, and the lowest observed effect concentration of 10μg/L on the organismic level emphasises the classification of diclofenac as a micropollutant that requires close attention.

Health effects of metoprolol in epibenthic and endobenthic invertebrates-A basis to validate future in vitro biotests for effect-based biomonitoring

ABSTRACT The aim of this study was to determine the effect data for metoprolol as a model substance for beta-blockers in aquatic invertebrates. The results will be used as a basis for the validation of future mode of action-based in vitro test systems targeting this class of pharmaceuticals. Effects of metoprolol were investigated in two autochthonous species with high relevance in stream ecology: the amphipod Gammarus fossarum and the oligochaete Lumbriculus variegatus. Mortality in G. fossarum was not observed in acute toxicity testing (48 h), and a significant increase of mortality at 45 mg/L was found when amphipods were exposed chronically (40 days). The most sensitive population-relevant endpoints were the juvenile-adult ratio and number of egg-bearing females with NOEC/LOEC-values of 5/15 mg/L. No proteotoxic effects were identified in G. fossarum. The sediment toxicity test with L. variegatus according to the OECD Guideline 225 with an exposure time of 28 days resulted in EC10-values of 92.5 and 126.1 mg/kgdw for the endpoints reproduction and biomass, respectively. In L. variegatus the response kinetics of Hsp70 showed no significant difference between the treatments. A tendency for rising lipid peroxide concentrations was found between 0.03 and 10 mg/kgdw, which were significant between the treatments, but not to the control.

Peregrine falcon egg pollutants

ABSTRACT The role of the peregrine falcon (Falco peregrinus) as a bioindicator for the accumulation of organohalogen compounds and other persistent organic pollutants has been established in field studies. Biometric indices for damage caused by pollutants such as the shell thickness and the shell index were determined and the egg contents were analyzed for various pollutants by gas chromatography/mass spectrometry. A wide range of chemically activated luciferase expression (CALUX®) bioassays were performed on subsamples of the eggs. The following organohalogen compounds were found in the eggs of 2009: dichlorodiphenyltrichloroethane (DDT) and dichlorodiphenyldichloroethane, heptachlor epoxide, hexachlorobenzene, dieldrin, hexachlorocyclohexane, polychlorobiphenyls and polychlorodibenzodioxins and polychlorodibenzofurans, polybromodiphenyl ethers, hexabromocyclododecane, tetrabromobisphenyl A, perfluoro compounds, and mercury. The DDT metabolite, dichlorodiphenyldichloroethene (DDE) (11,800 ng/g dry matter), was found to be the most highly concentrated egg contaminant followed by 2,2′,4,4′,5,5′-hexachlorobiphenyl (3800 ng/g). After a past general drop in pollution level, most egg contaminants presently plateau at levels that may still exceed limit values in foods of animal origin (DDE) or even toxicological thresholds (polychlorobiphenyls + polychlorodibenzodioxins, polybromodiphenyl ethers, perfluorooctanesulfonate, methylmercury). Accumulation of DDE could be shown in peregrine falcon eggs from the uplands of Southwest Germany with elevations up to 1500 m, presumably due to its global distribution and its cold condensation in higher altitudes. In contrast, the concentration of polychlorobiphenyls in falcon eggs decreases with elevation, indicating that these pollutants originate mainly from conurbations and local industrial sites. Significant negative correlations were found between both shell index and thickness and the concentration of Hg. A deleterious effect is also evident from a no-observed-adverse-effect level of 120 ng MeHg per gram egg determined by other authors in chronic feeding studies with ibises, which resulted in decreased egg productivity and male homosexual nesting and courtship behavior. The average Hg concentration in the peregrine falcon eggs from 2009 is almost four times higher than this level. MeHg accounted for 82.5% of the Hg present in the eggs of 2009 and 2010. The cell test DR CALUX® for screening of dioxin-like activities can be used to detect not only the 29 regulated dioxin-like substances but also many other persistent organic pollutants with dioxin-like potencies, such as mixed halogenated dioxins/biphenyls. In our case, the results of bioanalytical screening methods showed no additional effect of other compounds with dioxin-like activity. Ninety-three out of 177 analytes sought could be detected in the eggs. Chlorinated paraffins, organotin compounds, some pesticides that are still in use, and phthalic esters with the exception of traces of diethylhexyl phthalate could be excluded. All pollutants found in the eggs belong to substance classes banned by the Stockholm and Minamata Conventions.

The 2015 Annual Meeting of SETAC German Language Branch in Zurich (7-10 September, 2015): Ecotoxicology and environmental chemistry from: research to application

This report provides a brief review of the 20th annual meeting of the German Language Branch of the Society of Environmental Toxicology and Chemistry (SETAC GLB) held from September 7th to 10th 2015 at ETH (Swiss Technical University) in Zurich, Switzerland. The event was chaired by Inge Werner, Director of the Swiss Centre for Applied Ecotoxicology (Ecotox Centre) Eawag-EPFL, and organized by a team from Ecotox Centre, Eawag, Federal Office of the Environment, Federal Office of Agriculture, and Mesocosm GmbH (Germany). Over 200 delegates from academia, public agencies and private industry of Germany, Switzerland and Austria attended and discussed the current state of science and its application presented in 75 talks and 83 posters. In addition, three invited keynote speakers provided new insights into scientific knowledge ‘brokering’, and—as it was the International Year of Soil—the important role of healthy soil ecosystems. Awards were presented to young scientists for best oral and poster presentations, and for best 2014 master and doctoral theses. Program and abstracts of the meeting (mostly in German) are provided as Additional file 1.

Zwitterionische Imidazolium- und Phosphonium-Derivate der Methylenmeldrumsäure [1,2] / Zwitterionic Imidazolium and Phosphonium Derivatives of Methylene-Meldrum’s Acid [1,2]

2,2-Dimethyl-4,6-dioxo-5-pyridinomethyl-1,3-dioxan-5-yl-pyridinium ylide (9) reacts with 2,3-dihydro- 1,3-diisopropyl-4,5-dimethylimidazol-2-ylidene (1; R1 = iPr, R2 = Me) to give the zwitterionic imidazolium derivative 2,2-dimethyl-4,6-dioxo-5-(1,3-diisopropyl-4,5-dimethylimidazoliomethyl)- 1,3-dioxan-5-yl-imidazolium ylide (4) in good yield. Similarly, the phosphonium compound 2,2-dimethyl-4,6-dioxo-5-triphenylphosphoniomethyl-1,3-dioxan-5-yl-phosphonium ylide (5) is obtained from 9 and PPh3. The crystal structures of 4 and 5 are reported

Zur Reaktion von 2,3-Dihydro-1,3-diisopropy1-4,5-imidazol-2-yliden mit Bromderivaten der Meldrumsäure [1, 2] / On the Reaction of 2,3-Dihydro-1,3-diisopropy1-4,5-dimethylimidazol-2-ylidene with Bromine Derivatives of Meldrum’s Acid [1, 2]

The Imidazolium salts [ImH][MelBr] (7) and [ImBr][MelBr] (8) have been obtained from the carbene Im (5) and the Meldrum’s acid derivatives MelHBr (3) and MelBr2 (4). The crystal structure analyses of 7 and 8 reveal the presence of ion pairs linked by short OH (7: 2.163 Å ) and OBr (8: 2.872 Å ) contacts.