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The demand for potable water increases worldwide while fresh water resources are continuously decreasing. Therefore, procedures and processes for preserving water resources by removing or preventing water pollution become ever more important. Besides pathogens, organic trace pollutants cause major concerns in waste water reclamation schemes like managed aquifer recharge or direct production of potable water. Conventional waste water treatment plants (WWTP) show insufficient removal for micro-pollutants which show adverse effects on the environment in trace concentrations. In this study the removal of micro-pollutants by adsorption to powdered activated carbon and retention by nanofiltration (PAC/NF) was investigated. Therefore two substances, Bisphenol A and ethinyestradiol, were spiked to WWTP effluent which was treated by a PAC/NF pilot plant. The substances were chosen as indicators for moderately non polar and non polar micro-pollutants. With powdered activated carbon dosages of 100 mg/l or 350 mg/l, respectively, 99.9% of Bisphenol A and 99.8% ethinyestradiol were retained by the pilot plant. With respect to the highest concentrations detected in the environment to date, these removal rates lead to concentrations that do not show effects on the environment. These removal rates were primarily achieved by adsorption to powdered carbon. To investigate the adsorption of micro-pollutants from WWTP effluent, further experiments were performed to evaluate the adsorption kinetics and isotherms of ethinyestradiol, Bisphenol A, and additionally of Ciprofloxacin as a charged and polar micro-pollutant. All of them showed slower adsorption kinetics in WWTP effluent compared to adsorption in 5 mM phosphate buffer. Adsorptive capacity was also reduced by the presence of the WWTP effluent. Depending on the physical-chemical proprieties of the adsorbate, different mechanisms lead to reduced adsorptive capacities. Therefore no correlation between polarity and adsorptive capacity was found in WWTP effluent in contrast to adsorption in 5 mM phosphate buffer. Further investigation showed effects of biogenic WWTP effluent compounds like humic substances, proteins or carbohydrates on the adsorption of micropollutants in WWTP effluent. For the WWTP effluent of this study, humic acids and proteins as well as their subunits were identified as major compounds. Substitutes for carbohydrates, humic substances and proteins were selected to evaluate their influence on the adsorption of ethinyestradiol, Bisphenol A, and Ciprofloxacin to powdered activated carbon. Results showed that the influence depends on the physical-chemical properties of the adsorptive. In the presence of the substitutes, the non polar ethinyestradiol displayed a reduction of the adsorptive capacity, while the moderately non polar Bisphenol A as well as the polar and charged Ciprofloxacin showed enhanced adsorption. The results indicate that polar and ionic interactions could be responsible for this influence on the adsorption processes. The conducted experiments lead to the assumption that hydrophobic interactions play an important role in the removal of micro-pollutants from WWTP effluent.

Background Attempts to improve the tolerability of combined oral contraceptives (COCs) have included the substitution of ethinylestradiol (EE) with 17β-estradiol (E2). However, this has proved unsatisfactory, specifically in terms of cycle control. To improve upon the poor cycle control seen previously, E2 [in the form of estradiol valerate (E2V); 1 mg of E2V contains 0.76 mg of E2] was combined with dienogest (DNG) in a novel four-phasic regimen. In the current studies, the ovulation-inhibition potency of four variations of this regimen was assessed. Study Design Two randomized, open-label, Phase II studies were performed. The first study compared two regimens (Regimens 1A and 2A) with similar dosages of DNG but different lengths of application. Having established in Study 1 that the length of application of Regimen 2A was most suitable, but that the dosages of DNG were too low for effective ovulation inhibition, a second study, which compared two regimens (Regimens 2B and 2C) with similar lengths of application but with increased dosages of DNG, was undertaken. The primary efficacy variable in both studies was the proportion of women with a Hoogland score of 5 or 6 during Cycle 2. Results The full analysis set comprised 192 and 203 women in Studies 1 and 2, respectively. In Study 1, 10 women (10.9%) in Regimen 1A and 6 women (6.4%) in Regimen 2A had a Hoogland score of 5 or 6. In Study 2, three women (3.1%) in Regimen 2B and one woman (1.0%) in Regimen 2C had a Hoogland score of 5 or 6. There were no safety concerns with any of the regimens. Conclusion The results of these studies identified a four-phasic COC preparation comprising E2V/DNG that provides efficient ovulation inhibition. It is expected that this regimen will lead to an innovative COC containing E2 instead of EE.

The bile acids filtered through the glomeruli nearly completely escape urinary excretion due to an effecient tubular reabsorption process, which help to conserve bile acids. Reabsorption is mediated by the sodium-dependent bile acid transporter (ASBT) localized in the apical brush border membrane of the proximal tubular cell. The aim of the present study was to assess whether the ASBT-mediated transport of the bile acid taurocholate is regulated by sex hormones or glucocorticoids. In-vitro uptake experiments with freshly isolated proximal tubular cells from female and male sprague-dawley rats and in-vivo clearance experiments were performed using the radioactive bile acid 3H-taurocholate as a substrate. Furthermore, western blot analyse were performed to determine the ASBT-protein amount. The uptake experiments with freshly isolated proximal tubular cells showed a high significant difference of the 3H-taurocholate accumulation ratio of 5.63 +/- 0.28 in male versus 3.68 +/- 0.43 in female animals (p0.05). Western blot analysis could not show a difference of ASBT-protein amount. Thus, we could exclude possible regulation of the ASBT in the proximal tubule.

Zur Untersuchung der Effekte von Nonylphenol und Ethinylestradiol auf die Sukzession von Zooplanktongesellschaften wurden zwei mehrwöchige ökologische Freilandtests in aquatischen Mikrokosmen durchgeführt, die mit Sediment, Wasser und Plankton aus dem Litoralbereich des Ammersees befüllt wurden. Nonylphenol (Konzentrationsbereich: 10 - 120 µg/L) führte ab NOECCommunity -Werten von 19 bis 44 µg/L zu Abundanzabnahmen bei einigen Cladoceren-Arten und den Nauplien-Stadien der Copepoden. Für Ethinylestradiol wurden im getesteten Konzentrationsbereich (40 ng/L - 550 µg/L) keine Effekte auf das Zooplankton beobachtet. Effects of the endocrine disruptors Nonylphenol and Ethinylestradiol on the population dynamics of zooplankton communities were investigated in two longterm outdoor tests with aquatic microcosms, filled with sediment, water and the natural plankton biocenosis of a littoral area of Lake Ammersee. Nonylphenol (conc. 10 - 120 µg/L) caused reduced abundances for some cladocerans and the nauplia-larvae of the copepods. The NOECCommunity varied between 19 and 44 µg/L. Ethinylestradiol was tested in concentrations between 40 ng/L and 550 µg/L and did not cause any effect on the zooplankton.

Der Einfluss endokriner Disruptoren auf die Umwelt wird zunehmend bedeutender. In dieser Arbeit wurden das synthetische Steroid 17alpha-Ethinylestradiol (EE) und das in der pharmazeutischen Veterinärmedizin eingesetzte Trenbolon (TB) als Modellsubstanzen verwendet, um endokrine Effekte eines Östrogens und eines Androgens auf aquatische Biozönosen zu untersuchen. Aquatische Modellökosysteme (Mikrokosmen) sind aufgrund ihrer Heterogenität geeignete Hilfsmittel, um Risiken verschiedener Substanzen für die Umwelt, unter Berücksichtigung verschiedener trophischer Ebenen, abzuschätzen. Um möglichst naturnahe Modellökosysteme zu schaffen, wurden die Mikrokosmen mit Sediment und gefiltertem Wasser einer meso-oligotrophen Litoralstelle des Ammersees befüllt. Nach einer fünfwöchigen Vor-Applikationsphase wurden sechs Mikrokosmen mit EE, bzw. TB in verschiedenen Konzentrationen für sechs, bzw. neun Wochen mittels einer Controlled-Release-Methode dosiert, wodurch ein möglichst realistischer Eintrag in die aquatische Umwelt simuliert werden sollte. Sechs weitere Mikrokosmen dienten als Kontrollen. In der folgenden Post-Applikationsphase wurden die Mikrokosmen weitere 12, bzw. sechs Wochen beobachtet. Unter Berücksichtigung funktioneller und struktureller Parameter, sowie inter- und intraspezifischer Wechselwirkungen im Nahrungsnetz und nach Auswertung der Zooplanktondaten mittels uni- und multivariater statistischer Methoden, konnten EE und TB induzierte Effekte auf die Zooplanktongesellschaften aquatischer Modellökosysteme gezeigt werden. Um Aussagen zur Wirkungsweise von Substanzen auf Spezies- oder Populationsebene machen zu können ist ebenso die Kenntnis hormonell gesteuerter Prozesse auf molekularer Ebene zwingend notwendig. Folglich wurden Methoden zur Katecholaminanalytik eingesetzt, um so die Möglichkeit zur Etablierung neuer Testansätze und Definition neuer Biomarker für die Ökotoxikologie zu schaffen. In ersten Versuchen mit Danio rerio als Testspezies, konnten stressinduzierte Veränderungen des Katecholaminspiegels festgestellt werden. The influence of endocrine disruptors in the environment becomes more and more important. In this study the synthetic steroid 17alpha-ethinylestradiol (EE) and the veterinary pharmaceutical trenbolone (TB) were used as model substances to observe the endocrine effects of an estrogen and androgen on aquatic biocenosis. Aquatic model ecosystems (microcosms) are due to their heterogeneity suitable tools to assess the risks of substances for the environment considering different trophic levels. To get model ecosystems as close to nature as possible the microcosms were filled with sediment and filtrated water from an meso-oligotrophic litoral area of lake Ammersee. After a pre-application-phase of fife weeks six microcosms were dosed with EE, resp. TB in different concentrations for six, resp. nine weeks using a controlled released method to simulate the entry to the aquatic environment close to reality. Six microcosms served as untreated controls. In the following recovery-phase the microcosms were observed for another 12, resp. six weeks. Considering functional and structural parameters as well as interactions in the food web and calculating zooplankton data by uni- and multivariate statistical methods effects of EE and TB on the zooplankton community of aquatic model ecosystems could be shown. To make statements to the impact of substances on species or population level the knowledge of hormonal regulated processes on molecular level is necessary. Therefore methods of chemical analysis of catecholamines were used to create the possibility for the establishment of new test beginnings and definition of new biomarkers for ecotoxicology. In first tests with Danio rerio, stress-induced changes of the catecholamine level could be determined.

Die endokrine Wirksamkeit von 17a-Ethinylestradiol auf Zebrabärblinge wurde in einer Multigenerationsstudie im Konzentrationsbereich zwischen 10 und 0,05 ng/L untersucht.Zur Kontrolle dieser geringen Analytkonzentrationen wurde eine Analysenmethode erarbeitet, deren Bestimmungsgrenze bei 0,05 ng/L liegt. Die Extraktion wurde mit EMPORE disks vorgenommen. Anschließend erfolgte die Bestimmung des 17alpha-Ethinylestradiols nach Silylierung mit MSTFA mittels GC/MS/MS.