organisms. Determined half-maximal inhibitory concentrations (IC 50, PRZ, AZ s) of prochloraz suggested that H. azteca was by a factor of five less sensitive to prochloraz-induced CYP inhibition compared to G. pulex. However, these species sensitivity differences seem to be of minor importance with regard to risk assessment, since assessment factors are applied to account for interspecies variability. x xi Zusammenfassung Zusammenfassung In Gebieten mit vorwiegend landwirtschaftlicher

more »

... g werden häufig Pestizide mit Konzentrationen im ng L -1 bis µg L -1 Bereich in Oberflächengewässern nachgewiesen, die eine Gefahr für aquatische Ökosysteme darstellen. Verschiedene Pestizide, darunter Herbizide, Insektizide und Fungizide, können gemeinsam auftreten, was zu komplexen Mischungen führt. Hierbei können Kombinationswirkungen nicht ausgeschlossen werden. Pestizide können sobald sie in Oberflächengewässer eingetragen sind von aquatischen Organismen aufgenommen werden und dort bioakkumulieren. Die enzymkatalysierte Umwandlung von Chemikalien in Organismen bezeichnet man als Biotransformation. Sie stellt einen Schlüsselprozess dar, der einen grossen Einfluss auf das Bioakkumulationspotential von Chemikalien haben kann, indem er die interne Chemikalienkonzentration reduziert und dadurch die Toxizität beeinflusst. xiii Zusammenfassung xiv 1 Chapter 1 Introduction Chapter 1. 5 Chapter 1 REACH regulation are under discussion. [34][ 5] Models have been developed to predict mixture effects. Concentration Addition (CA) and Independent Action (IA) are the two major concepts to predict mixture toxicity. CA, first formulated by Loewe and Muischnek (1926) 36 , is mainly used for substances with similar modes of action, whereas IA, established by Bliss (1939) 37 , is mainly applied for substances with different modes of action. Both models assume that chemicals do not interact. CA has been shown to be a conservative first tier approach, which can also be used for dissimilar acting chemicals. 34,[38][3 ][40] In addition, IA is dependent on binary response data and predictions on data such as sublethal endpoints (e.g. growth) do not fit the underlying theory. If chemicals in a mixture jointly cause a higher effect than predicted by either of the models, the phenomenon is called synergism. Underlying mechanisms responsible for synergistic interactions are diverse and interactions between chemicals can affect different processes such as bioavailability, uptake, internal transport, biotransformation, binding at the target site, and excretion. 39 However, two reviews reported that only in a small fraction (approximately 5%) of investigated pesticide mixtures, effects were greater than two compared to the model of CA. [39][40] In addition to the complex mixtures composed of single substances present in the environment, every substance can undergo abiotic and biotic biotransformation processes, which further complicates risk assessment. As an example, the EU's Pesticide Directive requires the assessment of major and relevant transformation products of plant protection products before approval. 41 However, further investigations on how to prioritize transformation products with regard to their environmental risk are needed. 42 Aquatic Invertebrates as Test Species: Gammarus pulex and Hyalella azteca Among the order Amphipoda, the family Gammaridae has a widespread distribution across Europe and Asia and lives in freshwater, brackish and marine habitats. The genus Gammarus contains more than 200 described species of which 100 species are only found in freshwater habitats in the Northern Hemisphere. [43][ 4] One of the most diverse amphipod genus found in Switzerland is Gammarus, containing six native and two non-native species. Especially the two native Gammarus species, the Gammaurs fossarum species complex and Gammarus pulex are widely distributed in Switzerland. 45 Gammarus spp. are key organisms in many freshwater ecosystems and as shredders they highly contribute to the detritus processing in streams. Gammarus spp. often represent the dominant species in terms of number and/or biomass and are prey for fish. 46 Due to their high sensitivity towards a wide range of stressors, they are often used as bioindicators and for ecotoxicological testing. 44,[47][4 ] Additionally, their slow growth and relatively large size makes them suitable test species for bioaccumulation studies. [49][ 0][51][52] However, Gammarus spp. is not easily cultured in the lab and organisms need to be collected from the field for testing. The American relative to Gammarus spp. is the amphipod Hyalella azteca out of the family Hyalellidae. They inhabit preferably warm lakes and streams and are found in North and South America. In favored habitats they can reach high densities of >20 000 organisms/m 2 . Bioaccumulation and Bioconcentration Bioaccumulation and bioconcentration describe the processes that lead to higher chemical concentrations inside an organism compared to the surrounding medium. Both processes differ in their uptake routes. Bioconcentration considers the accumulation of waterborne chemicals through non-dietary uptake routes, such as respiratory and dermal surfaces, whereas bioaccumulation also includes uptake via food. For many aquatic organisms, the main uptake route of neutral polar organic micropollutants is from water and bioconcentration is therefore a net result of uptake, distribution, elimination and biotransformation processes. 57, 79 Bioaccumulation factors (BAFs) can be expressed as the ratio of the internal concentration of a chemical in an organism and the concentration in the surrounding medium at steady state: Linking Toxicokinetic Processes to an Effect To exert a detrimental effect, the chemical has to reach the target site via toxicokinetic processes (Figure 1 -2). Toxicodynamics ("what the chemical does to the organism") describes the interaction of a chemical at the target site that leads to an effect. 82, 85 To address differences in species sensitivities towards chemicals, toxicokinetic and toxicodynamic processes need to be considered. Moving from nominal external exposure concentrations to bioavailable external exposure concentrations and finally to internal concentrations has greatly improved the interpretation of toxicological effects. 86