Until recently pharmaceuticals have systematically escaped the attention of environmental toxicologists. Due to the high volumes of pharmaceuticals used in human and veterinary medicine and animal production considerable amounts of drugs can enter the water cycle through a number of different exposure routes, e.g. disposal of waste water during the production process (industrial route) and more important the excretion in sewage after therapeutic use (domestic route). Several studies have already identified a variety of drugs in waste-, surface- and drinking water in the ng-µg/l range. Dispite of 1) worldwide production and consumption of pharmaceuticals, 2) detection of unneglectable concentrations of pharmaceuticals in the environment and 3) the fact that these substances are specifically designed to be biologically very active there is still very little known about the occurence and effect of pharmaceuticals on non-target organisms. In this study we are evaluating the effects of (neuro)pharmaceuticals in a teleost (zebrafish) as model of aquatic non-target species. The modelchemicals, chosen based on their occurrence in the environment, known effects in non-target organisms and the importance of the effected pathways in fish are: diazepam, chlorpromazin, mianserin and ethynylestradiol. The ultimate aim is to elucidate the toxic working mechanisms of pharmaceuticals and to develop relevant biomarkers for the early detection of chronic effects of these substances in fish. A very important point in this research is the investigation for correlation of effects on the biomarker level and effects on higher levels of biological organization. More specific this aim consists of several aspects: 1) development of highly sensitive and specific LC/MS/MS detection protocols for measurement of environmental concentrations and controling experimental exposures, 2) moleculair toxicological characterization of the modelchemicals. In this part cDNA array hybridizations will be applied to study differential gene expression in brain caused by exposure to the model pharmaceuticals, 3) further characterize the differentially expressed genes and test them as potential biomarkers for neurotoxic effects in fish by forming a concentration/respons relationship, 4) correlate the developed moleculair biomarkers to effects at higher levels of biological organization (growth/reproduction/survival, physiology, behavior). The results generated in this research will lead to a better understanding of the ecotoxicology of neuropharmaceuticals and can lead to the development of specific assays for the detection of neurotoxic effects in fish which enable the environmental risk assessment of these chemicals.
pharmaceutical drugs, toxicogenomics, zebrafish
|De Coen, Wim||promotor|
|De Boeck, Gudrun||co-promotor|
|Ecophysiology, Biochemistry and Toxicology||unknown|
|Toxicity identification and evaluation of neuro-active chemicals for the zebrafish (Danio rerio) (I)||partner|
created:2011-12-14 14:18:59 UTC, source:iweto