Acute exposure of zebrafish (Danio rerio) larvae to environmental concentrations of selected antidepressants: Bioaccumulation, physiological and histological changes.

Antidepressants have been detected in surface waters worldwide at ng-μg/L concentration. These compounds can exert adverse effects on fish even at low levels. But, all previous analyses have concentrated on adult fish. The aim of the study was to assess the effect of environmental concentrations of sertraline, paroxetine, fluoxetine and mianserin, and their mixtures on such unusual endpoints as physiological and histological changes of zebrafish (Danio rerio) larvae. We also determined the bioconcentration of the pharmaceuticals. Fish Embryo Toxicity test was used to analyze the influence on developmental progression. Histological sections were stained with hematoxylin and eosin. Proliferating cells in liver were determined immunohistochemically by detection of Proliferating Cell Nuclear Antigens. The bioconcentration factor was measured by liquid chromatography coupled to mass spectrometry. Pharmaceuticals were used at low, medium and high concentrations in mixtures and at medium concentration as single compound. Exposure to the analyzed pharmaceuticals increased the rate of abnormal embryo and larvae development, accelerated the hatching time and affected the total hatching rate. Three-times lower proliferation of hepatocytes was observed in larvae exposed to paroxetine, mianserin, sertraline and the mixture of the pharmaceuticals at the highest concentrations. The highest bioaccumulation factor (BCF) was obtained for sertraline. The BCF of the analyzed compounds was higher if the organisms were exposed to the mixtures than to single pharmaceuticals. To conclude, the exposure of zebrafish larvae to selected antidepressants and their mixtures may cause disturbances in the organogenesis of fish even at environmental concentrations.