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.

中文翻译：

---

斑马鱼（Danio rerio）幼虫的急性暴露于所选抗抑郁药的环境浓度：生物蓄积，生理和组织学变化。

在全世界地表水中已检测到抗抑郁药，浓度为ng-μg/ L。这些化合物即使含量低也会对鱼类产生不利影响。但是，以前所有的分析都集中在成鱼上。该研究的目的是评估环境浓度舍曲林，帕罗西汀，氟西汀和米安色林及其混合物对斑马鱼（达尼奥里奥）幼虫的生理和组织学变化等异常终点的影响。我们还确定了药物的生物浓度。鱼胚胎毒性试验用于分析对发育进程的影响。组织切片用苏木精和曙红染色。通过检测增殖细胞核抗原以免疫组织化学方法测定肝脏中的增殖细胞。通过液相色谱法和质谱法测量生物浓缩因子。药物以低，中和高浓度混合使用，并以中等浓度作为单一化合物使用。接触分析的药物会增加异常胚胎和幼虫发育的速度，加快孵化时间并影响总孵化率。暴露于帕罗西汀，绵安素，舍曲林和浓度最高的药物混合物中的幼虫，肝细胞的增殖降低了三倍。舍曲林获得了最高的生物蓄积因子（BCF）。如果有机体暴露于混合物中，则所分析化合物的BCF值要高于单一药物。总而言之，