Due to their widespread use, pharmaceuticals can be metabolized, excreted and ultimately discarded in the environment, thereby affecting aquatic organisms. Lipid-regulating drugs are among the most prescribed medications around the world, controlling human cholesterol levels, in more than 20 million patients. Despite this growing use of lipid-regulating drugs, particularly those whose active metabolite is clofibric acid, the potential toxicological effects of these pharmaceuticals in the environment is not fully characterized. This work intended to characterize the toxicity of an acute (120 hours post-fertilization) and chronic (60 days post-fertilization) exposures to clofibric acid in concentrations of 10.35, 20.7, 41.4, 82.8, and 165.6 μg L^-1 in zebrafish (Danio rerio). The concentrations which were implemented in both exposures were based on predicted environmental concentrations for Portuguese surface waters. The acute effects were analysed focusing on behavioural endpoints (small and large distance travelled, swimming time and total distance travelled), biomarkers of oxidative stress (activity of the enzymes superoxide dismutase, Cu/Zn- and Mn SOD; catalase, CAT; glutathione peroxidase, Se- and total GPx), biotransformation (activity of glutathione S-transferases, GSTs) and lipid peroxidation (thiobarbituric acid reactive substances, TBARS). Chronically exposed individuals were also histologically analysed for sex determination and gonadal developmental stages. In terms of acute exposure, significant alterations were reported, in terms of behavioural alterations (hypoactivity), followed by an overall increase in all tested biomarkers. Chronically exposed organisms did not show alterations in terms of sex ratio and maturation stages, suggesting that clofibric acid did not act as an endocrine disruptor. Moreover, the metabolism of clofibric acid resulted in increased levels of both forms of SOD activity, especially for animals exposed to higher levels of this drug. An increase of CAT activity was observed in fish exposed to low levels, and a decrease in those exposed to higher amounts of clofibric acid. Both GPx forms had their activities increased. The enzyme of biotransformation GSTs were increased at low levels of clofibric acid but inhibited at higher amounts of this substance. Lipid peroxidation levels were also changed, with an induction of this parameter with increasing amounts of clofibric acid. Changes also occurred in behavioural endpoints and patterns for control organisms and for those exposed to clofibric acid were significantly distinct, for all types (light and darkness) of exposure, and for the two analysed endpoints (small and large distance). Results from this assay allow inferring that clofibric acid can have an ecologically relevant impact in living organisms exposed to this substance, with putative effects on the metabolism of individuals, affecting their behaviour and ultimately their survival.

由于其广泛使用，药物可以在环境中代谢，排泄并最终被丢弃，从而影响水生生物。调节血脂的药物是全世界控制2000年患者胆固醇水平最高的处方药之一。尽管越来越多地使用调脂药物，尤其是那些活性代谢产物为氯纤维酸的调脂药物，但这些药物在环境中的潜在毒理作用尚未得到充分表征。这项工作旨在表征急性毒性（120小时后，受精）和慢性（60天后受精）暴露在10.35浓度氯贝酸，20.7，41.4，82.8，和165.6微克大号^-1在斑马鱼（里约热内卢）。两次暴露中实施的浓度均基于葡萄牙地表水的预测环境浓度。分析了急性影响，重点关注行为终点（小距离和大距离旅行，游泳时间和总旅行距离），氧化应激的生物标志物（超氧化物歧化酶，Cu / Zn和Mn SOD酶的活性；过氧化氢酶，CAT；谷胱甘肽过氧化物酶，硒和总GPx），生物转化（谷胱甘肽S-转移酶的活性，GST）和脂质过氧化（硫代巴比妥酸反应性物质，TBARS）。长期暴露的个体也进行了组织学分析，以确定性别和性腺发育阶段。就急性暴露而言，据报道有明显改变，在行为改变（多动）方面，其次是所有测试生物标志物的总体增加。长期暴露的生物体在性别比和成熟阶段方面均未显示出变化，这表明氯纤维酸不充当内分泌干扰物。此外，氯纤维酸的代谢导致两种形式的SOD活性水平升高，特别是对于暴露于该药物水平较高的动物。暴露于低水平鱼中的CAT活性增加，而暴露于较高量的纤维蛋白酸中的CAT活性下降。两种GPx表格的活动都增加了。生物转化GST的酶在低水平的氯纤维酸中会增加，但在该物质的量较高时会被抑制。脂质过氧化水平也发生了变化，随着氯纤维酸含量的增加，该参数也随之升高。对照有机体的行为终点和模式也发生了变化，对于暴露于氯纤酸的生物，所有类型（明暗）的暴露以及两个被分析的终点（小距离和大距离）的行为终点和模式也明显不同。该测定的结果可以推断出，氯纤维酸可以对接触该物质的活生物体产生与生态有关的影响，对个体的新陈代谢具有假定的影响，从而影响其行为并最终影响其生存。