Knauer K, Lampert C, Gonzalez-Valero J
Syngenta Crop Protection AG, Schwarzwaldallee, 4002 Basel, Switzerland.
Chemosphere. 2007 Jul;68(8):1435-41. doi: 10.1016/j.chemosphere.2007.04.009. Epub 2007 May 21.
Acute toxicity to fish hepatoma cell line PLHC-1 and to juvenile rainbow trout was examined for 18 plant protection products. The main objective was to explore whether hepatoma cells could be used to predict acute toxicity in fish taking into account the mode of toxic action and compound properties. Acute fish toxicity was determined using the OECD guideline test 203 and compared to predicted baseline LC50 of acute fish toxicity calculated with a quantitative structure-activity relationship (QSAR) derived for guppy fish. Cytotoxicity was determined through the inhibition of neutral red uptake (NR(50)) into lysosomes and compared to predicted baseline cytotoxicity derived for goldfish GFS cells. In general, NR50 values were higher by a factor ranging from 3 to 3000 than the corresponding acute LC50. A weak correlation between NR50 and LC50 values was found (log/log: r2=0.62). Also the lipophilicity (log K(ow)) was not a good predictor for cytotoxicity (r2=0.43) and lethality (r2=0.57) of these pesticides. The neutral red assay is detecting general baseline toxicity only. Comparing LC50 data to QSAR results, the compounds can be classified to act as narcotics or reactive compounds with a specific mode of toxic action in fish. The results indicate that limitation of the neutral red assay in predicting acute fish toxicity. A promising alternative might be the assessment of toxicity in a set of in vitro systems addressing also cell-specific functions which are related to the mode of toxic action of the compound.
对18种植物保护产品进行了对鱼类肝癌细胞系PLHC - 1和幼年虹鳟鱼的急性毒性检测。主要目的是考虑到毒性作用模式和化合物性质，探讨肝癌细胞是否可用于预测鱼类的急性毒性。使用经合组织准则测试203确定急性鱼类毒性，并将其与通过孔雀鱼定量构效关系（QSAR）计算得出的急性鱼类毒性预测基线LC50进行比较。通过抑制中性红摄取到溶酶体中（NR(50)）来确定细胞毒性，并将其与金鱼GFS细胞的预测基线细胞毒性进行比较。一般来说，NR50值比相应的急性LC50高3至3000倍。发现NR50和LC50值之间存在弱相关性（对数/对数：r2 = 0.62）。这些农药的亲脂性（log K(ow)）也不是细胞毒性（r2 = 0.43）和致死性（r2 = 0.57）的良好预测指标。中性红试验仅检测一般基线毒性。将LC50数据与QSAR结果进行比较，这些化合物可被分类为在鱼类中作为麻醉剂或具有特定毒性作用模式的反应性化合物起作用。结果表明中性红试验在预测急性鱼类毒性方面存在局限性。一个有前景的替代方法可能是在一组体外系统中评估毒性，这些系统还涉及与化合物毒性作用模式相关的细胞特异性功能。
