German Federal Institute for Risk Assessment, Dept. Pesticides Safety, Max-Dohrn-Str. 8-10, 10589 Berlin, Germany.
Technical University of Berlin, Institute for Biochemistry, Straße des 17. Juni 153, 10623 Berlin, Germany.
Food Chem Toxicol. 2018 Feb;112:299-309. doi: 10.1016/j.fct.2017.12.067. Epub 2017 Dec 30.
Pesticide products contain one or more active substances as well as adjuvants, which are added for example as solvents or antioxidants. Nevertheless, only the active substances are evaluated with a comprehensive battery of mammalian toxicity tests. However, in some cases mixture effects of active substances and adjuvants may occur, leading to increased toxicity of the products. To address this issue, we investigated effects of active substances with known hepatotoxicity and two commonly used fungicides: Priori Xtra and Adexar. For this purpose, respective active substances individually and in combination as well as the products were applied to two human hepatoma cell lines (HepaRG and HepG2) in a broad dose range. The results of cytotoxicity analysis, nuclear receptor transactivation (AhR, CAR, PXR), mRNA and protein expression of xenobiotic metabolizing enzymes (CYP1A1, CYP2B6 and CYP3A4) allow the conclusion that active substances and plant protection products differ in terms of their in vitro toxicity. The products activate AhR, while the individual active substances as well as the combination of the active substances have no or only minor effects. The present results support the hypothesis that plant protection products may have a modified toxicity as compared to active substances alone, consequently requiring more comprehensive testing.
农药产品含有一种或多种活性物质以及助剂，例如溶剂或抗氧化剂。然而，只有活性物质才会通过全面的哺乳动物毒性测试进行评估。然而，在某些情况下，活性物质和助剂的混合物可能会产生影响，导致产品毒性增加。为了解决这个问题，我们研究了具有已知肝毒性的活性物质以及两种常用的杀菌剂：Priori Xtra 和 Adexar 的影响。为此，我们分别将相应的活性物质以及单独和组合的产品应用于两种人肝癌细胞系（HepaRG 和 HepG2），剂量范围很广。细胞毒性分析、核受体转录激活（AhR、CAR、PXR）、外源物质代谢酶（CYP1A1、CYP2B6 和 CYP3A4）的 mRNA 和蛋白表达的结果表明，活性物质和植保产品在体外毒性方面存在差异。产品会激活 AhR，而单独的活性物质以及活性物质的组合则没有或只有轻微的影响。目前的结果支持这样一种假设，即与单独的活性物质相比，植保产品的毒性可能会发生变化，因此需要更全面的测试。
