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Mixture effects of two plant protection products in liver cell lines
Food and Chemical Toxicology ( IF 3.9 ) Pub Date : 2017-12-30 , DOI: 10.1016/j.fct.2017.12.067
E. Zahn , J. Wolfrum , C. Knebel , T. Heise , F. Weiß , O. Poetz , P. Marx-Stoelting , S. Rieke

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.



中文翻译:

两种植物保护产品在肝细胞系中的混合作用

农药产品包含一种或多种活性物质以及佐剂,这些佐剂例如作为溶剂或抗氧化剂添加。尽管如此,只有一系列的哺乳动物毒性测试才能对活性物质进行评估。但是,在某些情况下,可能会发生活性物质和佐剂的混合效应,从而导致产品毒性增加。

为了解决这个问题,我们研究了已知的肝毒性和两种常用的杀真菌剂活性物质的影响:先验的Xtra ®和Adexar ®。为此目的,将各自的活性物质单独或组合使用以及将其产物以较宽的剂量范围施用于两种人肝癌细胞系(HepaRG和HepG2)。细胞毒性分析,核受体反式激活(AhR,CAR,PXR),异源生物代谢酶(CYP1A1CYP2B6CYP3A4)的mRNA和蛋白质表达的结果可以得出这样的结论,即活性物质和植物保护产品在体外存在差异毒性。该产品激活AhR,而单独的活性物质以及活性物质的组合则没有或只有很小的作用。

本结果支持以下假设:与单独使用活性物质相比,植物保护产品可能具有改良的毒性,因此需要更全面的测试。

更新日期:2017-12-30
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