Humans are exposed to pesticide residues through various food products. As these residues can occur in mixtures, there is a need to investigate possible mixture effects on human health. Recent exposure studies revealed the preponderance of imazalil, thiacloprid, and clothianidin in food diets. In this study, we assessed their toxicity alone and in binary mixtures in a 28-day gavage study in female Wistar rats. Five dose levels (up to 350 mg/kg bw/day) ranging from a typical toxicological reference value to a clear effect dose were applied. Data show that the liver was a target organ of all pesticides and their mixtures. Increases in liver weight were observed and histopathological examination revealed centrilobular hepatocellular hypertrophy and cytoplasm degeneration for all treatment conditions. No accumulation of hepatic triglycerides was reported. Tissue residue analysis showed altered pesticide residues in the liver and the kidney when being in mixture as compared to the levels of pesticide residues for the single compound treatment, indicating possible toxicokinetic interactions. Overall, all mixtures appeared to follow the additivity concept, even though quantitative analysis was limited for some endpoints due to the semi-quantitative nature of the data, raising no specific concern for the risk assessment of the examined pesticides.

中文翻译：

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农药咪唑，噻虫啉和噻虫胺的肝毒性-在28天的雌性Wistar大鼠研究中，其个体和混合物效应均如此。

人类通过各种食品暴露于农药残留中。由于这些残留物可能以混合物形式出现，因此有必要研究混合物可能对人体健康的影响。最近的接触研究表明，食物中的咪唑，噻虫啉和可比丁占优势。在这项研究中，我们对雌性Wistar大鼠进行了为期28天的管饲研究，评估了它们单独和在二元混合物中的毒性。从典型的毒理学参考值到明确的效应剂量，采用了五个剂量水平（最高350 mg / kg bw /天）。数据表明，肝脏是所有农药及其混合物的目标器官。观察到肝脏重量增加，并且组织病理学检查显示所有治疗条件下的小叶肝细胞肥大和细胞质变性。没有肝甘油三酸酯的积累的报道。组织残留分析表明，与单一化合物处理的农药残留水平相比，混合时肝脏和肾脏中的农药残留发生了变化，表明可能存在毒代动力学相互作用。总体而言，尽管由于数据的半定量性，某些终点的定量分析受到限制，但所有混合物似乎都遵循可加性概念，因此对所检查农药的风险评估没有特别的关注。