Center for Gender-Specific Medicine, Italian National Institute of Health, 00161 Rome, Italy.
Science Department, Università Degli Studi di Roma Tre, Viale Guglielmo Marconi 446, 00146 Rome, Italy.
Int J Environ Res Public Health. 2022 Apr 25;19(9):5202. doi: 10.3390/ijerph19095202.
Humans are daily exposed to multiple residues of pesticides with agricultural workers representing a subpopulation at higher risk. In this context, the cumulative risk assessment of pesticide mixtures is an urgent issue. The present study evaluated, as a case study, the toxicological profiles of thirteen pesticide mixtures used for grapevine protection, including ten active compounds (sulfur, potassium phosphonate, metrafenone, zoxamide, cyflufenamid, quinoxyfen, mancozeb, folpet, penconazole and dimethomorph), at concentrations used on field. A battery of in vitro tests for cell viability and oxidative stress endpoints (cytotoxicity, apoptosis, necrosis, ROS production, mitochondrial membrane potential, gene expression of markers for apoptosis and oxidative stress) was performed on two cellular models representative of main target organs of workers' and population exposure: pulmonary A549 and hepatic HepG2 cell lines. All the endpoints provided evidence for effects also at the lower concentrations used. The overall data were integrated into the ToxPI tool obtaining a toxicity ranking of the mixtures, allowing to prioritize effects also among similarly composed blends. The clustering of the toxicological profiles further provided evidence of common and different modes of action of the mixtures. The approach demonstrated to be suitable for the purpose and it could be applied also in other contexts.
人们每天都会接触到多种农药残留，农业工人是处于更高风险的亚人群之一。在这种情况下，对农药混合物的累积风险评估是一个紧迫的问题。本研究以葡萄保护中使用的十三种农药混合物为例，评估了其毒理学特征，包括十种活性化合物（硫磺、膦酸钾、唑虫酰胺、唑酰草胺、氟吡菌酰胺、喹氧氟草醚、代森锰锌、灭菌丹、丙环唑和烯酰吗啉），使用的浓度为田间实际使用浓度。采用体外细胞活力和氧化应激终点（细胞毒性、细胞凋亡、细胞坏死、ROS 产生、线粒体膜电位、细胞凋亡和氧化应激标志物的基因表达）检测试剂盒，对两种具有代表性的主要靶器官（肺 A549 和肝 HepG2 细胞系）的细胞模型进行了检测。所有终点都在较低的使用浓度下提供了作用证据。将整体数据整合到 ToxPI 工具中，对混合物进行毒性排序，从而能够在类似组成的混合物中也优先考虑作用。毒理学特征的聚类进一步提供了混合物具有共同和不同作用模式的证据。该方法证明适用于该目的，并且可以在其他情况下应用。
