Abstract：
With the widespread use of pesticides, the coexistence of multiple low-residue pesticides in environmental media has increased significantly, and the \"cocktail\" effect caused by this phenomenon has garnered increasing attention. However, owing to the scarcity of information regarding the modes of action (MOAs) of chemicals, the application of concentration addition (CA) models for evaluating and predicting the toxicity of mixture with similar MOAs is limited. Additionally, the joint toxicity laws of complex mixture systems to different toxicity endpoints in organisms remain unclear, and effective methods to test the mixture toxicity on lifespan and reproductive inhibition are lacking. Therefore, in this study, the similarity of pesticide MOAs was characterized using molecular electronegativity-distance vector (MEDV-13) descriptors based on eight pesticides (aldicarb, methomyl, imidacloprid, thiamethoxam, dichlorvos, dimethoate, methamidophos and triazophos). Additionally, the methods of lifespan and reproduction inhibition microplate toxicity analysis of elegans (EL-MTA and ER-MTA) were established to test the lifespan and reproduction inhibition toxicity of Caenorhabditis elegans. Finally, a unified scale synergistic-antagonistic heatmap (SAHscale) method was proposed to explore the combined toxicity of the mixtures on the lifespan, reproduction, and mortality of nematodes. The results showed that the MEDV-13 descriptors could effectively characterize the similarity in MOAs. The lifespan and reproductive ability of Caenorhabditis elegans were significantly inhibited when the pesticide exposure concentration was one order of magnitude lower than the lethal dose. The sensitivity of lifespan and reproductive endpoints to mixtures was dependent on the concentration ratio. The same rays in the mixture had consistent toxicity interactions on the lifespan and reproductive endpoints of Caenorhabditis elegans. In conclusion, we demonstrated the feasibility of MEDV-13 in characterizing the similarity of MOAs, and provided a theoretical basis for exploring the mechanism of chemical mixtures by studying their apparent toxicity of mixtures on nematode lifespan and reproduction endpoints.
摘要：
随着农药的广泛使用,环境介质中多种低残留农药的共存明显增加，由这种现象引起的“鸡尾酒”效应引起了越来越多的关注。然而,由于缺乏有关化学品作用方式(MOA)的信息，浓度添加（CA）模型在评估和预测具有相似MOA的混合物的毒性方面的应用受到限制。此外,复杂混合系统对生物体不同毒性终点的联合毒性规律尚不清楚，缺乏有效的方法来测试混合物对寿命和生殖抑制的毒性。因此,在这项研究中，使用基于八种农药（释灭威，灭多威,吡虫啉,噻虫嗪,敌敌畏,乐果,甲胺磷和三唑磷)。此外,建立了线虫寿命和生殖抑制微孔板毒性分析方法（EL-MTA和ER-MTA），以测试秀丽隐杆线虫的寿命和生殖抑制毒性。最后,提出了一种统一的尺度协同拮抗热图（SAHscale）方法来探索混合物对寿命的联合毒性，繁殖，和线虫的死亡率。结果表明，MEDV-13描述符可以有效地表征MOAs中的相似性。当农药暴露浓度比致死剂量低一个数量级时，秀丽隐杆线虫的寿命和生殖能力受到显着抑制。寿命和生殖终点对混合物的敏感性取决于浓度比。混合物中相同的射线对秀丽隐杆线虫的寿命和生殖终点具有一致的毒性相互作用。总之,我们证明了MEDV-13在表征MOAs相似性方面的可行性，并通过研究混合物对线虫寿命和繁殖终点的表观毒性，为探索化学混合物的机理提供了理论依据。
