Department of Legal Medicine and Toxicology, School of Medicine, University of Granada, Avenida de la Investigación 11, 18016, Granada, Spain.
Andalulsian School of Public Health, Granada, Spain.
Arch Toxicol. 2017 Oct;91(10):3211-3223. doi: 10.1007/s00204-017-2043-5. Epub 2017 Aug 28.
Pesticides can interact with each other in various ways according to the compound itself and its chemical family, the dose and the targeted organs, leading to various effects. The term interaction means situations where some or all individual components of a mixture influence each other's toxicity and the joint effects may deviate from the additive predictions. The various mixture effects can be greatly determined by toxicokinetic and toxicodynamic factors involving metabolic pathways and cellular or molecular targets of individual pesticides, respectively. However, the complexity of toxicological interactions can lead to unpredictable effects of pesticide mixtures. Interactions on metabolic processes affecting the biotransformation of pesticides seem to be by far the most common mechanism of synergism. Moreover, the identification of pesticides responsible for synergistic interactions is an important issue for cumulative risk assessment. Cholinesterase inhibiting insecticides (organophosphates and N-methylcarbamates), triazole fungicides, triazine herbicides, and pyrethroid insecticides are overrepresented in the synergistic mixtures identified so far. Since the limited available empirical evidence suggests that synergisms at dietary exposure levels are rather rare, and experimentally occurred at unrealistic high concentrations, synergism cannot be predicted quantitatively on the basis of the toxicity of mixture components. The prediction of biological responses elicited by interaction of pesticides with each other (or with other chemicals) will benefit from using a systems toxicology approach. The identification of core features of pesticide mixtures at molecular level, such as gene expression profiles, could be helpful to assess or predict the occurrence of interactive effects giving rise to unpredicted responses.
农药可以根据化合物本身及其化学家族、剂量和靶向器官以各种方式相互作用，导致各种影响。术语“相互作用”是指混合物的某些或全部成分相互影响彼此毒性的情况，并且联合效应可能偏离加性预测。各种混合效应可以很大程度上由涉及个体农药的代谢途径和细胞或分子靶标的毒代动力学和毒效动力学因素决定。然而，毒理学相互作用的复杂性可能导致农药混合物产生不可预测的影响。影响农药生物转化的代谢过程相互作用似乎是迄今为止协同作用最常见的机制。此外，确定导致协同相互作用的农药是累积风险评估的一个重要问题。迄今为止，已确定的协同混合物中胆碱酯酶抑制剂（有机磷和 N-甲基氨基甲酸酯）、三唑类杀菌剂、三嗪类除草剂和拟除虫菊酯类杀虫剂占很大比例。由于有限的经验证据表明，在饮食暴露水平下协同作用相当罕见，并且在不现实的高浓度下实验发生，因此不能根据混合物成分的毒性定量预测协同作用。通过使用系统毒理学方法预测农药之间（或与其他化学物质）相互作用引起的生物学反应将受益。在分子水平上识别农药混合物的核心特征，如基因表达谱，有助于评估或预测引起不可预测反应的相互作用的发生。
