Aix Marseille Univ, CNRS, LCE, Marseille, France; INRA, UMR 1331 TOXALIM, Laboratoire de Toxicologie Cellulaire et Moléculaire des Xénobiotiques, BP 167, 400 Route des Chappes, 06903, Sophia Antipolis Cedex, France.
INRA, UMR 1331 TOXALIM, Laboratoire de Toxicologie Cellulaire et Moléculaire des Xénobiotiques, BP 167, 400 Route des Chappes, 06903, Sophia Antipolis Cedex, France.
Chemosphere. 2017 Aug;181:666-674. doi: 10.1016/j.chemosphere.2017.04.116. Epub 2017 Apr 26.
General population exposure to pesticides mainly occurs via food and water consumption. However, their risk assessment for regulatory purposes does not currently consider the actual co-exposure to multiple substances. To address this concern, relevant experimental studies are needed to fill the lack of data concerning effects of mixture on human health. For the first time, the present work evaluated on human microsomes and liver cells the combined metabolic effects of, chlorfenvinphos, ethion and linuron, three pesticides usually found in vegetables of the European Union. Concentrations of these substances were measured during combined incubation experiments, thanks to a new analytical methodology previously developed. The collected data allowed for calculation and comparison of the intrinsic hepatic clearance of each pesticide from different combinations. Finally, the results showed clear inhibitory effects, depending on the association of the chemicals at stake. The major metabolic inhibitor observed was chlorfenvinphos. During co-incubation, it was able to decrease the intrinsic clearance of both linuron and ethion. These latter also showed a potential for metabolic inhibition mainly cytochrome P450-mediated in all cases. Here we demonstrated that human detoxification from a pesticide may be severely hampered in case of co-occurrence of other pesticides, as it is the case for drugs interactions, thus increasing the risk of adverse health effects. These results could contribute to improve the current challenging risk assessment of human and animal dietary to environmental chemical mixtures.
一般人群接触农药主要通过食物和水摄入。然而，目前针对监管目的的风险评估并未考虑到多种物质的实际共同暴露。为了解决这一问题，需要开展相关的实验研究，以填补关于混合物对人类健康影响的数据空白。本研究首次在人肝微粒体和肝细胞中评价了三种通常存在于欧盟蔬菜中的农药（氯芬磷、乙硫磷和利谷隆）联合代谢效应。在前期开发的新分析方法学的帮助下，在联合孵育实验中测量了这些物质的浓度。收集的数据允许计算和比较不同组合中每种农药的固有肝清除率。最后，结果表明存在明显的抑制作用，这取决于所涉及化学物质的组合情况。观察到的主要代谢抑制剂是氯芬磷。在共孵育时，它能够降低利谷隆和乙硫磷的固有清除率。在后两种情况下，在所有情况下都显示出主要由细胞色素 P450 介导的代谢抑制的潜力。在这里，我们证明了在其他农药同时存在的情况下，如药物相互作用，人体从农药中解毒可能会受到严重阻碍，从而增加不良健康影响的风险。这些结果可能有助于改善当前对人类和动物饮食中环境化学混合物的具有挑战性的风险评估。
