Abstract：
Acetochlor is a chloroacetamide herbicide applied to various crops worldwide and is one of the top selling herbicides on the global market. Due to rain events and run-off, the potential for acetochlor-induced toxicity is a concern for aquatic species. Here we review the current state of knowledge regarding the concentrations of acetochlor in aquatic ecosystems globally and synthesize the biological impacts of acetochlor exposure to fish. We compile toxicity effects of acetochlor, outlining evidence for morphological defects, developmental toxicity, endocrine and immune system disruption, cardiotoxicity, oxidative stress, and altered behavior. To identify mechanisms of toxicity, we utilized computational toxicology and molecular docking approaches to uncover putative toxicity pathways. Using the comparative toxicogenomics database (CTD), transcripts responsive to acetochlor were captured and graphically depicted using String-DB. Gene-ontology analysis revealed that acetochlor may disrupt protein synthesis, blood coagulation, signaling pathways, and receptor activity in zebrafish. Further pathway analysis revealed potential novel targets for acetochlor disruption at the molecular level (e.g., TNF alpha, heat shock proteins), highlighting cancer, reproduction, and the immune system as biological processes associated with exposure. Highly interacting proteins in these gene networks (e.g., nuclear receptors) were selected to model binding potential of acetochlor using SWISS-MODEL. The models were used in molecular docking to strengthen evidence for the hypothesis that acetochlor acts as an endocrine disruptor, and results suggest estrogen receptor alpha and thyroid hormone receptor beta may be preferential targets for disruption. Lastly, this comprehensive review reveals that, unlike other herbicides, neither immunotoxicity nor behavioral toxicity have been fully investigated as sub-lethal endpoints for acetochlor, and such mechanisms of toxicity should be emphasized in future research investigating biological responses of fish to the herbicide.
摘要：
乙草胺是一种氯乙酰胺除草剂，适用于全球各种作物，是全球市场上最畅销的除草剂之一。由于降雨事件和径流，乙草胺引起的潜在毒性是水生物种关注的问题。在这里，我们回顾了全球水生生态系统中乙草胺浓度的最新知识，并综合了乙草胺暴露于鱼类的生物学影响。我们汇编了乙草胺的毒性效应，概述形态缺陷的证据，发育毒性，内分泌和免疫系统的破坏，心脏毒性,氧化应激，和改变的行为。为了确定毒性机制，我们利用计算毒理学和分子对接方法来揭示推定的毒性途径.使用比较毒物基因组学数据库(CTD)，捕获响应乙草胺的转录本，并使用String-DB进行图形描绘。基因本体论分析显示乙草胺可能会破坏蛋白质合成，血液凝固，信号通路，和斑马鱼的受体活性。进一步的途径分析揭示了乙草胺在分子水平上破坏的潜在新目标(例如，TNFα，热休克蛋白），突出癌症，繁殖，和免疫系统作为与暴露相关的生物过程。这些基因网络中的高度相互作用的蛋白质(例如，核受体）选择使用SWISS-MODEL模拟乙草胺的结合潜力。这些模型用于分子对接，以加强乙草胺作为内分泌干扰物的假设的证据。结果表明，雌激素受体α和甲状腺激素受体β可能是破坏的优先目标。最后,这份全面的审查表明，与其他除草剂不同，免疫毒性或行为毒性已作为乙草胺的亚致死终点进行了充分研究，在未来研究鱼类对除草剂的生物反应时，应强调这种毒性机制。
