Marlatt Vicki L, Martyniuk Christopher J
Department of Biological Sciences, Simon Fraser University, 8888 University Drive, Burnaby, British Columbia, Canada.
Department of Physiological Sciences and Center for Environmental and Human Toxicology, UF Genetics Institute, College of Veterinary Medicine, University of Florida, Gainesville, FL 326111, USA; Canadian Rivers Institute, Canada.
Comp Biochem Physiol C Toxicol Pharmacol. 2017 Apr;194:9-21. doi: 10.1016/j.cbpc.2017.01.002. Epub 2017 Jan 19.
Urea-based herbicides are applied in agriculture to control broadleaf and grassy weeds, acting to either inhibit photosynthesis at photosystem II (phenylureas) or to inhibit acetolactate synthase acetohydroxyacid synthase (sulfonylureas). While there are different chemical formulas for urea-based herbicides, the phenylureas are a widely used class in North America and have been detected in aquatic environments due to agricultural run-off. Here, we summarize the current state of the literature, synthesizing data on phenylureas and their biological effects in two non-target animals, fish and amphibians, with a primary focus on diuron and linuron. In fish, although the acutely lethal effects of diuron in early life stages appear to be >1mg/L, recent studies measuring sub-lethal behavioural and developmental endpoints suggest that diuron causes adverse effects at lower concentrations (i.e. <0.1mg/L). Considerably less toxicity data exist for amphibians, and this is a knowledge gap in the literature. In terms of sub-lethal effects and mode of action (MOA), linuron is well documented to have anti-androgenic effects in vertebrates, including fish. However, there are other MOAs that are not adequately assessed in toxicology studies. In order to identify additional potential MOAs, we conducted in silico analyses for linuron and diuron that were based upon transcriptome studies and chemical structure-function relationships (i.e. ToxCast™, Prediction of Activity Spectra of Substances). Based upon these analyses, we suggest that steroid biosynthesis, cholesterol metabolism and pregnane X receptor activation are common targets, and offer some new endpoints for future investigations of phenylurea herbicides in non-target animals.
基于尿素的除草剂在农业中用于控制阔叶杂草和禾本科杂草，其作用机制要么是抑制光系统II的光合作用（苯基脲类），要么是抑制乙酰乳酸合酶（乙酰羟酸合酶）（磺酰脲类）。虽然基于尿素的除草剂有不同的化学配方，但苯基脲类在北美是广泛使用的一类，并且由于农业径流已在水生环境中被检测到。在此，我们总结了当前的文献状况，综合了关于苯基脲类及其在两种非靶标动物（鱼类和两栖动物）中的生物学效应的数据，主要关注敌草隆和利谷隆。在鱼类中，虽然敌草隆在幼鱼阶段的急性致死效应似乎大于1mg/L，但最近测量亚致死行为和发育终点的研究表明，敌草隆在较低浓度（即<0.1mg/L）时会产生不利影响。关于两栖动物的毒性数据要少得多，这是文献中的一个知识空白。就亚致死效应和作用模式（MOA）而言，利谷隆在脊椎动物（包括鱼类）中具有抗雄激素作用已得到充分证明。然而，毒理学研究中尚未充分评估其他作用模式。为了确定其他潜在的作用模式，我们基于转录组研究和化学结构-功能关系（即ToxCast™，物质活性谱预测）对敌草隆和利谷隆进行了计算机分析。基于这些分析，我们认为类固醇生物合成、胆固醇代谢和孕烷X受体激活是常见靶点，并为未来在非靶标动物中研究苯基脲类除草剂提供了一些新的终点指标。
