Atrazine (ATZ) is the second most commonly applied agricultural herbicide in the United States. Due to contamination concerns, the U.S. EPA has set the maximum contaminant level in potable water sources at 3 parts per billion (ppb; μg/l). Depending on the time of year and sampling location, water sources often exceed this limit. ATZ is an endocrine disrupting chemical in multiple species observed to target the neuroendocrine system. In this study the zebrafish vertebrate model was used to test the hypothesis that a developmental ATZ exposure generates metabolites similar to those found in mammals and alters morphology and behavior in developing larvae. Adult AB zebrafish were bred, embryos were collected, and exposed to 0, 0.3, 3, or 30 ppb ATZ from 1 to 120 h post fertilization (hpf). Targeted metabolomic analysis found that zebrafish produce the same major ATZ metabolites as mammals: desethyl atrazine (DEA), deisopropyl atrazine (DIA), and diaminochloroatrazine (DACT). The visual motor response test at 120 hpf detected hyperactivity in larvae in the 0.3 ppb treatment group and hypoactivity in the 30 ppb treatment group (p < 0.05). Further analysis into behavior during the dark and light phases showed zebrafish larvae exposed to 0.3 ppb ATZ had an increase in total distance moved in the first light phase and time spent moving in the first dark and light phases (p < 0.05). Alternatively, a decrease in total distance moved was observed in the second and third dark phases in zebrafish exposed to 30 ppb ATZ (p < 0.05). No significant differences were observed for any of the morphological measurements following ATZ exposure from 1 to 120 hpf (p > 0.05). These findings suggest that a ATZ exposure during early development generates metabolite profiles similar to mammals and leads to behavioral alterations supporting ATZ as a neurodevelopmental toxicant.

阿特拉津 (ATZ) 是美国第二大最常用的农业除草剂。由于污染问题，美国环保署将饮用水源中的最高污染水平设定为十亿分之三（ppb；微克/升）。根据一年中的时间和采样地点，水源通常会超过此限制。ATZ 是一种在多个物种中观察到靶向神经内分泌系统的内分泌干扰化学物质。在这项研究中，斑马鱼脊椎动物模型用于检验发育中的 ATZ 暴露产生类似于哺乳动物中发现的代谢物并改变发育幼虫的形态和行为的假设。饲养成年 AB 斑马鱼，收集胚胎，并在受精后 1 至 120 小时 (hpf) 暴露于 0、0.3、3 或 30 ppb ATZ。靶向代谢组学分析发现，斑马鱼产生与哺乳动物相同的主要 ATZ 代谢物：去乙基阿特拉津 (DEA)、去异丙基阿特拉津 (DIA) 和二氨基氯阿特拉津 (DACT)。120 hpf 的视觉运动反应测试检测到 0.3 ppb 处理组的幼虫活动过度和 30 ppb 处理组的活动减少（p  < 0.05)。对暗相和亮相行为的进一步分析表明，暴露于 0.3 ppb ATZ 的斑马鱼幼虫在第一个亮相阶段移动的总距离和在第一个暗相和亮相阶段移动的时间增加（p  < 0.05）。或者，在暴露于 30 ppb ATZ 的斑马鱼的第二个和第三个黑暗阶段观察到总移动距离减少（p  < 0.05）。ATZ 暴露于 1 至 120 hpf 后的任何形态测量均未观察到显着差异（p  > 0.05）。这些发现表明，在早期发育过程中接触 ATZ 会产生类似于哺乳动物的代谢物谱，并导致支持 ATZ 作为神经发育毒物的行为改变。