Effects‐directed analysis (EDA) is an important tool for identifying unknown bioactive components in a complex mixture. Such an analysis of endocrine‐active chemicals (EACs) from water sources has promising regulatory implications but also unique logistical challenges. We propose a conceptual EDA (framework) based on a critical review of EDA literature and concentrations of common EACs in waste and surface waters. Required water volumes for identification of EACs under this EDA framework were estimated based on bioassay performance (in vitro and in vivo bioassays), limits of quantification by mass spectrometry (MS), and EAC water concentrations. Sample volumes for EDA across the EACs showed high variation in the bioassay detectors, with genistein, bisphenol A, and androstenedione requiring very high sample volumes and ethinylestradiol and 17β‐trenbolone requiring low sample volumes. Sample volume based on the MS detector was far less variable across the EACs. The EDA framework equation was rearranged to calculate detector “thresholds,” and these thresholds were compared with the literature EAC water concentrations to evaluate the feasibility of the EDA framework. In the majority of instances, feasibility of the EDA was limited by the bioassay, not MS detection. Mixed model analysis showed that the volumes required for a successful EDA were affected by the potentially responsible EAC, detection methods, and the water source type, with detection method having the greatest effect on the EDA of estrogens and androgens. The EDA framework, equation, and model we present provide a valuable tool for designing a successful EDA. Environ Toxicol Chem 2020;39:1309–1324. © 2020 SETAC

中文翻译：

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影响内分泌活性化学物质效果导向分析设计的抽样策略的因素。

效果导向分析（EDA）是识别复杂混合物中未知生物活性成分的重要工具。对来自水源的内分泌活性化学物质（EAC）进行的这种分析具有令人鼓舞的法规含义，但在物流方面也面临着独特的挑战。我们基于对EDA文献以及废水和地表水中常见EAC浓度的严格审查，提出了概念性EDA（框架）。根据生物测定性能（体外和体内生物测定），质谱（MS）的定量限和EAC水浓度，估算了在此EDA框架下鉴定EAC所需的水量。在整个EAC中，EDA的样品量在生物测定检测器中显示出很大的变化，其中染料木黄酮，双酚A，雄烯二酮需要大量样品，乙炔雌二醇和17β-群勃龙需要少量样品。基于MS检测器的样品量在整个EAC中变化很小。重新排列了EDA框架方程以计算检测器的“阈值”，并将这些阈值与文献EAC水浓度进行比较以评估EDA框架的可行性。在大多数情况下，EDA的可行性受到生物测定法（而不是MS检测）的限制。混合模型分析表明，成功进行EDA所需的体积受潜在负责任的EAC，检测方法和水源类型的影响，其中检测方法对雌激素和雄激素的EDA影响最大。EDA框架，公式，2020年《环境毒理学》； 39：1309–1324。©2020 SETAC