Dioxin‐like compounds (DLCs) cause early life stage mortality of vertebrates through activation of the aryl hydrocarbon receptor (AhR). A prior study developed a cross‐species quantitative adverse outcome pathway (qAOP) which can predict full dose–response curves of early life stage mortality for any species of bird or fish exposed to DLCs using the species‐ and chemical‐specific 50% effect concentration (EC50) from an in vitro AhR transactivation assay with COS‐7 cells. However, calculating a reliable EC50 for input into this qAOP requires the maximal response of the concentration–response curve to be known, which is not always possible for low‐potency agonists, such as some polychlorinated biphenyls (PCBs). To enable predictions for these low‐potency agonists, the present study revised this qAOP to use the effect concentration threshold (EC_Threshold) from the in vitro AhR transactivation assay as input. Significant linear relationships were demonstrated between EC_Threshold and the dose to cause 0, 10, 50, or 100% mortality among early life stages of 3 species of birds and 7 species of fish for 4 DLCs: 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin, PCB 126, PCB 77, and PCB 105. These 4 linear relationships were combined to form the revised qAOP. This qAOP using the EC_Threshold enables prediction of experimental dose–response curves for lower‐potency agonists to within an order of magnitude on average, but the prior qAOP using EC50 predicts experimental dose–response curves for higher‐potency agonists with greater accuracy. Environ Toxicol Chem 2020;39:2055–2064. © 2020 SETAC

中文翻译：

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从暴露于芳烃受体的低效激动剂中预测鸟类和鱼类的生命早期死亡率：一种跨物种定量不良结果途径方法。

类二恶英化合物（DLC）通过激活芳烃受体（AhR）导致脊椎动物的早期生命死亡。先前的研究开发了跨物种定量不良结局途径（qAOP），可以使用物种和化学特异的50％效应浓度预测暴露于DLC的任何鸟类或鱼类的生命早期死亡率的全剂量反应曲线（EC50）来自使用COS-7细胞进行的体外AhR反式激活分析。然而，要计算出可靠的EC50作为输入到该qAOP中的浓度，就需要知道浓度-响应曲线的最大响应，这对于低效激动剂（例如某些多氯联苯（PCB））并非总是可能的。为了能够预测这些低效激动剂，本研究修订了该qAOP以使用效应浓度阈值（EC来自体外AhR反式激活测定的_阈值）作为输入。在4种DLC的3种鸟类和7种鱼类的生命早期阶段，EC_阈值与引起0、10、50或100％死亡率的剂量之间显示出显着的线性关系：2,3,7,8-四氯二苯并- p二氧杂环己烯，PCB 126，PCB 77和PCB 105。这些4个的线性关系被组合以形成经修订的qAOP。使用EC_阈值的qAOP可以将低效激动剂的实验剂量反应曲线预测平均在一个数量级内，但是先前使用EC50的qAOP可以预测更高效的激动剂的实验剂量反应曲线，其准确性更高。环境毒性化学2020; 39：2055-2064。©2020 SETAC