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Effect‐Based Trigger Values for Mixtures of Chemicals in Surface Water Detected with In Vitro Bioassays
Environmental Toxicology and Chemistry ( IF 3.6 ) Pub Date : 2020-11-30 , DOI: 10.1002/etc.4944 Beate I Escher 1, 2 , Peta A Neale 3
Environmental Toxicology and Chemistry ( IF 3.6 ) Pub Date : 2020-11-30 , DOI: 10.1002/etc.4944 Beate I Escher 1, 2 , Peta A Neale 3
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Effect‐based trigger (EBT) values for in vitro bioassays are important for surface water quality monitoring because they define the threshold between acceptable and poor water quality. They have been derived for highly specific bioassays, such as hormone‐receptor activation in reporter gene bioassays, by reading across from existing chemical guideline values. This read‐across method is not easily applicable to bioassays indicative of adaptive stress responses, which are triggered by many different chemicals, and activation of nuclear receptors for xenobiotic metabolism, to which many chemicals bind with rather low specificity. We propose an alternative approach to define the EBT from the distribution of specificity ratios of all active chemicals. The specificity ratio is the ratio between the predicted baseline toxicity of a chemical in a given bioassay and its measured specific endpoint. Unlike many previous read‐across methods to derive EBTs, the proposed method accounts for mixture effects and includes all chemicals, not only high‐potency chemicals. The EBTs were derived from a cytotoxicity EBT that was defined as equivalent to 1% of cytotoxicity in a native surface water sample. The cytotoxicity EBT was scaled by the median of the log‐normal distribution of specificity ratios to derive the EBT for effects specific for each bioassay. We illustrate the new approach using the example of the AREc32 assay, indicative of the oxidative stress response, and 2 nuclear receptor assays targeting the peroxisome proliferator–activated receptor gamma and the arylhydrocarbon receptor. The EBTs were less conservative than previously proposed but were able to differentiate untreated and insufficiently treated wastewater from wastewater treatment plant effluent with secondary or tertiary treatment and surface water. Environ Toxicol Chem 2021;40:487–499. © 2020 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
中文翻译：
使用体外生物测定法检测地表水中化学物质混合物的基于效应的触发值
体外生物测定的基于效果的触发 (EBT) 值对于地表水质量监测很重要，因为它们定义了可接受和较差水质之间的阈值。通过阅读现有的化学指导值，它们已被派生用于高度特异性的生物测定，例如报告基因生物测定中的激素受体激活。这种跨读方法不容易适用于指示适应性应激反应的生物测定，这些反应由许多不同的化学物质触发，也不适用于异生物质代谢的核受体激活，许多化学物质与之结合的特异性相当低。我们提出了一种替代方法，从所有活性化学物质的特异性比分布中定义 EBT。特异性比是给定生物测定中化学品的预测基线毒性与其测量的特定终点之间的比率。与许多以前推导 EBT 的跨读方法不同，所提出的方法考虑了混合效应并包括所有化学品，而不仅仅是高效化学品。EBT 源自细胞毒性 EBT，其定义为相当于天然地表水样品中 1% 的细胞毒性。细胞毒性 EBT 通过特异性比的对数正态分布的中位数进行缩放，以得出每个生物测定的特异性效应的 EBT。我们使用 AREc32 测定的例子来说明新方法，指示氧化应激反应，以及针对过氧化物酶体增殖物激活受体 γ 和芳烃受体的 2 种核受体测定。环境毒物化学2021；40：487–499。© 2020 作者。Wiley Periodicals LLC 代表 SETAC 出版的Environmental Toxicology and Chemistry 。
更新日期：2021-01-25
中文翻译：
使用体外生物测定法检测地表水中化学物质混合物的基于效应的触发值
体外生物测定的基于效果的触发 (EBT) 值对于地表水质量监测很重要，因为它们定义了可接受和较差水质之间的阈值。通过阅读现有的化学指导值，它们已被派生用于高度特异性的生物测定，例如报告基因生物测定中的激素受体激活。这种跨读方法不容易适用于指示适应性应激反应的生物测定，这些反应由许多不同的化学物质触发，也不适用于异生物质代谢的核受体激活，许多化学物质与之结合的特异性相当低。我们提出了一种替代方法，从所有活性化学物质的特异性比分布中定义 EBT。特异性比是给定生物测定中化学品的预测基线毒性与其测量的特定终点之间的比率。与许多以前推导 EBT 的跨读方法不同，所提出的方法考虑了混合效应并包括所有化学品，而不仅仅是高效化学品。EBT 源自细胞毒性 EBT，其定义为相当于天然地表水样品中 1% 的细胞毒性。细胞毒性 EBT 通过特异性比的对数正态分布的中位数进行缩放，以得出每个生物测定的特异性效应的 EBT。我们使用 AREc32 测定的例子来说明新方法，指示氧化应激反应，以及针对过氧化物酶体增殖物激活受体 γ 和芳烃受体的 2 种核受体测定。环境毒物化学2021；40：487–499。© 2020 作者。Wiley Periodicals LLC 代表 SETAC 出版的Environmental Toxicology and Chemistry 。
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