Helmholtz Centre for Environmental Research-UFZ, Leipzig, Germany.
Center for Applied Geoscience, Eberhard Karls University of Tübingen, Tübingen, Germany.
Environ Toxicol Chem. 2020 Dec;39(12):2552-2559. doi: 10.1002/etc.4868. Epub 2020 Oct 22.
Chemicals emitted into the environment are typically present at low concentrations but may act together in mixtures. Concentration-response curves of in vitro bioassays were often linear for effect levels <30%, and the predictions for concentration addition (CA) of similarly acting chemicals and for independent action (IA) of dissimilarly acting chemicals overlapped. We derived a joint CA/IA mixture model for the low-effect level portion of concentration-response curves. In a first case study, we evaluated the cytotoxicity of over 200 mixtures of up to 17 components that were mixed in concentration ratios as they occurred in river water. The predictions of the full IA model were indistinguishable from the predictions of the full CA model up to 10% effect, confirming the applicability of the joint CA/IA mixture model at low effect levels. In a second case study, we evaluated if environmental concentrations trigger effects at levels low enough for the joint CA/IA mixture model to apply. The detected concentrations were scaled by their toxic potencies to estimate the mixture effect of the detected chemicals in a complex mixture. In 86% of 156 samples the effects fell in the validity range of the joint CA/IA mixture model (<10% effect level), confirming the CA assumption for toxic unit summation. The joint CA/IA mixture model is not suitable for testing specific mixture hypotheses and interactions of chemicals in mixtures, where more refined models are required; but it is helpful for the interpretation of effects of complex (multicomponent) environmental mixtures, especially for water samples with relatively low effect level. Environ Toxicol Chem 2020;39:2552-2559. © 2020 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
环境中排放的化学物质通常浓度较低，但可能在混合物中共同作用。体外生物测定的浓度-反应曲线对于 <30%的效应水平通常呈线性，类似作用的化学物质的浓度加和（CA）预测和不同作用的化学物质的独立作用（IA）预测重叠。我们为浓度-反应曲线的低效应水平部分推导了一个联合 CA/IA 混合物模型。在第一个案例研究中，我们评估了超过 200 种混合物的细胞毒性，这些混合物由多达 17 种成分组成，混合比例与河水中的实际比例相同。在 10%的效应水平内，全 IA 模型的预测与全 CA 模型的预测无法区分，这证实了联合 CA/IA 混合物模型在低效应水平下的适用性。在第二个案例研究中，我们评估了环境浓度是否会在低到足以应用联合 CA/IA 混合物模型的水平引发效应。将检测到的浓度按其毒性潜力进行缩放，以估计复杂混合物中检测到的化学物质的混合物效应。在 156 个样本中的 86%，效应落在联合 CA/IA 混合物模型的有效性范围内（<10%的效应水平），这证实了毒性单位加和的 CA 假设。联合 CA/IA 混合物模型不适合测试特定的混合物假设和混合物中化学物质的相互作用，需要更精细的模型；但它有助于解释复杂（多成分）环境混合物的效应，特别是对于效应水平相对较低的水样。环境毒理学与化学 2020；39:2552-2559。©2020 作者。环境毒理学与化学由 Wiley 期刊发表代表 SETAC。
