Department of Science and Environment, Roskilde University, Roskilde, Denmark.
Department of Wildlife, Fish and Environmental Studies, Swedish University of Agricultural Sciences, Umeå, Sweden.
Environ Toxicol Chem. 2024 Aug;43(8):1767-1777. doi: 10.1002/etc.5894. Epub 2024 May 28.
Pharmaceuticals have been classified as an environmental concern due to their increasing consumption globally and potential environmental impact. We examined the toxicity of sediment-associated diclofenac and citalopram administered as both single compounds and in a mixture to the sediment-living amphipod Corophium volutator. This laboratory-based study addressed the following research questions: (1) What is the toxicity of sediment-associated diclofenac and citalopram to C. volutator? (2) Can the mixture effect be described with either of the two mixture models: concentration addition (CA) or independent action (IA)? (3) What is the importance of the choice of (i) exposure measure (start concentration, time-weighted average [TWA], full exposure profile) and (ii) effect model (concentration-response vs. the toxicokinetic-toxicodynamic model general unified threshold model for survival in its reduced form [GUTS-RED]) for the derived effect concentration values? Diclofenac was more toxic than citalopram to C. volutator as a single compound (10-day exposure). Diclofenac exposure to C. volutator provided median lethal concentrations (LC50s) within the same range (11 µg g dry wt sediment) using concentration-response based on TWA and both GUTS-RED models. However, concentration-response based on measured start concentrations provided an approximately 90% higher LC50 (21.6 ± 2.0 µg g dry wt sediment). For citalopram, concentration-response parameters were similar regardless of model or concentration used (LC50 85-97 µg g dry wt sediment), however, GUTS-RED with the assumption of individual tolerance resulted in a lower LC50 (64.9 [55.3-74.8] µg g dry wt sediment). The mixture of diclofenac and citalopram followed the CA quite closely, whereas the result was synergistic when using the IA prediction. In summary, concentration-response based on TWA and GUTS-RED provided similar and reasonably good fits compared to the data set. The implications are that GUTS-RED will provide a more flexible model, which, in principle, can extend beyond the experimental period and make predictions based on variable exposure profiles (toxicity at different time frames and at different variable exposure scenarios) compared to concentration-response, which provides contaminant toxicity at one point in time. Environ Toxicol Chem 2024;43:1767-1777. © 2024 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
由于药品在全球范围内的消耗量不断增加及其潜在的环境影响，它们已被归类为环境关注物质。我们研究了沉积物中结合的双氯芬酸和西酞普兰单一化合物和混合物对底栖端足类动物 Corophium volutator 的毒性。这项基于实验室的研究提出了以下三个研究问题：（1）沉积物中结合的双氯芬酸和西酞普兰对 C. volutator 的毒性如何？（2）混合物效应可以用两种混合物模型中的任何一种来描述吗：浓度加和（CA）或独立作用（IA）？（3）对于得出的效应浓度值，（i）暴露测量（起始浓度、时间加权平均值 [TWA]、全暴露曲线）和（ii）效应模型（浓度-反应与毒性动力学-毒性动力学模型一般统一阈值模型用于生存[GUTS-RED]）的选择有何重要性？双氯芬酸对 C. volutator 的毒性比西酞普兰单一化合物（10 天暴露）更强。双氯芬酸暴露于 C. volutator ，使用基于 TWA 和 GUTS-RED 两种模型的浓度-反应，提供了相同范围内的中位致死浓度（LC50）（11 µg g 干重沉积物）。然而，基于测量的起始浓度的浓度-反应提供了约 90%更高的 LC50（21.6 ± 2.0 µg g 干重沉积物）。对于西酞普兰，无论使用哪种模型或浓度，浓度-反应参数都相似（LC50 85-97 µg g 干重沉积物），但是，基于个体耐受假设的 GUTS-RED 导致 LC50 降低（64.9 [55.3-74.8] µg g 干重沉积物）。双氯芬酸和西酞普兰的混合物非常接近 CA，而使用 IA 预测则具有协同作用。总的来说，基于 TWA 的浓度-反应和 GUTS-RED 与数据集相比提供了相似且相当合理的拟合。这意味着 GUTS-RED 将提供一个更灵活的模型，原则上可以扩展到实验周期之外，并根据可变的暴露曲线进行预测（不同时间框架和不同变量暴露场景下的毒性），而不是基于浓度-反应，后者仅提供一个时间点的污染物毒性。环境毒理化学 2024；43:1767-1777。© 2024 作者。环境毒理化学由 Wiley Periodicals LLC 代表 SETAC 出版。
