Combining uptake and subcellular partitioning/toxicokinetics and toxicodynamics in modelling Cu2+ toxicity to zebra mussels, taking into account water chemistry

结合吸收和亚细胞分配/毒代动力学和毒动力学来模拟 Cu2 对斑马贻贝的毒性，同时考虑水化学

• 批准号: 322918513
• 负责人: Dr. Thi Thu Yen Le, Ph.D.
• 金额: --
• 依托单位: Abteilung Aquatische Ökologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2016
• 资助国家: 德国
• 起止时间: 2015-12-31 至 2019-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/322918513?language=en
• 关键词: Combining; uptake; subcellular; partitioning; toxicokinetics

Metal toxicity to organisms is determined by various factors. Abiotic ligands in the environment might affect the amount of metals available for uptake. Dissolved organic carbon may complex metals, reducing the interactions of the metals with organisms. Major cations, e.g. Na+ and Ca2+, might compete with toxic ions for binding to sites on biological surfaces, influencing the uptake of toxic metals. Bioaccumulation is a prerequisite, but not always a reliable predictor of metal toxicity, attributed to the capacity of organisms to sequester and detoxify metals. Therefore, subcellular partitioning is another determinant of metal toxicity. These factors have separately been considered in different approaches. Effects of environmental chemistry on metal speciation as well as accumulation at biological surfaces have been included in the Biotic Ligand Model. Metal bioaccumulation has been predicted as a balance of influxes and effluxes in biodynamic models and related to toxic effects in the Critical Body Residue approach. Subcellular partitioning has been taken into account in modelling metal toxicity, but shortcomings are inherent in available approaches. For instance, the assessment of metal exposure based on the induction of metallothionein-like proteins does not account for other detoxification mechanisms. Dynamic subcellular partitioning of metals cannot effectively be described by a ratio between metal concentrations in the metal-sensitive and biologically detoxified fractions. Further delineation of subcellular partitioning does not consider metal accumulation in sensitive fractions when detoxification mechanisms are not overwhelmed whereas relationships between subcellular partitioning and biological responses are lacking.The zebra mussel Dreissena polymorpha has widely been used in biomonitoring programs, particularly because of its widespread distribution, high filtering efficiency, and high capacity to accumulate metals. The delineation of metal subcellular partitioning in the zebra mussel facilitates more accurate estimates of metals biomagnified in other aquatic organisms like fish and crustaceans. Although bioavailability and toxicity of Cu2+ to aquatic organisms have been extensively investigated, uncertainties are still remaining in available approaches, probably related to the exclusion of some of the factors mentioned above.The proposed research aims at developing a model for predicting Cu2+ toxicity to the zebra mussel, taking into account influence of environmental conditions, bioaccumulation, and the ability of the zebra mussel to detoxify and sequester Cu. The proposed model is a combination of uptake kinetics and subcellular partitioning dynamics while accounting for effects of environmental chemistry. The toxicity of Cu2+ will be related to the accumulation of Cu at the metabolically-active organs represented by the metal-sensitive fraction, which will be simulated based on uptake, elimination, and detoxification.

金属对生物体的毒性是由多种因素决定的。环境中的非生物配体可能会影响可吸收的金属量。溶解的有机碳可以络合金属，减少金属与生物体的相互作用。主要阳离子，例如Na+ 和 Ca2+ 可能与有毒离子竞争与生物表面位点的结合，影响有毒金属的吸收。生物累积是金属毒性的先决条件，但并不总是可靠的预测因素，这归因于生物体螯合和解毒金属的能力。因此，亚细胞分配是金属毒性的另一个决定因素。这些因素已通过不同的方法分别考虑。环境化学对金属形态以及生物表面积累的影响已包含在生物配体模型中。金属生物富集被预测为生物动力学模型中流入和流出的平衡，并与临界身体残留方法中的毒性作用相关。在金属毒性建模中已经考虑了亚细胞分配，但现有方法存在固有的缺点。例如，基于金属硫蛋白样蛋白的诱导来评估金属暴​​露并没有考虑其他解毒机制。金属的动态亚细胞分配不能通过金属敏感级分和生物解毒级分中的金属浓度之间的比率来有效地描述。当解毒机制未被压倒时，亚细胞分配的进一步描述不考虑敏感部分中的金属积累，而亚细胞分配和生物反应之间缺乏关系。斑马贻贝 Dreissena polymorpha 已广泛应用于生物监测项目，特别是因为其广泛分布、高过滤效率和高积累金属能力。斑马贻贝中金属亚细胞分区的划分有助于更准确地估计鱼类和甲壳类等其他水生生物中生物放大的金属。尽管 Cu2+ 对水生生物的生物利用度和毒性已得到广泛研究，但可用的方法仍然存在不确定性，可能与排除上述一些因素有关。 本研究旨在开发一个模型来预测 Cu2+ 对斑马贻贝的毒性，同时考虑到环境条件、生物累积性以及斑马贻贝解毒和排毒能力的影响。 隔离铜。所提出的模型是吸收动力学和亚细胞分配动力学的结合，同时考虑了环境化学的影响。 Cu2+的毒性将与以金属敏感部分为代表的代谢活性器官中Cu的积累有关，这将基于吸收、消除和解毒来模拟。