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

金属对生物体的毒性由多种因素决定。环境中的非生物配体可能会影响可供吸收的金属量。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。主要的阳离子，如Na+和Ca2+，可能会与有毒离子竞争结合到生物表面上的位点，影响有毒金属的吸收。生物累积是一个先决条件，但并不总是金属毒性的可靠预测因素，因为生物体有能力螯合金属并使其解毒。因此，亚细胞分配是金属毒性的另一个决定因素。这些因素已在不同的方法中分别考虑。环境化学对金属形态的影响以及在生物表面的积累已经包括在生物配体模型中。在生物动力学模型中，金属的生物累积被预测为流入和流出的平衡，并与临界体内残留方法中的毒性效应有关。在模拟金属毒性时已考虑到亚细胞分配，但现有方法存在固有的缺点。例如，根据金属硫蛋白样蛋白的诱导对金属接触进行的评估没有考虑到其他解毒机制。动态亚细胞分配的金属不能有效地描述金属敏感和生物脱毒馏分中的金属浓度之间的比率。进一步划定的亚细胞分区不考虑金属积累在敏感的馏分时，解毒机制不不堪重负，而亚细胞分区和生物反应之间的关系是lacked.The斑马贻贝Dreissena polymorpha已被广泛用于生物监测程序，特别是因为它的广泛分布，高过滤效率，高容量，积累金属。斑马贻贝中金属亚细胞分配的划定有利于更准确地估计其他水生生物，如鱼类和甲壳类动物中的金属生物量。本研究旨在建立一个综合考虑环境条件、生物富集、生物毒性和生物毒性等因素影响的预测模型，并对该模型进行了初步的研究。以及斑马贻贝解毒和螯合Cu的能力。所提出的模型是吸收动力学和亚细胞分配动力学的组合，同时考虑环境化学的影响。Cu2+的毒性将与Cu在以金属敏感部分为代表的代谢活性器官中的累积有关，这将基于吸收、消除和解毒来模拟。

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.