Read-across假设约定，在药物的分子靶向目标保守的前提下，当药物在非靶向生物血浆中的浓度与人体治疗血浆浓度（HTPC）相近时，药物将会对非靶向生物产生药理学效应。若不同种类人用药物的Read-across假设成立，将利于从药物开发时的药理学及毒理学数据预测药物对非靶向生物的环境效应和风险。鱼血模型是水环境中Read-across假设研究的关键工具。本研究以鱼为模型生物，选取不同性质、不同作用模式（MOA）的人用药物为模型化合物，以自由溶解态浓度表征外暴露，以实测的鱼血浆浓度（FPC）表征内暴露，考察人用药物在鱼体中的生物吸收及药代动力学，建立适合于可离子化人用药物的鱼血模型，并通过实际环境（太湖）鱼样来验证；基于实测和鱼血模型预测的FPC，研究基于MOA的生物效应，考察生物效应是否仅仅在FPC>=HTPC时发生，以全面研究验证Read-across假设。

The Read-across Hypothesis stipulates that, in the condition of conservation of the drug molecular target, a drug will result in 
a pharmacological effect in non-target organisms only if plasma concentrations are similar to human therapeutic concentrations (HTPCs). If this hypothesis holds true for different classes of human pharmaceuticals, it should be possible to predict the potential environmental 
impact and risk from information obtained during the drug development process. The Fish Plasma Model is a critical tool in the study of the read-across hypothesis in the aquatic environment. Choosing fish as model aquatic organism, human pharmaceuticals with different physicochemical properties and various modes of action (MOA) as model compounds, basing on the free concentration (Cfree) characterized external exposure and fish plasma concentration (FPC) characterized internal exposure, the uptake and pharmacokinetics of human pharmaceuticals in fish is investigated. Then the Fish Plasma Model suitable for the ionizable human pharmaceuticals is established and then validated by the real environmental fish samples (from Taihu). Basing on the developed Fish Plasma Model and real FPC determination, the exposure system can produce FPCs below, equal and above the range of HTPCs; then the MOA based biological effects (endpoints) are investigated in several fish species to validate that the effects only occurs when the FPC>= HTPC, whereas no effects were observed at plasma concentrations below the HTPCs. This research provides direct evidence for the comprehensive validation of the Read-across hypothesis, thus provide theoretical principle and technical support for the aquatic environmental risk assessment of human pharmaceuticals.