生理毒代动力学模型及其在有机污染物水生生态毒理研究中的应用

人类生产和生活使用各种人工合成的化学品,种类和数量急剧增长,对生态系统和人体健康造成了极大威胁。因此,亟需采用高效的方法对数量巨大的化合物进行毒性评价。对生理毒代动力学(PBTK)模型的建立过程及其在污染物生态毒理研究中的应用进行了综述。PBTK模型,又称生理药代动力学(PBPK)模型,是利用生理学和解剖学等原理,将生物体简化为用血流连接的肝、肾和脂肪等各组织器官房室,模拟化合物在生物体内的吸收、分布、代谢和排泄过程。模型参数包括生理参数和生化参数2个部分,可用MATLAB等软件进行模拟。模型已应用于数百余种有机污染物在鱼体等水生生物体的毒代动力学模拟。已有模拟结果能够预测化合物在生物体内的有效剂量,对化合物毒性进行评估,并可用于不同物种、不同剂量和不同暴露途径间的外推,有力推进了污染物生态毒理研究工作的开展。

Physiologically Based Toxicokinetic Models and Application in Aquatic Ecotoxicological Studies of Organic Pollutants: A Review

Many varieties of synthetic chemicals are used in our daily life and production activities. Synthetic chemicals are increasing rapidly in terms of class, number and amount. This could pose serious threats to the ecosystem and human health. Hence, it is urgent to develop an efficient evaluation approach to assess the toxicity for these chemicals, instead of using traditional toxicity test methods. In this context, we reviewed physiologically based toxicokinetic (PBTK) model and its application in aquatic ecotoxicological studies for organic chemicals. PBTK model, also known as physiologically based pharmacokinetic (PBPK) model, has gradually become a powerful tool for ecotoxicological study. Based on the knowledge of physiology and anatomy, the organisms are simplified as several compartments to represent various tissues and organs, which are connected with each other via blood flow; so that the absorption, distribution, metabolism and excretion (ADME) processes of compounds in organisms can be simulated using the PBTK model. The parameters in the PBTK model normally include physiological parameters and biochemical parameters, which can be applied in the simulation using MATLAB or other software. So far, the PBTK model has been widely applied to the simulation of several hundreds of organic chemicals in fish species and some other aquatic organisms. In literature, several hundreds of organic chemicals in fish have been simulated by the PBTK model. The modeling results displayed good prediction of the effective dose for organic pollutants in organisms, which is then applied to evaluate the toxicity effects of the compounds. The PBTK model can also be used for the extrapolations among different species, different doses and different exposure pathways. As a result, the application of PBTK model promoted and enhanced the research on the ecotoxicology of organic chemicals.