构建新双酚类塑料添加剂污染物在野生淡水鱼中富集和组织分布的生理毒代动力学(PBTK)模型

Developing a physiologically based pharmacokinetic(PBTK)model for bioaccumulation and tissue distribution of bisphenol plastic additives in wild freshwater fish

双酚类(BPs)污染物为已知的内分泌干扰物,广泛存在于环境中,并能在生物体内富集且可能在生态食物链中传递.本研究基于6种常见野生淡水食用鱼(鲢鱼、翘嘴鲌、赤眼鳟、广东鲂、鲤鱼和黄尾鲴)中BPs的实测数据,开发了一种生理毒代动力学模型(PBTK),用于模拟预测BPs在野生淡水鱼类中的富集.研究将鱼体划分为10个房室,其中将鱼鳔划分为单独的房室考虑.针对各鱼种分别进行参数优化,提升模拟预测的精度,模型敏感性分析筛选出6个敏感参数,分别为组织/血液分配系数、血液/水分配系数、温度、肝脏清除率、血液中未结合化学物质的比例与有效呼吸体积.通过对比发现,89%~98%的预测结果与实验数据的误差在10倍以内.将来建立PBTK模型时考虑增加新的机理方程针对性描述生物的摄食方式、食物组成、习性等特征,从而提升模拟预测的精度.

Bisphenol compounds(BPs)are confirmed endocrine-disrupting contaminants.BPs have been widely detected in the environments.In addition,the BP contaminants are bio-accumulative and even bio-transferable in ecosystems.This study developed a physiologically based toxicokinetic(PBTK)model for predicting whole-body concentrations and tissue distribution of the BPs based on the measured BP concentrations in 6 species of edible wild freshwater fish,including sliver carp,topmouth culter,barbel chub,GD black bream,common carp and yellowtail.The fish body system was divided into 10 compartments among which the swim bladder was set as a separate compartment.Parameter optimization was performed depending on species.Sensitivity analysis revealed six parameters,which were tissue/blood partition coefficient,blood/water partition coefficient,temperature,hepatic clearance,proportion of unconjugated chemicals in blood and effective respiratory volume.The results showed that 89%-98%of predictions fell within a 10-fold factor of the experimental data.New mechanistic equations should be included in modelling to encapsulate feeding behavior,diet composition,habits,and other traits of organisms to improve simulation precision.