【作者】 张虹；

【导师】 冯剑丰；

【作者基本信息】 南开大学 ， 环境科学， 2022， 硕士

【摘要】 有机磷酸酯（Organophosphate esters,OPEs）作为溴代阻燃剂的替代物被广泛使用,在环境介质和生物中广泛存在。磷酸三（2-氯乙基）酯（Tris（2-chloroethyl）phosphate,TCEP）是赋存量最多的一种。而对于以水和食物为主要暴露途径的水生生物,不同暴露途径对富集特征的影响尚不明确。本研究以斑马鱼（Danio Rerio）为受试生物,将其暴露于染毒的水和食物进行毒代动力学实验,以TCEP为水相暴露,同时以稳定同位素标记的d₁₂-TCEP为食物相暴露,比较不同暴露途径下TCEP在斑马鱼体内不同组织特异性分布特征及其相对贡献,进一步建立了多途径暴露的基于生理学的毒代动力学（Physiologically based toxicokinetic,PBTK）模型。本研究可为水生生物TCEP的多途径暴露风险评估提供理论依据。本文主要研究结果如下:（1）在水相暴露下,TCEP在斑马鱼的血液和肝脏中富集能力较强,生物浓缩因子BCF分别为1.19±0.26和1.37±0.47 kg/L,而在肌肉和性腺中的富集能力较弱。这可能与血液的运输功能和肝脏的解毒功能有所关联。（2）在食物相暴露下,仅在血、肝、肠中检出了TCEP,相比之下血和肝对食物中TCEP的富集能力更高。整体来说,与水相暴露相比,斑马鱼对食物相中TCEP的富集能力较弱。生物放大系数BMF(0.013±0.004～0.707±0.287×10^-3)在各组织中均低于1,表明在斑马鱼体内未发现TCEP的生物放大作用。两种暴露途径的相对贡献随时间有所变化,且食物相暴露在两相中物质质量比为4:1时的相对贡献略高于3:1时。（3）将斑马鱼的鳃、脑、性腺、肌肉、肝和肠看作单独的隔室,以血液为中心室,构建不同暴露途径下TCEP在斑马鱼体内的PBTK模型,基于实验数据估计TCEP在各组织器官内的关键动力学参数。结果表明,TCEP在斑马鱼体内的浓度受间歇性饮食的影响,呈现日暴露的波动性。斑马鱼对食物相TCEP的清除速率大于吸收速率,因此斑马鱼对食物相富集的速度较慢。血液有着较高的向脑、性腺和肌肉转移TCEP的速率,TCEP可以很快在这些组织中达到相对稳定状态,并且浓度高于其他组织。PBTK模型有助于进一步了解不同暴露途径下的TCEP在斑马鱼体内的组织特异性分布。本文通过研究不同暴露途径下TCEP在斑马鱼的组织特异性分布,分析了TCEP多途径暴露在水生生物体内相对贡献。多途径暴露PBTK模型的建立,进一步解释了不同暴露途径下TCEP在斑马鱼各组织器官内的动力学特征并将外暴露剂量转化为内部剂量,为预测不同暴露途径TCEP在斑马鱼体内的分布特征提供了计算工具。更多还原

【Abstract】 Organophosphate esters（OPEs）are widely used as substitutes for brominated flame retardants and exist in environmental medium and organisms.Tris（2-chloroethyl）phosphate（TCEP）is one of the most abundant.Aquatic organisms mainly accumulate pollutants via waterborne and dietborne exposure.But the effects of different exposure routes on the bioaccumulation are still unclear.In this study,zebrafish（Danio Rerio）were used as the test organisms,and they were exposed to TCEP via water and diet.TCEP was used in waterborne exposure and stable isotope-labeled d₁₂-TCEP was used in dietary exposure.Tissue-specific distribution and relative contributions of TCEP in zebrafish under different exposure routes were compared.We then constructed a physiologically based toxicokinetic（PBTK）model to simulates waterborne and dietary exposure for zebrafish.This study can provide a theoretical basis for the multi-route exposure risk assessment of TCEP to aquatic organisms.The main findings of this study are as follows:（1）Under waterborne exposure,TCEP was highly accumulated in the blood and liver of zebrafish,the bioconcentration factor BCF was 1.19±0.26 and 1.37±0.47kg/L,respectively.However,the bioconcentration in muscle and gonad was weak.It may be related to the transport function of the blood and the detoxification function of the liver.（2）Under dietary exposure,TCEP was only detected in blood,liver and intestine.In contrast,blood and liver had higher bioaccumulation ability for TCEP in food.Overall,zebrafish had a weaker ability to absorb TCEP in food compared to the waterborne exposure.The biomagnification factor（BMF）was lower than 1 in all tissues(0.013±0.004～0.707±0.287×10^-3),indicating that the biomagnification effect of TCEP was not found in zebrafish.The relative contributions of the two exposure routes varied with time,and the relative contribution of dietary exposure was slightly higher when the mass ratio of substances in water and food was 4:1 than when it was3:1.（3）We regarded the gill,brain,gonad,muscle,liver and intestine of zebrafish as separate compartments,with blood as the central compartment,and established a PBTK model of TCEP in zebrafish under different exposure routes.And the transfer rate between them was estimated according to the differential equation describing the mass conservation of TCEP in various tissues,and the key kinetic parameters of TCEP in various tissues and organs are estimated based on experimental data.The results showed that the concentration of TCEP in zebrafish was affected by discrete diet,showing fluctuations in daily exposure.In dietary exposure the depuration rate of TCEP was higher than the uptake rate,resulting in a slower bioaccumulation rate in zebrafish.Blood has a high rate of transfer of TCEP to the brain,gonad and muscle,where TCEP could quickly reach a relatively stable state,higher than other tissues.The PBTK model was helpful to better understand the tissue-specific distribution of TCEP in zebrafish under different exposure routes.By investigating the tissue-specific distribution of TCEP in zebrafish under different exposure routes,this study analyses the relative contribution of TCEP in aquatic organisms under various exposure routes.The establishment of the multi-route exposure PBTK model further described the toxicokinetics of TCEP in various tissues and organs of zebrafish under different exposure routes,and converted the external exposure dose into the internal dose,which provided calculation tools for predicting the distribution of TCEP in zebrafish in different exposure routes.更多还原