生态毒理学报2024,Vol.19Issue(6) :1-11.DOI:10.7524/AJE.1673-5897.20241029001

中国成人磷酸三(2-氯乙基)酯的生理毒代动力学(PBTK)模型构建

Construction of a Physiologically Based Toxicokinetic(PBTK)Model of Tris(2-chloroethyl)Phosphate(TCEP)in Chinese Adults

彭宇 施妙盈 贾旭东 周萍萍 曹佩 王霞 王子健
生态毒理学报2024,Vol.19Issue(6) :1-11.DOI:10.7524/AJE.1673-5897.20241029001

中国成人磷酸三(2-氯乙基)酯的生理毒代动力学(PBTK)模型构建

Construction of a Physiologically Based Toxicokinetic(PBTK)Model of Tris(2-chloroethyl)Phosphate(TCEP)in Chinese Adults

彭宇 1施妙盈 2贾旭东 2周萍萍 2曹佩 2王霞 3王子健4
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作者信息

  • 1. 山东第二医科大学公共卫生学院,潍坊 261053;国家食品安全风险评估中心,北京 100022
  • 2. 国家食品安全风险评估中心,北京 100022
  • 3. 山东第二医科大学公共卫生学院,潍坊 261053
  • 4. 国家食品安全风险评估中心,北京 100022;中国科学院生态环境研究中心,北京 100085
  • 折叠

摘要

随着全球范围内对溴系阻燃剂的禁用,有机磷酸酯(OPEs)作为其主要替代品在中国被大量生产,并且在食品塑料器皿、家装材料、工业制造等多个领域得到广泛应用.其中,磷酸三(2-乙基)酯(TCEP)已经被欧盟相关法规定义为生殖毒性和疑似人类致癌物,列入管控对象.为了更好地理解TCEP膳食暴露与人体健康之间的关联,本研究基于中国成人的生理参数和TCEP理化特性,应用Gastroplus软件构建了描述TCEP内暴露的PBTK模型,解析了 TCEP在人体内的吸收、代谢、分布及排泄的动力学过程.所建PBTK模型能够预测TCEP暴露后在血液、脑、肝脏、肾脏等人体或哺乳动物组织器官中的分布和稳态浓度.对模型进行了精度、敏感性和相关性分析,说明模型具有管理可接受的表现.采用文献收集的小鼠血浆和中国成年人血清中TCEP实测值对模型进行了验证,表明其可以应用于TCEP膳食暴露的健康风险评估.

Abstract

With the global ban on brominated flame retardants,organophosphate esters(OPEs)have been exten-sively manufactured in China as a primary substitute.These compounds are widely used in various fields,including food plastic containers,interior decoration materials,and industrial manufacturing.Among them,tris(2-chloroethyl)phosphate(TCEP)has been classified as a reproductive toxin and a suspected human carcinogen by the relevant EU regulations,making it a controlled substance.To better understand and establish the link between dietary expo-sure to TCEP and human health,this study constructed a physiologically based toxicokinetic(PBTK)model using the Gastroplus software,based on the physiological parameters of Chinese adults and the physicochemical proper-ties of TCEP.This model described the absorption,metabolism,distribution,and excretion kinetics of TCEP in the human body.The constructed PBTK model predicted the steady-state concentrations of TCEP in human or mam-malian tissues and organs such as blood,brain,liver,and kidney following TCEP exposure.Accuracy,sensitivity,and correlation analyses were carried out,indicating that the model performance was acceptable for regulatory pur-poses.The model's validity was further supported by comparing TCEP plasma levels from mouse studies and serum levels from Chinese adults,as reported in the literature,affirming its utility for assessing health risks associated with dietary TCEP exposure.

关键词

磷酸三(2-氯乙基)酯/生理毒代动力学模型/膳食暴露/模型验证

Key words

tris(2-chloroethyl)phosphate(TCEP)/physiologically based toxicokinetic model(PBTK model)/dietary exposure/model verification

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出版年

2024
生态毒理学报
中国科学院生态环境研究中心

生态毒理学报

CSTPCDCSCD北大核心
影响因子:0.857
ISSN:1673-5897
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