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PC/BPA 研究进展

关于欧洲双酚A综合暴露和风险特征描述

发布日期:2017-01-11 16:02    来源:未知    浏览次数:70
Dimosthenis A. Sarigiannis, Spyros P. Karakitsios, Evangelos Handakas, et al. Integrated exposure and risk characterization of bisphenol-A in Europe. Food and Chemical Toxicology 98 (2016) 134-147.
http://dx.doi.org/10.1016/j.fct.2016.10.017

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关于欧洲双酚A综合暴露和风险特征描述

关于欧洲双酚A综合暴露和风险特征描述
 
摘要
       当前的研究旨在借助综合暴露模型化框架来开展双酚A的综合性风险特征描述。综合暴露模型化框由与动态生命周期的基于生理学的药代动力学模型(PBTK)相结合的远场和近场暴露建模构成。暴露评估通过欧洲关于双酚A残留和人体生物监测数据开展,人体监测数据进一步通过高级暴露重建模型化框架进行利用,评估双酚A的外剂量、系统性内剂量以及其代谢物。关键性发育期如妊娠期双酚A的暴露评估也通过母体-胎儿毒代动力学交互作用建模给予特别关注。我们的研究结果显示欧洲当前的暴露水平低于欧洲食品安全局设定的每千克体重每天4mg的临时可耐受每日摄入量(t-TDI)。考虑到年龄依赖的生物可及性差异,处于重症监护病房的早产儿的内暴露被认为接近生物学有效剂量,该剂量源于欧洲食品安全局的t-TDI转化的等效内剂量。与传统的暴露/风险特征描述体系相比,采用Tox-Cast 21生物学通路改变剂量(BPAD)作为备选的内剂量参考值使其安全边界增大。
 
关键词:综合暴露;风险评估;模型化平台;基于生理学的药代动力学(PBTK);内剂量;双酚A


Integrated exposure and risk characterization of bisphenol-A in Europe

Abstract
  The current study aims at a comprehensive risk characterization of bisphenol A (BPA) supported by an integrated exposure modelling framework that comprises far field and near field exposure modelling coupled to a dynamic lifetime PBTK model. Exposure analysis was done on European data of BPA food residues and human biomonitoring (HBM). The latter were further assimilated through an advanced exposure reconstruction modelling framework to estimate the corresponding external and internal systemic dose of BPA and its metabolites. Special attention was paid on the assessment of exposure to BPA during critical developmental stages such as gestation by modelling the mother-fetus toxicokinetic interaction. Our findings showed that current exposure levels in Europe are below the temporary Tolerable Daily Intake (t-TDI) of 4 mg/kg_bw/d proposed by the European Food Safety Authority. Taking into account age-dependent bioavailability differences, internal exposure of premature neonates hosted in intensive care units was reckoned close to the biologically effective dose (BED) resulting from translating the EFSA temporary total daily intake (t-TDI) into equivalent internal dose. Use of the Tox-Cast21 Biological Pathway Altering Dose (BPAD) as an alternative internal exposure reference value, resulted in increased margins of safety compared to the conventional exposure/risk characterization scheme.
 
Keywords: Integrated exposure; Risk assessment; Modelling platform; PBTK; Internal dose; Bisphenol A


 

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