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DOI10.1016/j.envint.2017.03.007
Evaluating the influence of half-life, milk:plasma partition coefficient, and volume of distribution on lactational exposure to chemicals in children
Verner, Marc-Andre1,2; Plouffe, Laurence1,2; Kieskamp, Kyra K.1; Rodriguez-Leal, Ines1; Marchitti, Satori A.3
发表日期2017-05-01
ISSN0160-4120
卷号102页码:223-229
英文摘要

Women are exposed to multiple environmental chemicals, many of which are known to transfer to breast milk during lactation. However, little is known about the influence of the different chemical-specific pharmacokinetic parameters on children's lactational dose. Our objective was to develop a generic pharmacokinetic model and subsequently quantify the influence of three chemical-specific parameters (biological half-life, milk:plasma partition coefficient, and volume of distribution) on lactational exposure to chemicals and resulting plasma levels in children. We developed a two-compartment pharmacokinetic model to simulate lifetime maternal exposure, placental transfer, and lactational exposure to the child. We performed 10,000 Monte Carlo simulations where half-life, milk:plasma partition coefficient, and volume of distribution were varied. Children's dose and plasma levels were compared to their mother's by calculating child:mother dose ratios and plasma level ratios. We then evaluated the association between the three chemical-specific pharmacokinetic parameters and child:mother dose and level ratios through linear regression and decision trees. Our analyses revealed that half-life was the most influential parameter on children's lactational dose and plasma concentrations, followed by milk:plasma partition coefficient and volume of distribution. In bivariate regression analyses, half-life explained 72% of child:mother dose ratios and 53% of child:mother level ratios. Decision trees aiming to identify chemicals with high potential for lactational exposure (ratio > 1) had an accuracy of 89% for child:mother dose ratios and 84% for child:mother level ratios. Our study showed the relative importance of half-life, milk:plasma partition coefficient, and volume of distribution on children's lactational exposure. Developed equations and decision trees will enable the rapid identification of chemicals with a high potential for lactational exposure. (C) 2017 Elsevier Ltd. All rights reserved.


语种英语
WOS记录号WOS:000400202400025
来源期刊ENVIRONMENT INTERNATIONAL
来源机构美国环保署
文献类型期刊论文
条目标识符http://gcip.llas.ac.cn/handle/2XKMVOVA/57861
作者单位1.Univ Montreal, Sch Publ Hlth, Dept Occupat & Environm Hlth, Montreal, PQ, Canada;
2.Univ Montreal, Publ Hlth Res Inst IRSPUM, Montreal, PQ, Canada;
3.US EPA, Natl Exposure Res Lab, Athens, GA USA
推荐引用方式
GB/T 7714
Verner, Marc-Andre,Plouffe, Laurence,Kieskamp, Kyra K.,et al. Evaluating the influence of half-life, milk:plasma partition coefficient, and volume of distribution on lactational exposure to chemicals in children[J]. 美国环保署,2017,102:223-229.
APA Verner, Marc-Andre,Plouffe, Laurence,Kieskamp, Kyra K.,Rodriguez-Leal, Ines,&Marchitti, Satori A..(2017).Evaluating the influence of half-life, milk:plasma partition coefficient, and volume of distribution on lactational exposure to chemicals in children.ENVIRONMENT INTERNATIONAL,102,223-229.
MLA Verner, Marc-Andre,et al."Evaluating the influence of half-life, milk:plasma partition coefficient, and volume of distribution on lactational exposure to chemicals in children".ENVIRONMENT INTERNATIONAL 102(2017):223-229.
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