Predicting plasma concentrations of bisphenol A in children younger than 2 years of age after typical feeding schedules, using a physiologically based toxicokinetic model.
Predicting plasma concentrations of bisphenol A in children younger than 2 years of age after typical feeding schedules, using a physiologically based toxicokinetic model.
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DOI：
10.1289/ehp.0800073
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发表时间：
2009-04
影响因子：
10.4
通讯作者：
Ritter L
中科院分区：
文献类型：
--
作者：
Edginton AN;Ritter L
双酚A（BPA）是一种存在于某些聚碳酸酯塑料和环氧树脂中的工业化学品，最近人们对人体接触双酚A的安全性提出了担忧。特别令人感兴趣的是，幼儿通过储存在含BPA包装中的食物接触BPA。在这项研究中，我们评估了年龄依赖性的BPA及其葡萄糖醛酸代谢产物，BPA-Glu，使用耦合BPA-BPA-Glu生理基础的毒代动力学（PBTK）模型。利用从成人毒代动力学研究中收集的信息，我们建立了PBTK模型。然后，我们根据与吸收、分布、代谢和排泄相关的生理参数的年龄依赖性，将模型扩展到< 2岁的儿童。我们估计，当给予相同的体重标准化剂量时，新生儿的平均稳态BPA血浆浓度是成人的11倍。由于葡萄糖醛酸化过程的快速发展，该比率在3月龄时降至2。据监管机构估计，典型喂养暴露的模拟显示，3个月和6个月大的婴儿的稳态BPA血浆浓度是成人的5倍，这反映了BPA代谢能力的降低和体重标准化BPA暴露的增加。由于定义成人肝脏BPA固有清除率的不确定性，这些值代表初步估计值。模拟成人和幼儿之间的BPA剂量差异表明，需要更灵敏的BPA分析方法，以更大的确定性来定义成人肝脏BPA固有清除率，以及需要幼儿的外部暴露数据。
Concerns have recently been raised regarding the safety of potential human exposure to bisphenol A (BPA), an industrial chemical found in some polycarbonate plastics and epoxy resins. Of particular interest is the exposure of young children to BPA via food stored in BPA-containing packaging. In this study we assessed the age dependence of the toxicokinetics of BPA and its glucuronidated metabolite, BPA-Glu, using a coupled BPA–BPA-Glu physiologically based toxicokinetic (PBTK) model. Using information gathered from toxicokinetic studies in adults, we built a PBTK model. We then scaled the model to children < 2 years of age based on the age dependence of physiologic parameters relevant for absorption, distribution, metabolism, and excretion. We estimated the average steady-state BPA plasma concentration in newborns to be 11 times greater than that in adults when given the same weight-normalized dose. Because of the rapid development of the glucuronidation process, this ratio dropped to 2 by 3 months of age. Simulation of typical feeding exposures, as estimated by regulatory authorities, showed a 5-fold greater steady-state BPA plasma concentration in 3- and 6-month-olds compared with adults, reflecting both a reduced capacity for BPA metabolism and a greater weight-normalized BPA exposure. Because of uncertainty in defining the hepatic BPA intrinsic clearance in adults, these values represent preliminary estimates. Simulations of the differential BPA dosimetry between adults and young children point to the need for more sensitive analytical methods for BPA to define, with greater certainty, the adult hepatic BPA intrinsic clearance, as well as a need for external exposure data in young children.
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DOI：
10.1038/jes.2008.20
发表时间：
2008-11-01
影响因子：
4.5
作者：
Lakind, Judy S.;Naiman, Daniel Q.
通讯作者：
Naiman, Daniel Q.
DOI：
10.1001/archpedi.1986.02140230103044
发表时间：
1986-09-01
影响因子：
--
作者：
CASEY, CE;NEIFERT, MR;NEVILLE, MC
通讯作者：
NEVILLE, MC
影响因子：
3.5
作者：
Andersen, ME
通讯作者：
Andersen, ME
DOI：
10.1080/15287390490428017
发表时间：
2004-04-23
影响因子：
2.6
作者：
Bruckner, JV;Keys, DA;Fisher, JW
通讯作者：
Fisher, JW
影响因子：
3.6
作者：
Hines, Ronald N.
通讯作者：
Hines, Ronald N.