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中国人群甲基汞经乳汁转运的生理药代动力学(PBPK)模型构建。

Physiologically based pharmacokinetic (PBPK) modeling of human lactational transfer of methylmercury in China.

机构信息

Ministry of Education Laboratory of Earth Surface Process, College of Urban and Environmental Sciences, Peking University, Beijing 100871, China.

School of Geographic Sciences, East China Normal University, Shanghai 200241, China.

出版信息

Environ Int. 2018 Jun;115:180-187. doi: 10.1016/j.envint.2018.03.018. Epub 2018 Mar 22.

Abstract

Methylmercury can readily cross the human placental barrier and the blood-brain barrier and cause damage to the vulnerable developing brains of the fetus and infants. Most of the previous studies on the maternal transfer of methylmercury to the next generation have focused on the prenatal period. In this study, human physiologically based pharmacokinetic (PBPK) models of methylmercury were established for breastfeeding mothers and suckling infants based on the existing model prototypes of previous studies. Relevant parameters of the models were modified, and the validation was conducted based on measured data in North China. The models could effectively describe the human lactational transfer of methylmercury, including the time-dependent methylmercury levels in different tissues and organs of the breastfeeding mothers and suckling infants. The results indicated that 77.2% and 14.9% of methylmercury were excreted via hair and breast milk, respectively, from breastfeeding mothers during the first year after delivery. Meanwhile, 79.2% was excreted from the suckling infants during the first year after delivery via hair. Lactational transfer of methylmercury was considered an important pathway of methylmercury exposure for the breastfeeding infants, which accounted for approximately 80% of the accumulated adverse impacts at the early stages of human development.

摘要

甲基汞很容易穿过胎盘屏障和血脑屏障,对胎儿和婴儿脆弱的发育中的大脑造成损害。之前关于母体向后代传递甲基汞的研究大多集中在产前阶段。在这项研究中,根据之前研究的现有模型原型,为哺乳期母亲和哺乳婴儿建立了人生理相关药代动力学(PBPK)甲基汞模型。对模型的相关参数进行了修改,并基于华北地区的实测数据进行了验证。该模型可以有效地描述甲基汞在人类哺乳期的转移,包括哺乳期母亲和哺乳婴儿不同组织和器官中甲基汞的时间依赖性水平。结果表明,在分娩后第一年,77.2%和 14.9%的甲基汞分别通过毛发和母乳从哺乳期母亲中排出。同时,在分娩后第一年,79.2%的甲基汞通过毛发从哺乳婴儿中排出。甲基汞的哺乳期转移被认为是哺乳婴儿甲基汞暴露的一个重要途径,这一途径在人类发育的早期阶段约占累积不良影响的 80%。

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