多氯联苯对小鼠哺乳期甲基汞传递的影响：基于生理药代动力学的建模。
Effect of PCBs on the lactational transfer of methyl mercury in mice: PBPK modeling.
机构信息
Quantitative and Computational Toxicology Group, Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collin, CO 80523.
出版信息
Environ Toxicol Pharmacol. 2009 Jan;27(1):75-83. doi: 10.1016/j.etap.2008.08.014.
MeHg and PCB exposure to lactating mice were analyzed and a physiologically-based pharmacokinetic (PBPK) model was developed to describe the lactational transfer of MeHg in mice. The influence of albumin on the lactational transfer of MeHg was incorporated into the PBPK model. Experimental results with lactating mice and their pups showed that co-exposure with PCB congeners increased the lactational transfer of MeHg to the pups, which was associated with the rise of albumin levels in maternal blood. Observed results were matched with PBPK model simulations conducted under the assumptions that (1) MeHg bound to plasma albumin is transferred to maternal milk, and (2) PCB congeners may increase the lactational transfer of MeHg by escalating albumin levels in maternal blood. Further refinement of PBPK model quantitatively described the pharmacokinetic changes of MeHg by co-exposure with PCBs in pup's tissues.
对哺乳期小鼠进行了 MeHg 和 PCB 的暴露分析，并建立了生理基础药代动力学（PBPK）模型来描述 MeHg 在小鼠中的哺乳期转移。该 PBPK 模型纳入了白蛋白对 MeHg 哺乳期转移的影响。用哺乳期小鼠及其幼崽进行的实验结果表明，与 PCB 同系物的共同暴露会增加 MeHg 向幼崽的哺乳期转移，这与母体血液中白蛋白水平的升高有关。观察到的结果与 PBPK 模型模拟结果相匹配，该模型模拟的假设条件为：（1）与血浆白蛋白结合的 MeHg 被转移到母乳中；（2）PCB 同系物可能通过提高母体血液中的白蛋白水平来增加 MeHg 的哺乳期转移。通过与 PCB 的共同暴露，进一步对 PBPK 模型进行了细化，定量描述了幼崽组织中 MeHg 的药代动力学变化。
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