A human physiological model describing acetone kinetics in blood and breath during various levels of physical exercise
A human physiological model describing acetone kinetics in blood and breath during various levels of physical exercise
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DOI：
10.1016/j.toxlet.2005.11.005
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发表时间：
2006-06-20
影响因子：
3.5
通讯作者：
Johanson, G
中科院分区：
文献类型：
--
作者：
Mork, AK;Johanson, G
基于生理学的毒代动力学（PBTK）人体实验数据建模表明，难以同时描述吸入极性溶剂在血液和呼吸中的时间过程，特别是如果暴露发生在体育锻炼期间。我们将此归因于气道中的冲洗-冲洗效应。目的是开发一个PBTK模型，解释不同水平的体育锻炼时血液和呼出空气中丙酮的行为。该模型包括通过粘膜和单独的隔室与血流交换吸入的溶剂蒸气，以描述工作和休息的肌肉。所开发的模型进行了对比，传统的PBTK模型，其中进行气道被视为一个惰性管。我们的模型预测同意与实验观察到的丙酮水平在动脉血和终端和混合呼出的空气从26吸入实验进行了18名志愿者在0，50，100和150 W的工作量。相比之下，惰性管模型无法描述数据。据我们所知，开发的模型是第一个解释丙酮在不同水平的体育锻炼中的毒性。它可能是有用的呼吸监测和获得更准确的估计吸收剂量在吸入极性挥发物。(c)2005爱思唯尔爱尔兰有限公司保留所有权利。
Physiologically based toxicokinetic (PBTK) modeling of human experimental data suggests difficulties to simultaneously describe the time courses of inhaled polar solvents in blood and breath, especially if exposures occur during physical exercise. We attribute this to the washin-washout effect in the airways. The aim was to develop a PBTK-model that explains the behavior of acetone in blood and exhaled air at different levels of physical exercise. The model includes exchange of inhaled solvent vapor with the blood flow via the mucosa and separate compartments to describe working and resting muscles. The developed model was contrasted to a traditional PBTK-model where the conducting airways were regarded as an inert tube. Our model predictions agrees well with experimentally observed acetone levels in both arterial blood and end- and mixed-exhaled air from 26 inhalation experiments conducted with 18 human volunteers at 0, 50, 100 and 150W workload. In contrast, the inert-tube model was unable to describe the data. The developed model is to our knowledge the first which explains the toxicokinetics of acetone at such various levels of physical exercise. It may be useful in breath monitoring and to obtain more accurate estimates of absorbed dose during inhalation of polar volatiles. (c) 2005 Elsevier Ireland Ltd. All rights reserved.