Mörk Anna-Karin, Johanson Gunnar
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Toxicol Lett. 2006 Jun 20;164(1):6-15. doi: 10.1016/j.toxlet.2005.11.005. Epub 2005 Dec 20.
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 150 W 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.
基于生理的人体实验数据毒代动力学（PBTK）模型表明，要同时描述血液和呼出气体中吸入的极性溶剂的时间进程存在困难，尤其是在体育锻炼期间接触这些溶剂时。我们将此归因于气道中的吸入-呼出效应。目的是开发一个PBTK模型，以解释不同体育锻炼水平下丙酮在血液和呼出气体中的行为。该模型包括吸入的溶剂蒸气通过粘膜与血流之间的交换，以及用于描述工作和休息肌肉的独立隔室。将开发的模型与传统的PBTK模型进行对比，在传统模型中，传导气道被视为惰性管道。我们的模型预测与18名人类志愿者在0、50、100和150瓦工作负荷下进行的26次吸入实验中动脉血、终末呼出气体和混合呼出气体中实验观察到的丙酮水平非常吻合。相比之下，惰性管道模型无法描述这些数据。据我们所知，开发的模型是第一个解释在如此不同体育锻炼水平下丙酮毒代动力学的模型。它可能有助于呼吸监测，并在吸入极性挥发物期间获得更准确的吸收剂量估计。
