Kumagai S, Matsunaga I
Department of Occupational Health, Osaka Prefectural Institute of Public Health, 1-3-69, Nakamichi, Higashinari-ku, Osaka, 537 Japan.
Inhal Toxicol. 2000 Jun;12(6):491-510. doi: 10.1080/089583700402888.
A simple lung model (mucosal blood flow and metabolism model, MBM model) was developed to describe the uptake of organic solvents and investigate the role of mucosal blood flow and metabolism. The model separates the lung into four compartments, the peripheral bronchial tract (gas phase), the mucus layer lining the wall surface of the tract, the alveolar space (gas phase), and the alveolar blood. Solvent molecules are absorbed in the mucus layer during inhalation and released during exhalation. The deposited solvent diffuses radially into the mucosal tissue of the respiratory tract and transfers to the mucosal blood flow. To describe this behavior, a hypothetical mucosal blood flow throughout the mucus layer was used. The solvent in the mucosal tissue may be also metabolized, and a hypothetical metabolism in the mucus layer was used. The rate of the hypothetical mucosal blood flow was determined to be 5.2 ml/min based on the best fitting of previously obtained data for seven polar organic solvents. The MBM model predicts that as the blood-air partition coefficient (lambda(B)) increases from 0.1 to 20, the relative end-exhalation (E(end)) will decrease from 0.89 to 0.07, and as lambda(B) increases to 500, E(end) will increase to 0.33. After lambda(B) = 500, E(end) is predicted to decrease again, and at lambda(B) = 10000, E(end) is 0.09. The model also predicts that as lambda(B) increases from 0.1 to 10, the relative uptake (U) increases from 0.08 to 0.61, and as lambda(B) increases to 150, U decreases to 0.50. After lambda(B) = 150, U increases again, and at lambda(B) = 10,000, U is 0.8. The predictions show good agreement with values observed in human experimental studies. The MBM model predicts that uptake by the mucosal blood (U(Al)) would be equal to uptake by the alveolar blood (U(Mu)) at lambda(B) of 1000 and U(Al) is more than 90% of total uptake at lambda(B) > 10,000. The model also shows that U is significantly increased by the mucosal metabolism at lambda(B) between 50 and 5000. Especially, U in the case of CL(Mu) = 100 ml/min is higher by 0.3 than that in the nonmucosal metabolism.
开发了一种简单的肺部模型（黏膜血流与代谢模型，即MBM模型）来描述有机溶剂的摄取情况，并研究黏膜血流和代谢的作用。该模型将肺部分为四个隔室，即外周支气管（气相）、支气管壁表面的黏液层、肺泡腔（气相）和肺泡血液。溶剂分子在吸入过程中被黏液层吸收，在呼气过程中释放。沉积的溶剂径向扩散到呼吸道的黏膜组织中，并转移到黏膜血流中。为描述这种行为，使用了贯穿黏液层的假设黏膜血流。黏膜组织中的溶剂也可能被代谢，因此使用了黏液层中的假设代谢。根据先前获得的七种极性有机溶剂数据的最佳拟合，确定假设黏膜血流速率为5.2毫升/分钟。MBM模型预测，随着血-气分配系数（λ(B)）从0.1增加到20，呼气末相对含量（E(end)）将从0.89降至0.07，当λ(B)增加到500时，E(end)将增加到0.33。在λ(B) = 500之后，预测E(end)会再次下降，在λ(B) = 10000时，E(end)为0.09。该模型还预测，随着λ(B)从0.1增加到10，相对摄取量（U）从0.08增加到0.61，当λ(B)增加到150时，U降至0.50。在λ(B) = 150之后，U再次增加，在λ(B) = 10000时，U为0.8。这些预测与人体实验研究中观察到的值显示出良好的一致性。MBM模型预测，在λ(B)为一千时，黏膜血液摄取量（U(Al)）将等于肺泡血液摄取量（U(Mu)），在λ(B) > 10000时，U(Al)超过总摄取量的90%。该模型还表明，在λ(B)介于50和5000之间时，黏膜代谢会显著增加U。特别是，在CL(Mu) = 100毫升/分钟的情况下，U比无黏膜代谢时高0.3。
