Toxicology Program, Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, CT, USA.
Pharmacol Ther. 2012 Dec;136(3):401-13. doi: 10.1016/j.pharmthera.2012.08.017. Epub 2012 Sep 1.
The lung is a route of entry and also a target site for inhaled vapors, therefore, knowledge of the total absorbed dose and/or the dose absorbed in each airway during inhalation exposure is essential. Vapor absorption characteristics result primarily from the fact that vapors demonstrate equilibrium/saturation behavior in fluids. Thus, during inhalation exposures blood and airway tissue vapor concentrations increase to a steady state value and increase no further no matter how long the exposure. High tissue concentrations can be obtained with highly soluble vapors, thus solubility, as measured by blood:air partition coefficient, is a fundamentally important physical/chemical characteristic of vapors. While it is classically thought that vapor absorption occurs only in the alveoli it is now understood that this is not the case. Soluble vapors can be efficiently absorbed in the airways themselves and do not necessarily penetrate to the alveolar level. Such vapors are more likely to injure the proximal than distal airways because that is the site of the greatest delivered dose. There are substantial species differences in airway vapor absorption between laboratory animals and humans making interpretation of laboratory animal inhalation toxicity data difficult. Airway absorption is dependent on vapor solubility and is enhanced by local metabolism and/or direct reaction within airway tissues. Modern simulation models that incorporate terms for solubility, metabolism, and reaction rate accurately predict vapor absorption patterns in both animals and humans and have become essential tools for understanding the pharmacology and toxicology of airborne vapors.
肺是吸入蒸气的进入途径和靶器官，因此，了解吸入暴露期间总吸收剂量和/或每个气道吸收的剂量至关重要。蒸气吸收特性主要归因于蒸气在液体中表现出平衡/饱和行为的事实。因此，在吸入暴露期间，血液和气道组织中的蒸气浓度增加到稳定状态值，并且无论暴露时间多长，都不会进一步增加。高溶解度的蒸气可获得高组织浓度，因此，溶解度（通过血：气分配系数测量）是蒸气的基本重要物理/化学特性。尽管经典上认为蒸气吸收仅发生在肺泡中，但现在已经了解并非如此。可在气道本身中有效地吸收可溶性蒸气，并且不一定渗透到肺泡水平。由于这是最大剂量的部位，因此这种蒸气更可能损伤近端气道而不是远端气道。在实验室动物和人类之间，气道蒸气吸收存在明显的种属差异，这使得难以解释实验室动物吸入毒性数据。气道吸收取决于蒸气的溶解度，并受局部代谢和/或气道组织内的直接反应增强。现代模拟模型将溶解度，代谢和反应速率的术语结合在一起，可准确预测动物和人类中的蒸气吸收模式，并且已成为了解空气传播蒸气的药理学和毒理学的重要工具。
