McDougal J N, Jepson G W, Clewell H J, MacNaughton M G, Andersen M E
Toxicol Appl Pharmacol. 1986 Sep 15;85(2):286-94. doi: 10.1016/0041-008x(86)90123-7.
Absorption of chemical vapors through the skin is a passive process that is not easily quantitated, but may be important in the assessment of health hazards in some occupational circumstances. Physiological modeling is a quantitative technique which may provide insight into the system being modeled and can be used for interspecies extrapolation. We developed a physiological model for the penetration of organic vapors through skin in vivo which allows the prediction of blood concentrations, after dermal vapor exposures in the rat, when chemical distribution coefficients, physiological and metabolic parameters, and skin permeability constants are known. We used the model in two distinct ways. First, permeability constants for dibromomethane (DBM), bromochloromethane (BCM), and methylene chloride (DCM) were calculated by using a physiologically based pharmacokinetic model for dihalomethanes to relate blood concentrations during dermal vapor exposures to the total amount of chemical which was absorbed through the skin. Second, a skin compartment was added to the model which had input based on the permeability-area-concentration product. This predictive model adequately described blood concentrations after DBM, BCM, and DCM dermal vapor exposures over a wide range of concentrations. This model could easily be modified for use with other organic vapors, and could be used to extrapolate to human vapor exposure conditions by substituting human physiological parameters for the animal values, providing permeability constants are known or can be determined.
化学蒸汽经皮肤吸收是一个被动过程，难以精确量化，但在某些职业环境中对健康危害评估可能很重要。生理建模是一种定量技术，可深入了解所建模的系统，并可用于种间外推。我们开发了一种用于有机蒸汽在体内经皮肤渗透的生理模型，当已知化学分配系数、生理和代谢参数以及皮肤渗透常数时，该模型可预测大鼠经皮肤蒸汽暴露后的血药浓度。我们以两种不同方式使用该模型。首先，通过使用基于生理的二卤甲烷药代动力学模型来计算二溴甲烷（DBM）、溴氯甲烷（BCM）和二氯甲烷（DCM）的渗透常数，以便将经皮肤蒸汽暴露期间的血药浓度与经皮肤吸收的化学物质总量联系起来。其次，在模型中添加一个皮肤隔室，其输入基于渗透面积浓度乘积。该预测模型充分描述了DBM、BCM和DCM在广泛浓度范围内经皮肤蒸汽暴露后的血药浓度。该模型可轻松修改以用于其他有机蒸汽，并且通过将人体生理参数代入动物值，在已知或可确定渗透常数的情况下，可用于外推至人体蒸汽暴露条件。
