Modeling Chemical Absorption Through Membranes.
AIR FORCE INST OF TECH WRIGHT-PATTERSONAFB OH
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Understanding the processes involved in dermal penetration of chemicals and drugs is important to both toxicologists and pharmacologists. Researchers developing new drugs are interested in enhancing the penetration of chemicals through the skin, while environmental professionals are interested in limiting such penetration. For both types of applications, predictive biologically-based mathematical models can be very useful in understanding the processes involved, particularly when such models are based on physiological and biochemical parameters which can be measured experimentally. In this thesis we study two existing physiologically-based pharmacokinetic PBPK models that predict concentrations of neat and aqueous dibromomethane DBM absorbed into and through different types of membranes, namely rat skin and butyl rubber. We evaluate the models and add modifications as necessary to improve the predictions. Nearly all of the parameters in these two models are measured experimentally in a laboratory. Sensitivity analysis on the permeability coefficient, the only parameter that is estimated, shows how much of an effect that parameter has on the models predictions. The objective in studying and developing these models is to gain a better understanding of the absorption process by first modeling simple membranes such as butyl rubber, and extrapolating the results for rat skin to other species such as humans.