Toxicologists increasingly are called upon to limit experiments using animals and to maximize the benefits obtained from those experiments which must be carried out. Means to reduce reliance on experimental animal use are needed to achieve these ends. Computer-assisted computations based on mathematical models may be substituted for certain types of data currently obtained from experiments using animals; but, to be most useful, the mathematical models must be firmly based on physicochemical and biological principles and must be validated with experimental data. During the previous funding period, such a model was developed to describe the uptake of stable vapors in the canine nasal cavity. In this model, inputs included only physicochemical data for the vapors and physiological data for the dog. An excellent fit between computed values and experimental data was obtained.
The specific aims of this renewal application are to extend the earlier model to include the uptake of stable vapors in the canine bronchial tree and to validate the model for nasal uptake of stable vapors in the rat. Ideally, achievement of these aims will establish the means to compute the uptake parameters of inhaled gases and vapors in rats and dogs and will allow confident extrapolation to humans.
