of Work: Computer simulations of physiologically based pharmacokinetic models are used to construct descriptions of the kinetics of uptake, metabolism, and elimination for compounds administered by inhalation. The data used to construct and validate models are acquired from uptake studies using a recirculating exposure system and from tissue disposition measurements resulting from constant concentration inhalation exposures conducted in both whole body and nose only exposure systems. The recirculating exposure system provides a non-invasive, low stress method of measuring the uptake of the test compound resulting from exposure via a test atmosphere. Inhaled xenobiotics often affect the ventilation mechanics of test animals. Physiological modeling and dosimetry depend heavily on the estimate of the rate of alveolar ventilation. A whole body plethysmograph has been developed for use with the nose only exposure systems to measure the minute volume in test animals under exposure conditions. This system has been tested under simulated exposure conditions to develop operational procedures and to verify performance. Uptake measurements will be used in conjunction with disposition and toxicity data in a physiological simulation to build a physiologically realistic description of the toxicokinetics of compounds under study. - PBPK Models Computer Simulation Pharmacokinetics Inhalation
