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.
|Dahl, A R (1996) Metabolism of isoprene in vivo. Toxicology 113:273-7|
|Dahl, A R; Gerde, P (1994) Uptake and metabolism of toxicants in the respiratory tract. Environ Health Perspect 102 Suppl 11:67-70|
|Dahl, A R; Lewis, J L (1993) Respiratory tract uptake of inhalants and metabolism of xenobiotics. Annu Rev Pharmacol Toxicol 33:383-407|
|Snipes, M B; Spoo, J W; Brookins, L K et al. (1991) A method for measuring nasal and lung uptake of inhaled vapor. Fundam Appl Toxicol 16:81-91|
|Maples, K R; Dahl, A R (1991) Blood levels of propylene oxide during propylene inhalation and effect on hepatic and nasal cytochrome P-450 concentrations. Drug Metab Dispos 19:835-7|
|Gerde, P; Dahl, A R (1991) A model for the uptake of inhaled vapors in the nose of the dog during cyclic breathing. Toxicol Appl Pharmacol 109:276-88|
|Dahl, A R; Snipes, M B; Gerde, P (1991) Sites for uptake of inhaled vapors in beagle dogs. Toxicol Appl Pharmacol 109:263-75|
|Dahl, A R (1990) Dose concepts for inhaled vapors and gases. Toxicol Appl Pharmacol 103:185-97|