IN-VIVO MEASUREMENTS OF UPTAKE

To elucidate the key physiologic/biochemical factors that influence the dose of inspired vapors delivered to the nasal cavity during inhalation exposure, upper respiratory tract uptake of a variety of vapors has been investigated in several small rodents, including the mouse, rat, hamster, and guinea pig. For nonreactive vapors, uptake was found to be dependent on the inspiratory flow rare and solubility. Species differences in nasal nonreactive vapor uptake were observed among rodents, with uptake being least efficient in the hamster and guinea pig. Vapors that are substrates for mixed-function oxidase or nasal carboxylesterase were also studied. Pretreatment with metabolic inhibitors significantly decreased uptake of these vapors, indicating that in situ metabolism can exert a strong influence on vapor uptake. These results highlight the importance of nasal metabolism in influencing dosimetry in that site as well as the need to incorporate metabolic terms in mathematic models of nasal vapor uptake.