One tenet of the science of toxicology is that of dose-response, viz., the magnitude of the response is dependent upon the dose of toxicant. Regional deposition is important in determining the local dose and, therefore, the response of the respiratory tract to inhaled toxic gases. Previous studies in this laboratory have shown that nasal deposition of ethanol and acetone vapors in the Sprague-Dawley rat can be described by pulmonary ventilation-perfusion models suggesting that the nasal epithelial membrane is sufficiently thin to allow equilibration of gas molecules between the inspired air and the nasal capillary blood. The proposed experiments are aimed at determining if pulmonary ventilation-perfusion models can be successfully applied to describe the nasal deposition process in a variety of species, and at providing detailed information on interspecies variability in the nasal gas deposition process. Towards these ends, acetone and ethanol deposition efficiencies will be measured in the surgically isolated nasal cavity of the anesthetized mouse, hamster, Fischer 344 rat, guinea pig and rabbit at a variety of physiologic inspiratory rates, and the data obtained will be analyzed by analogy to pulmonary ventilation-perfusion models. Goals of inhalation toxicologic research include prediction of toxic risk to man on the basis of animal studies, and elucidation of mechanisms of toxic injury. Since regional deposition is of primary importance in determining the dose of inhaled toxicant received by various regions of the respiratory tract, knowledge of interspecies variability in regional gas deposition would be extremely useful in selecting appropriate species for inhalation research and in interpreting and comparing the toxic responses of various species to inhaled gaseous toxicants. The proposed research, by providing detailed information on species-specific variability in the nasal gas deposition process, will, in the long-term, advance the science of inhalation toxicology. In addition, these experiments may elucidate a general mammalian phenomenon, viz., the exchange and equilibration of inert gas molecules across the nasal as well as the alveolar epithelial membranes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
1R01ES003676-01
Application #
3251233
Study Section
Toxicology Study Section (TOX)
Project Start
1985-03-01
Project End
1987-02-28
Budget Start
1985-03-01
Budget End
1986-02-28
Support Year
1
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of Connecticut
Department
Type
Schools of Pharmacy
DUNS #
City
Storrs-Mansfield
State
CT
Country
United States
Zip Code
Morris, J B (1999) A method for measuring upper respiratory tract vapor uptake and its applicability to quantitative inhalation risk assessment. Inhal Toxicol 11:943-65
Stanek, J J; Morris, J B (1999) The effect of inhibition of aldehyde dehydrogenase on nasal uptake of inspired acetaldehyde. Toxicol Sci 49:225-31
Morris, J B; Stanek, J; Gianutsos, G (1999) Sensory nerve-mediated immediate nasal responses to inspired acrolein. J Appl Physiol 87:1877-86
Morris, J B (1997) Uptake of acetaldehyde vapor and aldehyde dehydrogenase levels in the upper respiratory tracts of the mouse, rat, hamster, and guinea pig. Fundam Appl Toxicol 35:91-100
Morris, J B (1997) Dosimetry, toxicity and carcinogenicity of inspired acetaldehyde in the rat. Mutat Res 380:113-24
Morris, J B; Blanchard, K T (1992) Upper respiratory tract deposition of inspired acetaldehyde. Toxicol Appl Pharmacol 114:140-6
Morris, J B (1991) Deposition of acetone vapor in the upper respiratory tract of the B6C3F1 mouse. Toxicol Lett 56:187-96
Morris, J B; Clay, R J; Trela, B A et al. (1991) Deposition of dibasic esters in the upper respiratory tract of the male and female Sprague-Dawley rat. Toxicol Appl Pharmacol 108:538-46
Morris, J B (1990) First-pass metabolism of inspired ethyl acetate in the upper respiratory tracts of the F344 rat and Syrian hamster. Toxicol Appl Pharmacol 102:331-45
Cavanagh, D G; Morris, J B (1987) Mucus protection and airway peroxidation following nitrogen dioxide exposure in the rat. J Toxicol Environ Health 22:313-28

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