Air Pollution, the Automobile, and Public Health (1988) / Chapter Skim
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Dosimetry Modeling of Inhaled Toxic Reactive Gases
Dosimetry Modeling of Inhaled Toxic Reactive Gases
Pages 367-386
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From page 367... ...
MILLER U.S. Environmental Protection Agency Applications of Dosimetry Modeling / 368 Anatomical, Physiological, and Chemical Considerations / 368 Anatomical Models / 368 Liquid Lining of the Respiratory Tract / 369 Lung Tissue and Blood / 371 Physical and Chemical Factors Affecting Absorption of Reactive Gases / 372 Solubility / 372 Molecular Diffusion / 372 Convection in Respiratory Tract Fluids / 373 Chemical Reactions / 374 Dosimetry Modeling / 375 Upper Respiratory Tract and Total Respiratory Tract Models / 376 Lower Respiratory Tract Models / 376 Influence of Anatomical and Physiological Factors / 377 Influence of Physicochemical Factors / 380 Importance of Experimental Data / 382 Summary l 382 Summary of Research Recommendations / 383 Air Pollution, the Automobile, and Public Health.
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The review begins with a discussion of the physiological and chemical factors that must be quantified for dosimetry modeling. These factors are considered relative to anatomical models and to the characteristics of the liquid lining of the upper and lower respiratory tracts and their associated blood and tissue.
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With surface areas for each segment, even these simplistic upper-respiratory tract anatomical models (URT models) could prove useful in dosimetry modeling.
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Going from the tracheobronchial region to the pulmonary region, the liquid lining probably is continuous with the thinner lining of the pulmonary region; however, .
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1975~. Figure 1 illustrates some of these cells and their relationship to the liquid lining.
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1985~. Physical and Chemical Factors Affecting Absorption of Reactive Gases In general, the absorption of gases is affected by diffusion, convection, and, if relevant, chemical reactions in the gas phase (lumen and air spaces)
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For example, the values for O2 in water, ox serum, frog muscle, dog connective tissue, and rat lung tissue are, respectively, 3 x 0-5, 1.7 x 10-5, 1.2 x 10-5, 0.97 x 10-5, and 2.3 x 10-5 cm2/sec at 37°C (Altman and Dittmer 1971~. Convection in Respiratory Tract Fluids There are two lung fluids in which convection may play a role in the absorption of reactive gases the liquid lining of the upper respiratory tract and the tracheobronchial region, and capillary blood.
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If necessary, the important reactions can be determined by chemical kinetic modeling to gain information that will allow simplification of the system for use in dosimetry modeling by keeping only the important reactions. HCHO, NO2, and O3 are toxic reactive gases derived from mobile sources.
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Dosimetry Modeling By dosimetry models we mean mathematical or experimental models that predict, simulate, or are used to explain the quantitative uptake or absorption of gases in specific regions or locations. The formulation of such a model for inhaled gases requires information on the physical, biological, and chemical properties of the respiratory tract, as discussed previously, as well as an understanding of the nature of gas transport in the lumen and air spaces (as discussed by Ultman, this volume)
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Chemical reactions are not considered in the liquid lining, and the transfer coefficient is based on the physical properties of O3 and the lining (Henry's law constant, molecular diffusion coefficient, and lining thickness) and the requirement that the O3 concentration at the liquid lining/tissue interface be zero.
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Nevertheless, such enhancements are necessary to determine what processes and factors are important. Chemical reactions in the liquid lining are accounted for by assuming that the reaction rates of O3 with biochemical constituents are so fast that the reactions can be characterized by an "instantaneous reaction regime" similar to that discussed by Astarita (1967~.
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applied the Dosimetry Modeling of Inhaled Toxic Reactive Gases first-order chemical reaction model of Miller and coworkers (1985) to different anatomical models of laboratory animals.
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anatomical model for the purpose of estimating the effects of exercise on tissue dose in humans. The four curves presented have the same general shape: Tissue dose increases distally to some generation in the pulmonary region and then rapidly decreases.
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illustrated the importance of liquid lining thickness on predicted tissue dose. Their study indicated that a wide variation of tissue doses can be predicted using the range of liquid lining thickness reported in the literature.
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decreases in the tracheobronchial region as the mucous production rate increases, but no change occurs in the pulmonary region where the net and tissue doses are essentially the same. The discontinuity of the tissue dose profiles for the two largest mucous production rates is a result of the instantaneous reaction regime- either NO2 penetrates to the tissue or it does not.
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~ Recommendation 8. Methods of model validation and parameter estimation applicable to dosimetry models of toxic reactive gases should be identified or develaped.
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Recommendation4 The thickness of the liquid lining of human and laboratory animal respiratory tracts should be accurately characterized. Recommendation 5 The in viva kinetic mechanisms of the important reactions of toxic gases with biological substances of the respiratory tract should be determined.
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Kaliner, M., Marom, Z., Patow, C., and Shelhamer, Dosimetry Modeling of Inhaled Toxic Reactive Gases J
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1985. The influence of upper respiratory tract models on simulated lower respiratory tract uptake of 03, In: Program and Abstracts of the 1985 Annual Meeting of the American Associates for Aerosol Research, Nov.
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