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Instructions,
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Mucus flow and /or chemical reactions in mucus as parameters in determining the dosimetry of inhaled gases in the airway lining. Physiological models have been developed and are used to describe transport and deposition of gases in the upper respiratory tract (URT) of several animals including rats and monkeys. It is also known that gas uptake and the ultimate toxicity may occur through and may be mediated by the mucous layer lining most of the URT. Mucus is a mobile layer (fluid and dynamic) containing a number of chemical constituents that may react with inhaled materials. To accurately reflect the physiology, URT dosimetry models should incorporate two additional factors, when relevant. These are (a) factors that reflect transport through the mucous layer, and (b) any chemical reactions that may take place in this layer. Transport incorporates both diffusive capacity (transverse to mucus flow through the layer) and convective transport (parallel flow in the layer). In order to predict site-specific dosimetry in the URT to a high degree of resolution, the use of computational-fluid dynamics (CFD) modeling of gas distribution in the airway lumen is necessary. This process is computer-time intensive and expensive. To incorporate the fate of materials in the mucous layer would also require CFD modeling, and may or may not be significant with respect to the specific processes for any given material transported from the airway lumen to the underlying epithelium. Is a CFD model of mucus flow necessary? One way of determining a priori which processes are important and which are negligible for any physical system is to calculate upper and/or lower limits for the rates of those processes (chemical reactions and transport in the mucous lining). These calculations can be performed using algebra (without computer use). This would delineate which CFD models may benefit from incorporation of significant processes and which would save computer simulation time for a negligible process. Dr. Schlosser demonstrates two extreme cases of the possible results for such calculations using formaldehyde and ozone, two important air pollutants for which extensive toxicology data are available. These calculations provide the importance of mucus flow and/or chemical reactions in the mucus in determining the dosimetry of inhaled gases in the airway lining. His results show that with formaldehyde, chemical binding to amino groups in mucus is negligible, but the calculations indicate that the convective transport of formaldehyde by mucus flow should be quantified. In contrast to this, the chemical reaction (oxidation) of ozone in mucus is extremely important, while transport of ozone by mucus convection is negligible. Furthermore, in the case of ozone exposure, where the oxidation reaction products appear to be responsible for the toxic effects, similar calculations should be performed for each significant product. This information can be used most effectively in CFD modeling by incorporating only those processes that are significant for each gas. The purpose of the calculations is not to replace CFD models, only to estimate which existing CFD models are in error because they do not include mucus flow, and ultimately whether they are sufficient to adequately predict site-specific dosimetry. Source: Schlosser, P.M. 1999. Relative roles of convection and chemical reaction for the disposition of formaldehyde and ozone in nasal mucus. Inhalation Toxicol. 11:967-980. By: Arlene L. Weiss, MS. DABT, Contributing Editor
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