7
Breathing, Deposition, and Clearance

INTRODUCTION

Although epidemiological and animal studies provide information on the risks of lung cancer in relation to exposure, linkage of exposure to dose is essential for extrapolating the risk from the mining to the indoor environment. Since exposure does not equal absorbed dose, it is important to describe adequately the variables that determine exposure-dose relationships.

This chapter summarizes aerosol deposition and clearance mechanisms and discusses how both of these influence the amount of alpha energy from radon progeny delivered to target sites. The chapter also discusses approaches that can be used to describe the amount and distribution of doses and, finally, some factors that are known to influence the amount and distribution of retained aerosols.

A major goal of this chapter is to understand and predict differences in response to similar concentrations of inhaled radon progeny among different groups. However, exposure-dose relationships can vary in different individuals (e.g., children versus adults). Thus, even if the inspired concentration of radon progeny were similar, the dose deposited in the lungs may vary. Such factors as metabolic rate, breathing pattern, and lung structure determine the deposition of radon progeny and may differ among individuals. The impact of changes in breathing pattern and the effects of chronic lung disease on particle retention are also discussed in this chapter.

Many aspects of the deposition of aerosols in mammalian lungs have



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Comparative Dosimetry of Radon in Mines and Homes 7 Breathing, Deposition, and Clearance INTRODUCTION Although epidemiological and animal studies provide information on the risks of lung cancer in relation to exposure, linkage of exposure to dose is essential for extrapolating the risk from the mining to the indoor environment. Since exposure does not equal absorbed dose, it is important to describe adequately the variables that determine exposure-dose relationships. This chapter summarizes aerosol deposition and clearance mechanisms and discusses how both of these influence the amount of alpha energy from radon progeny delivered to target sites. The chapter also discusses approaches that can be used to describe the amount and distribution of doses and, finally, some factors that are known to influence the amount and distribution of retained aerosols. A major goal of this chapter is to understand and predict differences in response to similar concentrations of inhaled radon progeny among different groups. However, exposure-dose relationships can vary in different individuals (e.g., children versus adults). Thus, even if the inspired concentration of radon progeny were similar, the dose deposited in the lungs may vary. Such factors as metabolic rate, breathing pattern, and lung structure determine the deposition of radon progeny and may differ among individuals. The impact of changes in breathing pattern and the effects of chronic lung disease on particle retention are also discussed in this chapter. Many aspects of the deposition of aerosols in mammalian lungs have

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Comparative Dosimetry of Radon in Mines and Homes captured the energy and imagination of many investigators, and only a brief summary is provided here. Published symposia serve as excellent sources of information in this area, for example, the First (Oxford), Second (Cambridge), Third (London), Fourth (Edinburgh), Fifth (Cardiff), and Sixth (Cambridge) International Symposia on Inhaled Particles (Davies, 1961, 1964; Walton, 1971, 1977, 1982; Dodgson and McCallum, 1988). In addition, many papers and books reviewing deposition and clearance processes are available (Altshuler et al., 1957; Hatch and Gross, 1964; Aharonson et al., 1976; Brain et al., 1977; Lippmann, 1977; Raabe et al., 1977; Brain and Valberg, 1979, 1985; Heyder et al., 1980; Lippmann et al., 1980; Clarke and Pavia, 1984; Stuart, 1984; Morén et al., 1985). The distinction between retention (the amount of an aerosol present in the lungs at any time) and deposition (the initial attachment of suspended particles to a surface) should be kept in mind. Retention, but not deposition, is influenced by clearance and translocation. Even during a brief exposure to radon progeny (30 to 60 min), there may be loss and redistribution of deposited particles, especially in the large ciliated airways. To acknowledge the possibility of particle redistribution during a measured exposure period, the term retention is used to refer to the amount and distribution of particles in lungs at any time after an exposure to an aerosol. Many parameters that influence aerosol deposition have been studied. Total deposition in the lungs depends on particle size (Morrow, 1966), tidal volume (Taulbee et al., 1978), breathing frequency (Altshuler, 1961; Muir and Davies, 1967; Valberg et al., 1982), and lung volume (Davies et al., 1972). To date, little is known about the actual anatomic distribution of deposited radon progeny within the lungs, especially at the level of small airways and parenchyma. Since the rates and pathways of clearance are determined by the sites of aerosol deposition, it is necessary to study factors such as exercise and disease that strongly influence the distribution of the retained aerosol in the lungs. DEPOSITION OF RADON PROGENY: GENERAL PRINCIPLES Deposition is the process that determines what fraction of the inspired particles is caught in the respiratory tract and, thus, fails to exit with expired air. It is likely that all particles that touch a wet surface are deposited; thus, the site of contact is the site of initial deposition. Distinct physical mechanisms operate on inspired particles to move them toward respiratory tract surfaces. Major mechanisms are inertial forces, gravitational sedimentation, Brownian diffusion, interception, and electrostatic forces. The extent to which each mechanism contributes to the deposition of a specific particle depends on the particle's physical characteristics, the subject's breathing pattern, and the geometry of the respiratory tract. Radon progeny are unusual in that they tend to be smaller than

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Comparative Dosimetry of Radon in Mines and Homes most aerosols of concern to health (see Chapters 2 and 6), and thus, Brownian diffusion and sedimentation dominate, as discussed below. Detailed treatments of particle deposition have been given by Brain and Valberg (1979), Lippmann et al. (1980), Heyder et al. (1980, 1986), Morgan et al. (1983), Raabe (1982), Stuart (1984), and Agnew (1984). Comprehensive treatises on aerosol behavior are also available (Fuchs, 1964; Davies, 1967; Mercer, 1981; Hinds, 1982; Reist, 1984). The behavior of a particle in the respiratory system is largely determined by its size and density. Particles of varying shape and density may be compared by their aerodynamic equivalent diameter (Dae). Aerodynamic diameter is the diameter of the unit density (1 g/cm3) sphere that has the same gravitational settling velocity as that of the particle in question. Aerodynamic diameter is proportional to the product of the geometric diameter and the square root of density. FACTORS ACTING TO DEPOSIT PARTICLES IN THE LUNGS Diffusional Radon progeny undergo Brownian diffusion—a random motion caused by their collisions with gas molecules; this motion can lead to contact and deposition on respiratory surfaces. Diffusion is significant for particles with diameters of less than 1 µm; only then does their size approach the mean free path of gas molecules. Thus, this is probably the dominant mechanism for radon progeny since most of the alpha activity resides on such small particles. Unlike inertial or gravitational displacement, diffusion is independent of particle density; however, it is affected by particle shape (Heyder and Scheuch, 1983). For these particles, size is best expressed in terms of a thermodynamic equivalent diameter, Dt, the diameter of a sphere that has the same diffusional displacement as that of the particle. The probability that a particle would be deposited by diffusion increases with an increase in the quotient (t/Dt)1/2, where t is the residence time. Deposition is also independent of respired flow rate. Diffusion, like sedimentation, is most important in the peripheral airways and alveoli, where dimensions are smaller. However, as particle size becomes very small, diffusion may become an important mechanism even in the upper airways. Gravitational Gravity accelerates falling bodies downward, and terminal settling velocity is reached when viscous resistive forces of the air are equal and opposite in direction to gravitational forces. Respirable particles reach this constant terminal sedimentation velocity in less than 0.1 ms. Then, particles can be removed if their settling causes them to strike airway walls or alveolar surfaces. The

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Comparative Dosimetry of Radon in Mines and Homes probability that a particle will deposit by gravitational settling is proportional to the product of the square of the aerodynamic diameter (Dac2) and the residence time. Thus, breathholding enhances deposition by sedimentation. Sedimentation is most important for particles larger than about 0.2 µm and within the peripheral airways and alveoli, where airflow rates are slow and residence times are long (Heyder et al., 1986). Inertia Inertia is the tendency of a moving particle to resist changes in direction and speed. It is related to momentum: the product of the particle's mass and velocity. High linear velocities and abrupt changes in the direction of airflow occur in the nose and oropharynx and at central airway bifurcations. Inertia causes a particle entering bends at these sites to continue in its original direction instead of following the curvature of the airflow. If the particle has sufficient mass and velocity, it will cross airflow streamlines and impact on the airway wall. The probability that a particle will deposit by inertial impaction, therefore, increases with increasing product of Dae2 and respired flow rate. Generally, inertial impaction is an important deposition mechanism for particles with aerodynamic diameters larger than 2 µm. Thus, it is probably unimportant for radon progeny in indoor air. It can occur during both inspiration and expiration in the extrathoracic airways (oropharynx, nasopharynx, and larynx) and central airways. As particle size decreases, inertia and sedimentation become less important, but diffusion becomes more important. For example, a 2-µm-unit-density spherical particle is displaced by diffusion (Brownian displacement) by only about 9 µm in 1 s. It is important to know that this displacement varies with the square root of time. It settles by gravity by about 125 µm in the same period. However, as the particle size drops to 0.2 µm, the diffusional displacement in 1 s increases to 37 µm whereas gravitational displacement drops to only 2.1 µm. At 0.02 µm, gravitational displacement is only 0.013 µm/s while diffusional displacement in 1 s has soared to 290 µm. A comparison of settling and diffusion displacements for a range of particle sizes is shown in Table 7-1. Other Forces Deposition can also occur in the lungs when particles have dimensions that are significant relative to those of the air spaces. As aerosols move into smaller and smaller air structures, some particles may reach a point where the distance from their center to a surface is less than their radius. The resulting contact is called interception. Interception is most important for the deposition of fibers, but it is probably insignificant for most radon progeny unless they are attached to larger particles.

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Comparative Dosimetry of Radon in Mines and Homes TABLE 7-1 Root Mean Square Brownian Displacement in 1 Second Compared with the Distance Fallen in Air in 1 Second for Unit-Density Particles of Different Diameters   Particle Diameter (µm) Brownian Displacement (µm) Distance Fallen (µm) Settling greater in 1 s 50 1.7 70,000   20 2.7 11,500   10 3.8 2,900   5 5.5 740   2 8.8 125   1 13 33 Diffusion greater in 1 s 0.5 20 9.5   0.2 37 2.1   0.1 64 0.81   0.05 120 0.35   0.02 290 0.013   0.01 570 0.0063 NOTE: Temperature = 37°C; gas viscosity = 0.19 × 10-3 poise. Appropriate correction factors were applied for motion outside the range of validity of Stokes' law. Electrical forces may cause charged particles to deposit in the respiratory tract by the creation of image charges on airway walls. Image charges form within the airways when charged particles attract ions that have the opposite charge and repel airway ions of the same charge. Generally, electrical forces are a minor mechanism of deposition, unless the inspired particles are highly charged. When they are, electrical forces may cause significant losses within the device used to generate the aerosol. Deposition of 1.0-µm charged particles is increased over that of uncharged particles once there are about 40 charges on the particle; for 0.6-µm particles, an increase is seen once there are 30 charges, and for 0.3-µm particles only 10 charges are needed (Melandri et al, 1983). Ambient aerosols that have been airborne for several hours tend to be uncharged. However, fresh aerosols 1 to 10 µm in diameter produced by a grinding or cutting process may have hundreds of electrostatic charges per particle, which are sufficient to enhance deposition. The extent to which charge influences deposition of radon progeny is largely unknown. Other forces acting to affect deposition such as acoustic forces, magnetic forces, or thermal forces, are normally not significant in the respiratory tract. The effectiveness of these deposition mechanisms depends on (1) the effective aerodynamic diameters of the particles, (2) the pattern of breathing, and (3) the anatomy of the respiratory tract. These factors determine the fraction of the inhaled particles that is deposited as well as the site of deposition.

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Comparative Dosimetry of Radon in Mines and Homes Aerosol Characteristics A major factor governing the effectiveness of the deposition mechanisms is the size of the inspired particles. The effective aerodynamic diameter is a function of the size, shape, and density of the particles and affects the magnitude of forces acting on them. For example, while inertial and gravitational effects increase with increasing particle size, the displacements produced by diffusion decrease. The importance of particle size cannot be overemphasized. It is featured prominently in most discussions of aerosol deposition in the respiratory tract (Altshuler et al., 1957; Brain et al., 1977; Lippmann, 1977; Raabe et al., 1977; Brain and Valberg, 1979; Heyder et al., 1980, 1986; Lippman et al., 1980; Agnew, 1984; Stuart, 1984). Radon decay products have a particular size as molecular species but then attach to particles with a wide range of sizes. Since size helps to determine the site of deposition within the lungs, it is important to quantify the mass of particles within the size range that can penetrate the oropharynx. Aerosol mass distributions are characterized by two values, the mass median aerodynamic diameter (MMAD) and the geometric standard deviation (GSD). The MMAD denotes the particle size at which half of the total aerosol mass is contained in larger particles and half is contained in smaller particles. Since the MMAD is expressed as an aerodynamic diameter, it describes how the aerosol behaves in the respired air and can be used to estimate where and by what processes the aerosol deposits in the respiratory tract. The GSD denotes the spread of particle sizes. Most aerosols have sizes that are distributed log-normally; that is, on a plot of the frequency distribution versus particle diameter, the distribution looks Gaussian. An aerosol that is composed of particles of the same size would have a GSD equal to 1.0 and would be termed monodisperse. An aerosol with a GSD of 1.22 or larger is called polydisperse (Fuchs, 1964). Almost all naturally occurring aerosols are polydisperse. An aerosol with a MMAD of 2.0 µm and a GSD of 2.0 would have 1 GSD or 68% of its mass contained in particles between 1.0 and 4.0 µm in aerodynamic diameter. An important implication of a log-normal distribution is that much of the aerosol mass can be contained in the large particles, since mass is proportional to the cube of the diameter. Where these large particles deposit in the respiratory tract governs, to a large extent, where much of the dose is deposited. Mass can be measured gravimetrically by pulling air containing the aerosol through an absolute filter at a known volumetric flow rate. Particle size can be estimated by using light or electron microscopy to examine collected particles. Optical methods utilizing light scattering can give continuous estimates of particle size and/or concentration. These methods, however, describe only the cross-sectional or geometric diameter of the aerosol. Aerodynamic diameter is a more meaningful predictor of deposition site, since it accounts for particle size, shape, and density. Several devices can provide aerodynamic diameter directly,

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Comparative Dosimetry of Radon in Mines and Homes including cascade impactors and aerosol centrifuges. Real-time aerodynamic size measurements are possible using laser Doppler velocimeters (Hiller et al., 1978; Bouchikhi et al., 1988) or laser diffraction particle sizers (Clay et al., 1983). Accurate measurement of aerosol size distributions is complex because particle size is frequently dynamic. Evaporation, hygroscopicity, and agglomeration may cause rapid changes in particle size. Once hygroscopic particles are inhaled and mix with the warm humid air in the respiratory tract, they stop shrinking and start to adsorb water and grow in size. The relative humidity in the lungs beyond the major bronchi at resting inspiratory rates is about 99.5% (Ferron et al., 1988a); this is sufficient to cause dry salt particles to increase 3 to 4.5 times in diameter (Ferron and Gebhart, 1988). Thus, aerosol size measurements of hygroscopic particles made after drying or at a low relative humidity drastically underestimate their size in the lungs. In such cases it is possible to estimate the size attained in the lungs by taking into consideration the relative humidity, the molecular weight of the salt, and the number of ions into which it dissociates in water, among other factors. Such particle growth equations are presented by Ferron (1977, 1987) and Persons et al. (1987). Particle size may not be constant as a generated pharmacological aerosol moves through a delivery system and the respiratory tract. Volatile aerosols composed of Freon propellant or water become smaller through evaporation (Mercer, 1973), whereas hygroscopic aerosols such as sodium chloride particles may grow dramatically, especially as the relative humidity nears 100% (Cinkotai, 1971; Ferron, 1977; Ferron and Gebhart, 1988). The effect of hygroscopicity on deposition has been studied both experimentally (Blanchard and Willeke, 1983; Tu and Knutson, 1984) and theoretically (Ferron, 1977; Martonen et al., 1985; Xu and Yu, 1985; Persons et al., 1987; Ferron et al., 1988a,b), and has recently been reviewed (Morrow, 1986). The overall effect borne out in these studies is that, with increasing hygroscopicity and relative humidity, deposition fraction as a function of particle size is shifted to smaller particle sizes. That is, whereas the deposition minimum for nonhygroscopic particles is about 0.5 µm, the minimum for dry NaCl particles that grow in the 99.5% relative humidity of the lungs is about 0.1 µm (Xu and Yu, 1985). Consequently, the deposition of hygroscopic particles with diameters of greater than 0.1 µm when inhaled exceeds the deposition of nonhygroscopic particles of the same size. For example, a 1-µm NaCl particle has a deposition fraction or collection efficiency 3.8 times greater than that of a 1-µm nonhygroscopic particle (Xu and Yu, 1985). Many pharmacological aerosols are hygroscopic; the hygroscopic growth and deposition characteristics of histamine, for example, are similar to those of NaCl (Ferron, 1987).

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Comparative Dosimetry of Radon in Mines and Homes Breathing Pattern Another important factor affecting deposition is the breathing pattern. Minute volume defines the average flow velocity of the aerosol-containing air in the lung and the total number of particulates to which the lung is exposed. Respiratory frequency affects the residence time of aerosols in the lungs and, hence, the probability of deposition by gravitational and diffusional forces. A change in the lung volume alters the dimensions of the airways and parenchyma. Anatomy of the Respiratory System The anatomy of the respiratory tract is important since it is necessary to know the diameters of the airways, the frequency and angles of branching, and the average distances to the alveolar walls. Furthermore, along with the inspiratory flow rate, airway anatomy specifies the local linear velocity of the airstream and the character of the flow. A significant change in the effective anatomy of the respiratory tract occurs when there is a switch between nose and mouth breathing. There are inter-and intraspecies differences in lung morphometry; even within the same individual, the dimensions of the respiratory tract vary with changing lung volume, with aging, and with pathological processes. CLEARANCE OF RADON PROGENY: GENERAL PRINCIPLES The response to the alpha energy produced by radon progeny depends not only on the amount of aerosol deposited but also on the amount retained in the lungs over time. Retention is the amount of material present in the lungs at any time and equals deposition minus clearance. An equilibrium concentration is reached during continuous exposure to radon progeny when the rate of deposition equals the rate of clearance. The amount of particles retained within a specific lung region over time is a key determinant of dose. As discussed elsewhere in this chapter, such factors as particle size, hygroscopicity, and breathing pattern affect the site of deposition within the respiratory tract. In turn, where particles deposit in the lungs determines which mechanisms are used to clear them and how fast they are cleared. This influences the amount retained over time. Examples of the implications of particle characteristics on integrated retention were given by Brain and Valberg (1974) using a model developed by the Task Force on Lung Dynamics. They showed that the total amount as well as the distribution of retained dose among nose and pharynx, trachea and bronchi, and the pulmonary and lymphatic compartments were dramatically altered by particle size and solubility. Particles that deposit on the ciliated airways are cleared primarily by the mucociliary escalator. Those particles that penetrate to and deposit in

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Comparative Dosimetry of Radon in Mines and Homes the peripheral, nonciliated lung can be cleared by many mechanisms, including translocation by alveolar macrophages, particle dissolution, or movement of free particles or particle-containing cells into the interstitium and/or the lymphatics. These pathways are of great importance for materials that have a long biological half-life, such as silica, asbestos, or plutonium. However, one must realize that these fates are of relatively little importance for short-lived radon progeny. This is because the majority of the energy produced by alpha-particle emission is dissipated during the first hour. Thus, the movement of radon progeny very soon after deposition is relevant to dosimetry. What happens weeks or months later is irrelevant. Reviews of clearance processes have been prepared by Kilburn (1977), Pavia (1984), and Schlesinger (1985a). Mucociliary Transport Less soluble particles that deposit on the mucous blanket covering pulmonary airways and the nasal passages are moved toward the pharynx by cilia. Also present in this moving carpet of mucus are cells and particles that have been transported from the nonciliated alveoli to the ciliated airways. At the pharynx, mucus, cells, and debris coming from the nasal cavities and the lungs meet, mix with salivary secretions, and enter the gastrointestinal tract after being swallowed. In humans, the ciliated epithelium extends from the trachea down to the terminal bronchioles. The particles are removed with half-times of minutes to hours; the rate depends on the speed of the mucous blanket. The speed is faster in the trachea than it is in the small airways (Serafini et al., 1976). There is little time for solubilization of slowly dissolving materials. In contrast, particles deposited in the nonciliated compartments have much longer residence times; there, small differences in in vivo solubility can have great significance. The speed of mucous flow can be affected by factors influencing either the cilia or the amount and quality of the mucus. Ciliary action may be affected by the number of strokes per minute, the amplitude of each stroke, the time course and form of each stroke, the length of the cilia, the ratio of ciliated to nonciliated area, and the susceptibility of the cilia to intrinsic and extrinsic agents that modify their rate and quality of motion. The characteristics of the mucus are critically important. The thickness of the mucous layer and its rheological properties may undergo wide variations. Wanner (1977) and Camner and Mossberg (1988) reviewed many of these factors that influence clearance, including clinical implications. Mucociliary transport has been studied by a variety of techniques, such as monitoring the movement of inert or radiolabeled particles deposited on the tracheal mucus via a bronchoscope or as an inhaled bolus. Tracheal mucus velocity (TMV) can then be estimated from the distance the particles moved over time, as observed with either movies taken through a bronchoscope or by a gamma camera (Yeates et al., 1975; Chopra et al., 1979). Bronchoscopic

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Comparative Dosimetry of Radon in Mines and Homes techniques yield higher numbers for TMV (15-21 mm/min) than the noninvasive bolus techniques do (4.4 mm/min). These values are only characteristic for the trachea and large central airways. Transport in the small peripheral airways is slower probably due to the discontinuous mucous layer (Van As, 1977). Many investigators have estimated mucociliary transport from whole-lung clearance curves. These curves are generated by monitoring the amount of radioactivity in the lungs over time (hours to days) following the inhalation of a radiolabeled aerosol. Albert and Arnett (1955) first used this method and noted that the clearance curve can be divided into two phases: a fast and a slow phase. The fast phase was complete within 24 to 48 h and has generally been attributed to tracheobronchial clearance; the slow phase has been attributed to alveolar clearance (Booker et al., 1967; Morrow et al., 1968; Lippmann and Albert, 1969). This interpretation has been widely accepted and has been used to study clearance in normal and abnormal individuals (Lourenco et al., 1971; Sanchis et al., 1972; Poe et al., 1977; Camner and Philipson, 1978; Stahlhofen et al., 1980). However, evidence indicates that clearance from the airways might not be complete in the first 24 h. This may be even more pronounced in patients with lung disease. Gore and Patrick (1982) noted that particles instilled into the trachea can be sequestered in epithelial cells. Stahlhofen et al. (1986) noted fast and slow phases of clearance even in humans given a bolus of particles delivered only 45 cm3 beyond the larynx. Another approach is to examine deposition and clearance of particles in central versus peripheral regions (Smaldone et al., 1988). The uses of this type of analysis in the interpretation of clearance curves have recently been noted in an editorial by Foster (1988). More studies are needed to elucidate the best methodology to model mucociliary clearance and to understand its role and importance in patients with pulmonary disease. Clearly, it is also essential to understand the initial deposition pattern of an inhaled aerosol in order to assess the importance of mucociliary clearance on the disappearance of the aerosol from the lungs. Nonciliated Regions Particles deposited in the nonciliated portion of the lungs either are moved toward the ciliated region, primarily within alveolar macrophages, or they enter the lung connective tissue either as free particles or within macrophages. Macrophages are credited with keeping the alveolar surfaces clean and sterile. These cells rest on the continuous epithelial layer of the lung. It is their phagocytic and lytic potentials that provide most of the bactericidal properties of the lungs. Rapid endocytosis of insoluble particles by macrophages prevents particle penetration through the alveolar epithelia and facilitates alveolar-bronchiolar transport. Particles in connective tissue may slowly dissolve or may be transported to new sites through lymphatic pathways. Particles remaining on alveolar

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Comparative Dosimetry of Radon in Mines and Homes surfaces are cleared with biological half-times estimated to be days to weeks in humans, whereas particles that have penetrated into fixed tissues are cleared with half-times ranging from a few days to thousands of days depending on their solubility. Brain (1985) has summarized the biology of lung macrophages and in a recent review (Brain, 1988) has emphasized that many kinds of lung macrophages exist. These include alveolar, airway, connective tissue, pleural, and intravascular macrophages. Cough The function of cough is the removal of material from the respiratory tract when mucociliary transport is overwhelmed. Thus, there would probably be little or no transport of radon progeny in the airways produced by cough in individuals with normal amounts of secretions. However, in chronic smokers and other subjects with chronic bronchitis, cough can produce significant and rapid mucus transport. Whether cough is initiated by cough receptors or voluntarily, the subject's first action is usually inspiration. Following the inspiratory phase, the glottis is closed. At about the same time, expiratory muscles in the abdomen and chest wall contract, producing pleural and alveolar pressures of 100 mm Hg or more. When the glottis is opened abruptly, the result is extremely high linear velocities which may be hundreds of miles per hour. The kinetic velocity of this airflow is coupled to mucus and causes it to be propelled along the airways. Several reviews of cough are available (Brain et al., 1985; Leith et al., 1986). DIFFERENCES BETWEEN WORKERS AND THE PUBLIC The mechanisms responsible for deposition and clearance have already been discussed. The effectiveness of these mechanisms depends on various factors. Some major influences on the fraction of the inspired aerosol that deposits within the respiratory tract and its distribution are discussed here. Anatomic Variations The configuration of the lungs and airways is important since the efficiency of deposition depends, in part, upon the diameters of the airways, their angles of branching, and the average distances to alveolar walls. Furthermore, along with the inspiratory volumetric flow rate, airway anatomy specifies the local linear velocity of the airstream and, thus, whether the flow is laminar or turbulent. There are inter-and intraspecies differences in lung morphometry (Soong et al., 1979; Schlesinger and McFadden, 1981; Phalen, 1984; Nikiforov and Schlesinger, 1985); even within the same individual the dimensions of the respiratory tract vary with changing lung volume, with aging, and with pathological processes. Among individuals who breathe in the same manner,

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Comparative Dosimetry of Radon in Mines and Homes For pulmonary emphysema, the heterogeneity of deposition increased with increasing severity of the disease, as measured by changes in the mean linear intercept of the parenchyma (Sweeney et al., 1987). Variations in local deposition could not be explained by the anatomic distribution of emphysema throughout the lungs. In animals with emphysema, although the parenchyma is the primary site of the lesion, airways are also influenced in the later stages of the disease. Loss of elastic recoil caused by tissue destruction would tend to reduce airway caliber. With the progressive loss of supportive parenchymal tissue as emphysema progresses, the decreasing airway caliber would favor enhanced airway deposition and increased overall heterogeneity of deposition. Airway changes caused by physical obstruction of the airways because of mucus plugging (as in animals with chronic bronchitis) also produce increased heterogeneity with enhanced deposition in the affected airways (Sweeney et al., 1985). Nevertheless, extrapolation of these findings in animals to humans with chronic obstructive pulmonary disease or idiopathic pneumonitis with fibrosis must be done cautiously. These data in animals can be used to identify some factors influencing deposition, and thus risk, but they are limited in predicting causal relationships in human disease. Smoking There are many reasons to believe that smokers may have altered exposure-dose relationships as well as altered responses to radon progeny. First, and probably most important, there are mechanistic interactions among the carcinogens and irritants in tobacco smoke and radon progeny. However, in addition, smoking can alter the structure of the lung and thus alter both deposition and clearance kinetics. Cigarette smoking frequently leads to chronic bronchitis, a disease characterized by proliferation of mucus-secreting cells and glands. Thus, chronic bronchitis is often characterized by narrowing of airways, and this can enhance airway deposition. This should lead to increased deposition of radon progeny. Also enhancing the dose from radon progeny would be diminished clearance rates from airways. Counteracting this would be the protective effect of an increased mucous layer thickness. OTHER CHARACTERISTICS OF WORKERS AND THE PUBLIC Occupancy Data If one wants to compare exposure-dose relationships between miners and the general population, one factor that must be considered is where people spend their time. For early miners, the number of hours spent underground on a weekly basis has not been well described in published literature. Contemporary underground miners spend about 35 or 40 h/week in mining environments where

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Comparative Dosimetry of Radon in Mines and Homes radon progeny are encountered. The actual time spent there is probably less than that, since some time is spent preparing for work and descending into and ascending the mine. Clearly, the general population spends a much greater portion of its time in indoor environments. In 1955, Stewart et al. reported that the general population spent approximately 90% of its time indoors in the United Kingdom. In 1982, the United Nations Scientific Committee on the Effects of Atomic Radiation used a value of 80%. More recently, Francis (1987) produced a report describing indoor occupancy in the United Kingdom. On average, 92% of time was spent indoors. That was divided into 77% spent in their own residence and 15% spent in other indoor locations. Of the 77% spent indoors in their own residence, 42% was in the bedroom, 18% was in the living area, and the remaining 17% was in the kitchen, dining room, and bathroom. Similar data have been reported for adults in the United States; in a survey of 44 U.S. cities, participants spent less than 10% of their time outdoors (Szalai, 1972). The data suggested that occupancy patterns are relatively independent of season, but differences among different days of the week were noted. For example, Sundays in the winter yielded the highest indoor occupancy in residences (about 90%). They also encountered some variation among various population subgroups. Housewives spent approximately 97% of their time indoors; 88% was spent in their own residence, while 9% was spent in other indoor locations. Furthermore, of the remaining 3% that was spent outdoors, about half of that was taken up with traveling. Ethnic Differences Another issue that has been raised in relation to comparisons between miners and the general population are ethnic differences. Is it possible that different ethnic groups have different lung geometries, lung volumes, or breathing patterns? Recently, Roy and Courtay (in press) reviewed the existing literature in relation to ventilation rates and lung volumes. They assessed more than a dozen papers providing information in relation to black, Chinese, Japanese, Indians, Caucasian Americans, and other ethnic groups in the United States. The general conclusion was that there are some differences in lung size among different ethnic groups. American Caucasians tended to have greater portal capacities than did American blacks or Americans of Asian descent. Nevertheless, variability in ventilation among these groups was relatively small, especially when compared with variations in activity and therefore ventilation within individuals. A compelling conclusion is that ethnicity is not a major factor influencing exposure-dose relationships for inhaled particles.

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Comparative Dosimetry of Radon in Mines and Homes Altitude Frequently, underground miners, especially in the United States, work at elevated altitudes. Many of the uranium miners in the Colorado Plateau worked at altitudes of between 5,000 and 8,000 feet above sea level. The related effects caused by changes in oxygen concentration and gas density on breathing are slight in relation to work-ventilation relationships and other concerns addressed in this report. It is true that changes in gas density can affect deposition mechanisms such as sedimentation, but again, these effects are likely to be relatively small. Species Differences Animal models of radon deposition and retention have been used (Cross, 1988). However, even when the same aerosol size distribution is breathed by different species, very disparate lung doses may still result. There are both systematic and unusual variations in ventilation, collection efficiency, and lung anatomy among species that influence the amount and distribution of deposited aerosols. Thus, the problem of extrapolating findings from one species to another and from animals to humans is difficult. Several scientists (Palm et al., 1956; Friedlander, 1964; Kliment, 1973; Stauffer, 1975; McMahon et al., 1977; Raabe et al., 1977; Schlesinger, 1980; Phalen, 1984; Xu and Yu, 1986) have made either theoretical or experimental contributions, but the problem is far from solved. How well aerosol deposition in humans and animals compares has been reviewed recently by Schlesinger (1985b) and by Brain et al. (1988). It is essential to realize that different rates of clearance among species can also influence retention and thus the total dose retained by the lung. CONCLUSIONS Determination of the distribution of inhaled radon daughters within the respiratory tract is one dimension of the more general problem of determining exposure-dose and dose-response relations. It is likely that some of the variability in response among different individuals and various animal species may result from differences in the concentration of radon progeny at the site of action as well as variations in the inherent responsiveness of specific active tissues. Furthermore, the properties of the bronchial epithelium are important, since many radon daughters may breach epithelial barriers and come into contact with more reactive cells.

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