Air Pollution, the Automobile, and Public Health (1988) / Chapter Skim
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Biological Disposition of Airborne Particles: Basic Principles and Application to Vehicular Emissions
Biological Disposition of Airborne Particles: Basic Principles and Application to Vehicular Emissions
Pages 239-298
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From page 239... ...
Biological Disposition of Airborne Particles: Basic Principles en cl Application to Vehicular ~ · ~mlsslons RICHARD B SCHLESINGER New York University Medical Center Structure of the Respiratory Tract / 240 Upper Respiratory Tract / 240 Tracheobronchial Tree / 241 Pulmonary Region / 244 Research Recommendations / 246 Ventilation / 246 Ventilatory Parameters / 246 Comparative Aspects of Ventilation / 248 Airflow Patterns / 248 Research Recommendations / 249 Deposition of Inhaled Particles in the Respiratory Tract / 250 Deposition Mechanisms and Controlling Factors / 250 Measurement of Deposition / 253 Factors Modifying Deposition / 258 Localized Patterns of Deposition / 259 Mathematical Modeling / 260 Research Recommendations / 262 Retention of Deposited Particles / 263 Clearance Mechanisms: Basic Structure and Function / 263 Clearance Kinetics / 266 Factors Modifying Clearance / 272 Research Recommendations / 273 Disposition of Vehicular Particulate Emissions / 275 Diesel Exhaust Particles / 275 Metals / 276 Sulfates / 280 Research Recommendations / 281 Summary 1 283 Summary of Research Recommendations: Discussion / 284 Summary of Research Recommendations: Priorities / 285 Air Pollution, the Automobile, and Public Health.
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. sections accorc lug to tunctlon: one IS concerned with transporting air from the external environment to the sites of gas exchange and consists of the upper respiratory tract and the tracheobronchial tree; the other, the pulmonary region, is involved in gas exchange.
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Schematic diagram of tracheobronchial tree branching patterns: (A) human lung; (B)
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Recent qualitative observations on the tracheobronchial trees of two nonhuman primates-the rhesus monkey and the baboon suggest a branching pattern that is more irregular than that of humans, but not to the extent of the experimental animal species shown in figure 5 (Patra 1986~. But although there may be striking interspecies differences in the upper bronchial tree, the branching patterns in most mammals tend to approach more regular symmetry in distal conducting airways.
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lar and irregular dichotomous branching modes concerns the number of airways between the trachea and the terminal bronchioles. In a regular dichotomous branching system, the number of divisions and, 243 therefore, the path length, between the trachea and the most distal conducting airways is the same along any pathway.
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Pulmonary Region The pulmonary region extends from the respiratory bronchioles through the alveoli and contains airways involved in gas exchange between the air and blood (figure 6a)
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(A) Diagram of the human airways in the pulmonary region; (B)
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· Recommendation 1. Variability in morphometry of the tracheobronchial and pulmonary regions in normal humans as well as experimental animals (including different strains)
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, the latter being the amount of air entering the pulmonary region each minute. The effective portion of VA that participates in gas exchange is equal tOf(VT- VDIO')
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Comparative Aspects of Ventilation Since much of the toxicologic work with inhaled particles involves experimental animals, it is essential that their respiratory mechanics be quantitated. Various animal data exist (see, for example, Guyton 1947; Spell 1969)
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Patterns and distribution of airflow in the tracheobronchial tree of healthy adult experimental animals and humans should be determined. This information is important for the development of deposition models and for the extrapolation of results of toxicologic studies to humans.
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Impaction onto an airway surface occurs when a particle's momentum prevents it from changing course in an area where there is a rapid change in the direction of bulk airflow. It is the main deposition mechanism for particles having Dae ' 0 5 ,um in the upper respiratory tract and at or near tracheobronchial tree branching points.
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Electrostatic deposition results from image charges induced on the tlcle deposition in tile respiratory tract requires an appreciation of various controlling factors: characteristics of the inhaled particles, anatomy of the respiratory tract, and ventilation pattern. Characteristics of Inhaled Particles.
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Differences in pathway lengths in different lung lobes affect regional deposition. Lobes with the shortest average path length between the trachea and terminal bronchioles may have the highest concentration of deposited particles 21 ,um in the alveoli.
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For example, alveolar size differs among species; since particles with Dae ' 0.5 ,um that reach the alveoli will be deposited primarily by sedimentation, and different-size alveoli have different characteristics as sedimentation chambers, the net result will be that the pulmonary region of various species will have different deposition efficiencies. Differences in deposition patterns affect the dosimetry of inhaled particles and the ability to use the results of toxicity tests in experimental animals for human risk assessments.
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. Compilations of experimentally determined deposition values in humans and those experimental animals commonly used in inhalation toxicology studies are shown in figure 10.
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Figure 10a shows total respiratory tract deposition. In humans, nasal inhalation results in somewhat greater total deposition than oral exposures for particles with diameters >0.5 ,um because the nasal passages collect larger particles more efficiently than the oral passages.
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tracheobronchial tree, and (D) pulmonary region.
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Inasmuch as smaller particles can penetrate the upper respiratory tract at all flow rates, deposition for these is similar in all species. If deposition were plotted in a manner that would normalize for flow, which is not possible for most of the experimental animal studies because of the lack of such data, the experimental animals would probably show greater deposition efficiency for larger particles than would humans at equivalent size/flow normalization parameters.
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Patterns are similar for oral inhalation, although the particle size for peak deposition is greater in humans than in guinea pigs or dogs. This is probably due to the more efficient removal; of larger particles in the upper respiratory tract and tracheobronchial airways of these experimental animals.
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This suggests that as particle size increases, women (and perhaps children) may be at less risk from material in pulmonary airways but at a greater risk from deposition in the upper respiratory tract and tracheobronchial tree.
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Differences in the geometry of airways in humans and other species may result in differences in the microdistribution pat terns of particle deposition, a factor that should be accounted for in extrapolation Biological Disposition of Airborne Particles A ~-it< ~ /-~ ' |
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Although most models have been designed for assessing deposition of spherical particles in humans, some have been developed for experimental animals (Kliment et al. 1972; Kliment 1973, 1974; Schreider and Hutchens 1979; Schum and Yeh 1980)
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Microdistribution patterns of deposition should be studied under a wide range of exposure conditions. The nonuniformity of deposition in both the tracheobronchial tree and the pulmonary region may be important factors in ultimate dose.
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Recommendation 16. Intercomparisons of regional deposition patterns among experimental animals (unsedated)
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Tracheabronchial Tree. Most of the surface of the tracheobronchial tree through the terminal bronchioles is lined with ciliated epithelium overlaid by mucus, and insoluble particles are cleared primarily by the net movement of fluid toward the oropharynx.
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| Deposited Particle | ~ ~ ~Passage Through Phagocytosis by Alveolar Macrophages ~Pulmonary Capillary Endothelium ~ ~ ~ t Passage Through / Phagocytos~ by Alveolar Epithelium / Inte~tRial Macrophages Interstitium //~ ~ -'1~ Lymphatic Channels 1 __ Lymph Nodes~~ , _ _ ~ Figure 12. Flowchart of clearance pathways for particles depositing in the pulmonary region (dissolution is not included)
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The migration and grouping of particles and macrophages can lead to the redistribution of deposits into focal aggregates in the lungs (Heppleston 1953~. The specific clearance route for particles depositing in the pulmonary region may depend upon loading.
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Tissue doses to the upper respiratory tract and tracheobronchial tree are often limited by the rapid clearance from these regions and are thus proportional to concentration and exposure duration. On the other hand, doses from material deposited in the pulmonary region depend much more on the characteristics of both the particle matrix and any associated materials.
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Pulmonary region clearance is relatively slow, and therefore measurements should be performed over, perhaps, several months. When radioactively tagged tracer particles are used, a nuclide having a long half-life is required.
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These probably represent clearance of the tracer particles deposited in the "upper" and "lower" tracheobronchial tree, respectively. As the size of the tracer particles is reduced, resulting in more distal deposition, there is an increase in the fraction of total tracheobronchial clearance which is accounted for by the slower phase.
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Consequently, the kinetics of clearance from the pulmonary region are not definitively understood, although particles deposited there generally remain longer than do those deposited in ciliated airways. Data on clearance rates in humans are limited, and those for experimental animals (and humans)
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Even less is known about relative rates along specific pathways than about overall pulmonary region clearance kinetics. After deposition, the uptake of particles by alveolar macrophages is very rapid, unless the particles are cytotoxic (Lehnert and Morrow 1985; Naumann and Schlesinger 1986~.
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There are no data for changes in overall pulmonary region clearance related to aging. Functional differences have been found between alveolar macrophages from mature and senescent mice (Esposito and Pennington 1983)
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1982~. Reduced clearance from the pulmonary region of experimental animals with viral infections has also been observed (Cresia et al.
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Clearance kinetics of the growing lung and the aging lung should be studied. Studies of mucociliary clearance and pulmonary region clearance are needed; when combined with deposition studies, a comprehensive picture of defense capabilities in the young and elderly segments of the population can be developed.
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Following deposition, diesel particles are fairly evenly distributed throughout the pulmonary region. Gradually, within mac rophages, the particles are moved from peripheral lung regions toward the termi nus of the mucociliary transport system, from where they may be cleared via the tracheabronchial tree (White and Garg breathing conditions has been estimated~ 96-i J .
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Another clearance pathway from the pulmonary region is by the lymphatic system. Free diesel particles, as well as particleladen macrophages, have been found in parenchymal lymphoid aggregates, lymphatic vessels, and mediastinal lymph nodes (Vostal et al.
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The absorption efficiency for most metals is about 50 to 80 percent from the pulmonary region, and 5 to 15 percent from the upper respiratory tract and tracheobronchial tree (Natusch et al.
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Metals that deposit in the pulmonary region have the greatest toxic potential because of the likelihood of extended residence times. The more insoluble the metal, the more likely it is to be cleared from this area by movement to the tracheobronchial tree, followed by swallowing.
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Rabbit alveolar macrophages exposed to 5 ,um Teflon particles coated with various metals phagocytosed those with carbon or Cr to a greater degree than those coated with Pb, Mn, or silver (Ag) (Camper et al.
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. 280 Biological Disposition of Airborne Particles Nickel.
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Sulfuric acid exposures of experimental animals have also been associated with alterations in the rate of clearance of tracer particles from the pulmonary region (Phalen et al. 1980; Naumann and Schlesinger 1986; Schlesinger and Gearhart 1986)
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1 hr 1 hr 4 hr 4 hr J bronchial clearance 4 hr NC bronchial clearance ~1, pulmonary region clearance 1 hr/day, 5 ,, bronchial clearance within 3 days/week months up to 6 months 1 hr/day, 5 days/week up to 4 weeks 1 hr it bronchial clearance within 1 week 1 hr/day, 5 days/week, up to 8 months 2 hr/day, 14 days Sackner et al.
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The specific pathway depends on the region of the respiratory tract where the material deposits, physicochemical properties of the material, and, perhaps, exposure concentration and duration. The primary biological clearance mechanisms for insoluble particles are mucociliary transport in the nasal passages and tracheobronchial tree, and removal by resident macrophages from the pulmonary region.
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These materials alter the rates of clearance processes, both in conducting airways and in the pulmonary region, thus compromising the lung's defense capabilities. Summary of Research Recommendations: Discussion Many of the recommendations presented are for highly goal-oriented studies needed to expand or refine the data base on factors that control the disposition of inhaled particles.
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H I G H P R I O R I T Y These studies are essential in order to provide needed data for more accurate risk assessment. Recommendation 1 Interindividual variability of dimensions of the upper respiratory tract, tracheobronchial tree, and pulmonary region for adult hu mans and experimental animals (including strain differences)
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Recommendations Patterns and distribution of airflow in the nasal passages and 5, 6, 7 tracheobronchial tree of experimental animals and humans, and in the oral passages of humans, should be determined. This should include assessments in the growing, aging, and diseased lung.
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Recommendation 20 Pathways of clearance from the pulmonary region to sites of long-term retention in the parenchyma should be studied. Recommendations Regional deposition and ultimate fate of hydroscopic and soluble 15, 25 particles should be evaluated.
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1966. Regional aerosol deposition in the human respiratory tract, In: Inhaled Particles and Vapours II (C.
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1985. The response of rat alveolar macrophages to chronic inhalation of coal dust and/or diesel exhaust, Environ.
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1986. The relationships of aerosol deposition, lung size, and the rate of mucociliary clearance, Arch.
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1982. Accumulation of diesel soot in lungs of rodents exposed in life span studies to diluted diesel exhaust, In: Inhalation Toxicology Research Institute Annual Report 1981-1982, Lovelace Biomedical and Environmental Research Institute, Albuquerque, N.Mex., LMF-102, National Technical Information Service, Springf~eld, Va.
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1979. A model for tracheobronchial clearance of inhaled particles in man and a comparison with the data, IEEE Trans.
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1971b. Abnormal deposition and clearance of inhaled particles during upper respiratory and viral infections, J
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1966. Method for studies on inhaled particles in human respiratory system and retention of lead fume, Ind.
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1977. Polonium210: lead 210 ratios as an index of residence times of insoluble particles from cigarette smoke in bronchial epithelium, In: Inhaled Particles IV (W.
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1983b. Physiological and histological alterations in Biological Disposition of Airborne Particles the bronchial mucociliary clearance system of rabbits following intermittent oral or nasal inhalation of sulfuric acid mist, J
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1979. Lymphatic transport of inhaled diesel particles in the lungs of rats and guinea pigs exposed to diluted diesel exhaust, In: Proceedings of the International Symposium on Health EfJects of Diesel Engine Emission, U
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1983. Mucociliary transport and particle clearance in the human tracheobronchial tree, In: Aerosols in the Mining and Industrial Work Environments (V.
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