Air Pollution, the Automobile, and Public Health (1988) / Chapter Skim
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Biological Disposition of Vehicular Airborne Emissions: Particle-Associated Organic Constituents
Biological Disposition of Vehicular Airborne Emissions: Particle-Associated Organic Constituents
Pages 299-322
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From page 299... ...
BOND ALAN R DAHL Lovelace Biomedical and Environmental Research Institute Significance of Carrier Particles / 300 Characteristics of Particle-Associated Air Pollutants / 301 Inhalation of Airborne Particles / 302 Disposition of Inhaled Particle-Associated Organic Compounds / 302 Bioavailability of Particle-Associated Organic Compounds / 304 Toxicity of Inhaled Organic Compounds / 306 Varieties of Toxic Responses / 306 Metabolism of Chemical Carcinogens / 306 Effects on the Immune System / 312 Summary / 315 Summary of Research Recommendations / 315 Air Pollution, the Automobile, and Public Health.
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Thus, the simple presence of such a potentially toxic compound within a tissue or organ does not necessarily cause a health problem; the tissue or organ in question must be capable of transforming the compound into toxic metabolites. In addition to tissues and organs, pulmonary alveolar macrophages may play an important role in the disposition and metabolic fate of inhaled organic pollutants.
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This chapter proceeds with a discussion of the disposition of inhaled particle-associated organic compounds, including the effects of particle association on lung clearance and bioavailability of these organic compounds. This is followed by a discussion of the paths and mechanisms by which particle-associated inhaled organic compounds produce a biological effect.
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Inhalation of Airborne Particles Disposition of Inhaled Particle Associated Organic Compounds Particles carrying adsorbed organic compounds are deposited in the respiratory tract by the same mechanisms and according to the same principles as particles without adsorbed compounds. Inhaled aerosols of BaP or NP alone, BaP or NP adsorbed onto gallium oxide (Ga2O3)
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The data suggest that Ga203-associated organic material clears from lungs primarily by dissolution and direct absorption into the blood. In the pulmonary regions, the long-term retention of BaP or NP adsorbed onto diesel engine exhaust particles is as much as 230
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used ~4C-NP associated with diesel exhaust particles to study what form this organic material has after reaching nonrespiratory tract tissues. Within 1 hr after exposure, a large proportion of the i4C had cleared from the lungs to other tissues and more than 90 percent of the ~4C in these tissues was associated with NP metabolites.
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found that when pulmonary alveolar macrophages were incubated with diesel engine exhaust particles, amounts of organic compounds and mutagenic activity decreased measurably from the amount originally associated with these particles, suggesting that organics were removed from phagocytized particles. Collectively, these studies suggest that particle-associated organics become "bioavailable" to respiratory tract cells, allowing metabolic processes to occur.
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As discussed earlier in this chapter, many of the organic compounds in automotive exhaust are not released in their pure form, but are adsorbed onto the insoluble, carbonaceous soot of automotive exhaust. Clearance of insoluble particles from lungs depends on the phagocytic activity of pulmonary alveolar macrophages and their eventual translocation to the lymphatic system (Schlesinger, this volume)
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A number of reviews have been published relating to the metabolism or metabolic activation of chemical carcinogens (Miller and Miller 1966, 1981; Dipple et al.
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308 0 / ~ @~ 6, 1 2-qu~none tree ~ radical jMFO 0H HO ~ / 9-hvdroxv 1-hvdrox, 1~ radical ~ ~J _ MFO OH BENZOta] PYRENE 6-hydroxy tree |radical MFO - ° ~o 3,6-quinone 2,3-epoxide\ Particle-Associated Organic Constituents ., .
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1984; Dahl 1986~. Nasal tissue metabolism is important because many environmental pollutants contain known carcinogens adsorbed onto particles of sizes that deposit in the nasopharyngeal region of the respiratory tract (Task Group on Lung Dynamics 1966; Natusch and Wallace 1974~.
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However, in contrast, Bevan and Manger (1985) demonstrated that BaP hydroxylase activity in rat liver microsomes was slightly inhibited when BaP was adsorbed onto particulate matter.
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The role of pulmonary alveolar macrophages in metabolizing inhaled organic compounds has not been studied as extensively as other cells, but its importance should not be overlooked. Some particles deposited in lungs are phagocytized by macrophages, some macrophages with engulfed particles remain in the lung for extended periods of time (see Schlesinger, this volume)
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Toxic effects on pulmonary alveolar macrophages have been observed from organic chemicals associated with particles from a variety of sources including automotive emissions (Romert et al.
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found that, despite this toxicity, the effect on overall phagocytosis in vivo may be small because the number of pulmonary alveolar macrophages in rats increased in response to exposure to diesel exhaust. After exposure of rats to high concentrations of diesel exhaust, phagocytic neutrophils were recruited into the lung, thereby potentially further increasing the overall phagocytic capacity (figure 5~.
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Combustion aerosols from nonautomotive sources that have been studied with regard to immune responses include coal fly ash and cigarette smoke. Fly ash had no effect on the response to antigenic challenge in mice immunized with live bacillus Calmette-Guerin organisms, or on the ability of pulmonary alveolar macrophages to function in T-lymphocyte mutagenesis assays (Zarkower et al.
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Outlined below are the most critical areas of study that would provide the information needed for better estimations of the potential human health risks of inhaled atmospheric pollutants. Recommendation 2 Little information is available on the specific regions and/or cell types in the respiratory tract where inhaled organic compounds adsorbed onto particles become bioavailable.
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In this latter case, the slow release of compounds from particles may result in keeping the concentration below the "critical" dose, which may be a level where metabolic detoxification or repair can effectively occur. The toxicologic effects of particle-associated organic compounds and ~ , o ~ r the mechanism of those effects need to be tested in long-term inhalation studies using organic compounds that are retained substantially longer in the lungs when adsorbed onto particles than when inhaled in pure form.
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Recommendation 8 Following phagocytosis, particles and associated organic com nounds are translocated to luna-associated lymphoid tissue. This translocation may allow for the metabolism of these organic compounds in the lymph nodes.
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1973. Induction of aryl hydrocarbon hydroxylase in human pulmonary alveolar macrophages by cigarette smoking, J
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1982. Clearance of diesel soot particles from rat lung after a subchronic diesel exhaust exposure, Fundam.
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pyrene metabolism in normal human pulmonary alveolar macrophages, Cancer Lett.
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1983. Effects of air pollutants on the oxidative metabolism and phagocytic capacity of pulmonary alveolar macrophages, J
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pyrene and binding to DNA in cultured human bronchus, Cancer Res.
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