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Title: Health effects of exposure to diesel exhaust particles. Author: McClellan RO. Journal: Annu Rev Pharmacol Toxicol; 1987; 27():279-300. PubMed ID: 2437855. Abstract: Diesel-powered vehicles emit substantially more particles than do gasoline-powered vehicles with contemporary emission control systems. The DEP are submicron in size and readily inhaled. Approximately one-fourth of the particle mass inhaled by people is deposited in the pulmonary region, some of which is retained with a half-life of several hundred days. In animal studies, exposure to high levels of DEP overwhelms the normal clearance mechanisms and results in lung burdens of DEP that exceed those predicted from observations at lower exposure concentrations. A variable amount of the mass of DEP is extractable with strong organic solvents. The extracted material contains more than a thousand individual compounds and is mutagenic in a number of bacterial and mammalian cell assays. Bioassay-directed chemical analysis of DEP had identified several hundred compounds. Many are PAHs, some of which are considered to have human carcinogenic potential. A number of nitrated compounds have been identified that account for a significant portion of the mutagenicity assayed in bacteria. The mutagenicity of the DEPE is generally reduced by addition of an S-9 cellular fraction or of serum proteins. Macrophages rapidly reduce the recoverable mutagenic activity associated with DEP. These findings support a hypothesis that detoxification of DEP-associated organics occurs rapidly in vivo. The association of benzo(a)pyrene and nitropyrene with DEP prolongs their retention in the lungs. This increased retention suggests the need to clarify the relative importance of competing mechanisms that detoxify particle-associated compounds and those that serve to enhance the retention of toxicologically important compounds. Some extracts of DEP evoke tumorigenic responses in skin-tumor bioassays, suggesting their carcinogenic potential in mammals. A number of large-scale studies have been conducted with laboratory rodents to evaluate the effects of chronic inhalation exposure to DE. An increased incidence of lung tumors, some of which were diagnosed as malignant, was observed in 5 studies with rats following exposure for 2 or more years to high levels of DE. Most of the lung tumors were observed after 2 years. Similar studies in Syrian hamsters have yielded negative results. Studies with mice have given mixed results. The results of some studies with laboratory animals exposed to DE and known carcinogens suggest that exposure to DE enhances the effect of the known carcinogens. The specific mechanisms of tumor induction in the DE-exposed rats are unknown. Hypotheses and experimental data have been advanced in support of both genetic and epigenetic mechanisms of action of the DE.(ABSTRACT TRUNCATED AT 400 WORDS)[Abstract] [Full Text] [Related] [New Search]