Short-term exposure of rodents to diesel exhausts: usefulness for studies of genotoxic and immunotoxic effects

An exposure facility was tested with regard to the information obtainable f rom short-term animal experiments for the assessment of health hazards from automotive engine exhausts. Indicators of immunotoxicity and genotoxicity were studied in guinea pigs and mice, respectively, exposed for 2 weeks, 8 h/day, to ten times diluted exhausts from a one-cylinder research diesel en gine running at constant load. Regulated and non-regulated pollutants were determined. Besides increased number of lavageable cells in the airways, ex posed guinea pigs exhibited, after immunization and challenge to ovalbumin reduced leukotrienes B4 and C4 in lavage fluid and reduced anti-ovalbumin I gG in serum. Absence of increased CYP1A activity indicated that the exposur e was below the threshold for induction of these enzymes. Instead a certain reduction of this activity indicated interaction with active enzyme sites. In vivo doses of some reactive metabolites of lon molecular mass were meas ured by adducts to hemogobin. Doses from aliphatic epoxides were low, in ac cordance with low hydrocarbon levels in the exhaust. the levels of hemoglob in adducts from aldehydes showed no clearcut influences of exposure. Geneti c effects determined by DNA fingerprint analysis were indicated. It is conc luded that repeated dose inhalation exposure of small numbers of animals is a useful mode of exposure for studying parameters that may elucidate toxic effects of air pollutants emitted from automotive engines, with a possibil ity to evaluate engine and fuel with regard to health hazards. (C) 1999 Els evier Science Ireland Ltd. All rights reserved.