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 from 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 engine running at constant load. Regulated and non-regulated pollutants were determined. Besides increased number of lavageable cells in the airways, exposed guinea pigs exhibited, after immunization and challenge to ovalbumin, reduced leukotrienes B4 and C4 in lavage fluid and reduced anti-ovalbumin IgG in serum. Absence of increased CYP1A activity indicated that the exposure 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 low molecular mass were measured by adducts to hemoglobin. Doses from aliphatic epoxides were low, in accordance with low hydrocarbon levels in the exhaust. The levels of hemoglobin adducts from aldehydes showed no clearcut influences of exposure. Genetic effects determined by DNA fingerprint analysis were indicated. It is concluded 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 possibility to evaluate engine and fuel with regard to health hazards.
Nilsen
A
A
Department of Pharmacology and Toxicology, Norwegian University of Science and Technology, Trondheim.
Trønnes
T
T
Westerholm
R
R
Rannug
U
U
Nilsen
O G
OG
Helleberg
H
H
Kautiainen
A
A
Hedenskog
M
M
Törnqvist
M
M
D000280:Administration, Inhalation; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D016172:DNA Fingerprinting; D006168:Guinea Pigs; D007074:Immunoglobulin G / Q000097:blood*; D007975:Leukotriene B4 / Q000378:metabolism; D017997:Leukotriene C4 / Q000378:metabolism; D008168:Lung / Q000201:enzymology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018895:Microsatellite Repeats; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D009152:Mutagenicity Tests / Q000379:methods; D009153:Mutagens / Q000633:toxicity*; D010047:Ovalbumin / Q000276:immunology; D001335:Vehicle Emissions / Q000633:toxicity*
D007074:Immunoglobulin G; D009153:Mutagens; D001335:Vehicle Emissions; D007975:Leukotriene B4; D017997:Leukotriene C4; D010047:Ovalbumin; D003577:Cytochrome P-450 Enzyme System; D019363:Cytochrome P-450 CYP1A1