Inhalation of formaldehyde does not induce genotoxic effects in broncho-alveolar lavage (BAL) cells of rats.
Male Fischer-344 rats were exposed to formaldehyde (FA) by inhalation for 4 weeks (6h/day, 5 days/week). Groups of six rats each were exposed to the target concentrations of 0, 0.5, 1, 2, 6, 10 and 15ppm. Potential genotoxic effects in the lung were investigated as part of a comprehensive study on local and systemic toxic and genotoxic effects. Broncho-alveolar lavage (BAL) cells were obtained by lung lavage with physiological saline and counted. From one half of the cells, slides for the micronucleus test (MNT) were prepared by cytocentrifugation; with the other half, the comet assay was performed. DNA migration in the comet assay was measured both directly and after irradiation of the cells with 2Gy gamma-radiation. The latter modification of the comet assay was included to increase its sensitivity for the detection of DNA-protein cross-links (DPX). For the comet assay, four slides were analysed from each cell sample, two without and two with irradiation. From each slide, 50 randomly selected cells were measured by image analysis and tail intensity (% tail DNA) and tail moment were evaluated. The frequency of micronucleated BAL cells was determined in acridine orange-stained slides by analysing 2000 cells per animal. FA did not induce any significant effect in any of the genotoxicity tests performed. It can be concluded that inhalation of FA in a 28 days study with FA concentrations up to 15ppm does not lead to genotoxic effects in BAL cells of rats. Because detection of DPX by the comet assay is a very sensitive biomarker of FA exposure of cells, our results suggest that there is no genetically relevant exposure of the lung after FA inhalation. The results of our inhalation study, which was performed under GLP conditions, call into question the biological significance of previously reported genotoxic effects in the lung of rats after FA inhalation.
Neuss
Simone
S
Universität Ulm, Institut für Humangenetik, D-89069 Ulm, Germany.
Zeller
Jasmin
J
Ma-Hock
Lan
L
Speit
Günter
G
D000280:Administration, Inhalation; D000818:Animals; D018893:Bronchoalveolar Lavage; D020552:Comet Assay; D004249:DNA Damage; D004202:Disinfectants / Q000633:toxicity*; D005557:Formaldehyde / Q000633:toxicity*; D019570:Inhalation Exposure; D008168:Lung / Q000187:drug effects* / Q000528:radiation effects; D008264:Macrophages / Q000187:drug effects / Q000528:radiation effects; D008297:Male; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects*; D015162:Micronucleus Tests; D051381:Rats; D011916:Rats, Inbred F344
D004202:Disinfectants; D005557:Formaldehyde