Effects of di-n-butylamine on the respiratory system of Wistar (WU) rats after subchronic inhalation.
Aim of the study was to investigate the potential toxic effects of di-n-butylamine (DBA), a known skin and eye irritating compound, on the respiratory tract after inhalation exposure for up to 91 days in male and female rats [Crl:(WI)WU BR]. To check whether and to what degree the no-observed-(adverse)-effect level (NO(A)EL) decreases with increasing study duration, serial sacrifices were performed after 3 and 28 days, respectively. Based on two dose range-finding studies, the concentrations for this study were determined with 0 (clean air), 50, 150, and 450 mg/m(3). Animals were exposed for 3 days (6 h/day) 28, and 91 days (5 days/wk, 6 h/day), respectively, and immediately sacrificed thereafter. The results show clear irritating effects only in the upper part of the respiratory tract, that is, the nasal cavities. While after 3 and 28 days effects were found only in the high-dose group, slight adaptive effects, expressed as mucous (goblet) cell hyperplasia, could be diagnosed in the medium- and low-dose groups after 91 days of exposure. Pathological changes were most prominent after 3 days of exposure. In the lung, only marginal effects could be observed (increased relative lung weight only in females of the high concentration after 28 days, slight, not statistically significant histopathological effects in the high concentration after 3 days, no effects on parameters of bronchoalveolar lavage fluid), while no effects were found in the remaining groups.
Buschmann
Jochen
J
Fraunhofer-Institut für Toxikologie und Experimentelle Medizin, Nikolai-Fuchs-Str. 1, D-30625 Hannover, Germany. buschmann@item.fraunhofer.de
Dasenbrock
Clemens
C
Fuhst
Rainer
R
Pohlmann
Gerhard
G
Bartsch
Wilfried
W
Creutzenberg
Otto
O
Ernst
Heinrich
H
Ketkar
Madhukar
M
Schneider
Bernhard
B
Ott
Heidi
H
D000280:Administration, Inhalation; D000818:Animals; D001835:Body Weight; D001992:Bronchoalveolar Lavage Fluid; D002082:Butylamines / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007509:Irritants / Q000008:administration & dosage / Q000633:toxicity*; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008297:Male; D009929:Organ Size; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
D002082:Butylamines; D007509:Irritants; C045274:dibutylamine