Repeated pulmonary function measurements in rats after intratracheal instillation of a polyamine textile pigment component.
The pulmonary response of Wistar rats to a cumulative dose of 1 mg/kg body weight of a polymeric alpha,omega-diamine was examined using the intratracheal route of administration. Instillation of the test substance was on days 0 and 7 followed by a 3-month postobservation period. Static and dynamic pulmonary function tests, including arterial blood gas determinations, were performed during wk 5, 9, and 13. At all time points, significantly depressed flow-volume curves, reduced quasistatic compliance, and reduced vital capacity were observed. These were associated with increases of residual volume and functional residual capacity in the presence of unremarkable changes of total lung capacity (TLC). One of the most predominant dysfunctions of the lung was a severe maldistribution of ventilation, indicated by the single-breath nitrogen washout test. The carbon monoxide diffusing capacity (DL(CO)), in turn, was only mildly decreased, and differences between treatment and control groups did not reach statistical significance. Assessment of arterial blood gases demonstrated a statistically significantly increased venous admixture with subsequent slight hypoxemia. In summary, the predominant dysfunction appeared to be consistent with an obstructive rather than restrictive lung disease. The functional changes observed may account for the effect on arterial blood gases, suggesting a mismatch of the ventilation-perfusion relationship. Either measurement appear to demonstrate a relative stable dysfunction during the 3-mo postinstillation observation period. Collectively, this study supports the view held that polymeric alpha, omega-diamines appear to be potent pneumotoxicants.
Pauluhn
J
J
Institute of Toxicology, Bayer AG, Building No. 514, 42096 Wuppertal, Germany. juergen.pauluhn.jp@bayer-ag.de.
D000818:Animals; D001784:Blood Gas Analysis; D004396:Coloring Agents / Q000008:administration & dosage / Q000633:toxicity*; D007442:Intubation, Intratracheal; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D008173:Lung Diseases, Obstructive / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D009757:Nylons / Q000633:toxicity*; D010993:Plethysmography, Whole Body; D011140:Polyurethanes / Q000008:administration & dosage / Q000633:toxicity*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012129:Respiratory Function Tests; D013047:Specific Pathogen-Free Organisms
D004396:Coloring Agents; D009757:Nylons; D011140:Polyurethanes; C403629:acramin FWR