J. Pauluhn, Repeated pulmonary function measurements in rats after intratracheal instillation of a polyamine textile pigment component, INHAL TOXIC, 12(7), 2000, pp. 591-604
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 intratrach
eal route of administration. instillation of the test substance was on days
0 and 7 followed by a 3-month postobservation period. Static and dynamic p
ulmonary function tests, including arterial blood gas determinations, were
performed during wk 5, 9, and 13. At all time points, significantly depress
ed flow-volume corves, reduced quasistatic compliance, and reduced vital ca
pacity were observed. These tl cre associated with increases of residual vo
lume and functional residual capacity in the presence of unremarkable chang
es of total lung capacity (TLC). One of the most predominant dysfunctions o
f the lung war a severe maldistribution of ventilation, indicated by the si
ngle-breath nitrogen washout lest. The carbon monoxide diffusing capacity (
DLCO), in turn, was only mildly decreased, and differences between treatmen
t and control groups did not reach statistical significance. Assessment of
arterial blood gases demonstrated a statistically significantly increased v
enous admixture with subsequent slight hypoxemia. In summary, the predomina
nt dysfunction appeared to be consistent with an obstructive rather than re
strictive lung disease. The functional changes observed may account for the
effect on arterial blood gases, suggesting a mismatch of the ventilation-p
erfusion relationship. Either measurement appear to demonstrate a relative
stable dysfunction during the 3-mo postinstillation observation period. Col
lectively, this study supports the view held that polymeric alpha,omega-dia
mines appear to be potent pneumotoxicants.