The motivation of simulating real-world environmental exposure in a number
of long-term studies with dogs was to address the question of whether or no
t perpetual inhalation of air pollutants can initiate diseases in healthy l
ungs and can thus contribute to the increasing prevalence of respiratory di
seases in industrialized countries. The major conclusion of this article is
that this question has to be answered in the negative for the simultaneous
inhalation of the major constituents of combustion-related air pollution,
particle-associated sulfur(IV), and particle-associated hydrogen ions. Over
13 mo, 8 healthy beagle dogs were exposed in 2 whole-body chambers daily f
or 16.5 h to 1 mu m neutral sulfite [sulfur(IV)] particles at a mass concen
tration or 1.5 mg m(-3) and for 6 h to 1.1 mu m acidic sulfate particles ca
rrying 15 mu mol m(-3) hydrogen ions into the canine lungs. This longitudin
al study was characterized by repeated observations of individual respirato
ry response patterns. To establish baseline data the dogs were repeatedly e
xamined preexposure while the chambers were ventilated over 16 mo with clea
n air. Each individual served thus as its own control. Another eight dogs s
erved as additional controls. They were housed in 2 chambers ventilated wit
h clean air over the entire study period of 29 mo. To assess response patte
rns, respiratory lung function tests were performed pre- and postexposure,
segmental lung lavages were repeatedly performed to obtain epithelial linin
g fluid from the lungs for analysis of cell content, cell function, and bio
chemical indicators of lung injury, and radiolabeled test particles were us
ed to study pathways of intrapulmonary particle elimination. At the end of
the study, the lungs of all animals were morphologically and morphometrical
ly examined. Functional and structural responses were finally compared to t
hose observed previously as a result of a sole exposure of canine lungs to
neutral sulfite particles over 10 mo (Heyder et al., 1992). Interactions be
tween responses induced by neutral sulfite and acidic sulfate particles occ
urred, but antagonism rather than synergism was observed. The responses ind
uced by sulfur(IV) were less pronounced, not detectable, or even reversed w
hen hydrogen ions were also delivered to the lungs. On the other hand, resp
onses not induced by the sole exposure to sulfur(IV) were observed: The act
ivity of alkaline phosphatase was elevated and type II pneumocytes prolifer
ated. It can, however, be concluded that long-term exposure of healthy lung
s to particle-associated neutral sulfur(IV) and hydrogen ions at concentrat
ion close to ambient levels causes subtle respiratory responses but does no
t initiate pathological processes in the lungs. In other words, the perpetu
al inhalation of sulfur(IV) and hydrogen ions from the atmospheric environm
ent presents no health risk to the healthy lungs. ii is thus also very unli
kely that respiratory diseases can be initiated by the inhalation of these
pollutants.