Rb. Schlesinger et al., PULMONARY EFFECTS OF REPEATED EPISODIC EXPOSURES TO NITRIC-ACID VAPORALONE AND IN COMBINATION WITH OZONE, Inhalation toxicology, 6(1), 1994, pp. 21-41
Inhaled acids are associated with adverse health effects, a conclusion
based largely on studies with particulate-associated acid sulfates. T
he acidic component of ambient air in some regions, such as California
, contains nitric acid (HNO3) vapor, but there is a limited database c
oncerning its biological effects. Furthermore, effects of HNO3 may be
modulated by coexposure to other pollutants, such as ozone (O-3). Rabb
its were exposed for 4 h/day, 3 days/wk for 4 wk to HNO3 vapor at 0, 5
0, 150, and 450 mu g/m(3) alone; 0.15 ppm 0(3) alone; or to a mixture
of 50 mu g/m(3) HNO3 + 0.15 ppm 0(3). Exposure was followed by assays
of biochemical markers in lavage fluid pulmonary macrophage function,
and in vitro bronchial responsivity to smooth muscle constrictor chall
enge. Nitric acid had no effect on viability or numbers of cells recov
ered, nor on lactate dehydrogenase or total protein in lavage. All aci
d concentrations reduced both basal levels and stimulated production o
f superoxide anion by macrophages, while the release/activity of tumor
necrosis factor by stimulated macrophages was reduced following expos
ure to greater than or equal to 150 mu g/m(3) HNO3. Bronchi from rabbi
ts exposed to greater than or equal to 150 mu g/m(3) HNO3 exhibited re
duced smooth muscle responsivity in vitro compared to control. Althoug
h exposure to the HNO3/O-3 mixture resulted in no interaction for most
end points, antagonism was noted for stimulated superoxide production
, while synergism was noted for spontaneous superoxide production and
bronchial responsivity. Exposure to the mixture resulted in a total ab
rogation of response to spasmogens in most bronchi examined and a mark
ed attenuation in others. These results indicate that HNO3, when inhal
ed in vapor phase, may adversely impact upon pulmonary health by affec
ting target sites throughout the lungs, and that inhalation of an HNO3
/O-3 mixture can produce synergistic interaction in affecting some bio
logical parameters.