Air Quality Guidelines Global Update 2005 - World Health ...

NITROGEN DIOXIDE
linear, concentration-related increases in mortality due to pulmonary infection
(42). Additional studies have shown that the increase in mortality is highly dependent
on the exposure regimen. Concentration would appear to be more important
than duration of exposure in increasing susceptibility to infection.
These and other data show that peak exposures and patterns of exposure are
important in determining response (1,43,44). Some studies indicate that several
months of exposure to nitrogen dioxide levels of approximately 940 μg/m 3 (0.5
ppm) can increase susceptibility to other bacteria and viruses, and that acute exposure
to higher levels can decrease pulmonary bactericidal activity and alveolar
macrophage function. In summary, it is clear that the effects of nitrogen dioxide
are due more to concentration than to duration of exposure or to total dose
(expressed as C × T), that differences in species sensitivity exist, that the lowest
effective concentration of nitrogen dioxide also depends on the microbe used in
the test, and that low levels cause effects only after repeated exposures (1,4,5,22).
Extrapolation of these findings to humans cannot be made directly, because most
of the studies used pneumonia-induced mortality as an endpoint. However, the
infectivity model reflects alterations in the defence mechanisms of mice that are
shared by humans. This, together with other mechanistic studies, implies that
the specific host defences of humans (such as alveolar macrophages) can be influenced
by nitrogen dioxide. However, the quantitative relationship between effective
nitrogen dioxide levels in animals and in humans is unknown. Although
numerous studies provide evidence of the effects on the systemic humoral and
cell-mediated immune systems, these studies are difficult to interpret (1,4).
At the time of writing, there are no reports that nitrogen dioxide causes malignant
tumours or teratogenesis (1,4,45). Limited genotoxicity studies have produced
mixed results with in vitro and high-concentration in vivo studies (e.g.
50 000 μg/m 3 ; 27 ppm) (46). Extrapulmonary effects have also been observed but
cannot be interpreted with respect to human risk (1). Numerous studies of the
interaction of nitrogen dioxide with other air pollutants, predominantly ozone,
show that the effects are due to ozone alone, are additive, or are synergistic, depending
on the end-point and exposure regimen (30).
In vitro studies
The effects of nitrogen dioxide have been investigated using a variety of in vitro
test systems. Exposure of human blood plasma to 26 230 μg/m 3 (13.95 ppm) nitrogen
dioxide resulted in a rapid loss of ascorbic acid, uric acid and protein thiol
groups, in addition to lipid peroxidation and a depletion of alpha-tocopherol
(vitamin E) (47). In a separate study, exposure to nitrogen dioxide over a lower
concentration range (94–1880 μg/m 3 ; 0.05–1.0 ppm) resulted in the antioxidant
defences, uric acid and ascorbic acid being depleted in human BAL fluid (48).
More recently, Olker et al. showed that superoxide radical release from BAL cells
isolated from nitrogen-dioxide-exposed rats (18 800 μg/m 3 (10 ppm) for 1, 3 or
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