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

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AIR QUALITY GUIDELINES
20 days) is significantly impaired (49). This was explained by decreased production,
as a consequence of an inhibition of NADPH oxidase and complex III of the
respiratory chain and, to a lesser extent, increased scavenging brought about by
enhanced glutathione peroxidase and copper/zinc-superoxide dismutase mRNA
expression and enzyme activities.
The effects of nitrogen dioxide on various cell culture systems have also
been described. One system exposed cultured human bronchial epithelial cells
to 7520 and 15 040 μg/m 3 (4.0 and 8.0 ppm) nitrogen dioxide and elicited both
cell membrane damage and increased membrane permeability (50). It should
be remembered that confluent airway epithelial cell monolayers in vitro are not
fully differentiated and posses a markedly lower level of resistance to pollutants
compared to the epithelium in the intact human. However, in a more physiologically
relevant system, nitrogen dioxide (200 and 800 μg/m 3 ; 0.1 and 0.43 ppm)
has also been shown to trigger inflammation in cultured human nasal mucosa
explants using histamine release into the culture medium as a marker of the
inflammatory response (51). The early pro-inflammatory responses following
exposure to a brief high concentration of nitrogen dioxide (84 600 μg/m 3 ;
45 ppm) have also been assessed using human bronchial epithelial cells as an in
vitro model of inhalation injury (52). While immunofluorescence studies confirmed
oxidant-induced formation of 3-nitrotyrosine, the nitrogen-dioxide-exposed
cells exhibited marked increases in the levels of nitrite (used as an index
of nitric oxide), IL-8, IL-1β and TNF-α. Furthermore, in order to simulate a preexisting
“inflammatory” condition of the bronchial epithelium, such as would
exist in asthma and other hyperreactive airway diseases, cells were pre-treated
with various pro-inflammatory cytokines (IFN-γ, TNF-α, IL-1β and IL-8) for 24
hours prior to exposing them to nitrogen dioxide. The combination of cytokine
treatment and nitrogen dioxide exposure consistently enhanced the generation
of nitric oxide and IL-8.
Reproductive effects
A recent study examined effects in the rat of fetal exposure to diesel-engine exhaust
containing nitrogen dioxide (1504 or 188 μg/m 3 ; 0.80 or 0.10 ppm) with
or without PM (1.71 or 0.17 mg/m 3 ) on testicular cell numbers and daily sperm
production in adulthood (53). The mature rats that were exposed to diesel exhaust
during the fetal period (from gestational day 7 to delivery) showed a reduction
in the daily production of sperm owing to an insufficient number of Sertoli
cells. All exhaust-exposed groups showed almost the same reactions toward the
inhalation, indicating that the gaseous phase must have included the responsible
toxicants; these were not identified, although nitrogen dioxide would be a major
constituent.
Overall, acute exposures (hours) to low levels of nitrogen dioxide have rarely
been observed to cause effects in animals. Subchronic and chronic exposures