Abstract
BackgroundWe previously demonstrated that continuous exposure to nitrous acid gas (HONO) for 4 weeks, at a concentration of 3.6 parts per million (ppm), induced pulmonary emphysema-like alterations in guinea pigs. In addition, we found that HONO affected asthma symptoms, based on the measurement of respiratory function in rats exposed to 5.8 ppm HONO. This study aimed to investigate the dose-response effects of HONO exposure on the histopathological alterations in the respiratory tract of guinea pigs to determine the lowest observed adverse effect level (LOAEL) of HONO.MethodsWe continuously exposed male Hartley guinea pigs (n = 5) to four different concentrations of HONO (0.0, 0.1, 0.4, and 1.7 ppm) for 4 weeks (24 h/day). We performed histopathological analysis by observing lung tissue samples. We examined samples from three guinea pigs in each group under a light microscope and measured the alveolar mean linear intercept (Lm) and the thickness of the bronchial smooth muscle layer. We further examined samples from two guinea pigs in each group under a scanning electron microscope (SEM) and a transmission electron microscope (TEM).ResultsWe observed the following dose-dependent changes: pulmonary emphysema-like alterations in the centriacinar regions of alveolar ducts, significant increase in Lm in the 1.7 ppm HONO-exposure group, tendency for hyperplasia and pseudostratification of bronchial epithelial cells, and extension of the bronchial epithelial cells and smooth muscle cells in the alveolar duct regions.ConclusionsThese histopathological findings suggest that the LOAEL of HONO is < 0.1 ppm.
Highlights
We previously demonstrated that continuous exposure to nitrous acid gas (HONO) for 4 weeks, at a concentration of 3.6 parts per million, induced pulmonary emphysema-like alterations in guinea pigs
This study aimed to investigate the dose-response effects of HONO exposure associated with histopathological alterations in the respiratory tracts of guinea pigs to find the lowest observed adverse effect level (LOAEL) of HONO
Guinea pigs were continuously exposed to HONO for 4 weeks, the concentrations of Nitrogen dioxide (NO2) and nitric oxide (NO) in each chamber air were measured for 30 min per day for 5 days per week using NOx analyser after passing into annular denuders
Summary
We previously demonstrated that continuous exposure to nitrous acid gas (HONO) for 4 weeks, at a concentration of 3.6 parts per million (ppm), induced pulmonary emphysema-like alterations in guinea pigs. We found that HONO affected asthma symptoms, based on the measurement of respiratory function in rats exposed to 5.8 ppm HONO. This study aimed to investigate the dose-response effects of HONO exposure on the histopathological alterations in the respiratory tract of guinea pigs to determine the lowest observed adverse effect level (LOAEL) of HONO. Numerous epidemiological studies have shown the relationship between nitrogen dioxide (NO2) and the alterations of respiratory function or asthma symptoms [USEPA, 2016]. A few inhalation studies have examined the association between HONO exposure and respiratory symptoms and lung function in mildly asthmatic adult subjects or in healthy adult nonsmokers [3, 4]. In an epidemiological pilot study, we observed that indoor HONO was closely correlated with outdoor NO2 in one research year, and indoor HONO was significantly associated with asthma attacks, according to Mann–Whitney U test, in another year [7]
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