Lowest observed adverse effect level of pulmonary pathological alterations due to nitrous acid exposure in guinea pigs.
10.1186/s12199-020-00895-0
- Author:
Masayuki OHYAMA
1
;
Hiroshi NISHIMURA
2
;
Kenichi AZUMA
3
;
Chika MINEJIMA
4
;
Norimichi TAKENAKA
5
;
Shuichi ADACHI
6
Author Information
1. Department of Environmental Health, Osaka Institute of Public Health, 1-3-69, Nakamichi, Higashinari-ku, Osaka, 537-0025, Japan. ohyama@iph.osaka.jp.
2. Department of Planning and Coordination, Osaka Institute of Public Health, Osaka, 537-0025, Japan.
3. Department of Environmental Medicine and Behavioural Science, Kindai University Faculty of Medicine, Osakasayama, 589-8511, Japan.
4. Department of Natural Sciences, College of Liberal Arts, International Christian University, Mitaka, 181-8585, Japan.
5. Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, Sakai, 599-8531, Japan.
6. Department of Public Health, Sagami Women's University, Sagamihara, 252-0383, Japan.
- Publication Type:Journal Article
- Keywords:
Alveolar mean linear intercept;
Asthma;
LOAEL;
Nitrogen dioxide;
Nitrous acid;
Pulmonary emphysema
- MeSH:
Alveolar Epithelial Cells;
drug effects;
Animals;
Bronchi;
drug effects;
Dose-Response Relationship, Drug;
Emphysema;
chemically induced;
Epithelial Cells;
drug effects;
Guinea Pigs;
Hyperplasia;
chemically induced;
Inhalation Exposure;
adverse effects;
Lung;
drug effects;
pathology;
ultrastructure;
Male;
Microscopy, Electron, Scanning;
Microscopy, Electron, Transmission;
Myocytes, Smooth Muscle;
drug effects;
Nitrous Acid;
toxicity
- From:Environmental Health and Preventive Medicine
2020;25(1):56-56
- CountryJapan
- Language:English
-
Abstract:
BACKGROUND: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. 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.
METHODS:We 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).
RESULTS:We 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.
CONCLUSIONS:These histopathological findings suggest that the LOAEL of HONO is < 0.1 ppm.
