Lowest observed adverse effect level of pulmonary pathological alterations due to nitrous acid exposure in guinea pigs

Environmental Health and Preventive Medicine

Norimichi Takenaka¹  Masayuki Ohyama²  Kenichi Azuma³  Chika Minejima⁴  Hiroshi Nishimura⁵  Shuichi Adachi⁶ 

[1] Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 599-8531, Sakai, Japan;Department of Environmental Health, Osaka Institute of Public Health, 1-3-69, Nakamichi, Higashinari-ku, 537-0025, Osaka, Japan;Department of Environmental Medicine and Behavioural Science, Kindai University Faculty of Medicine, 589-8511, Osakasayama, Japan;Department of Natural Sciences, College of Liberal Arts, International Christian University, 181-8585, Mitaka, Japan;Department of Planning and Coordination, Osaka Institute of Public Health, 537-0025, Osaka, Japan;Department of Public Health, Sagami Women’s University, 252-0383, Sagamihara, Japan;

关键词: Nitrous acid;    Nitrogen dioxide;    Pulmonary emphysema;    Alveolar mean linear intercept;    Asthma;    LOAEL;   

DOI  :  10.1186/s12199-020-00895-0

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY