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Time-course of functional and pathological changes in chlorine exposed A/J mice.

Campbell HR; Ramos-Barbon D; Tuck SA; Martin JG
Am J Respir Crit Care Med 2002 Apr; 165(8)(Suppl):A522
Inhalation of irritants such as chlorine (CI,) can lead to the development of irritant induced asthma. Few animal models have been developed to study the effects of CI, on airway) cellular responses and changes in lung function. To investigate in vivo the effects of CI2 on airway inflammation and lung function, NJ mice were exposed to inhaled CI, (400 ppm) for 5 min. Animals were assessed 24h, 48h and 7 d after exposure by measuring respiratory system resistance (RRS) and elastance (ELRS) in response to i.v. methacholine (MCh). BAL was performed to determine total and differential cell counts and epithelial cell shedding. To determine the effects of inhibiting iNOS, a group of animals was treated with I400W in addition to being exposed to Cl, (400 ppm) for 5 minutes and studied 24 h after 0, exposure. Maximal inflammatory response to Cl, was observed 24 h after CI, expos... and was characterized by increased BAL total cell counts (n=6; p<0.001), granulocytes (n=6;p<0.002), macrophages (n=6;p<0.001) and epithelial cells (n=6;p<O.OOI). The total lymphocyte count was reduced in all CI, exposed groups (p<0.03). Neither baseline RRS was elevated at any time point, while ELRS was increased in response to 40,80 and 160 l1g/kg i.v. MCh (n=7; p<O.04) compared to controls at 24 h but not at 48 h or 7 d after exposure. Animals studied 24 h after treatment with 1400W and exposure to CI, (400 ppm) showed elevated RRS and ELS in response to 160 l1g/kg i.v. MCh (n=6;p<O.OS) compared to mice treated with 1400W alone. In conclusion, a single high-dose exposure inhaled CI, caused transient hyperresponsiveness to MCh, increased inflammatory cell influx and epithelial shedding. These changes had resolved by 48 h after CI, exposure indicating rapid recovery from the acute injury. The inhibition of iNOS in animals exposed to CI, did not abrogate hyperresponsiveness to MCh observed at 24 h, caused by the Cl2 exposure.
Inhalants; Chlorine-compounds; Respiratory-system-disorders; Pulmonary-system-disorders; Cellular-function; Lung-function; Animal-studies; In-vivo-study; Laboratory-animals
Publication Date
Document Type
Abstract; Conference/Symposia Proceedings
Funding Amount
Funding Type
Fiscal Year
Identifying No.
Issue of Publication
Priority Area
Disease and Injury: Asthma and Chronic Obstructive Pulmonary Disease
Source Name
American Journal of Respiratory and Critical Care Medicine, 2002 International Conference, The American Thoracic Society, Atlanta Georgia, May 17-22, 2002
Performing Organization
Hospital du Sacre-Coeur, Montreal, Quebec
Page last reviewed: September 17, 2021
Content source: National Institute for Occupational Safety and Health Education and Information Division