Related Experiment Video
Updated: Aug 7, 2026
Evaluation of Respiratory System Mechanics in Mice using the Forced Oscillation Technique
Published on: May 15, 2013
Modifications of breathing pattern induced by inhaled sulphur mustard in mice
1Pharmacology and Toxicology Division, Defence Research and Development Establishment, Gwalior, India.
Abstract:
A head-only exposure assembly was used for exposing mice to vapours of sulphur mustard (SM). The respiration was monitored using an on-line computer program, capable of recognizing the breathing pattern as sensory irritation, airflow limitation and pulmonary irritation. SM was dissolved in acetone and vapourized using a compressed air nebulizer. Mice were exposed to the vapours (8.5, 16.9, 21.3, 26.8, 42.3 and 84.7 mg/m3) for 1 h in a body plethysmograph fitted with a 20-gauge needle and a microphone for sensing the respiratory flow signals. The signals were amplified, digitized and integrated to give tidal volume, and stored in a computer for further analysis. The respiration of the mice was followed for modifications in the breathing pattern until 7 days post-exposure. SM induced sensory irritation during exposure, and there was a concentration dependent decrease in the respiratory frequency and an increase in tidal volume. Lower concentrations showed recovery after stopping the exposure. RD50, the concentration that depresses 50% of the respiration was estimated to be 27.4 mg/m3. Following exposure to higher concentrations the animals started dying after 6 days. The LC50 was estimated to be 42.5 mg/m3 (14 days observation period). The respiratory frequency decreased on subsequent days of exposure depending upon the exposure concentration, and the breathing pattern was characteristic of airflow limitation. The ratio of flow/tidal volume was decreased following exposure to concentrations of 26.8 and 42.3 mg/m3. The ratio of flow/tidal volume may be a better measurement than the measurements based on flow alone for the assessment of airflow limitation. Pulmonary irritation was not observed showing that the lungs were not affected. The body weight of the animals decreased progressively. The present methodology will be useful for identifying the effects of SM on the respiratory system, one of the endpoints considered when establishing occupational exposure limits.
Insights
Sulphur mustard (SM) exposure in mice caused breathing pattern changes, including sensory irritation and airflow limitation, with effects worsening at higher concentrations. This study provides a method for assessing SM
Area of Science:
- Toxicology
- Respiratory Physiology
- Chemical Warfare Agents
Background:
- Sulphur mustard (SM) is a chemical warfare agent with significant respiratory toxicity.
- Understanding the dose-response relationship and respiratory effects of SM is crucial for risk assessment and establishing occupational exposure limits.
Purpose of the Study:
- To investigate the respiratory effects of acute sulphur mustard (SM) vapor exposure in mice.
- To characterize the breathing pattern changes induced by SM and determine dose-response relationships.
- To evaluate the utility of a novel methodology for assessing SM-induced respiratory toxicity.
Main Methods:
- Mice were exposed head-only to varying concentrations of vaporized SM (8.5–84.7 mg/m³) for 1 hour in a body plethysmograph.
- Respiration was monitored continuously using an on-line computer program to analyze breathing patterns (sensory irritation, airflow limitation, pulmonary irritation).
- Respiratory signals were digitized and integrated to calculate tidal volume; body weight and survival were also monitored for 7–14 days post-exposure.
Main Results:
- SM exposure induced concentration-dependent sensory irritation and airflow limitation, characterized by decreased respiratory frequency and increased tidal volume.
- The RD50 (concentration causing 50% respiratory depression) was estimated at 27.4 mg/m³, and the LC50 (lethal concentration for 50% of subjects) was 42.5 mg/m³.
- A decreased ratio of flow/tidal volume suggested airflow limitation, potentially a more sensitive indicator than flow alone; pulmonary irritation was not observed.
Conclusions:
- The developed methodology effectively identifies SM-induced respiratory effects, including sensory irritation and airflow limitation.
- The study establishes dose-response relationships for SM respiratory toxicity, informing occupational exposure limit setting.
- While acute pulmonary irritation was not evident, significant respiratory distress and mortality occurred at higher SM concentrations.
