Inhalation Toxicity Studies on Methyl Isocyanate

The inhalation exposure chambers at NIOH were upgraded and used for conducting controlled exposure studies in experimental animals. For the experimental studies, nearly 500 ml methyl isocyanate (MIC) was synthesized under strictly controlled conditions. Acute exposure to different concentrations of MIC was done in Charles Foster rats of both sexes and a total of five experiments were carried out. High mortality was observed following MIC exposures and lethal concentrations were calculated to be between 2700 to 3000 ppm minute. Primary toxic effects of MIC were found to be on the respiratory system as indicated by gross morphological observations, blood gas analysis, analysis of bronco-alveolar lavage fluid and lung histopathology. There was evidence of liver injury and abnormalities in sperm counts and morphology were also observed. Decrease in muscle ATP and rise in plasma uric acid levels were also detected and may have been responsible for muscular fatigue. Fall in RBC- diphosphoglycerate level was also found and this could have aggravated tissue hypoxia in MIC exposed animals.

 

Following exposure, the animals exhibited severe respiratory distress accompanied by blood stained nasal discharge. Significant reduction in PO2 and rise in pCO2 was observed. Bronchoalveolar lavage revealed rise in total protein, sialic acid and appearance of neutrophils. On histopathological examination marked inflammatory changes were found in the airway epithelium with evidence of bronchiolitis obliterans.