Functional Evidence of Persistent Airway Obstruction in Rats Following a Two-Hour Inhalation Exposure to Methyl Isocyanate

Pulmonary function was assessed in male, F344 rats 1,2,4,7, and 13 weeks after a single 2-hr exposure to 0, 3, 10, or 30 ppm methyl isocyanate. No significant changes were observed in the rats exposed to 3 ppm through 13 weeks. Diffusing capacity ( DLco), quasistatic lung compliance, and homogeneity...

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Bibliographic Details
Published in:Environmental health perspectives 1987-06, Vol.72, p.89-94
Main Authors: Stevens, Michael A., Fitzgerald, Shelley, Ménache, Margaret G., Costa, Daniel L., Bucher, John R.
Format: Article
Language:English
Subjects:
Airway Obstruction - chemically induced
Animals
Boyles law
Chemical hazards
Cyanates - administration & dosage
Cyanates - toxicity
Inhalation
Isocyanates
Lungs
Male
Nitrogen
Pulmonary compliance
Pulmonary functions
Pulmonary Gas Exchange - drug effects
Rats
Rats, Inbred F344
The Toxicity of Methyl Isocyanate. March 12-13, 1986. Research Triangle Park, NC
Time Factors
Total Lung Capacity
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Summary:Pulmonary function was assessed in male, F344 rats 1,2,4,7, and 13 weeks after a single 2-hr exposure to 0, 3, 10, or 30 ppm methyl isocyanate. No significant changes were observed in the rats exposed to 3 ppm through 13 weeks. Diffusing capacity ( DLco), quasistatic lung compliance, and homogeneity of ventilation, as determined by multibreath nitrogen washout, were depressed in the rats exposed to 10 and 30 ppm by 1 week after exposure. None of the rats exposed to 30 ppm survived beyond 1 week. By 13 weeks, dramatic increases in lung volumes were observed in the rats exposed to 10 ppm, while DLcoand lung compliance were only mildly affected. However, volume-specific DLcoand compliance were depressed in the rats exposed to 10 ppm, suggesting that lung hyperinflation or other compensatory means of increasing lung size occurred in response to the methyl isocyanate-induced lung lesion. This group also exhibited increased expiratory times during tidal breathing and severely impaired distribution of ventilated air. Collectively, these results suggest the development and likely progression of a severe, obstructive airway lesion with associated gas trapping, and the existence of a pronounced concentration-response relationship between 3 and 10 ppm methyl isocyanate exposures.
ISSN:0091-6765
1552-9924
DOI:10.1289/ehp.877289