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Two-hour methyl isocyanate inhalation exposure and 91-day recovery: a preliminary description of pathologic changes in F344 rats

Journal Article · · Environ. Health Perspect.; (United States)
DOI:https://doi.org/10.1289/ehp.877271· OSTI ID:6061020
To study the pathology of acute inhalation exposure to MIC, the tissues of male and female Fischer 344 rats were evaluated immediately after a single 2-hr exposure to 0, 3, 10, or 30 ppm MIC, and through day 91. Early gross pathologic changes in the 30 ppm-exposed rats included a reddish white encrustation around the mouth and nose, a small thymus, and distension of the gastrointestinal tract with gas. Lungs (middle and median lobes) showed consolidation and hemorrhage and failed to deflate when the chest cavity was opened. Microscopic changes in the upper respiratory tract 3 hr after exposure included marked erosion and separation of olfactory and respiratory epithelia from the basement membrane with accumulation of serofibrinous fluid. On day 1, acute inflammation and fibrinopurulent exudate partially blocked the nasal passages. Epithelial cells had sloughed from the nasopharynx, trachea, bronchi, and major bronchioles, leaving the basement membrane covered with fibrin and exudate. Granulomatous inflammation and intraluminal fibrosis of the airways were observed with fibrin and exudate. Grandulomatous inflammation and intraluminal fibrosis of the airways were observed by day 3, with increased intraluminal fibrosis by day 7. Lower airways became blocked by exfoliated cells, mucous plugs, and/or intraluminal fibrosis. Damage to the lung parenchyma, even at lethal concentrations, was limited to moderate inflammation. Intraluminal fibrosis, mild bronchitis and bronchiolitis,and mucous plugs persisted throughout 91-day study. These changes could account for evidence of obstructive lung disease detected in pulmonary function studies in companion studies. Evidence of direct injury to nonrespiratory tissues was found.
Research Organization:
National Institute of Environmental Health Sciences, Research Triangle Park, NC
OSTI ID:
6061020
Journal Information:
Environ. Health Perspect.; (United States), Journal Name: Environ. Health Perspect.; (United States) Vol. 72; ISSN EVHPA
Country of Publication:
United States
Language:
English