Phenyl Isocyanate-Induced Asthma in Rats Following a 2-Week Exposure Period

This study was conducted to assess the toxic effects of repeatedinhalation exposures to phenyl isocyanate vapor in male Wistarrats. Rats were exposed to design concentrations of 0, 1, 4,7, or 10 mg/m³ phenyl isocyanate air for 2 weeks (6 hr/day,5 days/week). The rats were assessed for normal toxicologicparameters, and pulmonary function tests, blood gas measurements,and analysis of bronchoalveolar lavage fluid (BALF) parameterswere utilized shortly after exposures as well as 2 months postexposure.The results indicated that rats exposed to 7 and 10 mg/m³ experienceddecreased body weights, hypoactivity, hypothermia, signs ofrespiratory tract irritation, delayed onset of mortality, andchanges in organweights. In addition, pulmonary function testsdemonstrated decreased forced expiratory flow rates and quasistaticlung compliance. Arterial blood gases showed an arterial hypoxemiaand changes consistent with a pronounced venous-admixture-likeperfusion, suggesting severe mismatch of the ventilation/perfusionrelationship. Delayed onset of mortality appeared to be associatedwith respiratory acidosis and hypoxernia. Biochemical and cellularcomponents in BALF complemented the results of the functionalalterations. Remarkable changes were indicated by increasedactivities of the BALF parameters, -GPT, protein, and sialicacid. Histopathological findings provided evidence of increasedsecretory cell activity and a concentration-dependent increasein goblet cell hyperplasia at concentrations of 4 mg/m³ andabove. In rats exposed to 7 mg/m³ further findings consistedof intraluminal inflammation of airways, hypertrophia of bronchialsmooth muscle, epithelial desquamation, and eosinophilia ofthe airways. A complete regression of morphological lesionswas not found in the animals exposed to 4 mg/m³ and above atthe 2-month postexposure time period. In conclusion, the damageto the airways comprise most of the features characteristicof chronic airway inflammation or asthma.