PHENYL ISOCYANATE-INDUCED ASTHMA IN RATS FOLLOWING A 2-WEEK EXPOSURE PERIOD

This study was conducted to assess the toxic effects of repeated inhal ation exposures to phenyl isocyanate vapor in male Wistar rats. Rats w ere exposed to design concentrations of 0, 1, 4, 7, or 10 mg/m(3) phen yl isocyanate air for 2 weeks (6 hr/day, 5 days/week). The rats were a ssessed for normal toxicologic parameters, and pulmonary function test s, blood gas measurements, and analysis of bronchoalveolar lavage flui d (BALF) parameters were utilized shortly after exposures as well as 2 months postexposure. The results indicated that rats exposed to 7 and 10 mg/m(3) experienced decreased body weights, hypoactivity, hypother mia, signs of respiratory tract irritation, delayed onset of mortality , and changes in organ weights. In addition, pulmonary function tests demonstrated decreased forced expiratory flow rates and quasistatic lu ng compliance. Arterial blood gases showed an arterial hypoxemia and c hanges consistent with a pronounced venous-admixture-like perfusion, s uggesting severe mismatch of the ventilation/perfusion relationship. D elayed onset of mortality appeared to be associated with respiratory a cidosis and hypoxemia. Biochemical and cellular components in BALF com plemented the results of the functional alterations. Remarkable change s were indicated by increased activities of the BALF parameters, gamma -GPT, protein, and sialic acid. Histopathological findings provided ev idence of increased secretory cell activity and a concentration-depend ent increase in goblet cell hyperplasia at concentrations of 4 mg/m(3) and above. In rats exposed to 7 mg/m(3) further findings consisted of intraluminal inflammation of airways, hypertrophia of bronchial smoot h muscle, epithelial desquamation, and eosinophilia of the airways. A complete regression of morphological lesions was not found in the anim als exposed to 4 mg/m(3) and above at the 2-month postexposure time pe riod. In conclusion, the damage to the airways comprise most of the fe atures characteristic of chronic airway inflammation or asthma. (C) 19 95 Society of Toxicology.