Toxic and tumorigenic effects of asbestos on tracheal mucosa

The purpose of the studies was to examine the acute, chronic, and neoplastic effects of asbestos on mucosa of conducting airways. Heterotopic tracheal grafts were used as the experimental model. In the system employed, the test substance was introduced into the airway lumen and kept in intimate contact with the respiratory tract mucosa for weeks or months. UICC chrysotile A and crocidolite asbestos caused marked acute changes of the tracheal mucosa: epithelial hyperplasia, hypersecretion of mucus, and submucosal inflammation. With chrysotile, the hypersecretory state and goblet cell hyperplasia persisted for many months, resulting in a marked distension of the tracheal grafts. Other manifestations of chronic irritation were focal squamous metaplasias, epithelial erosions, and connective tissue changes involving the tracheal submucosa and adventitia as well as the host subcutaneous tissues. The connective tissue changes were characterized by formation of granulomas, often with necrotic centers. In a 29-month tumor-induction study carried out with chrysotile A, the total tumor incidence in 40 tracheal grafts was 40 percent; this included 2 squamous cell carcinomas (5%)(, and 14 sarcomas (35%) as compared with no carcinomas and 6 sarcomas (12%) in 49 vehicle-treated controls. Thus our studies show that chrysotile (1) causes chronic irritation of the tracheal mucosa, (2) augments sarcoma development, and (3) is a weakly but definitely carcinogenic agent for the respiratory tract mucosa.