EFFECT OF FIBROUS GLASS ON RAT PLEURAL MESOTHELIUM - HISTOPATHOLOGIC OBSERVATIONS

Female Fisher 344 rats (n = 25) were inoculated intrapleurally with a single 20-mg dose of (JM-100) fibrous glass. The mean length (2.2 mu m ) and width (0.15 mu m) of the fibrous glass particles was within resp irable range. Following inoculation, the rats were killed at timed int ervals ranging from 2 to 430 d from inoculation. The pleural histopath ologic changes were independently observed by a panel of three patholo gists blinded to the time elapsed from inoculation. Fibrous adhesions, nodular lesions, and grossly evident tumor were noted in 15, 2, and 1 rat, respectively. In 1 rat there were combined adhesive and nodular changes, and in 6 there were no grossly detectable abnormalities. Chro nic inflammation, fibrosis, and foreign body reaction were found in 9, 18, and 10 rats, respectively. Mesothelial hyperplasia and dysplasia were observed in 16 and 9 rats, respectively. Of 16 rats with the seve rest degree of hyperplasia and dysplasia, 3 developed malignant mesoth elioma. This study suggests that a spectrum of rat pleural mesothelial histopathologic changes occurs before development of mesothelioma. Th e association of severe dysplasia in 3 rats with fully developed mesot helioma suggests that there may be a gradual progression from mesothel ial hyperplasia or dysplasia to mesothelioma. Multivariate analysis fu rther suggests that gross pleural nodular lesions and dysplasia may be significantly associated with the development of mesothelioma in this experimental model.