Lung Injury After Acute Inhalation Of Perfluoroisobutylene: Exposure Concentration-Response Relationships

Abstract

Perfluoroisobutylene (PFIB) is a toxic, potentially lethal pneumoedematogenic gas. An investigation was undertaken to examine the kinetic course of the pulmonary injurious response to PFIB when inhaled by adult Fischer 344 rats for 10-min durations at mass concentrations ranging from 50 to 200 mg/m³. No lung gravimetric increases or histopathological changes were observed after exposure to 50 or 83 mg/m³ concentrations of PFIB. At ≥ 90 mg/m³, overt lung injury that was detectable by lung gravimetric and histopathological changes was observed within hours after the exposures, with the postexposure times or “latency periods” prior to onset of these responses being inversely related to exposure mass concentration. Latency periods occurring after exposure to 100, and 110 mg/m³ were ∼8 and 4 hr, respectively. No latency period was observed following the exposure of rats to 200 mg/m³. The ultimate severity of the pulmonary injurious response to PFIB increased with increasing exposure mass concentration. In a second component of the study, lungs of rats exposed to 100 or 200 mg PFIB/m³ were examined by transmission electron microscopy at various times after the exposures to obtain ultrastructural information about the postexposure course of alveolar injury at the cellular level, while also examining for cellular and architectural injury that may occur during a post-PFIB exposure “latency period”, as defined by lung gravimetric and conventional histopathological criteria. As of 1 hr after exposure to these concentrations of PFIB, alveolar epithelial cells and endothelial cells showed abnormal vacuolization and blebbing. These changes progressed over time, resulting in the denudement of the alveolar surface, endothelial cell swelling and the formation of fenestrations in the endothelial cell barrier, perivascular and interstitial edema, and the flooding of the alveoli with vascular constituents, including extravasated erythrocytes. Only the lung's alveolar macrophages and interstitial fibroblasts appeared to be relatively insensitive to the damaging effects of PFIB. While the severity and rate of development of these changes was greater with the higher 200 mg/m³ concentration of PFIB, such damage, while less extensive at comparable postexposure times, was also present during the latency period after exposure to 100 mg/m³. Thus, significant lung injury can occur shortly after exposure to PFIB that is not detectable by more conventional lung gravimetric and histopathological criteria.