Pulmonary and Pleural Responses in Fischer 344 Rats Following Short-Term Inhalation of a Synthetic Vitreous Fiber: II. Pathobiologic Responses

The pleura is a target site for toxic effects induced by a varietyof fibrous particulates, including both natural mineral andman made vitreous fibers. We examined selected cytological andbio chemical indicators of inflammation in both the pleuralcompart ment and pulmonary parenchyma in F344 rats followinginhala tion of RCF-1, a kaolin-based ceramic fiber. Male F344rats were exposed by Inhalation to 89 mg/m³ (2645 WHO fibers/cc)RCF-1 6 hr/day for 5 consecutive days. In lung parenchyma, cytologicaland biochemical inflammatory responses occurred rapidly followingexposure. In contrast, pleural responses were delayed in onsetand of a much smaller magnitude than those observed in lung.At both Day 1 and Day 28 postexposure, increased quantitiesof lactate dehydrogenase, N-acetyl glucosaminidase, alkalinephosphatase, albumin, and neutrophils were present in bronchoalveolarlavage fluid. These responses were attenuated at the lattertime point. No significant responses were detected in pleurallavage fluid until 28 days following exposure, at which timeelevated numbers of macrophages and eosinophils, but not neutrophils,were observed. Increased albumin and fibronectin were also observed in PLF at this latter time point. These findings demonstratethat the onset of pleural and pulmonary responses followinginhalation of RCF-1 are temporally separated and that pleuralinjury may increase in severity with time following exposure.The increase in severity of pleural inflammation found in thepostexposure period cannot be readily explained by fiber translocation.     

Pulmonary and Pleural Responses in Fischer 344 Rats Following Short-Term Inhalation of a Synthetic Vitreous Fiber: I. Quantitation of Lung and Pleural Fiber Burdens

The pleura is an important target tissue of fiber-induced disease,although it is not known whether fibers must be in direct contactwith pleural cells to exert pathologic effects. In the presentstudy, we determined the kinetics of fiber movement into pleuraltissues of rats following inhalation of RCF-1, a ceramic fiberpreviously shown to induce neoplasms in the lung and pleuraof rats. Male Fischer 344 rats were exposed by nose-only inhalationto RCF-1 at 89 mg/m³ (2645 WHO fibers/cc), 6 hr/day for 5 consecutivedays. On Days 5 and 32, thoracic tissues were analyzed to determinepulmonary and pleural fiber burdens. Mean fiber counts were22x10⁶/lung (25x10³/pleura) at Day 5 and 18x10⁶ (16x10/pleura)at Day 32. Similar geometric mean lengths (GML) and diameters(GMD) of pulmonary fiber burdens were observed at both timepoints. Values were 5 µm for GML (geometric standard deviationGSD 2.3) and 0.3 µm for GMD (GSD 1.9), with correlationsbetween length and diameter () of 0.2–0.3. Size distributionsof pleural fiber burdens at both time points were approximately1.5 µm GML. (GSD 2.0) and 0.09 µm GMD (GSD 1.5; 0.2–0.5). Few fibers longer than 5 µm were observedat either time point. These findings demonstrate that fiberscan rapidly translocate to pleural tissues. However, only short,thin (<5 µm in length) fibers could be detected overthe 32-day time course of the experiment.