Synthetic Vitreous Fibers Research Articles

Biopersistence of Synthetic Vitreous Fibers and Amosite Asbestos in the Rat Lung Following Inhalation

Fiber biopersistence as a major mechanism of fiber-induced pathogenicity was investigated. The lung biopersistence of 5 synthetic vitreous fibers (SVFs) and amosite asbestos was evaluated using the rat inhalation model. In contrast to several previous studies, this study examined fibers that dissolve relatively slowlyin vitroat pH 7.4. Fisher rats were exposed for 5 days by nose-only inhalation to refractory ceramic fiber (RCF1a), rock (stone) wool (MMVF21), 2 relatively durable special application fiber glasses (MMVF32 or MMVF33), HT stonewool (MMVF34), amosite asbestos, or filtered air. Lung burdens were analyzed during 1 year post-exposure. Fiber aerosols contained 150–230 fibers/cc longer than 20 μm (>20 μm). On post-exposure Day 1, long-fiber lung burdens for the 6 test fibers were similar (12–16 × 105fibers/lung >20 μm). After 1 year, the percentage of fibers >20 μm remaining in the lung was 0.04–10% for SVFs but 27% for amosite. Lung clearance weighted half-times (WT1/2) for fibers >20 μm were 6 days for MMVF34, 50–80 days for the other 4 SVFs, and >400 days for amosite. This study and 3 previous studies demonstrate a broad range of biopersistences for 19 different SVFs and 2 asbestos types. Ten of these fibers also have been (or are being) tested in chronic inhalation studies; in these studies, the very biopersistent fibers were carcinogenic (amosite, crocidolite, RCF1, MMVF32, and MMVF33), while the more rapidly clearing fibers were not (MMVF10, 11, 21, 22, and 34). These studies demonstrate the importance of biopersistence as an indicator of the potential pathogenicity of a wide range of fiber types.

Particulates and the Airways: Basic Biological Mechanisms of Pulmonary Pathogenicity

Abstract With strong evidence that materials such as silica and asbestos are associated with irreversible lung disease, efforts have been made to identify abrasive substitute materials for silica and produce various synthetic vitreous fibers as substitutes for asbestos. With the introduction of new materials, questions concerning potential health effects are raised. A clear understanding of the mechanisms by which certain inhaled particles induce lung damage and subsequent disease is vital to the ability to predict the relative safety of new materials, as well as, to provide appropriate measures for the safe use of old materials currently grouped together as particulates not otherwise classified/regulated. The following is a brief review of mechanisms currently thought to be important in the development and progression of particle-induced lung disease.

FREE RADICAL ACTIVITY OF SYNTHETIC VITREOUS FIBERS: IRON CHELATION INHIBITS HYDROXYL RADICAL GENERATION BY REFRACTORY CERAMIC FIBER

Synthetic vitreous fibers are in widespread use but the parameters that dictate their carcinogenicity are still a matter of scientific debate. The free radical activities of a panel comprising an asbestos sample and five different respirable synthetic vitreous fiber samples were determined, to address the hypothesis that carcinogenic fibers have greater free radical activity than noncarcinogenic fibers. On the basis of recent inhalation studies, the six samples were divided into three carcinogenic fibers-amphibole asbestos, silicon carbide, and refractory ceramic fiber 1 (designated with the abbreviation RCF 1)-and three noncarcinogenic fibers-man-made vitreous fiber 10 (a glass fiber sample designated with the abbreviation MMVF 10), Code 100/475 glass fiber, and RCF4. All experiments were carried out with equal fiber numbers. Of the two assays of free radical activity used, the plasmid assay of DNA scission showed only amosite asbestos to have free radical activity, while the salicylate assay of hydroxyl activity showed that both amosite asbestos and RCF1 release hydroxyl radicals; silicon carbide fibers had no free radical activity in either of the assays. None of the noncarcinogenic fibers demonstrated free radical activity in either of the assays. The differences in the two assays in demonstrating free radical activity with RCF1 may be due to increased release of Fe from RCF1 under the more acid conditions of the salicylate assay, which was confirmed by the fact that soluble iron caused hydroxylation of salicylate. Presence of an iron chelator inhibited the ability of the RCF1 fibers to cause hydroxylation of salicylate, demonstrating that RCF1 generates hydroxyl radical by Fenton chemical reaction in the same way as amphibole asbestos.

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 contact with pleural cells to exert pathologic effects. In the present study, we determined the kinetics of fiber movement into pleural tissues of rats following inhalation of RCF-1, a ceramic fiber previously shown to induce neoplasms in the lung and pleura of rats. Male Fischer 344 rats were exposed by nose-only inhalation to RCF-1 at 89 mg/m3(2645 WHO fibers/cc), 6 hr/day for 5 consecutive days. On Days 5 and 32, thoracic tissues were analyzed to determine pulmonary and pleural fiber burdens. Mean fiber counts were 22 × 106/lung (25 × 103/pleura) at Day 5 and 18 × 106/lung (16 × 103/pleura) at Day 32. Similar geometric mean lengths (GML) and diameters (GMD) of pulmonary fiber burdens were observed at both time points. Values were 5 μm for GML (geometric standard deviation GSD ≈ 2.3) and 0.3 μm for GMD (GSD ≈ 1.9), with correlations between length and diameter (τ) of 0.2–0.3. Size distributions of pleural fiber burdens at both time points were approximately 1.5 μm GML (GSD ≈ 2.0) and 0.09 μm GMD (GSD ≈ 1.5; τ ≈ 0.2–0.5). Few fibers longer than 5 μm were observed at either time point. These findings demonstrate that fibers can rapidly translocate to pleural tissues. However, only short, thin (<5 μm in length) fibers could be detected over the 32-day time course of the experiment.

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 variety of fibrous particulates, including both natural mineral and man-made vitreous fibers. We examined selected cytological and biochemical indicators of inflammation in both the pleural compartment and pulmonary parenchyma in F344 rats following inhalation of RCF-1, a kaolin-based ceramic fiber. Male F344 rats were exposed by inhalation to 89 mg/m3(2645 WHO fibers/cc) RCF-1 6 hr/day for 5 consecutive days. In lung parenchyma, cytological and biochemical inflammatory responses occurred rapidly following exposure. In contrast, pleural responses were delayed in onset and of a much smaller magnitude than those observed in lung. At both Day 1 and Day 28 postexposure, increased quantities of lactate dehydrogenase,N-acetyl glucosaminidase, alkaline phosphatase, albumin, and neutrophils were present in bronchoalveolar lavage fluid. These responses were attenuated at the latter time point. No significant responses were detected in pleural lavage fluid until 28 days following exposure, at which time elevated 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 demonstrate that the onset of pleural and pulmonary responses following inhalation of RCF-1 are temporally separated and that pleural injury may increase in severity with time following exposure. The increase in severity of pleural inflammation found in the postexposure 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

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

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

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

Statistical Analysis of Results of Carcinogenicity Studies of Synthetic Vitreous Fibres at Research and Consulting Company, Geneva

Statistical Analysis of Results of Carcinogenicity Studies of Synthetic Vitreous Fibres at Research and Consulting Company, Geneva

Statistical analysis of results of carcinogenicity studies of synthetic vitreous fibres at Research and Consulting Company, Geneva

Five inhalation studies of synthetic vitreous fibres have recently investigated experimental tumorigenic responses to four different refractory ceramic fibres (RCF), two fibre glasses, one stone (rock) wool and one slag wool. Except for one RCF, the source materials were typical commercial products. Three studies included positive control groups exposed to chrysotile or crocidolite asbestos. The studies were conducted using state-of-the-art technologies for fibre size separation, fibre lofting and nose-only inhalation exposure. The target average fibre size was 20 μm long by 1 μm diameter.Hamsters exposed to a kaolin RCF yielded a mesothelioma rate of 38%, but no lung cancers. There were no tumours among the chrysotile-exposed hamsters.At the highest dose of 30 mg m−3 in rat studies, the commercial RCF all produced significant numbers of lung tumours, and some mesotheliomas. The fourth RCF, which had been heat-treated to simulate an after-service fibre, did not produce a significant excess of lung cancers, but did produce one mesothelioma.A rat multi-dose experiment with three lower doses of the kaolin RCF yielded one mesothelioma among 379 rats, but no excess of lung tumours. The overall dose-response relation for lung cancer did not appear to be linear, consistent with the possibility of a threshold close to the Maximum Tolerated Dose.No insulation wool (glass, stone or slag) exposure group had a lung tumour rate that differed statistically significantly from the tumour rate for the respective concurrent control groups, sham-exposed to filtered air. There was no significant difference in the total tumour rates between the four insulation wool groups and the control animals, and no significant dose-response relation above the respective sham-exposed control tumour rates.The total lung tumour rates for rats in both chrysotile and crocidolite exposure groups were significantly raised. One animal in each asbestos-exposed group developed a mesothelioma, whereas no air control or insulation wool-exposed animal did so.

HEALTH EFFECTS OF SYNTHETIC VITREOUS FIBERS

This article reviews the terminology and manufacturing process for synthetic vitreous fibers. The in vitro and in vivo animal experimental data that correlate fiber toxicity with dose, dimensions, and durability are summarized. Occupational exposure data are presented as well as the potential irritant effects of synthetic vitreous fibers. The ongoing human morbidity and mortality studies are summarized along with current occupational exposure standards. The discussion correlates physical properties related to fiber toxicity and the types of synthetic vitreous fibers.