zeolites and Pulmonary-Fibrosis

To review the scientific literature on the health effects of refractory ceramic fibres (RCFs). The adverse effects of exposure to asbestos has led to concern about the potential for other fibrous materials to cause diseases. For this reason the human populations most heavily exposed to synthetic mineral fibres have been examined for any adverse effects and many types of fibre have been studied in animal experiments. One type of man made vitreous fibres (MMVFs), refractory ceramic fibres (RCFs), are principally used in thermal insulation at high temperatures--up to 1400 degrees C. As manufactured RCFs exist in a glassy, non-crystalline (sometimes called amorphous) state, they have various compositions, physical properties, and sized fibres.. All reports on the health effects of RCFs available up to the end of 1994 have been examined and the scientific literature reviewed although all publications have not necessarily been referenced.. In recent inhalation experiments conducted with both rats and hamsters at the Research and Consulting Company, Geneva, at the highest dose tested (30 mg/m3) there was an increased incidence of tumours in both species. Lower doses were only examined in the rat and at these doses there was no significant excess of lung tumours. Epidemiological investigations of workers engaged in the manufacture of ceramic fibres have shown a small excess of pleural plaques. This phenomenon is being further investigated but could be due to confounding exposures. The populations available for study are small and their exposures fairly short, but it is considered prudent that they should remain under surveillance for some time to come. This is despite the fact that present exposures in the ceramic fibre industry are low (< 1 f/ml) and are being reduced.

Topics: Adenocarcinoma; Adenoma; Aluminum Silicates; Animals; Carcinogenicity Tests; Case-Control Studies; Ceramics; Cohort Studies; Cricetinae; Humans; Longitudinal Studies; Mesothelioma; Occupational Exposure; Pulmonary Fibrosis; Rats; Respiratory Function Tests

This paper summarizes the biological effects of refractory ceramic fibres (RCFs). RCFs are aluminosilicate glass insulation wools with similar chemical properties to other synthetic vitreous fibres (SVFs) or 'man-made vitreous fibres' (MMVFs). There is concern that RCFs could be significantly more pathogenic than other SVFs. This paper critically reviews the data on which this perception is based. Morbidity studies on workers in RCF manufacturing indicated that, in the United states, RCF exposure was associated with an increased incidence of pleural plaques and in both the united states and Europe with statistically significant changes in some measures of lung function (though not at present exposure levels). No interstitial fibrosis was found. An ongoing mortality study of limited statistical power has failed to indicate any increased incidence of lung cancer or mesothelioma. Findings in several early animal studies led to a large series of inhalation studies where rats exposed to high levels of RCF developed fibrosis and tumours but not those exposed to other SVFs. Similarly hamsters exposed to one sample (RCF1) developed mesothelioma. Subsequent analyses of the data indicated that the RCF used in these experiments had a significantly greater proportion of non-fibrous particles than those present in the other types of SVFs tested or in workplace air. Short-term studies indicated that pulmonary overload occurred at the same as RCF tissue burdens as those in the long-term animal bioassay. When RCFs were prepared in the same way as the other SVFs, a sample resulted with a more representative ratio of particles to fibres; this sample did not produce overload in short-term tests. SVFs have various abilities to persist in the lung tissue and thus accumulate to varying degrees. It is suggested that biopersistence is a key property. While RCFs are among the more persistent they are similar to many other fibre types. The scientific and regulatory implications of these findings are examined.

Topics: Air Pollutants, Occupational; Aluminum Silicates; Animals; Carcinogenicity Tests; Ceramics; Data Collection; Humans; Lung Neoplasms; Mesothelioma; Mineral Fibers; Occupational Diseases; Pulmonary Fibrosis; Rats; Research Design

To investigate whether the results of intratracheal instillation studies on mineral fibers reflect the findings obtained by long-term inhalation data on mineral fibers, we have examined gene expression of cytokines and pathological features in lungs induced by intratracheal instillation and inhalation of mineral fibers. Male Wistar rats were given a single intratracheal instillation of 2 mg alumina silicate refractory fiber (RF1) or potassium octatitanate whisker (PT1), and were sacrificed 4 wk after the fiber instillation. Long-term inhalation studies were also performed. In these, animals were exposed to fiber aerosol of RF1 or PT1 for 5 days/wk for 1 yr, and sacrificed after 1 yr of inhalation. Expression of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and transforming growth factor-beta1 (TGF-beta1) from lungs was observed by reverse-transcription polymerase chain reaction (RT-PCR). The expression of TNF-alpha, IL-6, and TGF-beta1 mRNA in PT1-exposed lung was significantly higher than for those exposed to RF1 in both intratracheal instillation and inhalation studies. Pathological findings revealed that mild pulmonary fibrosis was seen in the lungs after intratracheal instillation and inhalation of PT1 but not RF1. Similarities were observed not only in gene expression of cytokines but in pathological features between both studies. These data suggested that the results of intratracheal instillation reflect the findings obtained from long-term inhalation data.

Topics: Aluminum Silicates; Animals; Cytokines; DNA Primers; Gene Expression; Interleukin-6; Intubation, Intratracheal; Lung; Male; Mineral Fibers; Pulmonary Fibrosis; Rats; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Titanium; Transforming Growth Factor beta; Transforming Growth Factor beta1; Tumor Necrosis Factor-alpha