Influence of characteristics of inhaled fibres on development of tumours in the rat lung.
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The objective was to examine and quantify the influence of fibre dimensions, persistence in the lung, and dissolution and cell toxicity in vitro, on the risks of developing lung tumours in rats. Data were brought together from the studies carried out at the IOM under the Colt Fibre Research Programme, and from studies carried out in Switzerland and the USA under the programme of the Thermal Insulation Manufacturers Association. In both studies, groups of rats were exposed by inhalation to a range of airborne fibres. At the end of their lives they were examined for the presence of benign and malignant lung tumours and mesothelioma. The studies differed in a number of details, but were combined on the basis of approximate equivalence of cumulative exposure to airborne fibres. Logistic regression models were used to relate differences in carcinogenicity to fibre characteristics; dimensions, persistence in the lung after intratracheal injection, dissolution rates from bench-top flow-through experiments, measures of inflammation, and other cell responses to fibres in vitro. Despite the small number of data points, the results suggested a primary influence of the airborne concentrations of the numbers of fibres thinner than 1 micron diameter and longer than 20 microns, and of the measured dissolution rate of the fibres. While these results are based on only a small number of fibre types, the statistical model fits the data reasonably well, and enables some cautious insights into the quantitative influences of dimensions and biopersistence. Results were broadly consistent with those from intraperitoneal injection studies of the same fibres, in that the responses were dependent on both the durability of the fibres and the numbers of long thin fibres. In vitro and in vivo cell responses did not predict significantly the risk of cancer following inhalation. (+info)
Comparison of pulmonary and pleural responses of rats and hamsters to inhaled refractory ceramic fibers.
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The present study was designed to determine whether pleural fiber burdens or subchronic pleural fibroproliferative and inflammatory changes can help explain the marked interspecies differences in pleural fibrosis and mesothelioma that are observed following long-term inhalation of RCF-1 ceramic fibers by rats and hamsters. Fischer 344 rats and Syrian golden hamsters were exposed to RCF-1 for 4 h per day, 5 days per week, for 12 consecutive weeks. Lung and pleural fiber burdens were characterized during and after exposure. For all time points, approximately 67% of fibers associated with lung tissues from both rats and hamsters were longer than 5 microns in length. In comparison, fibers longer than 5 microns recovered from the pleural compartment, following a 12-week exposure and 12 weeks of recovery, accounted for 13% (hamsters) and 4% (rats) of the distribution. In the 12 weeks after the cessation of exposure, the number of fibers longer than 5 microns in length remained constant in the hamster at approximately 150 fibers per cm2 pleura. This was 2 to 3 times the corresponding fiber surface density in the rat. Significant pulmonary and pleural inflammation was detected at all time points and for both species. DNA synthesis by pleural mesothelial cells was quantified by bromodeoxyuridine uptake following 3 days of labeling. Labeling indices were higher in hamsters than in rats, both for RCF-1-exposed and filtered air-control animals and was highest for the parietal surface of the pleura. Significantly greater collagen deposition was measured in the visceral pleura of hamsters 12 weeks post-exposure but was not significantly elevated in rats. These findings demonstrate that subchronic inhalation exposure to RCF-1 induces pleural inflammation, mesothelial-cell turnover, pleural fibrosis, and an accumulation of fibers with a length greater than 5 microns in the hamster. The accumulation of long fibers in the pleural space may contribute to the pathology observed in the hamster following chronic inhalation of RCF-1, whereas the presence of short, thin fibers may play a role in the acute-phase biological response seen in both species. (+info)
A new digestion method for recovery of MMMFs from lungs.
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A new tissue digestion method is proposed to recover man-made mineral fibers (MMMFs) from lungs, which is an improved Kjeldahl method using microwaves. Tissue digestion is carried out under five different conditions in this experiment, and the most suitable condition is found as follows; dried rat lung (0.5 g of wet weight) is put into a flask with 0.1 ml of H2SO4 and 2.0 ml of HNO3, and treated by microwaves for 5 min. After the treatment, 1.0 ml of H2O2 is added immediately and the sample is treated again under the same condition. Pure samples of glass fibers and refractory ceramic fibers are treated by this proposed method. Numbers and sizes of the fibers are measured before and after the treatment on enlarged photos taking by a scanning electron microscope. As no significant changes are observed in fiber dimensions and numbers, the proposed method is shown to be applicable to recover these MMMFs from lungs. (+info)
Environmental measurements of total dust and fiber concentration in manufacturer and user of man-made mineral fibers.
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Man-made mineral fibers (MMMF), most of which are referred to as man-made vitreous fibers (MMVF), are mostly amorphous silicates manufactured from glass, rock, or other minerals. Analysis for MMMF have been restricted largely to the measurement of total airborne mass concentrations, but more recently to the determination of airborne fiber levels by phase contrast optical microscopy. In Korea, many small factories are related with manufacturing and using MMMF without any special evaluation of environmental measurements. Though MMMF are known as the substitute of asbestos and their toxicity are regarded as very low, MMMF do not totally excluded from the respiratory and/or skin diseases now. Therefore, we evaluated the environments of many workplaces with total dust and fiber concentration. Most dust and fiber concentrations were below threshold limit value (TLV) at various industries and working processes. However, these data showed a slight relationship between total dust and fiber concentration. (+info)
Effects of mineral fibers on the gene expression of proinflammatory cytokines and inducible nitric-oxide synthase in alveolar macrophages.
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To determine which parameters are useful for the risk assessment of man-made mineral fibers (MMMFs), we examined the gene expression of interleukin-1 alpha (IL-1 alpha), tumor necrosis factor alpha (TNF alpha), interleukin-6 (IL-6) and inducible nitric-oxide synthase (iNOS) in mineral fiber-exposed alveolar macrophages (AMs). Male Wistar rats were intratracheally exposed to saline or mineral fibers suspended in saline (2 mg of crocidolite, chrysotile, alumina silicate refractory fiber (RF1) or potassium octatitanate whisker (TW)). Bronchoalveolar lavage was performed 4 weeks after the fiber-instillation, and the recovered AMs were stimulated by lipopolysaccharide for 2 or 6 hours. Expression of IL-1 alpha, TNF alpha, IL-6 and iNOS from AMs was observed using reverse transcription-polymerase chain reaction (RT-PCR). The levels of IL-1 alpha and IL-6 mRNA induced by mineral fiber exposure were greatest in AMs exposed to TW, crocidolite, chrysotile and RF1 in that order. However, both gene expression of iNOS and TNF alpha were not elevated in both crocidolite and TW exposure, despite their high pathological potential. These data suggested that IL-1 alpha and IL-6 may be useful indicators for the risk assessment of MMMFs. (+info)
Biological effects of man-made mineral fibers (II)--their genetic damages examined by in vitro assay.
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In order to study and compare genetic damage induced by 10 kinds of man-made mineral fibers (JFM fibers) in cells, human lung epithelial cells (A549) were exposed to JFM fibers and chrysotile for 1 h, then single-cell gel electrophoresis (SCGE) assay was used to detect DNA strand breaks, DNA-DNA interstrand crosslink and the ability of DNA to repair; The results showed that all 10 JFM fibers could induce DNA strand breaks, DNA-DNA interstrand crosslinks and inhibit the ability of DNA repair. When human embryo lung (HEL) cells were exposed to JFM fibers and chrysotile for 24 h respectively, the chromosomal aberration was analyzed and the results showed that chrysotile and most of JFM fibers at 5.0 micrograms/ml induced structural chromosomal aberration, but all of these effects were lower than that of chrysotile and were different among them, suggesting that 10 types of JFM fibers had genotoxicity with different degree in vitro, but all of them were lower than that of chrysotile. (+info)
Cancer incidence among European man-made vitreous fiber production workers.
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OBJECTIVES: This study analyzed cancer incidence among man-made vitreous fiber workers. METHODS: A cancer incidence follow-up was conducted among 3685 rock-slag wool (RSW) and 2611 glass wool (GW) production workers employed for > or =1 year in Denmark, Finland, Norway, or Sweden, and the standardized incidence ratios (SIR) were calculated on the basis of national incidence rates. RESULTS: Overall cancer incidence was close to expectation. Lung cancer incidence was increased among the RSW [SIR 1.08, 95% confidence interval (95% CI) 0.85-1.36] and GW (SIR 1.28, 95% CI 0.91-1.74) workers. For both subcohorts, a trend was suggested for time since first employment (P-value for linear trend 0.1 and 0.2, respectively). Neither subcohort showed an association with employment during the early technological phase, when fiber exposure was high. The incidence of oral, pharyngeal, and laryngeal cancer was increased among the RSW (SIR 1.46, 95% CI 0.99-2.07) and the GW (SIR 1.41, 95% CI 0.80-2.28) subcohorts. Despite a trend in risk for these neoplasms among the GW workers with time since first employment, the lack of a positive relation with other indirect indicators of fiber exposure points against a causal interpretation. No association between RSW or GW exposure and the risk of other neoplasms was suggested. CONCLUSIONS: These lung cancer results are similar to those of a mortality study that included a larger number of factories. For other cancers there was no suggestion of an association with RSW or GW exposure. (+info)
Mutations of p53 gene and SV40 sequences in asbestos associated and non-asbestos-associated mesotheliomas.
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AIM: To examine mesotheliomas for a possible relation between p53 immunostaining, p53 gene mutation, simian virus 40 (SV40), and asbestos exposure. METHODS: Paraffin sections from 11 mesotheliomas were used for p53 immunostaining and also to extract DNA. This was analysed for the presence of mutations in exons 5 to 8 of the p53 gene using a "cold" single strand conformational polymorphism method, together with sequencing. The DNA from the paraffin sections was also used to search for SV40 sequences. A 105 base pair segment at the 3' of the SV40 large T antigen (Tag) was targeted and any PCR amplification products were sequenced to confirm that they were of SV40 origin. EDAX electron microscopic differential mineral fibre counts were performed on dried lung tissue at a specialist referral centre. RESULTS: The fibre counts showed that seven of the mesotheliomas were associated with abnormally high asbestos exposure. Of these, two showed p53 immunostaining, none showed p53 gene mutation, and five showed SV40. Of the four other mesotheliomas, three showed p53 immunostaining, one showed a (silent) p53 mutation, and none showed SV40. The difference in frequency of SV40 detection was significant at the p < 0.05 level. CONCLUSIONS: Immunostaining for the p53 gene was relatively common but p53 mutations were rare in this series. SV40 virus sequence was detected in five of seven asbestos associated mesotheliomas but in none of the non-asbestos-associated mesotheliomas. This suggests there may be a synergistic interaction between asbestos and SV40 in human mesotheliomas. A study with a larger number of cases is needed to investigate these observations further. (+info)