Man-made Mineral Fibers Research Articles

Production of nitric oxide elevates nitrosothiol formation resulting in decreased glutathione in macrophages exposed to asbestos or asbestos substitutes

The purpose of this study was to investigate the effects of pneumoconiogenic particles, such as asbestos, on nitrosothiol formation in macrophages. In addition, the effects of man-made mineral fibers (MMMFs) were also evaluated, because they have come into heavy use as substitutes for asbestos. RAW264.7 cells and J774 cells of murine macrophage cell lines were cultured with chrysotile B (CH) asbestos, crocidolite (CR) asbestos, or MMMFs comprised of glass wool (GW), rock wool (RW), or ceramic (RF1). All of these fibers significantly increased nitric oxide (NO) production in the culture with macrophages. Chrysotile B, CR, and GW significantly decreased the level of reduced glutathione (GSH) in RAW264.7 cells. S-nitrosothiol (RS-NO) formation was increased by both types of cells on exposure to every fiber. A large portion of this increased RS-NO may be in the form of S-nitrosoglutathione (GS-NO), because GSH is the most abundant thiol substance in the cell. Both CH and GW significantly increased superoxide anion in the media cultured of RAW264.7 cells. These results indicate that macrophages exposed to asbestos or MMMFs are subject to oxidative stress, not only through the generation of reactive oxygen and nitrogen species, but also through decreases in the level of the cellular antioxidant, GSH, by GS-NO formation. The increase of RS-NO in macrophages exposed to asbestos or MMMFs may deserve more attention as the indicator of continuous oxidative stress by NO on cells and tissues, which causes inflammation and involves the development of asbestos-induced diseases.

Mineral fiber problems and their management: UK 1890-1935.

The first intimation that mineral fibers other than asbestos were biologically active, is generally identified with reports of experimental studies by Stanton and Wrench, and Pott and Friedrichs, in the early 1970s. In 1890 however, man-made mineral fiber was recognized to present human health hazards; in 1912 experimental study confirmed asbestos to be fibrogenic, and by 1935 other mineral fibers came to notice as potential lung hazards. Published and archival sources have been reviewed to trace the emergence between 1890 and 1935 of the awareness of the health hazards of various fibrous minerals, and the development of strategies for their control. By the early 1900s there was evidence that the asbestos substituted for the man-made mineral fiber insulation material employed to improve the thermal efficiency of steam powered engines, presented a serious health problem. In the early 1930s, other mineral fibers came to be suspected of causing pneumoconiosis. Containment, local exhaust ventilation and personal respiratory protection were instituted for the amelioration of asbestosis, but because of the limitations of what was perceived to be reasonably practicable on economic grounds, and what was feasible technologically, their benefits were severely limited. Initial and periodic medical examination were introduced as precautionary measures, based on hope rather than on experience. When in the early 1930s, the investigation of coal mine dust and siliceous dust, threw up the hypothesis that fibrous natural mineral dusts other than asbestos might be fibrogenic, this was ignored and no further investigations were pursued and no precautionary measures were set in train.

Current Man-Made Mineral Fibers (MMMF) Exposures Among Ontario Construction Workers

Current occupational exposures to man-made mineral fibers (MMMF), including refractory ceramic fibers (RCF), were measured as part of an exposure assessment program for an epidemiological study pertaining to cancer and mortality patterns of Ontario construction workers. The assessments were carried out at commercial and residential sites. A total of 130 MMMF samples (104 personal and 26 area) was collected and included 21 RCF (16 personal and 5 area). The samples were analyzed by the World Health Organization method in which both respirable and nonrespirable airborne fibers are counted. The results show that Ontario construction workers' full-shift exposure to MMMF (excluding RCF) is generally lower than the American Conference of Governmental Industrial Hygienists' (ACGIH®) recommended threshold limit value–time-weighted average (TLV®-TWA) of 1 fibers/cc and thus should not present any significant hazard. However, approximately 40% of the occupational exposures to RCF are higher than ACGIH's TLV-TWA of 0.2 fibers/cc and present a significant potential hazard. Workers generally wore adequate approved respiratory protection, especially while performing particularly dusty tasks such as blowing, spraying, and cutting, so the actual exposure received by workers was lower than the reported values. Adequate control measures such as ventilation and respiratory protection should always be used when work involves RCF.

Effect of Using a Cowl When Measuring the Fiber Number Concentration by the Membrane Filter Method

This article compares samples taken with three different sampling heads: (1) open-faced sampling head, (2) open-faced sampling head with stainless-steel extension cowl, and (3) open-faced sampling head with graphite-impregnated extension cowl. Sampling was performed in three factories producing man-made mineral fibers (alkaline silicate fibers, refractory ceramic fibers, glass fibers). Flow rate was varied (1 L/min or 2 L/min). The average densities measured on the sampling filter for fibers of <3 μm in diameter varied from 19 to 91 fibers/mm 2 . No significant difference in fiber density was observed in relation to the nature of the sampling head for fibers with a diameter of <3 μm. The deposits noted on the internal walls of the cowl were small and much less than that documented in the literature for man-made mineral fibers until now. They were greater for fibers with a diameter of >3 μm than for those with a diameter of <3 μm. For large-diameter fibers, it would appear that cowl deposit can be reduced by increasing the sampling flow rate.

Increased mortality in COPD among construction workers exposed to inorganic dust.

The aim of this study was to find out if occupational exposure to dust, fumes or gases, especially among never-smokers, increased the mortality from chronic obstructive pulmonary disease (COPD). A cohort of 317,629 Swedish male construction workers was followed from 1971 to 1999. Exposure to inorganic dust (asbestos, man-made mineral fibres, dust from cement, concrete and quartz), gases and irritants (epoxy resins, isocyanates and organic solvents), fumes (asphalt fumes, diesel exhaust and metal fumes), and wood dust was based on a job-exposure matrix. An internal control group with "unexposed" construction workers was used, and the analyses were adjusted for age and smoking. When all subjects were analysed, there was an increased mortality from COPD among those with any airborne exposure (relative risk 1.12 (95% confidence interval (CI) 1.03-1.22)). In a Poisson regression model, including smoking, age and the major exposure groups, exposure to inorganic dust was associated with an increased risk (hazard ratio (HR) 1.10 (95% CI 1.06-1.14)), especially among never-smokers (HR 2.30 (95% CI 1.07-4.96)). The fraction of COPD among the exposed attributable to any airborne exposure was estimated as 10.7% overall and 52.6% among never-smokers. In conclusion, occupational exposure among construction workers increases mortality due to chronic obstructive pulmonary disease, even among never-smokers.

Current chemical exposures among Ontario construction workers.

Current occupational exposures to chemical agents were assessed as part of an epidemiological study pertaining to the cancer and mortality patterns of Ontario construction workers. The task-based exposure assessment involved members from nine construction trade unions. Air samples were taken using personal sampling pumps and collection media. A DustTrak direct-reading particulate monitor was also employed. Exposure assessments included measurements of airborne respirable, inhalable, total, and silica dust; solvents; metals; asbestos; diesel exhaust and man-made mineral fibers (MMMF). In total, 396 single- or multi-component (filter/tube), 798 direct-reading, and 71 bulk samples were collected. The results showed that Ontario construction workers are exposed to potentially hazardous levels of chemical agents. The findings are similar to those reported by other researchers, except for silica exposure. In our study, silica exposure is much lower than reported elsewhere. The difficulty associated with assessing construction workers' exposures is highlighted.

IMMUNOMODULATORY EFFECTS OF GLASS FIBRES IN OCCUPATIONALLY EXPOSED WORKERS-COMPARISON WITH ASBESTOS

Background Recent research has implicated natural and man made mineral fibers as causes of lung disease. For these reasons, and because of the trend for substitution of asbestos with other man-made fibers, improved understanding, assessment and monitoring of the toxic effects of mineral fibers is increasingly important. Glass fibers belong to the family of synthetic inorganic fibers used as insulation materials. Methods Immune and hematological parameters were examined in 80 workers exposed to glass fibres and 36 in-factory controls; and 61 workers exposed to asbestos fibres and 46 town and 21 in-factory unexposed controls, respectively. Cellular immunity was determined by phenotypic analysis of human peripheral blood leukocytes (CD3, HLA DR, CD4, CD8, CD16+56, CD19). Immune function assays-proliferative response of lymphocytes and phagocytic activity of leukocytes were evaluated in exposed and unexposed populations. Humoral immunity was evaluated by levels of immunoglobulins and concentrations of interleukins in serum. Moreover expression of activation markers on eosinophils, expression of adhesion molecules on leukocytes and levels of soluble adhesion molecules in sera were assessed. Results Multifactorial analysis of variance showed significantly decreased expression of marker CD16+56 (natural killer cells) in people exposed to glass fibres. The proliferative capacity of T-cells was significantly altered in both populations of workers exposed to fibres. In the case of people from a former asbestos cement plant, significant suppression of T-cell proliferative activity was found. On the other hand significant elevation of T-cell proliferative capacity was found in workers exposed to glass fibres. The levels of soluble adhesion molecule ICAM-1 were higher in people from the asbestos plant. Moreover significantly increased expression of CD62L (L-selectin) on monocytes and granulocytes was found. Exposure to glass fibre increased levels of E-selectin in sera of exposed subjects. Significantly increased levels of immunoglobulin E, concentrations of IL-6 and IL-8 were found in abestos-exposed workers. Similar trend of elevated IL-8 was seen after glass fibre exposure. We found significantly increased expression in markers for activated eosinophils CD69 and CD66b among workers exposed to asbestos mineral fibres. Marker of CD66b was highly expressed also on peripheral blood eosinophils of humans exposed to glass fibres. Conclusions Our findings indicate that occupational exposure to both types of fibres modulates the immune response. Suppression of T-cell immunity and, to a lesser extent, B-cell immunity, were found in the case of exposure to asbestos, while stimulation of T-cell response was observed in the glass fibre exposed population. Increased levels of proinflammatory cytokines, levels of adhesion molecules in sera and elevated expression of activation markers on eosinophils may indicate hypersensitivity and an elevated inflammatory status in the exposed workers. This work was supported by the European Union (project no. QLK4-1999-01629, Fibretox), NIEHS Grant# 510 20 5240 00000 1 15010 9220 and Slovak Grant Agency for Science # 04.92.11.05.

Exposure to residential radon causes lung cancer. For the proposition.

Exposure to residential radon causes lung cancer. For the proposition.

Preparation and examination of proposed consensus reference standards for fiber-counting.

This study provided standard reference materials for fiber-counting by phase-contrast microscopy (PCM). PCM is subject to many sources of variation, including those dependent on the microscopist, so reference standards cannot be produced that are traceable to national or international standard units. Consensus standards using a "true value" agreed on by a number of laboratories may be acceptable. Reference slides for fiber-counting can be prepared using a proprietary process of grid overlay in which the fields of view defined by the grids are identifiable and relocatable. Multiple microscopists then can examine exactly the same areas of samples, reducing one source of potential variation. Twelve slides prepared from proficiency test samples of the American Industrial Hygiene Association (AIHA) Industrial Hygiene Laboratory Quality Program were used in this study, four each of chrysotile asbestos, amosite asbestos, and man-made mineral fibers. Five microscopists from AIHA-accredited laboratories, plus the inventor of the grid process, examined the slides in a blind study. This group represented commercial analytical companies, in-house corporate laboratories, research institutions, and universities. The six microscopists met to obtain consensus agreement on the fibers in each designated field classified as countable under National Institute for Occupational Safety and Health Method 7400. Slides and documentation were forwarded to AIHA for training or other purposes. Examination of the results by statistical methods showed that some microscopists' results were significantly different from others, even though all analysts would have been considered proficient with respect to the final consensus values. Although the reasons for the outliers are complex, this procedure may have value in selecting reference laboratories in proficiency test schemes, possibly leading to more defensible "true" values and tighter limits of variation.

A Dose-Response Model for Refractory Ceramic Fibers

Refractory ceramic fibers (RCFs) are man-made vitreous fibers commonly used in insulation applications above 1000°C. Although they have been subjected to considerable toxicologic evaluation, only the pooled results from two rat inhalation studies provide data that may be suitable for performing a numerical risk assessment. Even in these inhalation studies, good evidence exists that the maximum tolerated dose (MTD) was exceeded and that pulmonary overload occurred, a condition that will cause tumors whatever the dust responsible. Indeed, a significant yield of tumors was only obtained at the highest dose tested. If these results are omitted, there is no statistically significant evidence of carcinogenicity within the RCF results. Although there is little evidence that overload-related tumors are relevant to human risk, we adopted a conservative approach to obtain the estimates of risk regardless of overload, using a biologically based model, the two-stage clonal expansion model, as well as various statistical models, including the benchmark dose model. We argue that the data favor the use of a biologically based model, which gives the best fit when the highest dose RCF exposures are omitted. Continuing with this model, we show that available data from the RCF experiment, less outliers, coupled with results from other experiments with man-made mineral fibers (MMVFs), demonstrate that all MMVFs are potentially carcinogenic, with any risk mediated by the fibers' biopersistence. Application of this "all MMVF data set" model yields a maximum likely estimate for RCF excess unit risk of 4.6 × 10 -5 (95% upper confidence limit = 9.2 × 10 -5 per fiber/ml). This implies that the risk from occupational exposure to RCFs at 1 fiber/ml for a typical working lifetime would not exceed 10 -4 .

Comparative Cytotoxicity Study of Rock Wool and Chrysotile by Cell Magnetometric Evaluation

Rock wool (RW), a type of man-made mineral fiber (MMMF), is a building material used as an asbestos substitute for heat insulation, fire resistance, and reinforcement. RW is included in group 3 of the IARC classification. In the present study, the cytotoxicity of RW was investigated by cell magnetometry, enzyme assay, DNA ladder detection, and electron microscopic morphological evaluation in comparison with chrysotile fibers (CF). Specimens were prepared by 18-h incubation of Fischer rat alveolar macrophages in the presence of RW fibers as the study material, CF as positive control, and phosphate-buffered saline (PBS) as negative control, together with a relaxation indicator, Fe3O4, except for morphological evaluation, followed by additional procedures of external magnetization and subsequent 20-min remanent magnetic field measurement for magnetometric evaluation, and macrophage DNA extraction for evaluating possible apoptosis by DNA ladder detection. In magnetometry, relaxation, a marker of cytotoxicity, was rapid in both the RW- and PBS-treated groups, while it was delayed in both the long and short CF-treated groups. Differences in percent lactate dehydrogenase (LDH) release between the RW-treated group and PBS-treated group were not significant, but those between the RW-treated group and short CF-treated group were statistically significant. A DNA ladder was not detected in any of the study groups. Electron micrographs showed that RW did not cause any change, but CF caused changes in macrophages. Thus, magnetometric measurements suggested no cytotoxicity of RW. We plan, in the future, to evaluate the safety of RW by magnetometric measurement and morphological observation of the lungs in in vivo inhalation experiments.

Toxicity of Cellulose Fibres

Cellulose fibres are used to manufacture productssuch as textiles, paper and cardboard, to give struc-tural strength to cement and other construction prod-ucts and to insulate buildings. This manufacture anduse can produce respirable airborne cellulose fibres.Cellulose fibres have not been subjected to thesame rigorous toxicity testing that has been applied toasbestos and man-made mineral fibres (Davis, 1993).Previously, there have been only limited numbers ofshort-term studies in animals using lung instillationand inhalation, all with relatively high doses. Thoseexperiments produced some pathological changes,such as granuloma, alveolitis, epithelial hyperplasiaand fibrosis (see references in Davis, 1993; Cullen

PARTICLE TOXICOLOGY: FROM COAL MINING TO NANOTECHNOLOGY

Particle research has been historically closely connected to industrial activities or materials, such as coal, asbestos, man-made mineral fibers, and more recently ambient particulate matter (PM). It is the purpose of this review to combine insights and developments in particle toxicology with the historical context of exposure and organizations sponsoring such research in Europe. In supporting research on particle-induced respiratory effects and mechanisms, research programs of the European Community on Steel and Coal (ECSC) have played a tremendous role. Current particle research in Europe is dominated by PM, and funded by the World Health Organization (WHO), European Union Framework programs, and the Health Effects Institute (HEI). Differences between historical and current research in particle toxicology include the exposure concentrations, particle size, target populations, endpoints, and length of exposure. Inhaled particle effects are no longer confined to the lung, since particles are suggested to translocate to the blood while lung inflammation invokes systemic responses. Finally, the particle size and concentrations have both been reduced about 100-fold from 2-5 mg/m 3 to 20-50 mg/m 3 and from 1-2 µm to 20-100 nm (ultrafine) as domestic fuel burning has decreased and vehicle sources have increased and attention has moved from coal mining industry to general environment. There is, however, a further occupational link to nanotechnology, which continuously produces new materials in the ultrafine range. Although inhalation exposure is considered to be minimal in this technology, some particles are produced to be used for carrier purpose in medical applications. Based on our current knowledge of particle toxicology, it is highly desirable that toxicology and technology are linked in this extremely rapid developing area, to learn more about potential risks and also to develop knowledge on the role of surface and size in particle toxicity.

Effect of Size of Man-Made and Natural Mineral Fibers on Chemiluminescent Response in Human Monocyte-Derived Macrophages

Fiber size is an important factor in the tumorigenicity of various mineral fibers and asbestos fibers in animal experiments. We examined the time course of the ability to induce lucigenin-dependent chemiluminescence (CL) from human monocyte-derived macrophages exposed to Japan Fibrous Material standard reference samples (glass wool, rock wool, micro glass fiber, two types of refractory ceramic fiber, refractory mullite fiber, potassium titanium whisker, silicon carbide whisker, titanium oxide whisker, and wollastonite). We determined how fiber length or width might modify the response of cells. We found that the patterns of time-dependent increase of CL (sigmoid type) were similar for each sample except wollastonite. We observed a strong correlation between geometric-mean length and ability to induce CL in seven samples &gt; 6 microm in length over the time course (largest r(2) = 0.9760). Although we also observed a close positive correlation between geometric-mean width and the ability to induce CL in eight samples &lt; 1.8 microm in width at 15 min (r(2) = 0.8760), a sample of 2.4 microm in width had a low ability to induce CL. Moreover, the relationship between width and the rate of increase in ability to induce CL had a negative correlation at 30-60 min (largest r(2) = 0.7473). Our findings suggest that the release of superoxide from macrophages occurs nonspecifically for various types of mineral fibers depending on fiber length.

Effect of size of man-made and natural mineral fibers on chemiluminescent response in human monocyte-derived macrophages.

Fiber size is an important factor in the tumorigenicity of various mineral fibers and asbestos fibers in animal experiments. We examined the time course of the ability to induce lucigenin-dependent chemiluminescence (CL) from human monocyte-derived macrophages exposed to Japan Fibrous Material standard reference samples (glass wool, rock wool, micro glass fiber, two types of refractory ceramic fiber, refractory mullite fiber, potassium titanium whisker, silicon carbide whisker, titanium oxide whisker, and wollastonite). We determined how fiber length or width might modify the response of cells. We found that the patterns of time-dependent increase of CL (sigmoid type) were similar for each sample except wollastonite. We observed a strong correlation between geometric-mean length and ability to induce CL in seven samples > 6 microm in length over the time course (largest r(2) = 0.9760). Although we also observed a close positive correlation between geometric-mean width and the ability to induce CL in eight samples < 1.8 microm in width at 15 min (r(2) = 0.8760), a sample of 2.4 microm in width had a low ability to induce CL. Moreover, the relationship between width and the rate of increase in ability to induce CL had a negative correlation at 30-60 min (largest r(2) = 0.7473). Our findings suggest that the release of superoxide from macrophages occurs nonspecifically for various types of mineral fibers depending on fiber length.

Dustiness of Different High-Temperature Insulation Wools and Refractory Ceramic Fibres

Recent regulations are encouraging the replacement of older types of man-made mineral fibre by more soluble and, thus, less biopersistent compositions. In order for there to be any health benefits from this policy and to gain maximum benefit from such substitutions, the use of the new materials should not increase exposure. The work reported here was undertaken to investigate the use of new high-temperature glass insulation wools in place of refractory ceramic fibres (RCF). Airborne fibre levels occurring during the manufacture of both RCF and calcium magnesium silicate wools (CMS) were compared using measurements of genuine workplace exposure from a routine monitoring operation on the same plant. Exposures during use were compared in one customer facility where RCF and CMS blankets were used for the same task. Further comparisons were made in a laboratory test of dustiness using a "shaking box test". For some manufacturing tasks there are only a few workplace samples and there are few opportunities for genuine comparisons with both RCF and CMS in identical uses. However, both materials produced very similar exposure levels during manufacture, use and in the laboratory test. The novel magnesium silicate fibre was significantly dustier in the laboratory test.

Dustiness of different high-temperature insulation wools and refractory ceramic fibres

Recent regulations are encouraging the replacement of older types of man-made mineral fibre by more soluble and, thus, less biopersistent compositions. In order for there to be any health benefits from this policy and to gain maximum benefit from such substitutions, the use of the new materials should not increase exposure. The work reported here was undertaken to investigate the use of new high-temperature glass insulation wools in place of refractory ceramic fibres (RCF). Airborne fibre levels occurring during the manufacture of both RCF and calcium magnesium silicate wools (CMS) were compared using measurements of genuine workplace exposure from a routine monitoring operation on the same plant. Exposures during use were compared in one customer facility where RCF and CMS blankets were used for the same task. Further comparisons were made in a laboratory test of dustiness using a “shaking box test”. For some manufacturing tasks there are only a few workplace samples and there are few opportunities for genuine comparisons with both RCF and CMS in identical uses. However, both materials produced very similar exposure levels during manufacture, use and in the laboratory test. The novel magnesium silicate fibre was significantly dustier in the laboratory test.

Long Man-Made Fibers and Lung Cancer Risk

We show that available experimental data from long-term oncogenicity experiments in Fisher rats are consistent with the hypothesis that the oncogenic potential of long man-made mineral fibers is determined mainly by their biopersistence. We present analyses of these data within the initiation–promotion–progression paradigm of carcinogenesis. Our method of analysis can take the temporal pattern of the burden of long fibers in the lungs of individual animals into explicit account. For this analysis, the temporal pattern of lung burden for each animal was imputed from the information obtained from sacrificed animals. The data are consistent with the hypothesis that fibers act as initiators in the rat lung. We present an estimate of the dose-dependent initiation parameter that is based on all the available data.

In Vitro Studies on Biological Effects of Fibrous Minerals.

Asbestos substitutes have been used recently in industrial various applications. Since certain asbestos substitutes have similar characteristics of asbestos, they require urgent in vitro and in vivo evaluation of these asbestos substitutes prior to occupational applications. Though in vitro studies do not offer precise assessment of toxicity of the fibers, it is possible to provide useful information as to the biological effects of asbestos and its substitutes. This review articles described the findings of in vitro experiments in investigation of biological effects of asbestos and man made mineral fibers (MMMF) and their correlation with in vivo assays; 1. Cytotoxicity, geometry and dimension of fibers. 2. In vitro biological effects of fibers on a mass basis and a numerical basis. 3. Mechanism of cytotoxicity, carcinogenecity and cell proliferation including in vitro cytokines production. The relationships between the in vitro and the in vivo biological effects of fibers do not always coincide. Therefore, safety of the fibers must be assessed in both in vivo and in vitro using an inert fiber as negative control. Additionally, evaluation of safety of these fibers in vitro must be conducted in comparable concentrations, sizes and numbers of fibers for used in in vivo experiments.

A trial on the quantitative risk assessment of man-made mineral fibers by the rat intraperitoneal administration assay using the JFM standard fibrous samples.

We tried to evaluate the carcinogenic risk of man-made mineral fiber based on the mesothelioma incidence in female F344 rats after intraperitoneal administration. Rats (female F344/ Nslc, 5-week-old, n=330) were observed for 2 years after the intraperitoneal administration of 5 to 20 mg of 9 types of the JFM (Japan Fibrous Material Research Association) standard fiber samples (glass wool, rock wool, micro fiber glass, three types of refractory fiber, potassium titanate whisker, silicon carbide whisker, titanium oxide whisker), wollastonite (natural fiber) and UICC chrysotile B. All rats administered 10 mg of silicon carbide whisker had developed peritoneal mesothelioma within a year. The cumulative incidence of peritoneal mesothelioma at the end of the experiment was 85% for 10 mg UICC chrysotile B, 77% for 10 mg of potassium titanate whisker, 70% for 5 mg of silicon carbide whisker, 20% for 5 mg of potassium titanate whisker, 20% for 20 mg of refractory fiber 2 and 10% for 20 mg of refractory fiber 1. Carcinogenicity was estimated 2.4 times for silicon carbide whisker and 0.23 for potassium titanate whisker in comparison with UICC chrysotile B. It has been well documented from several experimental studies that man-made fibers are safer than asbestos because of the different durability in the lung. Present results consistently suggest that man-made fibers with high durability have similar or higher risk as carcinogen than asbestos.