Man-made Vitreous Fibers Research Articles

Subchronic inhalation study of stone wool fibres in rats.

Pathology results after subchronic inhalation in rats of three separate fibres representing the new biosoluble high-aluminium low-silica HT type stone wool are given, and the results were compared with the results from a similar study done with the traditional stone wool MMVF21. Male Wistar rats were exposed at one exposure level by nose-only inhalation to well-characterized fibre test atmospheres. The fibres had been size selected to be largely rat respirable. The target dose was an exposure to 150 long fibres/ml (length>20 microm) in each group, and this dose was achieved for all the fibres. The negative control groups were exposed to filtered air. The exposure duration was 6 h/day, 5 days/week for 3 months, with a subsequent non-exposure period lasting 3 months. The rats were killed 1 week after the last exposure and additional post-exposure kills were performed at 1.5 and 3 months to monitor the progression of pulmonary change and fibre numbers in the lung. The assessments included bronchoalveolar lavage fluid (BALF) for evaluation of inflammatory response (e.g. protein content, enzymes, increase in polymorphonuclear leucocytes) and measurement of cell proliferation, assessment of early fibrosis through histological examination and comparison of body weight and lung lobe weights. After exposure of rats to the new biosoluble fibres no biologically significant effects were observed except that a statistically significant increase in lung weight was observed up to 1.5 months post-exposure in all three treatment groups. At 3 months post-exposure, the small increase was no longer significant. The increase in lung weight was still present in the MMVF21 group at the 3 months post-exposure kill. After 3 months exposure, lung retention of long fibres (length>20 microm) varied from 0.4 to 5.2 x 10(6) per lung for the biosoluble fibres. At 3 months post-exposure, the long fibre concentration in the lungs had decreased to 1-7% of this figure. The fibre with the relatively highest biopersistence (RIF41001) showed the highest fibre retention. The retention of the more biopersistent traditional stone wool MMVF21 was 5.7 x 10(6) per rat lung after 3 months exposure and had decreased to 64% of this figure at 3 months post-exposure. There was no clear difference in the bronchoalveolar lavage fluid cell concentration and percentage of cells between MMVF21 and the HT groups. Fibre inhalation caused a significant increase after 3 months in all the biochemical parameters measured in the BALF. Cell proliferation was enhanced at the end of exposure for MMVF21 for all three labelling indices, but only for the bronchiolar epithelium in the RIF41001 group and for alveolar parenchymal cells in the RIF43006-1 group. At the termination of the 3 month exposure period, as well as after 1.5 and 3 month recovery periods, minimal morphological changes were diagnosed in the biosoluble fibre groups. These changes included alveolar macrophage aggregation and/or microgranulomas at the bronchiolar-alveolar junction in the few rats affected. No fibrogenic potential was noted for any of the three fibres. No clear-cut difference between the different biosoluble fibre types was noted. In the MMVF21 group, minimal interstitial fibrosis was observed that gradually decreased after the 1.5 and 3 month non-exposure periods. In this study, the pathological changes found in the lungs of exposed rats were in accordance with the pathology previously reported from full lifespan inhalation studies. This may indicate that for fibres belonging to the man-made vitreous fibres group a well conducted biopersistence study is sufficient to predict possible pathogenic effects for new fibre types. The biological parameters examined in a 90 day study may indicate little additional information to contribute to the prediction of the outcome of carcinogenicity studies.

Evaluation of Exposure to Man-Made Vitreous Fibers by Nasal Lavage

The objectives of this study were to develop a biomonitoring method for the assessment of exposure to man-made vitreous fibers (MMVF), to examine the level of exposure to MMVF in the prefabricated house industry, and to study nasal inflammatory reactions and respiratory symptoms associated with MMVF among workers. Nasal lavage was performed on workers from two factories, and concentrations of MMVF were measured by electron microscopy. Cytokines (IL-6, IL-8, TNF-α, and IFN-γ) were also assayed and inflammatory cells (lymphocytes, eosinophils, neutrophils, and macrophages) were counted microscopically. Concentrations of airborne fibers (longer than 5 μm) were measured for comparison. Moreover, the exposure to MMVF and the related symptoms were studied with a structured questionnaire. In nasal lavage samples, the mean concentration of MMVF (length > 1.5 μm) was 3260 f/mL in Factory 1, 1680 f/mL in Factory 2, and below 500 f/mL in the control group. About 52% of the retained fibers were longer than 100 μm. The group-specific mean concentrations of MMVF in nasal lavage samples correlated with production rates and airborne fiber levels in both plants. The airborne concentrations of MMVF both in the breathing zone and fixed-point samples were low (below 0.1 f/cm3). No significant differences in the biological response (inflammatory cells, cytokines) were found between the groups exposed and the control group. The workers complained of some irritation of the skin, eyes, and upper respiratory tract, which could be reduced by appropriate protective equipment. It is concluded that nasal lavage can be used as a biomonitoring method in the assessment of MMVF exposure.

Extrapolation of the Carcinogenic Potency of Fibers from Rats to Humans

In 1999 Berry published a model for mesothelioma incidence following fiber exposure. He concluded, that the influence of the solubility of fibers on the mesothelioma rate is 17 times higher in humans than in rats. This conclusion may be helpful for evaluating the carcinogenic risk from man-made vitreous fibers, but it had little influence on some recent discussions. It has been demonstrated using this model, that in an injection experiment with rats, fibers with elimination constants of 0.1/year and 1/year—which would approximately correspond to crocidolite and perhaps ceramic fibers—differ in their mesothelioma risk only by a ratio of 3.2:1. In contrast, for humans exposed continuously from age 20 to age 60 a risk ratio of 4,750:1 is obtained. This result may be helpful for the assessment of the human cancer risk e.g., from exposure to refractory ceramic fibers. However, uncertainty is large, since the life-span of rats is too low to measure the elimination rate of bio-persistent fibers sufficiently.

Historical cohort study of U.S. man-made vitreous fiber production workers IX: summary of 1992 mortality follow up and analysis of respiratory system cancer among female workers.

We report the 1946-1992 mortality experience of 4008 females employed in any of 10 U.S. fiberglass manufacturing plants between 1945 and 1978 relative to external population rates. We also examine respiratory system cancer (RSC) mortality as a function of estimated exposure to respirable fibers (RFib), formaldehyde (FOR), silica, phenolics, urea, and other agents based on internal cohort comparisons. No statistically significantly elevated standardized mortality ratios were observed for all-cause mortality (930 deaths), any of the 25 nonmalignant causes considered, all malignant neoplasms (266 deaths), or any of the 27 malignant causes considered. Internal cohort comparisons revealed no significant positive associations between RSC mortality (53 cases) and exposure to RFib, FOR, or any of the other agents considered, although exposure levels were generally low. Some demographic subgroups appear to be at relatively increased risk of RSC.

Influence of airspace geometry and surfactant on the retention of man-made vitreous fibers (MMVF 10a).

Inhaled and deposited man-made vitreous fibers (MMVF) 10a (low-fluorine preparation of Schuller 901 insulation glass) were studied by electron microscopy in hamster lungs, fixed by intravascular perfusion within 23 +/- 2 min (SD) of the initial inhalation. We found fibers on the surfaces of conducting airways and alveoli. In the airways, 89% of the fibers were totally and 11% partially covered by lining-layer material. In the alveoli, 32% of the fibers were totally submersed; others touched the alveolar wall, stuck at one end, bridging the airspace. Studies in a surface balance showed that fibers were immersed into the aqueous subphase by approximately 50% at film surface tensions of 20-25 mJ/m2) and were submersed (totally immersed; i.e., totally surrounded by fluid) at approximately 10 mJ/m2). Fibers were also found to be phagocytosed by macrophages. We found a substantial number of particle profiles within alveolar blood capillaries. Fiber length and alveolar geometry appear to be important limiting factors for the submersion of vitreous fibers into the lungs' surface lining layer.

Occupational exposures and gastrointestinal cancers among Finnish women.

A cohort including all female workers born 1906 through 1945 (n = 413,877) in Finland was identified through the Population Census of Finland of 1970. Incident cases of cancers of the gastrointestinal tract were explored during 1971 to 1995. Job titles in census records were converted to exposures of 31 occupational agents through a job-exposure matrix. For each agent, the product of level and probability of exposures was calculated and subdivided in three categories: zero, low and medium/high. Poisson regression models estimated relative risks (RR) for each agent, standardized for birth cohort, follow-up period, and socioeconomic status. Adjustment at job title level was done for alcohol use for cancers of the esophagus and liver and smoking for pancreatic cancer. The results showing either statistically significant RR at the medium/high level of exposure (RRH) or statistically significant trend (P < 0.05) over the exposure categories were considered as positive findings. Colon cancer risk (2009 cases) was positively associated with sedentary work (RRH 1.3, 95% CI = 1.1-1.6; P trend 0.001) and negatively associated with perceived workload (P trend = 0.007). For stomach cancer (1881 cases), we observed an association with exposure to electromagnetic fields (RRH 1.44, 95% CI = 1.01-2.05) and man-made vitreous fibers (MMVF) (p trend 0.03). Rectal cancer (1323 cases) showed an association with chromium (RRH 1.9, 95% CI = 1.2-3.1) and oil mist (RR 2.0; 95% CI = 1.0-3.9). For pancreas cancer (1302 cases) we found associations with exposure to chromium (RRH 1.8; 95% CI = 1.0-3.1; P trend 0.01), electromagnetic fields (RRH 1.8; 95% CI = 1.2-2.8; P trend 0.02), and sedentary work (RRH 1.3; 95% CI = 1.0-1.7; P trend 0.05). We found no significant associations between any FINJEM agents and cancers of the esophagus (389 cases), liver (389 cases), and gallbladder (651 cases). Having examined the associations between seven cancer sites and over 30 exposures there exists the real possibility that some of the associations detected are chance findings. Therefore, the associations observed should need to be confirmed in other studies.

Modeling the Retention and Clearance of Manmade Vitreous Fibers in the Rat Lung

A mathematical model describing the dissolution and disintegration of long fibers and the clearance of short fibers is developed. For short fiber clearance, the model is based on previous modeling of the retention and clearance of particles, and most model parameters are taken from that particulate model. In addition to modeling the disappearance of long fibers, the present study includes a quantitative measure of goodness of fit of the model to observed data. Data from chronic inhalation experiments with insulation glass wools (MMVF10 and MMVF11) and rockwool (MMVF21) were provided for this study. These data comprised lung burdens at 10 time points at each of 3 concentrations for each fiber in inhalation experiments lasting up to 104 wk. At the two higher concentrations, the model had to take into account the effects of lung burden on macrophage-mediated clearance. The modeling shows that the overload dependence appears remarkably similar to that for low-toxicity particles in that the critical volumetric lung burden is similar to that for low toxicity dust. The model describes overload as leading to alveolar sequestration of short fibers or particles, and the estimated rate of alveolar sequestration for MMVF10 was similar to that for particles, but the estimated rate was lower for the other two fibers. Two alternative hypotheses to describe the process of the disappearance of longer fibers were tested by assessing their effect on a quantitative measure of fit of model predictions to the lung-burden data. These tests indicated that (a) dissolution leading to disintegration of long fibers into shorter fibers gave a much better fit than the alternative assumption that dissolution would leave only nonfibrous residue and (b) the relative rates of disintegration of the fibers in the lung appear to be directly dependent on their rates of in vitro dissolution and their diameters.

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 .

Occupational irritant contact dermatitis from synthetic mineral fibres according to Finnish statistics.

Synthetic mineral fibres (i.e. man-made vitreous fibres, MMVF) are classified into glass filament, mineral wool (glass wool, rock wool and slag wool), refractory ceramic fibres, and fibres for special purposes. This paper analyses the data on occupational irritant contact dermatitis (ICD) caused by MMVF during 1990-99 in Finland according to the Finnish Register of Occupational Diseases (FROD). A total of 63 cases from MMVF were reported. 56 were diagnosed as ICD, and 2 as allergic contact dermatitis, both from rock wool. 53 out of 63 cases were due to mineral wool or glass filaments; half of the cases, according to a rough estimate, were due to mineral wool and a half due to glass filaments used in lamination work. Carpenters, building workers and insulation workers have the highest risk of ICD from mineral wool. 4 cases in carpenters, 4 in building workers and 2 in insulation workers were reported from MMVF. For every 100 000 employed workers, only 1.6 cases of ICD in carpenters, 2.7 in building workers and 9.1 in insulation workers were annually due to MMVF, respectively. Mineral wool used in construction work, insulation, etc., cannot be considered to be a common cause of occupationally induced ICD. However, information on harmful skin effects of MMVF is useful to exposed persons in the prevention of the effects.

Results from a Long-Term Carcinogenicity Study in Rats with Intraperitoneal Injection of Soluble Fibrous Dusts

This long-term study evaluated the potential carcinogenic effects (mesotheliomas) of various man-made vitreous fibres, when administered intraperitoneally (2–20 injections) in rats. Four new insulation wool fibres (designated M, O, P and V), considered as highly soluble, were tested at dose-levels up to 5000 × 106 WHO fibres. They were compared to crocidolite (dose-level up to 1000 × 106 WHO fibres) and to reference, highly soluble fibre (fibre B, dose-levels up to 5000 × 106 WHO fibres). The tested fibres did not produce notable adverse effects on the basis of mortality, clinical signs and body weight, except at high dose-levels. Histopathological investigations distinguished the various fibres: (i) fibres M and O did not induce mesotheliomas at dose-levels up to 5000 × 106 fibres; (ii) fibres P and V induced up to 16% and 28%, respectively, of mesotheliomas at the same dose-level, i.e. in the same range as for the reference fibre B (18% of animals with mesotheliomas); (iii) 90% of the crocidolite-treated animals displayed mesotheliomas at a dose-level of 1000 × 106 fibres.

Respiratory cancer and exposure to man-made vitreous fibers: a systematic review.

Man-made vitreous fibers (MMVF's) have some structural features similar to those found in asbestos. This has lead to concern that exposure to MMVF's could increase the risk of respiratory cancer. Bibliographic resources were used to identify 10 case-control and 10 cohort studies, which analyzed the relationship between exposure to MMVF's and cancer of the respiratory system. Standardized mortality ratio's (SMR's) were extracted from the cohort studies for a meta-analysis. A significant increase in SMR was observed for workers exposed to rock and glass wool, but not in workers exposed to glass filament. Meta-analysis of SMR's after stratification by fiber type resulted in aggregate estimates of risk of 1.23 (95% CI = 1.10-1.38), 1.08 (95% CI = 0.93-1.26), and 1.32 (95% CI = 1.15-1.52) for exposure to glass wool, glass filament, and rock wool, respectively. Some or all of the increased mortality could be attributed to tobacco use. The results highlight the difficulty of assessing small increases in risk of respiratory cancer potentially caused by occupational exposure in populations with high prevalence of tobacco use.

No effect or no information? Comments on a nested case-control study of lung cancer among European rock and slag wool production workers.

The author considers the validity of a recent study of lung cancer among European rock and slag wool workers. The study failed to demonstrate an association between lung cancer and exposure to man-made vitreous fibers and also did not manage to demonstrate a relationship between lung cancer and asbestos exposure, an odd finding that casts doubt on its validity. This article deals with bias towards the null and other aspects of the reviewed study that may explain its failure to demonstrate an effect of asbestos, concluding that the study does not add to knowledge about a possible carcinogenic effect of rock and slag wool fibers, the apparent null results simply being non-informative because of the study's poor ability to detect existing associations.

High-Alumina Low-Silica HT Stone Wool Fibers: A Chemical Compositional Range with High Biosolubility

Man-made vitreous fibers (MMVF) are classified within the European Union (EU) as carcinogenic category 3 (possibly carcinogenic), but criteria exist to exonerate fibers from this classification. The HT stone wool fiber type is a MMVF that fulfills European regulatory requirements for exoneration from classification as a carcinogen based on in vivo testing. The chemical composition of the fibers and the results of the in vivo and in vitro studies that defined the chemical compositional range for a CAS registry number for these fibers are presented and discussed. Results from in vitro dissolution measurements at pH 4.5 of 52 fiber compositions (9–23 wt% Al 2O 3 and 32–47 wt% SiO 2) ranging from traditional stone wool to the biosoluble HT fibers are presented. The results are evaluated as a function of the ratio Al/(Al+Si) in the glass network and as a function of the fraction of Si-O-Si linkages in the glass. It is suggested that the dissolution mechanism for these fibers relates to the density of the surface silica layer on dissolving fibers and that the fraction of Si-O-Si linkages influences this.

Sinonasal cancer and occupational exposures: a pooled analysis of 12 case-control studies.

In order to examine the associations between sinonasal cancer and occupational exposures other than wood dust and leather dust, the data from 12 case-control studies conducted in seven countries were pooled and reanalyzed. The pooled data set included 195 adenocarcinoma cases (169 men and 26 women), 432 squamous cell carcinomas (330 men and 102 women), and 3136 controls (2349 men and 787 women). Occupational exposures to formaldehyde, silica dust, textile dust, coal dust, flour dust, asbestos, and man-made vitreous fibers were assessed with a job-exposure matrix. Odds ratios (ORs) were adjusted for age, study, wood dust, and leather dust, or other occupational exposures when relevant. 95% confidence intervals (CIs) were estimated by unconditional logistic regression. A significantly increased risk of adenocarcinoma was associated with exposure to formaldehyde. The ORs for the highest level of exposure were 3.0 (Cl = 1.5-5.7) among men and 6.2 (CI=2.0-19.7) among women. An elevated risk of squamous cell carcinoma was observed among men (OR=2.5, CI=0.6-10.1) and women (OR = 3.5, CI = 1.2-10.5) with a high probability of exposure to formaldehyde. Exposure to textile dust was associated with non-significantly elevated risk of adenocarcinoma, among women only: the OR for the high level of cumulative exposure was 2.5 (CI = 0.7-9.0). High level of asbestos exposure was associated with a significantly increased risk of squamous cell carcinoma among men (OR = 1.6, CI = 1.1-2.3). The results of this pooled analysis support the hypothesis that occupational exposure to formaldehyde increases the risk of sinonasal cancer, particularly of adenocarcinoma. They also indicate an elevated risk of adenocarcinoma among women exposed to textile dust, and suggest that exposure to asbestos may increase the risk of squamous cell carcinoma.

Asbestos and man‐made vitreous fibers as risk factors for diffuse malignant mesothelioma: Results from a German hospital‐based case‐control study

Background This study examines the role of occupational factors in the development of diffuse malignant mesothelioma with special emphasis on the dose–response relationship for asbestos and on the exposure to man-made vitreous fibers (MMVFs). Methods One hundred and twenty-five male cases, diagnosed by a panel of pathologists, were personally interviewed concerning their occupational and smoking history. The same number of population controls (matched for sex, age and region of residence) underwent similar interviews by trained interviewers. Odds ratios (OR) were calculated for an expert-based exposure index using conditional logistic regression. Results Exposure to asbestos shows the expected sharp gradient with an OR of about 45 for a cumulative exposure > 1.5 fiber years (arithmetic mean 16 fiber years). A significant OR was calculated even for the lowest exposure category “> 0 − ≤ 0.15 fiber years”. Although the mean cumulative exposure to MMVF is roughly 10% of the exposure to asbestos, an increased OR is observed in an ever/never evaluation. This observation is heavily hampered by methodical problems. A corresponding case–control study was performed using a lung tissue fiber analysis in addition to interviews. Both interviews and the lung tissue analysis yielded similar OR levels between the reference and the maximum exposure intervals. Conclusions Despite a possible influence as a result of selection and information bias, our results confirm the previously reported observation of a distinct dose–response relationship even at levels of cumulative exposure below 1 fiber year. Moreover, the study confirms that asbestos is a relevant confounder for MMVF. A causal relationship between exposure to MMVF and mesothelioma could neither be detected nor excluded, as in other studies. Am. J. Ind. Med. 39:262–275, 2001. © 2001 Wiley-Liss, Inc.

Differential Responses of Rat Alveolar and Peritoneal Macrophages to Man-Made Vitreous Fibers in Vitro

Different approaches, including inhalation and intraperitoneal injection assays, have been used to assess the potential health effects of man-made vitreous fibers (MMVF). The purpose of this study was to compare the phagocytic activity and the formation of reactive oxygen species by rat alveolar macrophages (AM) and peritoneal macrophages (PM) upon exposure to MMVF10 glass wool and MMVF21 rock wool fibers. Macrophage (MØ) phagocytosis of mineral fibers was assessed by optical videomicroscopy and computer-aided image analysis. MØ were classified as cells not associated with fibers, cells with attached fibers, cells with incompletely phagocytized fibers (an appearance known as “frustrated phagocytosis”), and cells with completely phagocytized fibers. The production of superoxide anions by AM and PM upon incubation with MMVF10 and MMVF21 fibers was determined by the superoxide dismutase-inhibitable reduction of ferricytochrome C. PM were found to have a lower phagocytic activity than AM. A significantly higher percentage of AM than of PM underwent frustrated phagocytosis of MMVF10 and MMVF21 fibers. In line with these findings, AM generated higher levels of oxygen radicals than PM upon exposure to MMVF21 fibers. In contrast, MMVF10 fibers failed to induce the generation of reactive oxygen species by both AM and PM. Our in vitro results show that the phagocytic activity, in particular the frustrated phagocytosis of mineral fibers, was significantly lower in PM than in AM. The data support the idea that the durability and biopersistence of mineral fibers are higher in the peritoneal cavity than in the lung.

Asbestos and man-made vitreous fibers as risk factors for diffuse malignant mesothelioma: results from a German hospital-based case-control study.

This study examines the role of occupational factors in the development of diffuse malignant mesothelioma with special emphasis on the dose-response relationship for asbestos and on the exposure to man-made vitreous fibers (MMVFs). One hundred and twenty-five male cases, diagnosed by a panel of pathologists, were personally interviewed concerning their occupational and smoking history. The same number of population controls (matched for sex, age and region of residence) underwent similar interviews by trained interviewers. Odds ratios (OR) were calculated for an expert-based exposure index using conditional logistic regression. Exposure to asbestos shows the expected sharp gradient with an OR of about 45 for a cumulative exposure > 1.5 fiber years (arithmetic mean 16 fiber years). A significant OR was calculated even for the lowest exposure category "> 0 - < or = 0.15 fiber years". Although the mean cumulative exposure to MMVF is roughly 10% of the exposure to asbestos, an increased OR is observed in an ever/never evaluation. This observation is heavily hampered by methodical problems. A corresponding case-control study was performed using a lung tissue fiber analysis in addition to interviews. Both interviews and the lung tissue analysis yielded similar OR levels between the reference and the maximum exposure intervals. Despite a possible influence as a result of selection and information bias, our results confirm the previously reported observation of a distinct dose-response relationship even at levels of cumulative exposure below 1 fiber year. Moreover, the study confirms that asbestos is a relevant confounder for MMVF. A causal relationship between exposure to MMVF and mesothelioma could neither be detected nor excluded, as in other studies.

Image analysis of insulation mineral fibres.

We present two methods for measuring the diameter and length of man-made vitreous fibres based on the automated image analysis of scanning electron microscopy images. The fibres we want to measure are used in materials such as glass wool, which in turn are used for thermal and acoustic insulation. The measurement of the diameters and lengths of these fibres is used by the glass wool industry for quality control purposes. To obtain reliable quality estimators, the measurement of several hundred images is necessary. These measurements are usually obtained manually by operators. Manual measurements, although reliable when performed by skilled operators, are slow due to the need for the operators to rest often to retain their ability to spot faint fibres on noisy backgrounds. Moreover, the task of measuring thousands of fibres every day, even with the help of semi-automated image analysis systems, is dull and repetitive. The need for an automated procedure which could replace manual measurements is quite real. For each of the two methods that we propose to accomplish this task, we present the sample preparation, the microscope setting and the image analysis algorithms used for the segmentation of the fibres and for their measurement. We also show how a statistical analysis of the results can alleviate most measurement biases, and how we can estimate the true distribution of fibre lengths by diameter class by measuring only the lengths of the fibres visible in the field of view.

Mechanism of refractory ceramic fiber- and rock wool-induced cytotoxicity in alveolar macrophages.

Man-made vitreous fibers (MMVFs) can induce cytotoxicity in a way similar to that of other particles, including silica and asbestos fibers. However, as yet the mechanism of MMVF-induced cytotoxicity is still not clear. This report aims to clarify the mechanism of MMVF-induced cytotoxicity in the alveolar macrophage (AM). In this mechanism, an attempt to prove the involvement of the adenosine triphosphate (ATP) generation system and the polyinosinic acid-inhibitable scavenger receptors was made. Several parameters were observed for cytotoxicity, such as cell viability, the release of lactic dehydrogenase (LDH) and ATP levels in rat AM's that were treated with refractory ceramic fibers (RF2) and rock wool (RW1). A specially designed ATP generation system was used to determine the effect of MMVF on ATP generation. A scavenger receptor ligand was applied to evaluate the relationship between scavenger receptors and MMVF-induced ATP depletion. A 3-(4,5-dimethylthiazol)-2,5-diphenyl tetrazolium bromide (MTT) assay indicated that both RF2 and RW1 caused a decrease in cell viability and this decrease was concentration-dependent. RF2 and RW1 increased the release of LDH with increasing fiber concentration. From these parameters, RF2 was shown to exhibit greater cytotoxicity than did RW1. Both fibers decreased the intracellular ATP content and this decrease was concentration-dependent. The decrease was more pronounced in RW1 than in RF2 at all fiber concentrations. These fibers suppressed succinate-triggered oxygen consumption. Polyinosinic acid, a ligand of the scavenger receptor, inhibited the MMVF-induced decrease in ATP concentration. These results suggest that RF2 and RW1 can induce cytotoxicity and ATP depletion in the AM through the polyinosinic acid-inhibitable scavenger receptor. ATP depletion was the important factor in MMVF cytotoxicity, especially by RW1.

Laryngeal and hypopharyngeal cancer and occupational exposure to asbestos and man‐made vitreous fibers: Results of a case‐control study

Background The data from a case-control study performed in France between 1989 and 1991 were used to test whether exposure to either asbestos or to man-made vitreous fibers (MMVF) is a risk factor for cancer of the larynx or the hypopharynx. Methods This study involved 315 incident cases of laryngeal cancer, 206 cases of hypopharyngeal cancer, and 305 hospital-based controls with other types of cancer, all recruited in 15 hospitals in six French cities. The subjects' past occupational exposure to asbestos and to four types of MMVF (mineral wool, refractory ceramic fibers, glass filaments, and microfibers) was evaluated based on their job history, with the aid of a job-exposure matrix. Odds ratios were calculated with unconditional logistic regression, with adjustment for smoking and drinking levels. Results Exposure to asbestos resulted in a significant increase in the risk of hypopharyngeal cancer (OR = 1.80, 95% CI: 1.08–2.99) and a nonsignificant increase in the risk of laryngeal cancer (OR = 1.24, 95% CI: 0.83–1.90). Risk was highest for the epilarynx (highest cumulative level of exposure: OR = 2.22, 95% CI: 1.05–4.71). Exposure to mineral wools was of borderline significance for the risk of hypopharyngeal cancer (OR = 1.55, 95% CI: 0.99–2.41), and nonsignificantly associated with the risk of laryngeal cancer (OR–1.33, 95% CI: 0.91–1.95). The risk was again highest for the epilarynx (OR = 1.85, 95% CI: 1.08–3.17). No significant results were observed for the other MMVF. Conclusions These results suggest that asbestos exposure increases the risk of epilaryngeal and hypopharyngeal cancers. It is difficult to reach a conclusion about the effects of mineral wools, because nearly all the exposed subjects were also exposed to asbestos. The possible effects of other MMVF were difficult to assess in this study, because of the paucity of exposed subjects. Am. J. Ind. Med. 37:581–589, 2000. © 2000 Wiley-Liss, Inc.