A. Dufresne

The 1891-1920 birth cohort of Quebec chrysotile miners and millers: mortality 1976-88.

A cohort of some 11,000 men born 1891-1920 and employed for at least one month in the chrysotile mines and mills of Quebec, was established in 1966 and has been followed ever since. Of the 5351 men surviving into 1976, only 16 could not be traced; 2508 were still alive in 1989, and 2827 had died; by the end of 1992 a further 698 were known to have died, giving an overall mortality of almost 80%. This paper presents the results of analysis of mortality for the period 1976 to 1988 inclusive, obtained by the subject-years method, with Quebec mortality for reference. In many respects the standardised mortality ratios (SMRs) 20 years or more after first employment were similar to those for the period 1951-75--namely, all causes 1.07 (1951-75, 1.09); heart disease 1.02 (1.04); cerebrovascular disease 1.06 (1.07); external causes 1.17 (1.17). The SMR for lung cancer, however, rose from 1.25 to 1.39 and deaths from mesothelioma increased from eight (10 before review) to 25; deaths from respiratory tuberculosis fell from 57 to five. Among men whose exposure by age 55 was at least 300 million particles per cubic foot x years (mpcf.y), the SMR (all causes) was elevated in the two main mining regions, Asbestos and Thetford Mines, and for the small factory in Asbestos; so were the SMRs for lung cancer, ischaemic heart disease, cerebrovascular disease, and respiratory disease other than pneumoconiosis. Except for lung cancer, however, there was little convincing evidence of gradients over four classes of exposure, divided at 30, 100, and 300 mpcf.y. Over seven narrower categories of exposure up to 300 mpcf.y the SMR for lung cancer fluctuated around 1.27 with no indication of trend, but increased steeply above that level. Mortality form pneumoconiosis was strongly related to exposure, and the trend for mesothelioma was not dissimilar. Mortality generally was related systematically to cigarette smoking habit, recorded in life from 99% of survivors into 1976; smokers of 20 or more cigarettes a day had the highest SMRs not only for lung cancer but also for all causes, cancer of the stomach, pancreas, and larynx, and ischaemic heart disease. For lung cancer SMRs increased fivefold with smoking, but the increase with dust exposure was comparatively slight for non-smokers, lower again for ex-smokers, and negligible for smokers of at least 20 cigarettes a day; thus the asbestos-smoking interaction was less than multiplicative. Of the 33 deaths from mesothelioma in the cohort to date, 28 were in miners and millers and five were in employees of a small asbestos products factory where commercial amphiboles had also been used. Preliminary analysis also suggest that the risk of mesothelioma was higher in the mines and mills at Thetford Mines than in those at Asbestos. More detailed studies of these differences and of exposure-response relations for lung cancer are under way.

Mesothelioma in Quebec chrysotile miners and millers: Epidemiology and aetiology

In a cohort of some 11,000 men born 1891-1920 and employed in the Quebec chrysotile production industry, including a small asbestos products factory, of 9780 men who survived into 1936, 8009 are known to have died before 1993, 38 probably from mesothelioma--33 in miners and millers and five in factory workers. Among the 5041 miners and millers at Thetford Mines, there had been 4125 deaths from all causes, including 25 (0.61%) from mesothelioma, a rate of 33.7 per 100,000 subject-years; the corresponding figures for the 4031 men at Asbestos were eight out of 3331 (0.24%, or 13.2 per 100,000 subject-years). At the factory in Asbestos, where all 708 employees were potentially exposed to crocidolite and/or amosite, there were 553 deaths, of which five (0.90%) were due to mesothelioma; the rate of 46.2 per 100,000 subject-years was 3.5 times higher than among the local miners and millers. Six of the 33 cases in miners and millers were in men employed from 2 to 5 years and who might have been exposed to asbestos elsewhere; otherwise, the 22 cases at Thetford were in men employed 20 years or more and the five at Asbestos for at least 30 years. The cases at Thetford were more common in miners than in millers, whereas those at. Asbestos were all in millers. Within Thetford Mines, case-referent analyses showed a substantially increased risk associated with years of employment in a circumscribed group of five mines (Area A), but not in a peripherally distributed group of ten mines (Area B); nor was the risk related to years employed at Asbestos, either at the mine and mill or at the factory. There was no indication that risks were affected by the level of dust exposure. A similar pattern in the prevalence of pleural calcification had been observed at Thetford Mines in the 1970s. These geographical differences, both within the Thetford region and between it and Asbestos, suggest that the explanation is mineralogical. Lung tissue analyses showed that the concentration of tremolite fibres was much higher in Area A than in Area B, a finding compatible with geological knowledge of the region. These findings, probably related to the far greater biopersistence of amphibole fibres than chrysotile, have important implications in the control of asbestos related disease and for wider aspects of fibre toxicology.

Inferences on the kinetics of asbestos deposition and clearance among chrysotile miners and millers

BACKGROUND The health effects of asbestos are intimately related to the fate of inhaled fibers in the lungs. The kinetics of asbestos fibers have been studied primarily in rodents. The objective of this study was to explore the application of these kinetic models to human autopsy data. METHODS We analyzed the asbestos fiber content of the lungs of 72 Quebec chrysotile miners and millers and 49 control subjects using analytical transmission electron microscopy. Statistical methods included standard multivariate linear regression and locally weighted regression methods. RESULTS The lung burdens of asbestos bodies and chrysotile and tremolite fibers were correlated, as were the concentrations of short, medium, and long fibers of each asbestos variety. There were significant associations between the duration of occupational exposure and the burdens of chrysotile and tremolite. The concentration of chrysotile decreased with the time since last exposure but the concentration of tremolite did not. The clearance rate varied inversely with the length of chrysotile fibers. For fibers greater than 10 mu in length the clearance half-time was estimated to be 8 years. CONCLUSIONS The patterns in our data are compatible with both of the hypotheses suggested from rodent experiments; the existence of a long-term sequestration compartment and overload of clearance mechanisms in this compartment.

Evaluation of Occupational Exposure to Mixed Dusts and Polycyclic Aromatic Hydrocarbons in Silicon Carbide Plants

Workers in the silicon carbide industry have experienced occupational health diseases, particularly lung disorders such as silicosis. The silicon carbide production process mainly employs petroleum coke, sawdust, pure crystalline silica and graphite. Since crystalline silica is present in the occupational environment, the airborne dust content of various polymorphs of silica, especially quartz, cristobalite and tridymite, was determined by X-ray diffraction analysis. The analytical method was modified to eliminate graphite, since it overlaps with the main diffraction plane of quartz. Exploratory field surveys were conducted to identify the minerals present in that occupational environment and to evaluate the validity of the analytical method. The surveys provided information on the mineralogical nature of the dust, its respirable content and the concentration of silica polymorphs. Polycyclic aromatic hydrocarbons also were measured, and the effect of their adsorption on graphite was evaluated.

Cytotoxicity of ambient air particles to rat lung macrophages: Comparison of cellular and functional assays.

The biological reactivity of ambient air particles was studied in five in vitro lung macrophage assays, involving the release of cytoplasmic and lysosomal enzymes, cellular ATP, neutral red uptake, tetrazolium reduction, and chemiluminescence. Macrophages from rat lungs (2 x 10(5) cells; 1 cm(2) attachment surface; 1 ml culture medium) were exposed for 18 hr to 0-100 mug of (1) the urban dust SRM 1649, (2) titanium dioxide (TiO(2)) or (3) DQ-12 quartz. On the basis of the depressions of neutral red uptake and cellular ATP, and the extracellular releases of lactate dehydrogenase, acid phosphatase and beta-glucuronidase, the ranking of cytotoxicity was as follows: quartz (EC(50) = 20-60 mug/ml) > > SRM 1649 approximately TiO(2) (EC(50) > 100mug/ml). The decrease in 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) reduction was more sensitive to effects of the urban dust, with an EC(50) value for SRM 1649 (35mug/ml) intermediate between those for quartz (15mug/ml) and TiO(2) (82mug/ml). Although SRM 1649 could affect mitochondrial function, the impact of the urban dust on cellular integrity after 18 hr was comparable to that of TiO(2) particles. In contrast, SRM 1649 had profound effects on phagocytosis-related chemiluminescence values measured during a 5-hr exposure period. Quartz and TiO(2) particles induced an oxidative burst from the macrophages. However, whereas a low dose of SRM 1649 (25mug) induced an oxidative burst, a further increase of the dose of particles (100-250mug) resulted in a decrease of the luminol-dependent luminescence (P < 0.05) and, to a lesser extent, of the lucigenin-dependent luminescence. The data imply an early adverse effect of ambient air particles on the bactericidal activity of macrophages with minimal alterations in the structural integrity of the cells.

Determinants of ultrafine particle exposures in transportation environments: findings of an 8-month survey conducted in Montréal, Canada.

An 8-month sampling campaign was conducted in Montréal, Canada to explore determinants of ultrafine particle (UFP) exposures in transportation environments and to develop models to predict such exposures. Between April and November 2006, UFP (0.02–1 μm) count exposure data were collected for one researcher during 80 morning and evening commutes including a 0.5-km walk, a 3-km bus ride, and a 26-km automobile ride in each direction. Ambient temperature, relative humidity, precipitation, and wind speed/direction data were collected for each transit period and the positions of bus and automobile windows were recorded. Mixing heights were also estimated. Morning UFP exposures were significantly greater than those in the evening, with the highest levels observed in the automobile and the lowest while walking. Wind speed and mixing height were highly correlated, and as a result only wind speed was considered in multivariable models owing to the accessibility of quantitative hourly monitoring data. In these models, each 10°C increase in morning temperature was associated with decreases of 14,560/cm3 (95% CI=11,111 to 18,020), 8160/cm3 (95% CI=5060 to 11,260), and 11,310/cm3 (95% CI=6820 to 15,810) for UFP exposures in walk, bus, and automobile environments, respectively. Likewise, each 10-km/h increase in morning wind speed corresponded to decreases of 8252/cm3 (95% CI=5130 to 11,360), 6210/cm3 (95% CI=3420 to 9000), and 6350/cm3 (95% CI=2440 to 10,260) for UFP exposures in walk, bus, and automobile environments, respectively. Similar trends were observed in the evening hours. In an evaluation of model performance, moderate correlations were observed between measured and predicted UFP exposures on new bus (r=0.65) and automobile (r=0.77) routes. Further research is required to incorporate variables such as traffic density and vehicle ventilation settings into the models presented.

Case-control study of lung cancer among sugar cane farmers in India.

OBJECTIVES: To investigate the risk of lung cancer among sugar cane farmers and sugar mill workers. METHODS: A case-control study was conducted based in six hospitals in the predominantly sugar cane farming districts of the province of Maharashtra in India. Newly diagnosed, histologically confirmed cases were identified from these hospitals between May 1996 and April 1998. Other cancers were chosen as controls and matched to cases by age, sex, district of residence, and timing of diagnosis. RESULTS: Adjusting for confounders, an increased risk of lung cancer was found for workers ever employed on a sugar cane farm (odds ratio (OR) 1.92, 95% confidence interval (95% CI) 1.08 to 3.40). Increased risks were found for work involving preparation of the farm (OR 1.81, 95% CI 0.99 to 3.27) and burning of the farm after harvesting (OR 1.82, 95% CI 0.99 to 3.34). Non-significant increases in risks were found for harvesting the crop (OR 1.41, 95% CI 0.70 to 2.90) and processing the cane in the mills (OR 1.70, 95% CI 0.20 to 12.60). CONCLUSIONS: Exposure to fibres of biogenic amorphous silica (BAS) formed from silica absorbed from the soil and deposited in the leaves of the sugar cane crop or crystalline silica formed as a result of conversion of BAS to cristobalite at high temperatures may account for the increased risks of lung cancer among sugar cane farmers.

Enzyme activities of lung lavage in silicosis

The cytotoxic effect of quartz on lung cells has been well documented by in vitro and animal studies, but the pertinence of these findings to humans has not yet been documented. We measured lactate dehydrogenase (LDH) activities in the lung lavage of 24 long-term workers in the Québec granite industry and 25 control subjects. We found significant increases in LDH activities in the workers’ lung lavage, even in the absence of established silicosis (9 subjects). We looked at a similar observation in the sheep model of early silicosis, measured quartz content of lung lavage, and found significant correlation with LDH levels (R=0.64, p<0.001). All of the quartz particles in human and sheep lung lavage were in the alveolar macrophages. To test further the relationship of macrophage damage (cytotoxicity of quartz) we measured the release of LDH by sheep alveolar macrophage in 24 h cell culture under control conditions, exposure to inert dust, titanium, minusil-5 quartz, or aluminum-treated quartz. The LDH release was at control levels during titanium exposure and showed a significantly dose-related increase during quartz exposure. The latter cytotoxic effect was largely attenuated by aluminum treatment of quartz. These in vitro data agreed with previous reports. This study presents evidence of a cytotoxic effect of quartz inhalation in humans. The effect is related to the intensity of quartz retention in the lung macrophages; it is not a nonspecific dust exposure effect and can be attenuated by surface modification of the quartz.

Mineralogy of Lung Tissue in Dental Laboratory Technicians' Pneumoconiosis

This article reports on a case of pneumoconiosis in a dental laboratory technician with a history of respiratory exposure to dental materials. Special attention is paid to the mineralogical analysis of the lung biopsy. The abundance of chromium, cobalt, and silica particles suggests that the dental technicians pneumoconiosis is the result of the combined effects of hard metal dusts and silica particles generated during finishing dental frameworks. Adequate technical protection such as a local ventilation system should be considered in dental laboratories to prevent respiratory exposure of dental technicians to airborne contaminants.

Asbestos Fiber Type and Length in Lungs of Chrysotile Textile and Production Workers: Fibers Longer than 18 μm

Excess lung cancer risk for a cohort of chrysotile textile plant workers was many times the risk observed in a cohort of chrysotile miners/millers. The latter had greater exposure to chrysotile/tremolite. A previous lung burden study confirmed this excess exposure in miners/millers and showed little difference in fiber length. Selection of too short a fiber length cut-off (5 µm or more) in the previous study could have masked differences in lung-retained fiber length. In this follow-up, we counted only those intrapulmonary fibers exceeding 18 µm in length. Lung fiber concentration and dimension were assessed by transmission electron microscopy (TEM) and energy-dispersive x-ray spectrometry (EDS) for autopsy samples from 64 textile workers and 43 chrysotile miners and millers. These long fibers were significantly more concentrated in the lungs of chrysotile miners and millers, consistent with their greater exposure. However, when only these longest fibers were compared, there was a somewhat greater mean and median intrapulmonary fiber length for chrysotile textile workers (mean fiber length, all fiber types combined, 25.2 ± 10.2 µm vs. 22.9 ± 6.6 µm in miners/millers, < .001; medians 21.6 vs. 20, p < .05). Despite their lesser apparent lung cancer risk, chrysotile, tremolite, total amphibole, and total long fiber asbestos concentrations were all highest in the lungs of miners/millers. Twenty-two of 64 textile workers had lung content of crocidolite and/or amosite (32.5% of 508). These amosite/crocidolite fibers were present in the lungs of workers who ceased employment prior to the first use of such fibers recorded in this industry. The results suggest that (I) asbestos fiber length differences cannot explain the difference in lung cancer risk excess and slope between cohorts and (2) the experience of textile workers should not be used to assess risk of lung cancer in miners, cement workers, and friction product workers, regardless of fiber type.