1 From The Cancer Registry of Norway, Oslo, Norway.
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ABSTRACT |
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lung neoplasms; silicon compounds; silicon dioxide; stomach neoplasms;
Abbreviations: CI, confidence interval; PAH, polycyclic aromatic hydrocarbons; SiC, silicon carbide; SIR, standardized incidence ratio.
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INTRODUCTION |
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SiC particles may be covered with a film or islets of silica glass (amorphous silica) or crystalline silica (1). Experimental studies have shown that these particles have low toxicity, and some studies have considered them inert (2
4
). Other studies have indicated that SiC dust might contribute to pneumoconiosis (5
, 6
). More recently, however, this condition has been attributed to the presence of SiC fibers in the dust (7
, 8
). SiC appears in several crystal modifications based on how the different silicon and carbon layers are stacked. In addition to particles, the compound also may exist as whiskers (monocrystals) or continuous fibers (9
). In contrast to most other man-made fiber materials such as ceramic fibers and fiberglass, which consist mainly of silicon and aluminum, SiC fibers are crystalline and consist of only silicon and carbon. Substantial interest has been focused on SiC fibers or SiC whiskers, which, in experimental studies, have been shown to have carcinogenic and fibrogenic properties comparable to those of asbestos (10
13
). The finding of SiC fibers in the work environment of SiC smelters (1
, 9
, 14
) and in the lung tissue of workers in that industry (15
, 16
) has suggested the presence of a possible, unrecognized hazard.
To our knowledge, only one epidemiologic study has been published on mortality in this industry (17). The study investigated cause-specific mortality among 585 workers from three SiC plants in Quebec, Canada, and showed an increased mortality from lung and stomach cancers. Because of a limited study size and the use of total dust as the only exposure measure, firm conclusions could not be reached.
The present study was initiated to investigate cancer incidence among men employed in the Norwegian SiC industry. We were particularly interested in a possible association between exposure to SiC fibers and the incidence of lung cancer.
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MATERIALS AND METHODS |
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The process is dusty and leads to emission of crystalline silica (quartz and cristobalite), SiC particles, and SiC fibers. In addition, carbon monoxide and sulfur dioxide gases are released, together with small amounts of volatile polycyclic aromatic hydrocarbons (PAH).
Study population
Three Norwegian SiC smelters were included in the pres-ent study. Plant A started operating in 1913, plant B in 1963, and plant C in 1965.
Workers employed at the smelters for more than 6 months were included in the study. Information on each employee was obtained from company records that listed name, date of birth, all departments of hire, types of jobs held, and dates of job changes. Since 1964, all inhabitants of Norway have received a unique identification number, and these numbers were used to link different data sources. Dates of death or emigration were found by linkage to the population registry of Norway. Before 1964, the cohort was linked to the death and cancer registry data by name and date of birth. The company records included 2,720 men; 40 had died before the start of follow-up, and 60 (3 percent) were not traceable. Thus, 2,620 men were left to study.
Exposure assessment
A job exposure matrix covering all three plants was constructed to estimate individual exposure to various particulate materials (table 1). Estimation of exposure was based mainly on industrial hygiene measurements and on descriptions of changes in the process technology and work practices over time. Since 1950, more than 6,000 dust measurements were sampled at the plants. Until 1974, only short-term measurements of dust sampled by using a Watson thermal precipitator (Cassella, London, United Kingdom) were available (n = 4,200). In addition, we had access to 2,062 gravimetric personal measurements of total dust sampled from 1974 to 1996. To categorize the dust, we used 216 short-term SiC fiber measurements sampled from 1982 to 1988 and about 200 measurements of crystalline silica (quartz and cristobalite). Fibers had been counted by using an optical phase contrast microscope (9), and the quantity of crystalline silica had been measured by infrared spectrophotometry in the period before 1980, which thereafter was supplemented by x-ray diffraction. Quartz and cristobalite were present in roughly equal quantities in the oven and in the sorting departments, while the quantity of quartz exceeded the quantity of cristobalite in the preparation and mix departments. No fibers were detected in the final abrasive products. However, fibers were observed in the products intended for metallurgical use (9
). The quantity of SiC particles was estimated by subtracting the quantity of silica from the quantity of inorganic material. Only a few measurements existed that described the respirable fraction of the dust. These measurements suggested that the respirable fraction was probably 530 percent in the mix and refinery departments and 1040 percent in the oven departments.
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Exposure to asbestos was assessed qualitatively by assigning jobs as exposed or unexposed on the basis of the frequency and duration of work generating airborne asbestos dust. In Norway, use of asbestos has been moderate in this industry, mainly restricted to maintenance work between 1940 and 1980.
Cumulative exposure was used as an indicator of individual dose and was calculated as the product of the intensity and duration of exposure. In the analyses, "unexposed" person-time constituted one exposure category, and the remaining exposed person-years were allocated into three exposure categories with roughly equal numbers of expected cases. Cumulative exposure was treated as a dynamic variable so that one man could contribute person-time in several exposure categories. Potential induction and latency periods were investigated by lagging exposure 0, 10, and 20 years (18, 19
). In this study, a lag of 20 years meant that exposure during the last 20 years prior to each year of observation was disregarded.
Smoking habits were abstracted from medical files in the health departments of the smelters. The year that smoking status was recorded, and the duration and amount of smoking, were mainly unknown. Those data were therefore used to categorize the workers as never, current, or former smokers or those whose smoking status was unknown. Smoking habits were determined for 80 percent of the cohort, 26 percent of whom were never smokers, 63 percent of whom were current smokers, and 11 percent of whom were former smokers. Compared with 74 percent of ever smokers in the present study, the proportion of ever smokers in a similar distribution of birth cohorts of Norwegian men was calculated to be about 70 percent (20). Because of the lack of information on date of smoking cessation by the former smokers, these men were treated as former smokers throughout the follow-up.
Analysis of cancer incidence
Because of the inclusion criterion of 6 months of employment, follow-up of cancer incidence started after 6 months of employment, net of any gaps, or from January 1, 1953, if the 6-month date of employment was reached before then. Observation continued until December 31, 1996, or until the date of death or emigration, giving 59,251 person-years of follow-up. For this time period, The Cancer Registry of Norway offers complete coverage of the population for all sites and types of cancer except basal cell carcinoma of the skin, which was omitted in the present study. Registration of cancer is built on multiple compulsory reporting by pathology laboratories and hospital departments. Coding of cancers was based on a modified version of the International Classification of Diseases, Seventh Revision (three-digit codes) throughout the entire follow-up period. Standardized incidence ratios were calculated as the ratios between the observed and expected numbers of cancer cases; the latter were calculated from national incidence rates during 5-year calendar periods for 5-year age groups. The 95 percent confidence intervals were calculated by assuming a Poisson distribution of the observed numbers. Homogeneity in the standardized incidence ratios across age and calendar period strata was checked by using a chi-square goodness-of-fit test in the program package StatXact 4 (Cytel Software Corporation, Cambridge, Massachusetts).
Poisson regression analysis was used to investigate internal dose-response relations and to evaluate potential confounding by smoking. Age was included in the models and was divided into six groups (age <55, 5564, 6569, 7074, 7579, and 80 years), and period of diagnosis was included by using three calendar periods (19531970, 19711984, and 19851996). Trend tests to investigate potential dose-response relations were performed by assigning scores (1
, 2
, 3
, 4
) to the exposure categories or by applying the mean cumulative exposure to the exposure categories.
To evaluate the correlation between an agent and its possible impact on the analyses, correlation coefficients, r, were calculated for cumulative exposure for pairs of agents weighted by person-years throughout follow-up. Standardized incidence ratios and Poisson regression analyses were calculated by using the program package EPICURE (21).
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RESULTS |
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DISCUSSION |
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Exposure
Despite more than 6,000 measurements, our estimation of exposure was inevitably subject to uncertainties, particularly in the categorization of total dust into different types of particulates. Compared with the exposure estimates of total dust from the Canadian study (based on 118 total dust measurements) (17), our estimates were considerably lower for most of the jobs. A difference also was evident in the cumulative exposure estimates, which seemed to be more than five times higher in the Canadian study than in the present study. The reason for this difference is difficult to understand, as the technology and process were comparable. However, the large number of measurements available in the present study gives credibility to the exposure estimates used in the present investigation.
Better identification of specific exposures possibly could have improved our ability to separate the effect of individual types of particulates. However, because exposure in this industry generally involves a mixture of different particulates, this task may be difficult.
Lung cancer
Two of the smelters were located in the southern part and one in the midregion of Norway. Since the incidence of lung cancer varies in different parts of Norway, our use of national incidence rates may have biased the overall standardized incidence ratio estimate. If we had used local rates, the overall standardized incidence ratio for lung cancer would have been slightly lower, since the incidence rate of lung cancer in the region that contributed the largest number of cases was slightly higher than national rates. The potential bias introduced by using national rates probably did not affect the dose-response findings, which in this study were regarded as the most important element in evaluating a possible causal association. Furthermore, our use of external and internal comparison produced almost similar results.
Although the smoking variable was crude, well-known associations between lung cancer and smoking habits were observed. In the present study, a relative risk of lung cancer of about 20 for smokers compared with never smokers is compatible with risk levels found in other studies. Since internal regression analyses showed only minor changes in the effect measure estimates after control for smoking, smoking probably could be excluded as an important confounder in the present study.
Asbestos has been used on only a small scale in these plants, with the highest level of exposure among maintenance workers. The standardized incidence ratio of lung cancer for more than 5 years of maintenance work was 1.7 (95 percent CI: 0.8, 3.3) compared with 3.1 (95 percent CI: 1.9, 4.9) for more than 5 years of work in the sorting or oven department. Thus, asbestos was not a likely explanation for the observed excess of lung cancer.
PAH have been present in the oven departments of these plants but in low concentrations and in the form of mainly volatile and presumably less carcinogenic PAH (22, 23
). Measurements sampled at the Norwegian plants suggested exposure levels of less than 10 µg/m3 for particulate PAH (n = 10) and less than 0.1 µg/m3 for benzo(a)pyrene (n = 3). Crystalline silica exposure would be a more likely causal agent, but the general exposure level also seemed to be low when compared with the substantial lung cancer risk observed in the present study. Epidemiologic studies that have investigated the association of exposure to quartz with lung cancer generally have reported both higher exposures and lower relative risks (24
). Larger studies of silica-exposed workers with reasonably well-documented exposure suggest a moderate excess risk of lung cancer, with a combined overall relative risk of about 1.3 (24
). Still, the silica cover on SiC particles may be of biologic importance (1
).
In experimental studies (1013
), SIC fibers have shown a high carcinogenic potency and a long durability in human lung tissue, suggesting that they may be a plausible cause of the observed excess of lung cancer (15
, 16
). In the present study, the analysis in which both quartz exposure and SiC fiber exposure were included showed some empirical evidence that the latter is a better indicator of lung cancer risk than is crystalline silica (table 6). However, uncertainties regarding exposure assessment and the strong correlation between the different exposures precluded firm conclusions based on the current data.
The shape of the dose-response relation is particularly important in predicting risk at lower levels of exposure. Our data suggested a supralinear-curved relation (steeper at a lower concentration). However, the approximate nature of the exposure estimates and chance may have led to errors that easily could have biased the shape of the relation.
Stomach cancer
Because the elevated risk of stomach cancer was restricted mainly to employment in the refinery departments, a potential environmental cause should be sought there. The main exposure at these departments has been SiC particles, which, in experimental studies, have shown little biologic activity (3, 4
). Nevertheless, a possible role of the silica layer on these particles should be evaluated further (1
).
Stomach cancer has several nonoccupational causes such as Helicobacter pylori bacteria and salt, which were not accounted for in this study (25). Furthermore, the association between stomach cancer risk and SiC particles was modest, and it disappeared with lag times of longer than 10 years. The evidence for a causal association with the work environment thus was considered weak. However, since stomach cancer also was elevated in the Canadian mortality study (17
), and since some studies of silica-exposed persons have indicated an elevated risk (26
), this site should be investigated further.
Conclusions
This study found an excess risk of lung cancer and stomach cancer. The results suggested a causal relation between agents in the work environment and lung cancer. Exposure to SiC fibers was a plausible cause, but the strong correlation between the different exposures made it difficult to reach a conclusion based on our data. Whether the increased incidence of stomach cancer should be attributed to risk factors in the work environment is questionable.
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ACKNOWLEDGMENTS |
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The authors acknowledge the support of Ole Tormod Fure at the Safety, Health, and Environment Secretariat for the Norwegian smelters. They also thank Jan Ivar Martinsen for valuable help in programming and data analyses and Geir Helland-Hansen for collecting and handling the data. They are grateful to Tor Enger for his support and to Tom Grimsrud for his constructive comments.
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NOTES |
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REFERENCES |
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