American Journal of Industrial Medicine 21:825-834 (1992)
Lung Cancer Risk Among Workers Exposed to Man-Made Mineral Fibers (MMMF) in the Swedish Prefabricated House Industry Per Gustavsson, MD, Nils Plato, MSc, Olav Axelson, MD, Helle Noorlind Brage, BSC, Christer Hogstedt, YD, Gunilla Ringback, BSC, Goran Tornling, MD,and Gun Wingren, BSC
Mortality and cancer incidence was investigated among 2,807 workers, employed for at least one year before 1972, at 11 Swedish companies manufacturing prefabricated wooden houses. A total of 1,068 workers had been exposed to man-made mineral fibers (MMMF) used for insulation. Mortality was followed from 1969 to 1988 and cancer incidence from 1969 to 1985. Exposure conditions were investigated at all plants. There were 14 deaths from lung cancer in the total cohort, whereas 20.7 would be expected (SMR = 68; 95% CI:37-113), based on regional mortality. After a latency of 20 years or more, two lung cancer cases had occurred among all workers exposed to MMMF, whereas 4.3 would be expected (SMR = 46; 95% CI: 5-168). The exposure levels that have prevailed do not seem to be associated with an increased lung cancer rate, but extended follow-up is necessary for a definitive evaluation. 0 1992 Wiley-Liss, Inc.
Key words: cohort cancer study, occupational exposure, rock wool, glass wool, prefabricated houses, wood dust
INTRODUCTION Insulation wool is produced from man-made mineral fibers (MMMF); the products are termed rock wool, glass wool, or slag wool, depending on the source material. An epidemiological study of 13 European MMMF-producing plants indicated an increased lung cancer risk among workers active during the so-called “early production phase” (before 1945) in the rock and slag wool industry [Simonato et al., 19861, and a study of 17 U.S. MMMF-producing plants showed an excess of deaths from respiratory cancer [Marsh et al., 19901. In an overall conclusion and evaluation from an international symposium on MMMF, the fibers were considered to be at least in part responsible for the lung Departments of Occupational Medicine (P.G. ,N.P.,C.H. ,G. R. ,G.T.) and Thoracic Medicine (G.T.), Karolinska Hospital, Stockholm, Sweden. Unit of Occupational Medicine, National Institute of Occupational Health, Solna, Sweden (P.G. ,C.H.). Department of Occupational Medicine, University Hospital, Linkoping, Sweden (O.A. ,H.N.B. ,G.W.). Address reprint requests to Dr. Per Gustavsson, Department of Occupational Medicine, Karolinska Hospital, S-104 01 Stockholm, Sweden. Accepted for publication October 9, 1991.
0 1992 Wiley-Liss, Inc.
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cancer excess [Doll, 19871. The International Agency for Research on Cancer (IARC) considered rock wool, as well as glass wool, “possibly carcinogenic to humans” [IARC, 19881, and the material also induces pleural and peritoneal cancers in experimental animals. However, the significance of the epidemiological findings have been debated, since it has been argued that concurrent exposures such as asbestos, combustion fumes from the furnaces, or arsenic from the ore might explain the cancer excess [Miettinen and Rossiter, 19901. The aim of the present study was to investigate the lung cancer risk after exposure to MMMF in an occupational environment where confounding exposures were absent or insignificant. The Swedish prefabricated wooden house industry met these criteria and the present investigation was initiated in 1986. This paper reports the epidemiological findings of the study. The details of an occupational hygienic investigation, aimed at characterizing the past and present exposure to MMMF and other substances in the prefabricated house industry, will be reported separately. The main findings of the hygienic investigation are summarized in the present report. MATERIALS AND METHODS Source Materials Companies manufacturing prefabricated wooden houses were identified from the records of the Swedish Employers’ Union of the prefabricated wooden house industry. All companies that had used MMMF before 1970 and were still active were initially included in the study. Very small companies were excluded. One company was excluded since it also produced wooden boards, a process associated with exposure to formaldehyde and other chemicals possibly influencing the lung cancer risk. Two companies were excluded because of insufficient records. Eleven remaining plants met the inclusion criteria. Company records or the records of the local trade union were used as source material for identification of individuals. Individual data on job type and work sites were obtained from the records when possible. At all plants, interviews were performed with older workers, retirees, foremen, and trade union representatives, in order to confirm or obtain additional information on job types and job localities for all members of the cohort. Data regarding the type of insulation wool used, time when the material was introduced, work sites, production process, and ventilation were also obtained in these interviews, as well as individual data on smoking habits of the cohort members. Information on smoking habits was possible to obtain at the eight smaller plants; the workers had less personal knowledge of each other at the larger plants. Criteria for Eligibility All men employed for at least one year between the time MMMF was introduced at the plant and December 31, 1971, were included in the cohort. For one factory (No. 8), only those active after 1963 could be included in the cohort, due to incomplete records, although MMMF had already been introduced in 1954. Of 2,872 workers eligible for the study, 2,807 remained for analysis after necessary exclusions (Table I). A few individuals had worked at more than one plant. This has been taken into account in exposure time calculations; in Tables I and I11 they are listed under the
827
Lung Cancer Among Workers Exposed to MMMF TABLE I. Time When MMMF Was Introduced and Number of Individuals in the Cohort, by Factory in Study of Employees in Swedish Prefabricated House Industry
Plant 1 2 3 4
5 6 7 8 9 10 11 Total
Year when MMMF was introduced
No. identified in company records
Unknown beginning of exposure
1957 1953 1950 1952 1957 1959 1946 1954 1968 1950 1952
704 11 341 106 190 754 86 138 51 397 88 2,872
0 0 0 0 0
5 0 3 0
2 1 1 0 0 0 4
16 0 1 1 5 1 36
-
Emigrated
4
Lost to follow-up
Eligible for analysis
16 0 0 0 2 5 0 0 0 2 0 25
683 11 344 106 184 73 1 85 136 50 390 81 2,807
plant were they worked for the longest time. Only years following the introduction of MMMF were utilized in the calculation of employment time. Characterizationof the Exposure
Current exposure levels were measured at all plants and past exposures were estimated by occupational hygienists. Full shift (8 h) personal and area sampling were performed. The results of this investigation formed the basis of the exposure classification. The MMMF exposure level was classified for every work period in the work history for all individuals in the cohort. Data were insufficient to assign fiber-levels to all job types and time periods, and a four-level ordinal scale was used. Exposure category 0 refers to work periods without exposure to MMMF (e.g., saw mill workers, outside workers). Exposure category 1 refers to background levels of MMMF for part of the working day (e.g., truck drivers, repairmen, transportation workers). The current mean background exposure level was 0.06 f-ml-', range 0.02-0.08. Exposure category 2 includes work periods with full-time employment in locations where MMMF was handled, but without direct handling of MMMF (e.g., woodcutters). The current mean exposure was 0.09 f m - ' , range 0.05-0.13. Exposure category 3 applies to work periods with direct handling of MMMF during most of the working day (insulators), with a current mean exposure of 0.1 1 feml-', range 0.05-0.17. The highest exposure in category 3 occurred during 1975-1980 and was estimated as 0.20-0.25 f-ml-'. Retrospective assessment of exposure levels in the other categories was not performed. Work periods with unknown exposure were assigned to exposure category 9. When the 2,807 workers were classified according to their work periods with the highest exposure, there were 1,342, 215, 375, 478, and 397 individuals in categories 0, 1, 2, 3, and 9, respectively. It was not possible to distinguish exposure to glass wool from rock wool, since most plants had used both types of materials during different time periods. Exposure to wood dust was common at all of the investigated plants, and all of
828
Gustavsson et al.
the cohort members have, to some extent, been exposed to wood dust. Respirable dust levels were measured by personal sampling for job types with exposure to MMMF; the range of the 8 h TWA was 0.09-1.9 mg/m3 with a mean of 0.5 mg/m3. Follow-Up and Data Analysis The life outcome of the cohort members was traced by a computerized register of the Swedish population, via the clerical parish offices, and via the taxation authorities (Table I). Four individuals were excluded due to insufficient exposure data, 36 had emigrated, and 25 (0.9%) were lost to follow-up. Data on the time of employment termination were missing for 229 individuals; they were retained in the cohort but were excluded in analyses of mortality by duration of exposure. The expected numbers of deaths were calculated according to the person-year method [Breslow and Day, 19871, accounting for age, calendar year, and geographical region (county). For each case, the registered underlying cause of death was obtained from Statistics Sweden, and in a few cases from the clerical parish offices. Mortality was followed from 1969 to 1988. The cancer incidence was calculated analogously, although without account for variations in incidence by geographic region. Data on cancer incidence were obtained from the Swedish Cancer Registry, and cancer incidence was investigated from 1969 to 1985. The Standard Mortality Ratio (SMR) calculations were performed with the OCMAP-PC computer program [Marsh et al., 19861.
RESULTS Mortality and Cancer Incidence The overall mortality in the cohort was lower than expected, mainly because of a low mortality in circulatory diseases (Table 11). The number of stomach cancers was higher than expected, and the number of lung cancers was somewhat lower than expected. The observed figures for the other causes of death corresponded well with those anticipated. There were no cases of pleural mesothelioma. There were some differences in mortality between the plants (Table 111), but the fluctuations can probably be explained by chance due to small numbers. Neither total nor cause-specific mortality correlated with time since first employment (latency) (Table IV). The lung cancer mortality did not correlate to the level of exposure to MMMF (Table V). The excess of stomach cancer was nearly entirely among those with no exposure to MMMF. Neither lung cancer mortality nor any of the other causes of death correlated positively to employment time (Table VI). The highest excess of stomach cancer was seen among those with the shortest employment periods. After a latency of 20 years or more, two lung cancer cases had occurred among those exposed to MMMF (exposure categories 1-3), whereas 4.3 would be expected (SMR = 46, 95% CI: 5-168). The analysis of cancer incidence (Table VII) gave results similar to those of the mortality analysis.
Lung Cancer Among Workers Exposed to MMMF
829
TABLE 11. Mortality Among Prefabricated House Industry Employees in Sweden 1969-1988* Cause of death (ICD 8=) All causes (1-999) All malignant tumors (140-209) Esophageal cancer (150) Stomach cancer (151) Bowel cancer (152-153) Rectal cancer ( 154) Liver cancer (155) Pancreatic cancer (157) Lung cancer (162) Prostatic cancer (185) Bladder cancer (188) Kidney cancer (189) Brain tumor (191) Malignant lymphomas (200-202) Myeloma (203) Leukemia (204-207) Hemato-lymphatic cancer (200-209) Circulatory diseases (390-458) Ischemic heart diseases (410-414) Cerebrovascular diseases (430-438) Respiratory diseases (460-5 19) Asthma, bronchitis, emphysema (490-493) Digestive diseases (520-577) Liver cirrhosis (571) Genitourinary diseases (580-629) Nephritis, nephrosis (580-584) Violent death and intoxication (E800-E999) Suicide (E950-E959)
Observed
Expected
SMR
95% CIb
554 137 2 22 9 5 4 13 14 21 4 3 1 8 2 5 15 288 208 40 32 11 17 6 10 3 49 14
623.1 134.6 2.3 13.8 11.0 6.8 2.4 9.7 20.7 20.7 4.1 6.3 4.2 4.9 3.O 5.5 14.4 343,3 250.2 52.3 33.6 11.2 19.8 6.2 9.9 2.3 50.3 17.6
89 102 86 159 81 73 167 134 68 101 98 47 24 163 67 91 105 84 83 77 95 98 86 96 101 132 97 79
82-97 85-120 10-310 100-241 37-155 24-171 45-428 7 1-229 37-1 13 63-155 26-250 9-138 0-133 70-322 7-24 1 29-212 58-172 74-94 72-95 55-104 65-135 49-176 50-137 35 -209 48-186 26-384 72-129 43-133
*There were 49,527 person-years of observation. Expected numbers were based on local mortality. "International Classification of Diseases-8th revision. bCI =confidence interval.
Smoking Habits Smoking data could be obtained for 73% of the cohort members in the 8 factories where smoking habits were investigated. Of these, 45% (n = 331) were current or former smokers during the time they were employed at the plant. A survey of smoking habits in Sweden was performed in 1963 [Statistics Sweden, 19651. The national survey data indicate a frequency of about 50% of current smokers in ages 18-49 in the type of geographic areas where the house plants are located. It thus seems as if the workers in the prefabricated house industry have smoked somewhat less than the average. The regionally based reference rates for mortality do not fully account for the lower smoking rate in the cohort, and a small residual negative confounding effect on the lung cancer rate may be present.
DISCUSSION Lung cancer mortality in the cohort was somewhat lower than expected, and the risk did not correlate to duration of employment or intensity of exposure. Mortality from stomach cancer was increased, but mainly among those not exposed to MMMF, and among the short-term employed. The excess of stomach
1 ~2
3 ~
4
5 ~
6 ~~~~~
7 _
8
_9
10
_ 11
0.5 56 54.6 11 13.2 31 43.4 156 162.7 34 31.7 20 21.6 0.1 12 12.2 1 3.0 9 8.8 43 36.1 8 6.2 7 4.1 0.0 2 1.3 0 0.3 3 0.9 4.0 1 0.8 1 0.3 7 0.0 2 2.1 0 0.4 0 1.1 2 6.7 2 1.0 2 0.7 0.0 1 1.3 0 0.4 1 0.9 4 3.7 2 0.6 1 0.5 0.1 32 28.4 6 6.5 17 24.4 75 89.2 20 19.0 11 11.7 0.0 2 2.5 0 0.5 2 2.6 11 8.3 0 1.7 0 1.0 0.0 1 1.8 1 0.5 1 1.3 4 5.2 1 1.0 1 0.8 0.2 5 6.0 2 1.6 2 3.2 19 13.5 3 1.7 0 2.5
*Expected numbers were based on local mortality.
0 0 0 0 0 0 0 0 0
0 0 0 1 0 0 0
1
2
2.6 79 93.0 14 18.1 0.6 16 20.1 3 3.4 0.0 1 2.0 0 0.3 0.1 1 2.9 0 0.5 0.1 3 2.2 1 0.4 1.0 46 51.5 9 10.1 0.1 5 5.3 1 0.9 0.1 2 2.9 0 0.6 0.7 7 6.9 1 1.7
Obs Exp Obs Exp Obs Exp Obs Exp Obs Exp Obs Exp Obs Exp Obs Exp Obs Exp Obs Exp Obs Exp
ALL CAUSES 151 181.8 All malignant tumors 37 40.0 4.0 Stomach cancer 7 5.8 Lung cancer 5 4.3 Hemato-lymphatic cancer 2 Circulatory diseases 71 101.4 Respiratory diseases 11 10.6 5.5 Digestive diseases 6 Violent death and intoxication 10 12.2
Cause of death
Plant No.
TABLE 111. Observed and Expected Numbers of Selected Causes of Deaths at the 11 Prefabricated House Facilities 1%9-1988*
Lung Cancer Among Workers Exposed to MMMF
831
TABLE IV. Mortality Among Prefabricated House industry Employees in Sweden, by Latency From Start of Employment* Latency
< 10 years Cause of death ALL CAUSES All malignant tumors Stomach cancer Bowel cancer Lung cancer Prostatic cancer Hemato-lymphatic cancer Circulatory diseases Ischemic heart disease Cerebrovasculardiseases Respiratory diseases Digestive diseases Violent death and intox.
10-19 years
220 years
Obs
Exp
SMR
Obs
Exp
SMR
Obs
Exp
SMR
39 10 3 I
51.6 11.2 1.2 1.4 1.7 0.9 1.5 22.6 16.7 3.3 1.7 2.0 9.8
76 89 252 69 59 0 67 71 78 60 173 49 71
155
162.7 35.8 3.7 4.5 5.7 4.7 4.1 85.2 62.6 12.6 7.5 5.7 17.3
95 123 190 66 70 85 197 83 82 79 54 105
313 74 10 10 9 13 5 177 126 25 24 7 16
368.8 79.2 8.1 10.6 12.0 13.8 7.9 213.9 155.2 33.0 22.2 10.8 19.3
85 93 124 95 75 94 63 83 81 76 108 65 83
1
0 1 16 13 2 3 1 7
44 7 3 4 4 8 71 51 10 4 6 19
110
*Expected numbers based on local mortality.
cancer is thus less likely to be caused by MMMF or any other occupational exposure such as wood dust. The stomach cancer rate is higher in rural than in urbanized areas in Sweden [National Board of Health and Welfare, 1958-19851. The facilities manufacturing prefabricated wooden houses are generally located in the countryside or in small towns. The analyses were standardized for geographical region (county), but there may still be some residual confounding from this geographical trend, since the counties are large areas including urbanized as well as rural areas. Uncontrolled variations in the background rate may also have contributed to the apparently lowered risk for lung cancer, since this disease has an inverse geographical trend with higher rates in urbanized areas. Also, fluctuations from chance cannot be ruled out as regards both lung and stomach cancer. No excess of stomach cancer was found in the large European [Simonato et al., 19861 and U.S. [Marsh et al., 19901 MMMF cohort studies, but excesses have been reported from two single factories included in the larger cohorts [Robinson et al., 1982; Claude and Frentzel-Beyme, 19861. The overall mortality of the group was lower than expected. This is probably related to the so-called “healthy worker effect,” which is usually seen in cohort studies of this type, resulting from incomparability between the study and referent groups regarding employment status [McMichael, 19761. There are no previous reports describing the mortality among prefabricated wooden house industry workers. Exposure to wood dust is associated with an increased risk of nose and sinonasal cancer [Hernberg et al., 19831, and there are also sporadic reports of increased risks of lung cancer [Esping and Axelson, 19801 and Hodgkin’s lymphoma [Alderson, 19861 in association with exposure to wood dust. There were no cases of nose or sinonasal cancers in this cohort. The number of malignant lymphomas was slightly increased, but this may be caused by chance. Use of chlorophenols for wood preservation could not be verified at any of the plants. The results of the smoking data analysis should be interpreted with caution, since
352.9 76.8 8.0 11.5 8.0 197.7 19.8 10.9 24.5
306 79 15 9 8 152 20 9 26
ALL CAUSES All malignant tumors Stomach cancer Lung cancer Hemato-lymphatic cancer Circulatory diseases Respiratory diseases Digestive diseases Violent death and intoxication
87 103 187 78 100 77 101 82 106
SMR 45 12 2 1 1 23 2 1 7
Obs 49.5 10.9 1.1 1.7 1.2 27.3 2.5 1.6 4.0
Exp 91 110 185 58 85 84 80 63 176
SMR
Exposure category 1 75 13 1 1 3 49 6 3 2
Obs
~
90.4 19.2 2.0 3.0 2.0 50.5 4.8 2.9 6.9
Exp
Exposure category 2
*See text for explanation of exposure categories. Expected numbers were based on local mortality.
Exp
Obs
Cause of death
Exposure category 0 83 68 51 33 149 97 124 103 29
SMR 61 20 3 2 2 29 2 1 6
Obs
~-
71.3 15.1 1.4 2.4 1.8 37.2 3.4 2.4 8.2
Exp
Exposure category 3
TABLE V. Mortality Among Prefabricated House Industry Employees in Sweden, by Exposure to MMMF*
85 133 207 85 114 78 58 41 73
SMR
1 1 35 2 3 8
I
67 13
Obs
58.9 12.8 1.3 2.1 1.4 30.6 2.9 1.9 6.7
Exp
Exposure category 9 114 102 76 48 70 115 69 155 120
SMR
Lung Cancer Among Workers Exposed to MMMF
833
TABLE VI. Mortality Among Prefabricated House Industry Employees in Sweden, by Duration of Employment* ~
Duration of employment
Lung Cancer Risk Among Workers Exposed to Man-Made Mineral Fibers (MMMF) in the Swedish Prefabricated House Industry Per Gustavsson, MD, Nils Plato, MSc, Olav Axelson, MD, Helle Noorlind Brage, BSC, Christer Hogstedt, YD, Gunilla Ringback, BSC, Goran Tornling, MD,and Gun Wingren, BSC
Mortality and cancer incidence was investigated among 2,807 workers, employed for at least one year before 1972, at 11 Swedish companies manufacturing prefabricated wooden houses. A total of 1,068 workers had been exposed to man-made mineral fibers (MMMF) used for insulation. Mortality was followed from 1969 to 1988 and cancer incidence from 1969 to 1985. Exposure conditions were investigated at all plants. There were 14 deaths from lung cancer in the total cohort, whereas 20.7 would be expected (SMR = 68; 95% CI:37-113), based on regional mortality. After a latency of 20 years or more, two lung cancer cases had occurred among all workers exposed to MMMF, whereas 4.3 would be expected (SMR = 46; 95% CI: 5-168). The exposure levels that have prevailed do not seem to be associated with an increased lung cancer rate, but extended follow-up is necessary for a definitive evaluation. 0 1992 Wiley-Liss, Inc.
Key words: cohort cancer study, occupational exposure, rock wool, glass wool, prefabricated houses, wood dust
INTRODUCTION Insulation wool is produced from man-made mineral fibers (MMMF); the products are termed rock wool, glass wool, or slag wool, depending on the source material. An epidemiological study of 13 European MMMF-producing plants indicated an increased lung cancer risk among workers active during the so-called “early production phase” (before 1945) in the rock and slag wool industry [Simonato et al., 19861, and a study of 17 U.S. MMMF-producing plants showed an excess of deaths from respiratory cancer [Marsh et al., 19901. In an overall conclusion and evaluation from an international symposium on MMMF, the fibers were considered to be at least in part responsible for the lung Departments of Occupational Medicine (P.G. ,N.P.,C.H. ,G. R. ,G.T.) and Thoracic Medicine (G.T.), Karolinska Hospital, Stockholm, Sweden. Unit of Occupational Medicine, National Institute of Occupational Health, Solna, Sweden (P.G. ,C.H.). Department of Occupational Medicine, University Hospital, Linkoping, Sweden (O.A. ,H.N.B. ,G.W.). Address reprint requests to Dr. Per Gustavsson, Department of Occupational Medicine, Karolinska Hospital, S-104 01 Stockholm, Sweden. Accepted for publication October 9, 1991.
0 1992 Wiley-Liss, Inc.
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cancer excess [Doll, 19871. The International Agency for Research on Cancer (IARC) considered rock wool, as well as glass wool, “possibly carcinogenic to humans” [IARC, 19881, and the material also induces pleural and peritoneal cancers in experimental animals. However, the significance of the epidemiological findings have been debated, since it has been argued that concurrent exposures such as asbestos, combustion fumes from the furnaces, or arsenic from the ore might explain the cancer excess [Miettinen and Rossiter, 19901. The aim of the present study was to investigate the lung cancer risk after exposure to MMMF in an occupational environment where confounding exposures were absent or insignificant. The Swedish prefabricated wooden house industry met these criteria and the present investigation was initiated in 1986. This paper reports the epidemiological findings of the study. The details of an occupational hygienic investigation, aimed at characterizing the past and present exposure to MMMF and other substances in the prefabricated house industry, will be reported separately. The main findings of the hygienic investigation are summarized in the present report. MATERIALS AND METHODS Source Materials Companies manufacturing prefabricated wooden houses were identified from the records of the Swedish Employers’ Union of the prefabricated wooden house industry. All companies that had used MMMF before 1970 and were still active were initially included in the study. Very small companies were excluded. One company was excluded since it also produced wooden boards, a process associated with exposure to formaldehyde and other chemicals possibly influencing the lung cancer risk. Two companies were excluded because of insufficient records. Eleven remaining plants met the inclusion criteria. Company records or the records of the local trade union were used as source material for identification of individuals. Individual data on job type and work sites were obtained from the records when possible. At all plants, interviews were performed with older workers, retirees, foremen, and trade union representatives, in order to confirm or obtain additional information on job types and job localities for all members of the cohort. Data regarding the type of insulation wool used, time when the material was introduced, work sites, production process, and ventilation were also obtained in these interviews, as well as individual data on smoking habits of the cohort members. Information on smoking habits was possible to obtain at the eight smaller plants; the workers had less personal knowledge of each other at the larger plants. Criteria for Eligibility All men employed for at least one year between the time MMMF was introduced at the plant and December 31, 1971, were included in the cohort. For one factory (No. 8), only those active after 1963 could be included in the cohort, due to incomplete records, although MMMF had already been introduced in 1954. Of 2,872 workers eligible for the study, 2,807 remained for analysis after necessary exclusions (Table I). A few individuals had worked at more than one plant. This has been taken into account in exposure time calculations; in Tables I and I11 they are listed under the
827
Lung Cancer Among Workers Exposed to MMMF TABLE I. Time When MMMF Was Introduced and Number of Individuals in the Cohort, by Factory in Study of Employees in Swedish Prefabricated House Industry
Plant 1 2 3 4
5 6 7 8 9 10 11 Total
Year when MMMF was introduced
No. identified in company records
Unknown beginning of exposure
1957 1953 1950 1952 1957 1959 1946 1954 1968 1950 1952
704 11 341 106 190 754 86 138 51 397 88 2,872
0 0 0 0 0
5 0 3 0
2 1 1 0 0 0 4
16 0 1 1 5 1 36
-
Emigrated
4
Lost to follow-up
Eligible for analysis
16 0 0 0 2 5 0 0 0 2 0 25
683 11 344 106 184 73 1 85 136 50 390 81 2,807
plant were they worked for the longest time. Only years following the introduction of MMMF were utilized in the calculation of employment time. Characterizationof the Exposure
Current exposure levels were measured at all plants and past exposures were estimated by occupational hygienists. Full shift (8 h) personal and area sampling were performed. The results of this investigation formed the basis of the exposure classification. The MMMF exposure level was classified for every work period in the work history for all individuals in the cohort. Data were insufficient to assign fiber-levels to all job types and time periods, and a four-level ordinal scale was used. Exposure category 0 refers to work periods without exposure to MMMF (e.g., saw mill workers, outside workers). Exposure category 1 refers to background levels of MMMF for part of the working day (e.g., truck drivers, repairmen, transportation workers). The current mean background exposure level was 0.06 f-ml-', range 0.02-0.08. Exposure category 2 includes work periods with full-time employment in locations where MMMF was handled, but without direct handling of MMMF (e.g., woodcutters). The current mean exposure was 0.09 f m - ' , range 0.05-0.13. Exposure category 3 applies to work periods with direct handling of MMMF during most of the working day (insulators), with a current mean exposure of 0.1 1 feml-', range 0.05-0.17. The highest exposure in category 3 occurred during 1975-1980 and was estimated as 0.20-0.25 f-ml-'. Retrospective assessment of exposure levels in the other categories was not performed. Work periods with unknown exposure were assigned to exposure category 9. When the 2,807 workers were classified according to their work periods with the highest exposure, there were 1,342, 215, 375, 478, and 397 individuals in categories 0, 1, 2, 3, and 9, respectively. It was not possible to distinguish exposure to glass wool from rock wool, since most plants had used both types of materials during different time periods. Exposure to wood dust was common at all of the investigated plants, and all of
828
Gustavsson et al.
the cohort members have, to some extent, been exposed to wood dust. Respirable dust levels were measured by personal sampling for job types with exposure to MMMF; the range of the 8 h TWA was 0.09-1.9 mg/m3 with a mean of 0.5 mg/m3. Follow-Up and Data Analysis The life outcome of the cohort members was traced by a computerized register of the Swedish population, via the clerical parish offices, and via the taxation authorities (Table I). Four individuals were excluded due to insufficient exposure data, 36 had emigrated, and 25 (0.9%) were lost to follow-up. Data on the time of employment termination were missing for 229 individuals; they were retained in the cohort but were excluded in analyses of mortality by duration of exposure. The expected numbers of deaths were calculated according to the person-year method [Breslow and Day, 19871, accounting for age, calendar year, and geographical region (county). For each case, the registered underlying cause of death was obtained from Statistics Sweden, and in a few cases from the clerical parish offices. Mortality was followed from 1969 to 1988. The cancer incidence was calculated analogously, although without account for variations in incidence by geographic region. Data on cancer incidence were obtained from the Swedish Cancer Registry, and cancer incidence was investigated from 1969 to 1985. The Standard Mortality Ratio (SMR) calculations were performed with the OCMAP-PC computer program [Marsh et al., 19861.
RESULTS Mortality and Cancer Incidence The overall mortality in the cohort was lower than expected, mainly because of a low mortality in circulatory diseases (Table 11). The number of stomach cancers was higher than expected, and the number of lung cancers was somewhat lower than expected. The observed figures for the other causes of death corresponded well with those anticipated. There were no cases of pleural mesothelioma. There were some differences in mortality between the plants (Table 111), but the fluctuations can probably be explained by chance due to small numbers. Neither total nor cause-specific mortality correlated with time since first employment (latency) (Table IV). The lung cancer mortality did not correlate to the level of exposure to MMMF (Table V). The excess of stomach cancer was nearly entirely among those with no exposure to MMMF. Neither lung cancer mortality nor any of the other causes of death correlated positively to employment time (Table VI). The highest excess of stomach cancer was seen among those with the shortest employment periods. After a latency of 20 years or more, two lung cancer cases had occurred among those exposed to MMMF (exposure categories 1-3), whereas 4.3 would be expected (SMR = 46, 95% CI: 5-168). The analysis of cancer incidence (Table VII) gave results similar to those of the mortality analysis.
Lung Cancer Among Workers Exposed to MMMF
829
TABLE 11. Mortality Among Prefabricated House Industry Employees in Sweden 1969-1988* Cause of death (ICD 8=) All causes (1-999) All malignant tumors (140-209) Esophageal cancer (150) Stomach cancer (151) Bowel cancer (152-153) Rectal cancer ( 154) Liver cancer (155) Pancreatic cancer (157) Lung cancer (162) Prostatic cancer (185) Bladder cancer (188) Kidney cancer (189) Brain tumor (191) Malignant lymphomas (200-202) Myeloma (203) Leukemia (204-207) Hemato-lymphatic cancer (200-209) Circulatory diseases (390-458) Ischemic heart diseases (410-414) Cerebrovascular diseases (430-438) Respiratory diseases (460-5 19) Asthma, bronchitis, emphysema (490-493) Digestive diseases (520-577) Liver cirrhosis (571) Genitourinary diseases (580-629) Nephritis, nephrosis (580-584) Violent death and intoxication (E800-E999) Suicide (E950-E959)
Observed
Expected
SMR
95% CIb
554 137 2 22 9 5 4 13 14 21 4 3 1 8 2 5 15 288 208 40 32 11 17 6 10 3 49 14
623.1 134.6 2.3 13.8 11.0 6.8 2.4 9.7 20.7 20.7 4.1 6.3 4.2 4.9 3.O 5.5 14.4 343,3 250.2 52.3 33.6 11.2 19.8 6.2 9.9 2.3 50.3 17.6
89 102 86 159 81 73 167 134 68 101 98 47 24 163 67 91 105 84 83 77 95 98 86 96 101 132 97 79
82-97 85-120 10-310 100-241 37-155 24-171 45-428 7 1-229 37-1 13 63-155 26-250 9-138 0-133 70-322 7-24 1 29-212 58-172 74-94 72-95 55-104 65-135 49-176 50-137 35 -209 48-186 26-384 72-129 43-133
*There were 49,527 person-years of observation. Expected numbers were based on local mortality. "International Classification of Diseases-8th revision. bCI =confidence interval.
Smoking Habits Smoking data could be obtained for 73% of the cohort members in the 8 factories where smoking habits were investigated. Of these, 45% (n = 331) were current or former smokers during the time they were employed at the plant. A survey of smoking habits in Sweden was performed in 1963 [Statistics Sweden, 19651. The national survey data indicate a frequency of about 50% of current smokers in ages 18-49 in the type of geographic areas where the house plants are located. It thus seems as if the workers in the prefabricated house industry have smoked somewhat less than the average. The regionally based reference rates for mortality do not fully account for the lower smoking rate in the cohort, and a small residual negative confounding effect on the lung cancer rate may be present.
DISCUSSION Lung cancer mortality in the cohort was somewhat lower than expected, and the risk did not correlate to duration of employment or intensity of exposure. Mortality from stomach cancer was increased, but mainly among those not exposed to MMMF, and among the short-term employed. The excess of stomach
1 ~2
3 ~
4
5 ~
6 ~~~~~
7 _
8
_9
10
_ 11
0.5 56 54.6 11 13.2 31 43.4 156 162.7 34 31.7 20 21.6 0.1 12 12.2 1 3.0 9 8.8 43 36.1 8 6.2 7 4.1 0.0 2 1.3 0 0.3 3 0.9 4.0 1 0.8 1 0.3 7 0.0 2 2.1 0 0.4 0 1.1 2 6.7 2 1.0 2 0.7 0.0 1 1.3 0 0.4 1 0.9 4 3.7 2 0.6 1 0.5 0.1 32 28.4 6 6.5 17 24.4 75 89.2 20 19.0 11 11.7 0.0 2 2.5 0 0.5 2 2.6 11 8.3 0 1.7 0 1.0 0.0 1 1.8 1 0.5 1 1.3 4 5.2 1 1.0 1 0.8 0.2 5 6.0 2 1.6 2 3.2 19 13.5 3 1.7 0 2.5
*Expected numbers were based on local mortality.
0 0 0 0 0 0 0 0 0
0 0 0 1 0 0 0
1
2
2.6 79 93.0 14 18.1 0.6 16 20.1 3 3.4 0.0 1 2.0 0 0.3 0.1 1 2.9 0 0.5 0.1 3 2.2 1 0.4 1.0 46 51.5 9 10.1 0.1 5 5.3 1 0.9 0.1 2 2.9 0 0.6 0.7 7 6.9 1 1.7
Obs Exp Obs Exp Obs Exp Obs Exp Obs Exp Obs Exp Obs Exp Obs Exp Obs Exp Obs Exp Obs Exp
ALL CAUSES 151 181.8 All malignant tumors 37 40.0 4.0 Stomach cancer 7 5.8 Lung cancer 5 4.3 Hemato-lymphatic cancer 2 Circulatory diseases 71 101.4 Respiratory diseases 11 10.6 5.5 Digestive diseases 6 Violent death and intoxication 10 12.2
Cause of death
Plant No.
TABLE 111. Observed and Expected Numbers of Selected Causes of Deaths at the 11 Prefabricated House Facilities 1%9-1988*
Lung Cancer Among Workers Exposed to MMMF
831
TABLE IV. Mortality Among Prefabricated House industry Employees in Sweden, by Latency From Start of Employment* Latency
< 10 years Cause of death ALL CAUSES All malignant tumors Stomach cancer Bowel cancer Lung cancer Prostatic cancer Hemato-lymphatic cancer Circulatory diseases Ischemic heart disease Cerebrovasculardiseases Respiratory diseases Digestive diseases Violent death and intox.
10-19 years
220 years
Obs
Exp
SMR
Obs
Exp
SMR
Obs
Exp
SMR
39 10 3 I
51.6 11.2 1.2 1.4 1.7 0.9 1.5 22.6 16.7 3.3 1.7 2.0 9.8
76 89 252 69 59 0 67 71 78 60 173 49 71
155
162.7 35.8 3.7 4.5 5.7 4.7 4.1 85.2 62.6 12.6 7.5 5.7 17.3
95 123 190 66 70 85 197 83 82 79 54 105
313 74 10 10 9 13 5 177 126 25 24 7 16
368.8 79.2 8.1 10.6 12.0 13.8 7.9 213.9 155.2 33.0 22.2 10.8 19.3
85 93 124 95 75 94 63 83 81 76 108 65 83
1
0 1 16 13 2 3 1 7
44 7 3 4 4 8 71 51 10 4 6 19
110
*Expected numbers based on local mortality.
cancer is thus less likely to be caused by MMMF or any other occupational exposure such as wood dust. The stomach cancer rate is higher in rural than in urbanized areas in Sweden [National Board of Health and Welfare, 1958-19851. The facilities manufacturing prefabricated wooden houses are generally located in the countryside or in small towns. The analyses were standardized for geographical region (county), but there may still be some residual confounding from this geographical trend, since the counties are large areas including urbanized as well as rural areas. Uncontrolled variations in the background rate may also have contributed to the apparently lowered risk for lung cancer, since this disease has an inverse geographical trend with higher rates in urbanized areas. Also, fluctuations from chance cannot be ruled out as regards both lung and stomach cancer. No excess of stomach cancer was found in the large European [Simonato et al., 19861 and U.S. [Marsh et al., 19901 MMMF cohort studies, but excesses have been reported from two single factories included in the larger cohorts [Robinson et al., 1982; Claude and Frentzel-Beyme, 19861. The overall mortality of the group was lower than expected. This is probably related to the so-called “healthy worker effect,” which is usually seen in cohort studies of this type, resulting from incomparability between the study and referent groups regarding employment status [McMichael, 19761. There are no previous reports describing the mortality among prefabricated wooden house industry workers. Exposure to wood dust is associated with an increased risk of nose and sinonasal cancer [Hernberg et al., 19831, and there are also sporadic reports of increased risks of lung cancer [Esping and Axelson, 19801 and Hodgkin’s lymphoma [Alderson, 19861 in association with exposure to wood dust. There were no cases of nose or sinonasal cancers in this cohort. The number of malignant lymphomas was slightly increased, but this may be caused by chance. Use of chlorophenols for wood preservation could not be verified at any of the plants. The results of the smoking data analysis should be interpreted with caution, since
352.9 76.8 8.0 11.5 8.0 197.7 19.8 10.9 24.5
306 79 15 9 8 152 20 9 26
ALL CAUSES All malignant tumors Stomach cancer Lung cancer Hemato-lymphatic cancer Circulatory diseases Respiratory diseases Digestive diseases Violent death and intoxication
87 103 187 78 100 77 101 82 106
SMR 45 12 2 1 1 23 2 1 7
Obs 49.5 10.9 1.1 1.7 1.2 27.3 2.5 1.6 4.0
Exp 91 110 185 58 85 84 80 63 176
SMR
Exposure category 1 75 13 1 1 3 49 6 3 2
Obs
~
90.4 19.2 2.0 3.0 2.0 50.5 4.8 2.9 6.9
Exp
Exposure category 2
*See text for explanation of exposure categories. Expected numbers were based on local mortality.
Exp
Obs
Cause of death
Exposure category 0 83 68 51 33 149 97 124 103 29
SMR 61 20 3 2 2 29 2 1 6
Obs
~-
71.3 15.1 1.4 2.4 1.8 37.2 3.4 2.4 8.2
Exp
Exposure category 3
TABLE V. Mortality Among Prefabricated House Industry Employees in Sweden, by Exposure to MMMF*
85 133 207 85 114 78 58 41 73
SMR
1 1 35 2 3 8
I
67 13
Obs
58.9 12.8 1.3 2.1 1.4 30.6 2.9 1.9 6.7
Exp
Exposure category 9 114 102 76 48 70 115 69 155 120
SMR
Lung Cancer Among Workers Exposed to MMMF
833
TABLE VI. Mortality Among Prefabricated House Industry Employees in Sweden, by Duration of Employment* ~
Duration of employment
