Performance of two general job-exposure matrices in a study of lung cancer morbidity in the Zutphen cohort.

Data from a general population cohort of 878 men from the town of Zutphen, The Netherlands, were used to evaluate the performance of two general job-exposure matrices. Exposures generated by the job-exposure matrices on the basis of job histories were compared. The validity of those exposures was measured against exposures reported by the participants in 1977/1978. The performance of the different exposure measures was assessed in proportional hazards analyses of lung cancer morbidity incidence. The two general job-exposure matrices generally disagreed with regard to exposure classification because of differences in exposure assessment and level of detail of the job axis. When compared with self-reported exposures, the sensitivity of both job-exposure matrices was low (on average, below 0.51), while the specificity was generally high (on average, above 0.90). Self-reported exposures to asbestos, pesticides, and welding fumes showed elevated risk ratios for lung cancer which were absent for exposures generated by the two job-exposure matrices. Thus, a population-specific job-exposure matrix is proposed as an alternative to general job-exposure matrices developed elsewhere. Such a matrix can be constructed from the results of in-depth interviews of a job-stratified sample of cohort members. Sound validation and documentation of exposure assessment methods used in job-exposure matrices are recommended.     

Formaldehyde exposure and respiratory cancer among woodworkers--an update

Respiratory cancer was examined in relation to occupational formaldehyde exposure in a case-referent study (136 cases, 408 referents) nested in a woodworker cohort. Plant- and time-specific job-exposure matrices were constructed for formaldehyde exposure. Over 3 ppm-months of formaldehyde exposure was associated with an odds ratio of 1.4 [90% confidence interval (90% CI) 0.5-4.1]. The odds ratios for lung cancer were near unity, the excess risk concentrating on the upper respiratory tract. That for combined exposure to formaldehyde-phenol exposure (all respiratory cancers) was 1.6 (90% CI 0.6-4.4) but 1.0 for formaldehyde only. No consistent exposure-response patterns emerged for the level, duration, or cumulative exposure. The results are hardly more than debatable support for the hypothesis concerning formaldehyde as a carcinogen in humans, the possible risk seemingly concentrating on the upper respiratory tract rather than the lung.     

Cohort mortality study of North American industrial sand workers. III. Estimation of past and present exposures to respirable crystalline silica

BACKGROUND: Lung cancer and silicosis mortality were examined longitudinally and by a case-referent analysis in a cohort of workers selected from the North American industrial sand industry. Date of hire in the case-referent sub-cohort extended as far back as the second decade of the twentieth century. OBJECTIVE: The aim of this study component was to develop estimates of average and cumulative exposure to respirable crystalline silica for the 342 selected cases and referents. METHODS: Process and dust control histories were developed for each plant, and quantitative exposure data obtained from each of them and from a trade organization. An algorithm was developed to convert historical exposures reported in particle count concentrations to modern measures of mass concentration of respirable crystalline silica. Personal exposures were adjusted for use of protective equipment based on frequency of use and type of protection. FINDINGS: Between 1974 and 1998, a total of 14249 exposure measurements had been taken using a cyclone and membrane filter and gave an overall geometric mean of 42 microg/m3. The only exposure data identified earlier were based on approximately 500 samples collected across the industry between 1947 and 1955 using the Greenburg-Smith impinger, with analysis by microscopy. These data were converted to modern measures using a factor of 1 mppcf = 276 microg/m3 respirable dust and then adjusting for percentage silica. In general, the highest exposures occurred in bagging and bulk-loading operations and the lowest in wet processing of sand.Conclusions: There has been a substantial decline in exposure levels in this industry over time. The decline was rapid between the 1940s and 1970s and current exposures are, on average, less than 50 microg/m3. The use of personal protective equipment was judged to have had little impact on exposure before the 1970s.     

Lung cancer mortality in stainless steel and mild steel welders: A nested case-referent study

The association between welding and lung cancer has been studied in a nested case-referent study within a cohort of 8,372 metal workers. Lifetime exposure data on welding and other occupational exposures, as well as alcohol and smoking habits, were obtained by interviews of spouses and colleagues. Analysis was based on 439 deceased referents and 94 deceased cases. There was 70% excess of lung cancer associated with “welding exposure ever” (OR ± 95% C.I.: 1.68, 1.02–2.78). Overall OR “mild steel (MS) welding ever” was 1.64, 0.99-2.72. The risk estimates for welding exposures showed an increasing tendency up to 15 years of exposure. The pattern of stainless steel (SS) welding resembles that of mild steel with an estimated OR of 1.65, 0.88–3.0. The general conclusion is that MS welding as well as SS welding seems to be associated with an increased risk of lung cancer. Further followup of the cohort will enhance precision of the estimates. © 1996 Wiley-Liss, Inc.     

Lymphohaematopoietic malignancies and quantitative estimates of exposure to benzene in Canadian petroleum distribution workers.

OBJECTIVE: To evaluate the relation between mortality from lymphohaematopoietic cancer and long term, low level exposures to benzene among male petroleum distribution workers. METHODS: This nested case control study identified all fatal cases of lymphohaematopoietic cancer among a previously studied cohort. Of the 29 cases, 14 had leukaemia, seven multiple myeloma, and eight non-Hodgkin's lymphoma. A four to one matching ratio was used to select a stratified sample of controls from the same cohort, controlling for year of birth and time at risk. Industrial hygienists estimated workplace exposures for benzene and total hydrocarbons, without knowledge of case or control status, for combinations of job, location, and era represented in all work histories. Average daily benzene concentrations ranged from 0.01 to 6.2 parts per million (ppm) for all jobs. Company medical records were used to abstract information on other potential confounders such as cigarette smoking, although the data were incomplete. Odds ratios (ORs) were calculated with conditional logistic regression techniques for several exposure variables. RESULTS: Risks of leukaemia, non-Hodgkin's lymphoma, and multiple myeloma were not associated with increasing cumulative exposure to benzene or total hydrocarbons. For leukaemia, the logistic regression model predicted an OR of 1.002 (P < 0.77) for each ppm-y of exposure to benzene. Duration of exposure to benzene was more closely associated with risk of leukaemia than other exposure variables. It was not possible to completely control for other risk factors, although there was suggestive evidence that smoking and a family history of cancer may have played a part in the risk of leukaemia. CONCLUSION: This study did not show a relation between lymphohaematopoietic cancer and long term, low level exposures to benzene. The power of the study to detect low-such as twofold-risks was limited. Thus, further study on exposures to benzene in this concentration range are warranted.     

Mental retardation and parental occupation: a study on the applicability of job exposure matrices.

In a case-referent study on mental retardation and parental occupation, the applicability of job exposure matrices for the identification of risk factors was evaluated. The parents of 306 mentally retarded children (cases) and 322 referents were interviewed about their occupational activities in the pregnancy period. Detailed occupational histories were obtained that were compared with exposures generated by two different job exposure matrices. The agreement between interview and matrices was low: the sensitivity ranged from 17.9% to 32.4% and the percentages of false positive exposures from 66.7% to 96.0%. By means of the interview, significantly increased odds ratios (ORs) were found for exposure of the mother in late pregnancy to radiation (OR = 9.3), mercury (OR = 8.7), organic solvents (OR = 1.7), hair cosmetics and dyes (OR = 3.7), paint (OR = 2.7), hexachlorophene/phenylphenol (OR = 3.1), antibiotics (OR = 2.9), and dust (OR = 2.2) and for working with copying machines (OR = 3.0) or in occupations with poor climatological circumstances and permanent contact with people. The last was confirmed by the British matrix (OR = 1.7). Otherwise, most of the mentioned associations were missed by the job exposure matrices. Therefore, these matrices were not considered to be applicable in this particular study, nor in most other reproductive epidemiological studies in view of their general properties and limitations.     

Renal cell cancer and occupational exposure to chemical agents

A case-referent study of occupational risk indicators of renal cell adenocarcinoma was conducted. Each incident case in Finland in 1977-1978 was matched with two population referents. Lifelong job histories were collected and translated into indicators of industry, occupation, and occupational exposures. The analyses of 338 sets of cases and referents revealed elevated risks for a history of employment in white-collar occupations; the printing industry; the chemical industry; the manufacturing of metal products; mail, telephone, and telegraph services; and iron and metalware work. A decreased risk was observed for male farmers. An elevated risk and an exposure-response relationship were found for gasoline exposure. The excess risk was highest at a latency period of approximately 30 years. The findings support the hypothesis that exposure to some constituent(s) of gasoline increases the incidence of renal adenocarcinoma in humans. Suggestions of elevated risks appeared for exposures to inorganic lead, cadmium, and nonchlorinated solvents.     

Leukemia risk associated with low-level benzene exposure

BACKGROUND: Men who were part of an Australian petroleum industry cohort had previously been found to have an excess of lympho-hematopoietic cancer. Occupational benzene exposure is a possible cause of this excess. METHODS: We conducted a case-control study of lympho-hematopoietic cancer nested within the existing cohort study to examine the role of benzene exposure. Cases identified between 1981 and 1999 (N = 79) were age-matched to 5 control subjects from the cohort. We estimated each subject's benzene exposure using occupational histories, local site-specific information, and an algorithm using Australian petroleum industry monitoring data. RESULTS: Matched analyses showed that the risk of leukemia was increased at cumulative exposures above 2 ppm-years and with intensity of exposure of highest exposed job over 0.8 ppm. Risk increased with higher exposures; for the 13 case-sets with greater than 8 ppm-years cumulative exposure, the odds ratio was 11.3 (95% confidence interval = 2.85-45.1). The risk of leukemia was not associated with start date or duration of employment. The association with type of workplace was explained by cumulative exposure. There is limited evidence that short-term high exposures carry more risk than the same amount of exposure spread over a longer period. The risks for acute nonlymphocytic leukemia and chronic lymphocytic leukemia were raised for the highest exposed workers. No association was found between non-Hodgkin lymphoma or multiple myeloma and benzene exposure, nor between tobacco or alcohol consumption and any of the cancers. CONCLUSIONS: We found an excess risk of leukemia associated with cumulative benzene exposures and benzene exposure intensities that were considerably lower than reported in previous studies. No evidence was found of a threshold cumulative exposure below which there was no risk.     

Spontaneous abortions and congenital malformations among the wives of men occupationally exposed to organic solvents

A case-referent study nested in a cohort monitored biologically for exposure to six organic solvents (styrene, toluene, xylene, tetrachloroethylene, trichloroethylene, and 1,1,1-trichloroethane) was conducted to investigate the effects of paternal exposure on pregnancy outcome. The pregnancies were identified from medical registers. The exposures of the men during the spermatogenesis preceding the pregnancies and of the women during the first trimester of the pregnancies were obtained with questionnaires, and the available biological monitoring measurements were used in the exposure assessment. Factors which significantly increased the odds ratio of spontaneous abortion were paternal exposure to organic solvents in general, high/frequent exposure to toluene or miscellaneous organic solvents (including thinners), and maternal heavy lifting. No significant association between paternal or maternal exposure and congenital malformations was found, but because of the few cases no firm conclusions can be drawn.     

Respiratory cancers and chemical exposures in the wood industry: a nested case-control study.

A cohort of 3805 men who had worked for at least one year in the particleboard, plywood, sawmill, or formaldehyde glue industries between 1944 and 1965 was followed up until 1981. From within the cohort the 57 patients with verified "respiratory" cancer (ICD 7 codes: 160-162.1, 141, 143-8) were defined as "cases," and 171 men without respiratory cancer from within the cohort were matched on birth year and used as controls. The comparison of exposures was carried out according to work histories and job exposure matrices for each plant. The odds ratio for exposure to wood dust was 1.03 (32 exposed cases) without provision for any latent period, and 0.97 (27 exposed cases) when provision for a minimum latent period of ten years was applied. The odds ratios were 1.60 and 1.68, respectively, when smoking was controlled by stratification. These results did not differ significantly from unity. The estimated average level of exposure to wood dust among the exposed was 1-2 mg/m3 and the mean duration of exposure about ten years. Significantly (one sided test, 5% level) raised odds ratios were observed for exposure to pesticides and phenol. No single pesticide could be identified as "causative" because of frequent multiple exposures. The raised odds ratios for phenol were partly explained by smoking and exposure to pesticides which confounded the observed associations for phenol exposure. Exposure to terpenes and other heating products of coniferous woods was significantly associated with a risk of respiratory cancer when the duration of exposure exceeded five years.     

Respiratory cancers and chemical exposures in the wood industry: a nested case-control study

A cohort of 3805 men who had worked for at least one year in the particleboard, plywood, sawmill, or formaldehyde glue industries between 1944 and 1965 was followed up until 1981. From within the cohort the 57 patients with verified "respiratory" cancer (ICD 7 codes: 160-162.1, 141, 143-8) were defined as "cases," and 171 men without respiratory cancer from within the cohort were matched on birth year and used as controls. The comparison of exposures was carried out according to work histories and job exposure matrices for each plant. The odds ratio for exposure to wood dust was 1.03 (32 exposed cases) without provision for any latent period, and 0.97 (27 exposed cases) when provision for a minimum latent period of ten years was applied. The odds ratios were 1.60 and 1.68, respectively, when smoking was controlled by stratification. These results did not differ significantly from unity. The estimated average level of exposure to wood dust among the exposed was 1-2 mg/m3 and the mean duration of exposure about ten years. Significantly (one sided test, 5% level) raised odds ratios were observed for exposure to pesticides and phenol. No single pesticide could be identified as "causative" because of frequent multiple exposures. The raised odds ratios for phenol were partly explained by smoking and exposure to pesticides which confounded the observed associations for phenol exposure. Exposure to terpenes and other heating products of coniferous woods was significantly associated with a risk of respiratory cancer when the duration of exposure exceeded five years.     

A triangulation approach to historical exposure assessment for the carbon black industry

The determination of cumulative exposures for individual workers is necessary for research and practice of occupational health and hygiene. Reconstruction of exposures for a study of respiratory morbidity was needed to study the effects of exposure to carbon black production. Approximately 15,800 exposure estimates were needed. There were 22 plants, a 40-year time span, six job categories, and three types of dust-exposure metrics (respirable, inhalable, and "total" dust). Three information sources were used: 1) Industrial hygiene air level measurements where available (several industry-wide surveys had been conducted). 2) A formal process survey identifying specific dates and types of process and control changes. 3) An Historical Relative Exposure Rating Scale; plant health and safety personnel used this spreadsheet-based rating scheme to quantify exposures before and between years of actual measurement relative to a reference year in which measurements were available. A job-exposure matrix was calculated by integrating these three methods. Linear scaling factors were identified to interconvert geometric to arithmetic means and to interconvert total and inhalable dust. Individual worker cumulative exposures were then calculated based upon job histories linked with the job-exposure matrix. The nine-step process for integrating all available relevant data was effective in estimating the exposures for each of the cells of the job-exposure matrix. Among the 1680 workers participating, the mean cumulative inhalable dust exposure was 48.4 mg-years/m3. Early years contribute disproportionately to the cumulative exposures of individuals since levels have declined significantly over time. The use of multiple sources of information, including a relative exposure rating instrument, significantly facilitates reconstruction of historical exposures. Inadequate adjustment for temporal trends can lead to underestimation of cumulative exposures and significantly affect estimation of dose-effect relationships. These methods are applicable to other situations requiring estimation of cumulative exposure with sparse industrial hygiene data in early years.     

Lung cancer mortality at a UK tin smelter

BACKGROUND: An earlier study of mortality among male former employees at a tin smelter in Humberside, UK, had identified excess mortality from lung cancer, which appeared to be associated with occupational exposure. AIMS: The aim of the present study was to investigate the relationship between lung cancer mortality and quantitative measures of exposure. METHODS: Using available records of occupational hygiene measurements, we established exposure matrices for arsenic, cadmium, lead, antimony and polonium-210 ((210)Po), covering the main process areas of the smelter. We established work histories from personnel record cards for the previously defined cohort of 1462 male employees. Three different methods of extrapolation were used to assess exposures prior to 1972, when no measurement results were available. Lung cancer mortality was examined in relation to cumulative inhalation exposure by Poisson regression analysis. RESULTS: No significant associations could be found between lung cancer mortality and simple cumulative exposure to any of the substances studied. When cumulative exposures were weighted according to time since exposure and attained age, significant associations were found between lung cancer mortality and exposures to arsenic, lead and antimony. CONCLUSIONS: The excess of lung cancer mortality in the cohort can most plausibly be explained if arsenic is the principal occupational carcinogen (for which the excess relative risk diminishes with time since exposure and attained age) and if there is a contribution to excess mortality from an enhanced prevalence of smoking within the cohort. The implications of the dose-response for arsenic exposure for risk estimation merit further consideration.     

Cohort mortality study of North American industrial sand workers. II. Case-referent analysis of lung cancer and silicosis deaths

BACKGROUND: A cohort mortality study of 2670 men in nine North American industrial sand plants resulted in 83 deaths from lung cancer 20 or more years after hire (standardized mortality ratio 139) and 37 deaths from silicosis (including seven from silico-tuberculosis). The lung cancer excess was unrelated to duration of employment and not found in all plants.Objectives: The primary aim was to determine whether lung cancer risk among these employees was related to quantitative estimates of crystalline silica exposure, after allowance for cigarette smoking. A secondary aim was to do the same for silicosis mortality, partly as a means of validating the estimated levels of exposure. METHODS: A nested case-referent study was undertaken with cases matched with up to two controls on plant, age and date of first employment from men who survived the case. Exposures were estimated by linking work histories to a job-exposure matrix, undertaken separately. Cigarette smoking information was obtained from medical records and other sources, blind as to case-control status. Matched statistical analyses were conducted using conditional logistic regression. FINDINGS: Odds ratios for silicosis mortality were significantly related to cumulative silica exposures and tended to a relationship with category of average crystalline silica concentration, but inconsistently with length of employment. After accounting for a strong effect of cigarette smoking, odds ratios for lung cancer were related to cumulative crystalline silica exposure and to average silica concentration, but not to length of employment. CONCLUSION: These findings support a causal relationship between lung cancer and quartz exposure after allowance for cigarette smoking, in the absence of cristobalite or other known occupational carcinogens.     

Occupational exposure to magnetic fields in relation to mortality from brain cancer among electricity generation and transmission workers.

OBJECTIVE: To investigate whether the risks of mortality from brain cancer are related to occupational exposure to magnetic fields. METHODS: A total of 112 cases of primary brain cancer (1972-91) were identified from a cohort of 84,018 male and female employees of the (then) Central Electricity Generating Board and its privatised successor companies. Individual cumulative occupational exposures to magnetic fields were estimated by linking available computerised job history data with magnetic field measurements collected over 675 person-workshifts. Estimated exposure histories of the case workers were compared with those of 654 control workers drawn from the cohort (nested case-control study), by means of conditional logistic regression. RESULTS: For exposure assessments based on arithmetic means, the risk of mortality from brain cancer for subjects with an estimated cumulative exposure to magnetic fields of 5.4-13.4 microT.y v subjects with lower exposures (0.0-5.3 microT.y) was 1.04 (95% confidence interval (95% CI) 0.60 to 1.80). The corresponding relative risk in subjects with higher exposures (> or = 13.5 microT.y) was 0.95 (95% CI 0.54 to 1.69). There was no indication of a positive trend for cumulative exposure and risk of mortality from brain cancer either when the analysis used exposure assessments based on geometric means or when the analysis was restricted to exposures received within five years of the case diagnosis (or corresponding period for controls). CONCLUSIONS: Although the exposure categorisation was based solely on recent observations, the study findings do not support the hypothesis that the risk of brain cancer is associated with occupational exposure to magnetic fields.     

Analysis of excess lung cancer risk in short-term employees

An excess of lung cancer found in a cohort of 741 New York State tremolitic talc workers observed from 1947 through 1978 has been shown paradoxically to be concentrated in short-term workers. Review of past work histories suggests that the excess of lung cancer in these short-term workers may be accounted for by prior exposures rather than by exposures at the employment under investigation. This finding has significant implications in view of the developing practice of including short-term workers in occupational cohort studies in contrast to the more traditional practice of excluding short-term workers. The traditional practice was based on the assumption that the inclusion of short-term workers with little exposure, and thus little risk, might dilute an otherwise apparent association between mortality and exposure. This study suggests that in certain instances the inclusion of short-term workers may magnify rather than dilute the estimation of risk, reflecting the presence of confounding variables.     

Malignant lymphomas and leukemias,and exposures in the wood industry: an industry-based case-referent study

Summary Jobs and exposures in woodwork may entail an elevated risk of lymphomas and leukemias. Exposures occurring in woodwork were scrutinized in a small industry-based case-referent study of four cases of Hodgkin's disease, eight cases of non-Hodgkin's lymphoma, 12 cases of leukemia, and 152 matched referents, all from the Finnish wood industry. Past exposures to wood dust, chlorophenols, terpenes, and engine exhaust, individually reconstructed through plant- and period-specific job exposure matrices, were unrelated to lymphoma/leukemia risk. Exposures to various solvents were associated with an odds ratio (OR) of 5.6 (95% confidence interval 1.0–32.0). The OR for formaldehyde was 2.5 (nonsignificant). The results are interpreted as providing limited evidence of the role of exposure to some as yet unidentified organic solvents in increasing the risk of malignant lymphomas. Formaldehyde may be another woodwork-related risk factor for some lymphomas, but the power of the study was too low for empirical confirmation of this possibility. Leukemias did not seem to be associated with any of the exposures studied.     

Validity of exposure data obtained by questionnaire. Two examples from occupational reproductive studies

Exposure data from self-administered questionnaires were compared with independent information on occupational exposures in two studies of reproductive outcome. Agreement in the case-referent study concerning dry-cleaning work and tetrachloroethylene exposure was good. However, exposure reporting was indicated to be more accurate for the cases than the referents. Correction for misclassification slightly changed the odds ratio from 1.02 to 1.27 for nonspecific exposure and from 0.92 to 0.82 for tetrachloroethylene exposure. Missing information on the latter exposure was more crucial, since adding the employer information for such exposure increased the risk estimate to 1.24. In a prospective follow-up study, exposure information was validated in a sample of the study population. Reporting of heavy lifting appeared to be fairly correct, whereas the underreporting of chemical exposures was a problem. Validation of self-reported exposure data is desirable, and the direction and magnitude of possible misclassification bias should be evaluated in each specific situation.     

Chemical exposures and respiratory cancer among Finnish woodworkers.

A case-control study of respiratory cancer, nested within a cohort of male woodworkers, was updated in Finland. The update extended the initial follow up of 3805 workers from 19 plants to 7307 workers from 35 plants. Each case of respiratory cancer (n = 136) diagnosed between 1957 and 1982 within the cohort was matched by year of birth with three controls (n = 408) from the cohort. Chemical exposures were assessed for the cases and the controls by a plant and period specific job exposure matrix. An excess of respiratory cancer was associated with phenol. Concomitant exposures to several other agents occurred as well, however, and no exposure-response relation for phenol was seen. An excess risk and an increasing exposure-response relation were found for engine exhaust from petrol and diesel driven factory trucks. The excess risk associated with pesticides was lower than in our previous study, an indication of qualitative and quantitative differences in exposure between the initial and augmented cohorts. Slightly increased risks were found for terpenes and mould spores, which may be due to chance although the contribution of occupational exposure cannot be ruled out. Exposure to wood dust, mainly from pine, spruce and birch, at a level of about 1 mg/m3, was not associated with lung cancer, upper respiratory cancer, or adenocarcinoma of the lung.