Exposure assessment for a nested case-control study of lung cancer among European asphalt workers.

OBJECTIVE: Development of a method for retrospective assessment of exposure to bitumen fume, bitumen condensate, organic vapour, polycyclic aromatic hydrocarbons, and co-exposures to known or suspected lung carcinogens for a nested case-control study of lung cancer mortality among European asphalt workers. METHODS: Company questionnaires and structured questionnaires used in interviews and industry-specific job-exposure matrices (JEMs) were elaborated and applied. Three sources of information were eventually used for exposure assessment and assignment: (i) data obtained in cohort phase, (ii) data from living subjects, next-of-kin, and fellow-workers questionnaires, and (iii) JEMs for bitumen exposure by inhalation and via skin and co-exposures to known or suspected lung carcinogens within and outside cohort companies. Inhalation and dermal exposure estimates for bitumen were adjusted for time trends, time spent in a job, and other determinants of exposure (e.g. oil gravel paving). Clothing patterns, personal protective devices, and personal hygiene were taken into consideration while estimating dermal exposure. RESULTS: Occupational exposures could be assessed for 433 cases and 1253 controls for relevant time periods. Only 43% of work histories were spent inside original asphalt and construction companies. A total of 95.8% of job periods in cohort companies could be coded at a more detailed level. Imputation of work time and 'hygienic behaviour' multipliers was needed for <10% of work history years. Overall, downward trends in exposure were present and differences existed between countries and companies. As expected, correlations were strongest (r > 0.7) among bitumen-related agents, while correlations between coal tar, bitumen-related agents, and established lung carcinogens were weaker (r < 0.4). CONCLUSIONS: A systematic and detailed approach was developed to estimate inhalation and dermal exposure for a nested case-control study among asphalt workers.

A case-control study of lung cancer nested in a cohort of European asphalt workers.

BACKGROUND: We conducted a nested case-control study in a cohort of European asphalt workers in which an increase in lung cancer risk has been reported among workers exposed to airborne bitumen fume, although potential bias and confounding were not fully addressed. OBJECTIVE: We investigated the contribution of exposure to bitumen, other occupational agents, and tobacco smoking to the risk of lung cancer among asphalt workers. METHODS: Cases were cohort members in Denmark, Finland, France, Germany, the Netherlands, Norway, and Israel who had died of lung cancer between 1980 and the end of follow-up (2002-2005). Controls were individually matched in a 3:1 ratio to cases on year of birth and country. We derived exposure estimates for bitumen fume and condensate, organic vapor, and polycyclic aromatic hydrocarbons, as well as for asbestos, crystalline silica, diesel motor exhaust, and coal tar. Odds ratios (ORs) were calculated for ever-exposure, duration, average exposure, and cumulative exposure after adjusting for tobacco smoking and exposure to coal tar. RESULTS: A total of 433 cases and 1,253 controls were included in the analysis. The OR was 1.12 [95% confidence interval (CI), 0.84-1.49] for inhalation exposure to bitumen fume and 1.17 (95% CI, 0.88-1.56) for dermal exposure to bitumen condensate. No significant trend was observed between lung cancer risk and duration, average exposure, or cumulative exposure to bitumen fume or condensate. CONCLUSIONS: We found no consistent evidence of an association between indicators of either inhalation or dermal exposure to bitumen and lung cancer risk. A sizable proportion of the excess mortality from lung cancer relative to the general population observed in the earlier cohort phase is likely attributable to high tobacco consumption and possibly to coal tar exposure, whereas other occupational agents do not appear to play an important role.

Detection of p53 protein in induced sputum after occupational exposure to crystalline silica.

OBJECTIVE: To examine the possibility of detecting p53 protein in the supernatant of induced sputum (IS) of workers exposed to crystalline silica. METHODS: Personal interviews were used to obtain demographic data, occupational and exposure histories, and health habits of the study participants. Sputum samples were collected from all subjects. RESULTS: The all-male study cohort included 35 workers (mean age 43.8 years) exposed to silica and 7 unexposed workers (34.7 years, P < 0.05). The mean duration of exposure was 13.4 years, and the range of exposure levels to silica was 0.02 to 0.33 ppm. The mean level of p53 protein was higher in the exposed group compared with in the unexposed group (76.47 pg/mL and 62.43 pg/mL, respectively). CONCLUSIONS: p53 may serve as a biomarker to identify workers at high risk for developing pulmonary malignancies. IS can detect p53 protein in sputum.

Bladder cancer incidence and exposure to polycyclic aromatic hydrocarbons among asphalt pavers.

OBJECTIVES: To investigate the association between exposures to polycyclic aromatic hydrocarbons (PAH) that arises during asphalt paving, and risk of bladder cancer. METHODS: 7298 men included in the historical cohort were first employed between 1913 and 1999 in companies applying asphalt in Denmark, Norway, Finland and Israel. The minimal duration of employment for inclusion in the cohort was two seasons of work. Occupational histories were extracted from personnel files. A follow-up for cancer incidence was conducted through national cancer registries. The authors estimated exposures to benzo(a)pyrene as a marker for 4-6 ring PAH. Exposures were reconstructed by using information about changes in asphalt paving technology in each company over time, the modelled relation between production characteristics and exposure levels, and job histories. Relative risks and associated 95% confidence intervals were estimated using Poisson regression. RESULTS: 48 bladder cancers among asphalt paving workers were detected; of these, 39 cases were exposed at least 15 years before the diagnosis. Cumulative exposure to PAH was not associated with the incidence of bladder cancer. The association with average exposure became stronger when 15-year lag was considered, revealing a twofold increase in relative bladder cancer risk in the two higher exposure categories. There was an indication of exposure-response association with lagged averaged exposure. Risk estimates were adjusted for age, country, duration of employment and calendar period, did not show heterogeneity among countries and did not materially change when re-estimated after excluding non-primary cancers from follow-up. Previously conducted sensitivity analysis indicates that confounding by cigarette smoking is an unlikely explanation for the observed exposure-response trends. CONCLUSIONS: The authors were unable to control for all possible sources of confounding and bias. The results do not allow conclusion on the presence or absence of a causal link between exposures to PAH and risk of bladder cancer among asphalt workers.

The risk of breast cancer in relation to health habits and occupational exposures.

BACKGROUND: The age-adjusted incidence rate of breast cancer has increased for Israeli women. Our aim was to explore the hypothesis that occupational exposures are important risk factors, taking into consideration main known risk factors. METHODS: The study population included 326 breast cancer cases from one hospital in the center of the country and 413 women without known diagnosis of cancer. Every participant was interviewed using a structured questionnaire. RESULTS: We found that working in textile and clothing and in various industries, OR (95% confidence interval), 1.8 (1.1-3.0), 4.3 (2.0-9.3) respectively, and exposure to ionizing radiation OR 5.3 (2.4-14.1) as well as age and having a family history of breast cancer significantly increased the risk of developing breast cancer. Administrative work, adherence to high fiber diet and low salt diet significantly lowered the risk of breast cancer. CONCLUSIONS: Our study supported the assumption that occupational exposure may contribute to the etiology of breast cancer.

Parental occupational exposure and the risk of acute lymphoblastic leukemia in offspring in Israel.

OBJECTIVE: Parental employment in occupations that have potential exposures to organic solvents or pesticides could be associated with the risk of childhood acute lymphoblastic leukemia (ALL) in their offspring. METHODS: We explored this hypothesis by studying the association with respect to exposure time windows. Our case-control study included 224 children, 112 diagnosed with ALL and 112 matched controls. RESULTS: A significantly higher odds ratio (OR) was found between childhood ALL and reported parental occupational exposures. Analysis of exposures of both parents by exposure time windows revealed significant OR during the preconception and postnatal periods separately. CONCLUSIONS: The results provide support to the association between parental occupational exposures and ALL in their children. These results should be interpreted cautiously because of the small numbers, biases characterizing case-control studies, and the use of hospital-based controls.

Polycyclic aromatic hydrocarbons and fatal ischemic heart disease.

BACKGROUND: Several toxicologic and epidemiologic studies have produced evidence that occupational exposure to polycyclic aromatic hydrocarbons (PAH) is a risk factor for ischemic heart disease (IHD). However, a clear exposure-response relation has not been demonstrated. METHODS: We studied a relation between exposure to PAH and mortality from IHD (418 cases) in a cohort of 12,367 male asphalt workers from Denmark, Finland, France, Germany, Israel, The Netherlands and Norway. The earliest follow up (country-specific) started in 1953 and the latest ended in 2000, averaging 17 years. Exposures to benzo(a)pyrene were assessed quantitatively using measurement-driven exposure models. Exposure to coal tar was assessed in a semiquantitative manner on the basis of information supplied by company representatives. We carried out sensitivity analyses to assess potential confounding by tobacco smoking. RESULTS: Both cumulative and average exposure indices for benzo(a)pyrene were positively associated with mortality from IHD. The highest relative risk for fatal IHD was observed for average benzo(a)pyrene exposures of 273 ng/m or higher, for which the relative risk was 1.64 (95% confidence interval=1.13-2.38). Similar results were obtained for coal tar exposure. Sensitivity analysis indicated that even in a realistic scenario of confounding by smoking, we would observe approximately 20% to 40% excess risk in IHD in the highest PAH-exposure categories. CONCLUSIONS: Our results lend support to the hypothesis that occupational PAH exposure causes fatal IHD and demonstrate a consistent exposure-response relation for this association.

Cancer incidence among laboratory workers in biomedical research and routine laboratories in Israel: Part I-the cohort study.

BACKGROUND: Laboratory work is associated with exposure to a mixture of carcinogens. METHODS: The cohort is comprised of 4,300 laboratory workers. Cancer incidence was followed from 1960 to 1997. RESULTS: A total of 230 cases were included in the cohort. The overall cancer standardized incidence ratio (SIR) was 1.04 (0.91-1.18). When a 20-year latency was introduced, SIR was increased significantly: 1.35 (1.13-1.61). Among routine workers and researchers, SIR was elevated significantly for the total population and for women, when a 20-year latency was introduced. SIR was also elevated significantly in research, routine, bacteriology and virology, and isotope laboratories. With respect to specific sites, significantly increased SIR was observed in breast, ovary, and thyroid cancer among women; and prostate cancer, leukemia, and melanoma among men. CONCLUSIONS: We suggest that work in research and biomedical laboratories might involve an increased risk of certain types of cancer. Am. J. Ind. Med. 44:600-610, 2003.

Cancer incidence among laboratory workers in biomedical research and routine laboratories in Israel: Part II-nested case-control study.

BACKGROUND: A case-control study nested within a cohort study of biomedical laboratory workers was conducted to examine whether the excess cancer morbidity that we found can be explained by exposure to a particular group of substances, taking into consideration potential confounders. METHODS: The study population included 163 cases and two matched control groups: laboratory workers (311) and general population (448) workers. RESULTS: Multiple conditional regression analysis showed that working in research laboratories involved an increased risk of cancer generally among women [risk ratio 2.2 (1.2-4.3)], and of breast cancer particularly [risk ratio 2.3 (1.1-4.7). Seventy-six percent (76%) of breast, 87% of thyroid, 60% of ovary and prostate, 94% of melanoma, and 50% of leukemia cases were ever exposed to at least one known human carcinogen. CONCLUSION: Our results exclude the possibility that the excess cancer morbidity was related to personal risk factors but they may be explained by exposure factors. Am. J. Ind. Med. 44:611-626, 2003.

Mortality from obstructive lung diseases and exposure to polycyclic aromatic hydrocarbons among asphalt workers.

Work in the asphalt industry has been associated with nonmalignant respiratory morbidity and mortality, but the evidence is not consistent. A historical cohort of asphalt workers included 58,862 men (911,209 person-years) first employed between 1913 and 1999 in companies applying and mixing asphalt in Denmark, Finland, France, Germany, Israel, the Netherlands, and Norway. The relations between mortality from nonmalignant respiratory diseases (including the obstructive lung diseases: chronic bronchitis, emphysema, and asthma) and specific chemical agents and mixtures were evaluated using a study-specific exposure matrix. Mortality from obstructive lung diseases was associated with the estimated cumulative and average exposures to polycyclic aromatic hydrocarbons and coal tar (p values of the test for linear trend = 0.06 and 0.01, respectively). The positive association between bitumen fume exposure and mortality from obstructive lung diseases was weak and not statistically significant; confounding by simultaneous exposure to coal tar could not be excluded. The authors lacked data on smoking and full occupational histories. In conclusion, exposures to polycyclic aromatic hydrocarbons, originating from coal tar and possibly from bitumen fume, may have contributed to mortality from obstructive lung diseases among asphalt workers, but confounding and bias cannot be ruled out as an explanation for the observed associations.

Estimating exposures in the asphalt industry for an international epidemiological cohort study of cancer risk.

BACKGROUND: An exposure matrix (EM) for known and suspected carcinogens was required for a multicenter international cohort study of cancer risk and bitumen among asphalt workers. METHODS: Production characteristics in companies enrolled in the study were ascertained through use of a company questionnaire (CQ). Exposures to coal tar, bitumen fume, organic vapor, polycyclic aromatic hydrocarbons, diesel fume, silica, and asbestos were assessed semi-quantitatively using information from CQs, expert judgment, and statistical models. Exposures of road paving workers to bitumen fume, organic vapor, and benzo(a)pyrene were estimated quantitatively by applying regression models, based on monitoring data, to exposure scenarios identified by the CQs. RESULTS: Exposures estimates were derived for 217 companies enrolled in the cohort, plus the Swedish asphalt paving industry in general. Most companies were engaged in road paving and asphalt mixing, but some also participated in general construction and roofing. Coal tar use was most common in Denmark and The Netherlands, but the practice is now obsolete. Quantitative estimates of exposure to bitumen fume, organic vapor, and benzo(a)pyrene for pavers, and semi-quantitative estimates of exposure to these agents among all subjects were strongly correlated. Semi-quantitative estimates of exposure to bitumen fume and coal tar exposures were only moderately correlated. EM assessed non-monotonic historical decrease in exposures to all agents assessed except silica and diesel exhaust. CONCLUSIONS: We produced a data-driven EM using methodology that can be adapted for other multicenter studies.

Cancer mortality among European asphalt workers: an international epidemiological study. II. Exposure to bitumen fume and other agents.

BACKGROUND: An increased risk of lung cancers among asphalt workers has been suggested in epidemiological studies based on large scale statistical analyses. METHODS: In a multi-country study of 29,820 male workers employed in road paving, asphalt mixing and roofing, 32,245 ground and building construction workers and 17,757 other workers from Denmark, Finland, France, Germany, Israel, the Netherlands, Norway, and Sweden, with mortality that was documented from 1953-2000. Exposures to bitumen fume, coal tar, 4-6 ring polycyclic aromatic hydrocarbons, organic vapor, diesel exhaust, asbestos, and silica dust were assessed via a job-exposure matrix. Standardized mortality ratios (SMRs) and 95% confidence intervals (CIs) based on national mortality rates, as well as relative risks (RRs) based on Poisson regression models were calculated. RESULTS: The SMR of lung cancer among workers exposed to bitumen fume (1.08, 95% CI 0.99-1.18) was comparable to that of non-exposed workers (SMR 1.05, 95% CI 0.92-1.19). In a sub-cohort of bitumen-exposed workers without exposure to coal tar, the SMR of lung cancer was 1.23 (95% CI 1.02-1.48). The analysis based on the semi-quantitative, matrix-based exposures in the whole cohort did not suggest an increased lung cancer risk following exposure to bitumen fume. However, in an analysis restricted to road pavers, based on quantitative estimate of bitumen fume exposure, a dose-response was suggested for average level of exposure, applying a 15-year lag, which was marginally reduced after adjustment for co-exposure to coal tar. The results for cancer of the head and neck were similar to those of lung cancer, although they were based on a smaller number of deaths. There was no clear suggestion of an association with bitumen fume for any other neoplasm. CONCLUSIONS: The results of the analysis by bitumen fume exposure do not allow us to conclude on the presence or absence of a causal link between exposure to bitumen fume and risk of cancer of the lung and the head and neck.

Cancer mortality among European asphalt workers: an international epidemiological study. I. Results of the analysis based on job titles.

BACKGROUND: Inhalation of bitumen fumes is potentially carcinogenic to humans. METHODS: We conducted a study of 29,820 male workers exposed to bitumen in road paving, asphalt mixing and roofing, 32,245 ground and building construction workers unexposed to bitumen, and 17,757 workers not classifiable as bitumen workers, from Denmark, Finland, France, Germany, Israel, the Netherlands, Norway, and Sweden, with mortality follow-up during 1953-2000. We calculated standardized mortality ratios (SMRs) and 95% confidence intervals (CIs) based on national mortality rates. Poisson regression analyses compared mortality of bitumen workers to that of building or ground construction workers. RESULTS: The overall mortality was below expectation in the total cohort (SMR 0.92, 95% CI 0.90-0.94) and in each group of workers. The SMR of lung cancer was higher among bitumen workers (1.17, 95% CI 1.04-1.30) than among workers in ground and building construction (SMR 1.01, 95% CI 0.89-1.15). In the internal comparison, the relative risk (RR) of lung cancer mortality among bitumen workers was 1.09 (95% CI 0.89-1.34). The results of cancer of the head and neck were similar to those of lung cancer, based on a smaller number of deaths. There was no suggestion of an association between employment in bitumen jobs and other cancers. CONCLUSIONS: European workers employed in road paving, asphalt mixing and other jobs entailing exposure to bitumen fume might have experienced a small increase in lung cancer mortality risk, compared to workers in ground and building construction. However, exposure assessment was limited and confounding from exposure to carcinogens in other industries, tobacco smoking, and other lifestyle factors cannot be ruled out.

Performance of different exposure assessment approaches in a study of bitumen fume exposure and lung cancer mortality.

BACKGROUND: We compared performance of different exposure assessment approaches in a cohort study of cancer risk among European asphalt workers. METHODS: Three bitumen fume exposure indices (duration of exposure (years), average exposure (mg/m3) and cumulative exposure (mg/m3*years)) and two latency models (with and without a 15 year lag) were considered for an association between lung cancer mortality and bitumen fume. RESULTS: There was no association between lung cancer risk and either duration or cumulative exposure. However, there was the suggestion of an increase in lung cancer risk accompanying rise in average exposure. Only models with average bitumen fume exposure (with or without lag) improved model fit, albeit to the same extent. CONCLUSIONS: Constructing quantitative indices of exposure intensity was justified because they produced the greatest improvement in fit of models that explored possible relationship between bitumen fume exposure and lung cancer risk. The identified associations require further investigation.

Epidemiologic study of cancer mortality among Israeli asphalt workers.

BACKGROUND: We describe the results of a cancer mortality study among asphalt workers in Israel. METHODS: Personal identifiers and employment histories of 2,176 workers were extracted from company records. RESULTS: Mortality from all malignant neoplasms was significantly reduced in the whole cohort (SMR 0.68, 95% confidence interval (CI) 0.56-0.83). SMR for lung cancer was elevated in workers exposed to bitumen (SMR 1.05, 95% CI 0.62-1.66). No significant elevation or reduction in mortality was observed in relation to a specific site. SMRs for lung cancer was higher among ever exposed to bitumen than among unexposed. There was no association between lung cancer risk and estimated exposure to bitumen fume, and no dose-response was apparent. CONCLUSIONS: While the results of this cohort study indicate a slightly increased SMR for lung cancer, it did not produce evidence of a causal link between lung cancer and exposure to bitumen fume.

Sister chromatid exchange in pathology staff occupationally exposed to formaldehyde.

Sister chromatid exchange (SCE) was measured in peripheral lymphocytes of 90 workers from 14 hospital pathology departments in Israel who were occupationally exposed to formaldehyde (FA) and of 52 unexposed workers from the administrative section of the same hospitals. The mean exposure period to FA was 15.4 years (range 1-39). The results of SCEs are expressed in two variables: (a) mean number of SCEs per chromosome and (b) proportion of high frequency cells (cells with more than eight SCEs). A high correlation was found between these two variables. The adjusted means of both SCEs variables were significantly higher among the exposed compared with that of the unexposed group (P<0.01). Adjustment was made for age, sex, smoking habits, education workers and origin. Evaluation of the influence of years of exposure on the frequency of SCEs showed that the two variables of SCEs were higher among those who were exposed to FA for 15 or more than among those with less than 15 years of exposure. Concerning levels of exposure, both variables of SCEs were the same in the low and in the high levels of exposure sub-groups. However, among the smokers, both variables of SCEs were higher in the high exposure sub-group than in the low exposure sub-group. Our finding of a significant increase of SCEs frequency in peripheral lymphocytes in pathology staff indicates a potential cytogenetic hazard due to FA exposure. We conclude that our data indicate that FA is mutagenic to humans.