Gregorius Agricola memorial lecture: Lung cancer-A work-related disease for 500 years, as predicted by Agricola.

In the early 16th century Gregorius Agricola reported on Bergsucht (miner's consumption) in mine workers in the Erzgebirge. About 350 years later, Härting and Hesse reported on large numbers of lung cancers among the mine-workers in the same mine district, thus confirming that Bergsucht primarily was lung cancer, but could also have been pnumoconiosis or tuberculosis or a combination of both. Mining for bismuth continued another 75 years--through World War II. Bismuth mining was replaced by large scale uranium mining from the late 1940 through 1989, employing some 400-450,000 workers, resulting in the major local epidemic of work-related cancer larger than anywhere in the world, so far amounting to ± 14-15,000 cases. Had the mine developers listened to the warnings by Agricola and Härting and Hesse, the epidemic could have been prevented.

Hypersensitivity pneumonitis in a cluster of sawmill workers: a 10-year follow-up of exposure, symptoms, and lung function.

BACKGROUND: The long-term prognosis of repeated acute episodes of hypersensitivity pneumonitis (HP) is not well described. We report on a 10-year follow-up of a 10-person cluster from a Norwegian sawmill who had all experienced relapsing episodes of HP. OBJECTIVES: To evaluate the health symptoms, work-related sick-leave, and lung function of 10 workers exposed to mold in a Norwegian sawmill. METHODS: Participants were evaluated at baseline and 10 years later at follow-up. A structured interview, measurement of serum IgG antibodies to Rhizopus microsporus (R. microsporus) antigens, lung function tests, high resolution computed tomography (HRCT) of the chest, and personal measurements of exposure to mold spores and dust were completed for each participant. RESULTS: At baseline, nearly all workers reported acute episodes of HP more than twice a month. At follow-up, both the frequency and intensity of symptoms had declined. Sick-leave was reduced and gas diffusing capacity improved - paralleling the gradually reduced air levels of mold spores. CONCLUSIONS: In spite of an initially high occurrence of symptoms, long-term clinical and physiological outcome was good. With reduced exposure to mold spores, symptoms declined and lung function was restored.

Sinonasal adenoid cystic carcinoma following formaldehyde exposure in the operating theatre.

We present a case report of an auxiliary nurse who developed an adenoid cystic carcinoma in her left maxillary sinus following occupational exposure to formaldehyde in the operating theatre. Currently, the epidemiological evidence that formaldehyde can cause cancer in humans is considered to be limited. Previous case-control-studies of formaldehyde and sinonasal cancer have mainly investigated subjects who were concomitantly exposed to wood dust, a known risk factor to the development of sinonasal adenocarcinoma of intestinal type. Our case report presents a patient who has developed an adenoid cystic carcinoma following exposure to formaldehyde. We suggest that the occupational physician remains alert to formaldehyde as an occupational hazard among health care workers.

Methods to recognize work-related cancer in workplaces, the general population, and by experts in the clinic, a Norwegian experience.

BACKGROUND: In most countries, the numbers of work-related cancer identified are much lower than are the estimated total burden of cancer caused by exposure at work. Therefore, there is a great need to use all available practical as well as epidemiological methods for identification as well as to develop new methods of recognizing cases of work-related cancers. METHODS: Primarily based on practical experiences from Norway, methods to identify cases of possible work-related cancers in the general population and at workplaces as well as methods to recognize more specific cases after referral to specialized clinics are reviewed in this publication. RESULTS: Countries applying a number of the available methods to detect work-related cancer reach a reporting rate of 60 such cases per million, while other countries that do not employ such methods hardly identify any cases. As most subjects previously exposed to cancer causing agents and substances at work are gradually recruited out of work, methods should be versatile for identification of cases in the general population, as well as at work. CONCLUSIONS: Even in countries using a number of the available methods for identification, only a limited fraction of the real number of work-related cancer are notified to the labour inspectorate. Clinicians should be familiar with the methods and do the best to identify work-related cancer to serve prevention.

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.

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.

A critique of benzene exposure in the general population.

Benzene risk assessment indicates that exposure to a time-weighted average (TWA) of 1-5 parts per million (ppm) benzene in ambient air for 40 years is associated with an increased risk of acute myeloid leukemia. Decreased white blood cell count, platelet count and other hematological indices have also been observed in persons exposed to as low as 1 ppm airborne benzene. Evidence from studies worldwide consistently shows elevated levels of benzene biomarkers that are equivalent to 0.1-2 ppm benzene in ambient air, or even higher in the general population without occupational exposure to benzene (including children). The public health significance of these observations depends on to what extent these levels reflect actual benzene exposure, and whether such exposures are life-long or at least occur frequently enough to pose a possible health threat. We reviewed the evidence and discussed possible explanations for these observations. It was concluded that while there is reason to suspect that benzene contributes significantly to elevated levels of biomarkers in the general population, there is growing concern that this cannot be definitively ascertained without concomitant consideration of the role of other factors such as metabolic polymorphisms and sources of biomarkers other than benzene, which have been insufficiently studied to date. Such studies are urgently needed for valid assessment of this potential public health problem.

Monitoring of chromium and nickel in biological fluids of grinders grinding stainless steel.

OBJECTIVE: Stainless steel (SS) welders usually spend some of their working time grinding, to finish and smoothen the welding groove. The aim of this study was to investigate possible relations between the concentrations of nickel (Ni) and chromium (Cr) in the work atmosphere generated by grinders grinding SS, and to compare the air levels to the levels of Cr and Ni in their biological fluids. Hereby, it might be possible to identify the contribution of grinding to the levels of Cr and Ni in biological fluids in SS welders. Also the airborne levels of Cr and Ni in SS grinders were compared to corresponding levels in SS welders. METHOD/DESIGN: The subjects examined in this study were selected among SS grinders not performing welding. Nine grinders were monitored for 1 workweek, measuring Cr and Ni in air, blood and urine. They were questioned about their exposure to Cr and Ni during their working careers. RESULTS: Air levels of total Cr up to 95 microg/m(3) and Ni levels up to 25 microg/m(3) were measured. Chromium(VI) (Cr(VI)) was detectable only in five air samples; the levels in the remaining samples were below the detection limit. The levels of Cr in blood and urine were also low. The levels of Ni in urine were close to those for MMA and MIG/MAG SS welders. In spite of high levels of total Cr and Ni observed in air, the levels found in biological fluids were low. The Cr levels in more than 50% of the whole blood and red cell samples and about 1/3 of the Cr-plasma levels were below the detection limits. The mean blood levels for Cr were 0.43, 0.60 and 0.35 microg/l, in whole blood, plasma and red cells, respectively. The mean levels for Cr in the urine was 1.6, 1.4 and 1.4 microg/g creatinine for the first void, just before and just after work. For Ni the mean blood levels were 0.87 microg/l in whole blood and 0.68 microg/l in plasma. The mean levels and ranges of Ni from the first void, just before and after work in urine were 3.79 microg/g creatinine, 3.39 and 4.56, respectively. The Cr concentrations found in whole blood, plasma and red cells were approximately the same as those found in the unexposed controls and among TIG SS welders, while the urinary levels were somewhat higher, but still lower than in the welders applying other welding techniques. The mean levels of Ni in the urine of grinders were higher than those of welders, except for SS welders welding the MIG/MAG-method. CONCLUSION: SS Grinding seems not to contribute significantly to the uptake of Cr, which may be explained by the fact that most of Cr in the air is present in the metallic (0-valent) or trivalent form, and hardly any as Cr(VI), and therefore hardly being taken up in the airways. The grinders' uptake of Ni seems to take place to the same extent as in SS welders.

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 of Nordic asphalt workers.

OBJECTIVES: The aim of the study was to investigate cancer risk following employment in the asphalt industry. METHODS: Cancer incidence was studied among 22 362 male asphalt workers employed for more than one season in jobs entailing exposure to bitumen (mainly road pavers) in Denmark, Finland, Norway, and Sweden. These workers are part of a European cohort of asphalt workers, for which results on mortality have been reported. The follow-up was almost complete, and reference rates were obtained from national cancer registries. RESULTS: The incidence of cancer was reduced in all four countries [overall standardized incidence ratio (SIR) 0.89, 95% confidence interval (95% CI) 0.86-0.94]. Lung cancer incidence was increased in all four countries, yielding an overall SIR of 1.21 (95% CI 1.07-1.36), but no trend was detected according to time since first employment. No overall increased incidence of bladder cancer was observed, but there was a suggestion of a tendency towards higher risk with longer time since first employment, with a relative risk of 1.85 (95% CI 0.90-3.78) for more than 30 years versus 1-14 years (P-value for trend 0.1). The incidence of lip and stomach cancer was nonsignificantly increased, and the excess was present mainly in Denmark. No increased incidence was detected for other neoplasms, notably malignant melanoma, nonmelanoma skin cancer, and kidney cancer. CONCLUSIONS: The results of this study confirm the pattern of cancer risk detected in the mortality analysis of the European cohort; in addition, they provide suggestive evidence of an excess risk of bladder cancer among asphalt workers.

Monitoring of chromium and nickel in biological fluids of stainless steel welders using the flux-cored-wire (FCW) welding method.

OBJECTIVE: This study was undertaken to investigate the exposure to chromium (Cr) and nickel (Ni) in flux-cored wire (FCW) welders welding on stainless steel (SS). METHOD/DESIGN: Seven FCW welders were monitored for 3 days to 1 workweek, measuring Cr and Ni in air, blood, and urine. The welders were questioned about exposure to Cr and Ni during their whole working careers, with emphasis on the week of monitoring, about the use of personal protective equipment and their smoking habits. RESULTS: The air concentrations were mean 200 microg/m(3) (range 2.4-2,744) for total Cr, 11.3 microg/m(3) (<0.2-151.3) for Cr(VI), and 50.4 microg/m(3) (<2.0-416.7) for Ni during the workdays for the five welders who were monitored with air measurements. The levels of Cr and Ni in biological fluids varied between different workplaces. For Cr in whole blood, plasma, and erythrocytes, the mean levels after work were 1.25 (<0.4-8.3) and 1.68 (<0.2-8.0) and 0.9 (<0.4-7.2) microg/l, respectively. For Ni most of the measurements in whole blood and plasma were below the detection limits, the mean levels after work being 0.84 (<0.8-3.3) and 0.57 microg/l (<0.4-1.7), respectively. Mean levels for Cr and Ni in the urine after work were 3.96 (0.34-40.7) and 2.50 (0.56-5.0) microg/g creatinine, respectively. CONCLUSION: Correlations between the Cr(VI) levels measured in air and the levels of total Cr in the measured biological fluids were found. The results seem to support the view that monitoring of Cr in the urine may be versatile for indirect monitoring of the Cr(VI) air level in FCW welders. The results seem to suggest that external and internal exposure to Cr and Ni in FCW welders welding SS is low in general.

Mortality among workers employed in the titanium dioxide production industry in Europe.

OBJECTIVES: To assess the risk of lung cancer mortality related to occupational exposure to titanium dioxide (TiO2). METHODS: A mortality follow-up study of 15,017 workers (14,331 men) employed in 11 factories producing TiO2 in Europe. Exposure to TiO2 dust was reconstructed for each occupational title; exposure estimates were linked with the occupational history. Observed mortality was compared with national rates, and internal comparisons were based on multivariate Cox regression analysis. RESULTS: The cohort contributed 371,067 person-years of observation (3.3% were lost to follow-up and 0.7% emigrated). 2652 cohort members died during the follow-up, yielding standardized mortality ratios (SMRs) of 0.87 (95% confidence interval [CI] 0.83-0.90) among men and 0.58 (95% CI 0.40-0.82) among women. Among men, the SMR of lung cancer was significantly increased (1.23, 95% CI 1.10-1.38); however, mortality from lung cancer did not increase with duration of employment or estimated cumulative exposure to TiO2 dust. Data on smoking were available for over one third of cohort members. In three countries, the prevalence of smokers was higher among cohort members compared to the national populations. CONCLUSIONS: The results of the study do not suggest a carcinogenic effect of TiO2 dust on the human lung.

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.