Sverre Langård

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

AbstractObjectives: 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.

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/m3 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.

Update of the follow-up of mortality and cancer incidence among European workers employed in the vinyl chloride industry.

Although vinyl chloride is an established cause of liver angiosarcoma, the evidence is inconclusive on whether it also causes other neoplastic and nonneoplastic chronic liver diseases as well as neoplasms in other organs. Furthermore, the shape of the dose-response relation for angiosarcoma is uncertain. We have extended for approximately 8 years the mortality and cancer incidence follow-up of 12,700 male workers in the vinyl chloride industry in four European countries. All-cause mortality was lower than expected, whereas cancer mortality was close to expected. A total of 53 deaths from primary liver cancer (standardized mortality ratio 2.40, 95% confidence interval = 1.80–3.14) and 18 incident cases of liver cancer were identified, including 37 angiosarcomas, 10 hepatocellular carcinomas, and 24 liver cancers of other and unknown histology. In Poisson regression analyses we observed a marked exposure response for all liver cancers, angiosarcoma, and hepatocellular carcinoma. The exposure-response trend estimated for liver cancer in analyses restricted to cohort members with cumulative exposures of <1,500 parts per million-years was close to that estimated for the full cohort (relative risk of 2.0 per logarithmic unit of cumulative dose). No strong relation was observed between cumulative vinyl chloride exposure and other cancers. Although cirrhosis mortality was decreased overall, there was a trend with cumulative exposure.

Incidence of cancer among vinyl chloride and polyvinyl chloride workers.

The results of a follow up study of the incidence of cancer and the mortality in a cohort of 454 male workers producing vinyl chloride and polyvinyl chloride are presented. The study population was restricted to employees with more than one years work experience in the study plant between 1950 and 1969 and the cohort was followed up from 1953 to the end of 1979. Twenty three new cases of cancer were observed compared with 20.2 expected; one case of liver angiosarcoma was found. Five cases of lung cancer were found (2.8 expected) and four cases of malignant melanoma of the skin were observed (0.8 expected). The possibility of a causal relationship between exposure to vinyl chloride and the development of malignant melanomas is discussed.

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.

Incidence of cancer among welders of mild steel and other shipyard workers.

The incidence of cancer among 4571 shipyard workers with first employment between 1940 and 1979, including 623 welders of mild steel, was investigated in a historical cohort study. The loss to follow up was 1.1%. The total number of deaths was 1078 (974.5 expected) and there were 408 cases of cancer v 361.3 expected. Sixty five cases of lung cancer were found v 46.3 expected based on the national rates for males. Four pleural mesotheliomas had occurred (1.2 expected), none among the welders. An excess of lung cancers was found among the welders (nine cases v 3.6 expected). There were six cases of lung cancer v 1.6 expected in a high exposure group of 255 welders. A survey of the smoking habits as of 1984 indicated 10%-20% more daily smokers among the shipyard production workers than among Norwegian males. Exposure to smoking and asbestos were confounding variables in this study.

Incidence of cancer among workers exposed to vinyl chloride in polyvinyl chloride manufacture.

Based on results from two previous studies where an excess of melanomas was found in a cohort of workers exposed to vinyl chloride (VCM), a follow up of the incidence of cancer in the same cohort of 428 workers was carried out to scrutinise whether or not the excess could be confirmed by new cases. The total number of deaths in the study group from 1953 to the end of 1993 was 132 v141 expected, and the total number of incident cancer cases was 56v 57 expected. There were 11 cases of lung cancer v eight expected, seven cases of melanomas v 2.07 expected, and two cases of thyroid cancer v 0.34 expected. Five of the seven melanoma cases had occurred in the group that had been most heavily exposed to VCM v 0.7 expected. In the present follow up we also found five cases of the spinocellular cancer of the skin v 1.7 expected. Out of these five cases four were diagnosed after 1984. Two of the five casesv 0.7 expected had occurred in the most heavily exposed group. The total number of skin cancers (melanomas and spinocellular cancers) were 12 v 3.7 expected. There was one new case of melanoma between 1985 and 1993v 0.7 expected. Hence, the strength of the relation between the observed and expected number of cases was reduced compared with the last follow up, and does not strengthen the previously indicated causal relation between exposure to VCM and development of malignant melanoma. There was no excess of testicular cancers in this study. The present results may indicate that occurrence of spinocellular skin cancer could bear some relation to work in the manufacture of polyvinyl chloride (PVC). Confirmation is needed from studies on other cohorts exposed to VCM.

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.

Cancer incidence among workers in the Norwegian ferroalloy industry.

The total mortality and the incidence of cancer was studied among a cohort of employees at the six oldest ferrosilicon and ferromanganese plants in Norway. The cohort consisted of 6494 men employed for more than 18 months before 1970 and has been followed up from 1953 to 1982. The standardised incidence ratio (SIR) for cancer (all sites) was 0.94. The observed number of cancers was as expected for lung cancer (SIR = 0.99) and for most of the other cancer sites studied. A statistically significant reduction of stomach cancer was found (SIR = 0.72). There was an increased incidence of lung cancer (SIR = 1.75) and cancer of the prostate (SIR = 1.56) in the workers at one ferrosilicon plant and of colonic cancer (SIR = 1.90) at another ferrosilicon plant.

Incidence of cancer among Norwegian boiler welders.

OBJECTIVES: The cancer incidence among 2957 boiler welders was investigated. The subjects were registered electrical welders from 1942 to 1981. A subcohort of 606 stainless steel welders was studied separately. METHODS: The investigation was a historical prospective cohort study based on a national registry. The loss of follow up was 4.9%. RESULTS: There were 625 deaths (659 expected). There were 269 cancer cases (264 expected). An excess of lung cancer was found; 50 cases v 37.5 expected. There were three cases of pleural mesotheliomas v 1.1 expected. The subcohort of stainless steel welders had six cases of lung cancer v 5.8 expected, and one case of pleural mesothelioma v 0.2 expected. CONCLUSIONS: The welders in the study were assumed to represent a qualified work force. These welders had a small excess risk of lung cancer. The excess risk did not seem to be associated with stainless steel welding. Smoking and asbestos exposure were potential confounders.