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Toxicological information

Epidemiological data

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Administrative data

Endpoint:
epidemiological data
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1980-01-01 to 2005-06
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study is classified as reliable without restrictions because it is an acceptle, well documented study.

Data source

Reference
Reference Type:
publication
Title:
A case-control study of lung cancer nested in a cohort of European asphalt workers
Author:
IARC
Year:
2009
Bibliographic source:
IARC
Report Date:
2009

Materials and methods

Study type:
case control study (retrospective)
Endpoint addressed:
carcinogenicity
Test guideline
Qualifier:
according to
Guideline:
other: guidelines for a nested case-control study
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Bitumen fumes and condensate
- Substance type: Bitumen
- Physical state: Not reported
- Analytical purity: Not reported
- Composition of test material, percentage of components: Not reported

Method

Type of population:
occupational
Ethical approval:
not specified
Details on study design:
HYPOTHESIS TESTED (if cohort or case control study): In a previous cohort study an increase in the risk of lung cancer was observed among asphalt workers. This nested case-control study was conducted in order to disentangle the role of bitumen on the increase in lung cancer in the cohort from tobacco smoking and exposure to other known and suspected occupational lung carcinogens.


METHOD OF DATA COLLECTION
- Type: Interview and Questionnaires
- Details: Living subjects completed a general questionnaire (smoking history, general work history) and a detailed questionnaire regarding the jobs held within the asphalt companies included in the cohort and regarding hygiene and clothing behaviour. For deceased subjects one or more next-of-kin (NOK) was contacted for obtaining information about smoking habits and general work history.


STUDY PERIOD: January 1, 1980 to the end of follow-up ranged from December 2002 in France to June 2005 in Finland.


SETTING: Denmark, Finland, France, Germany, the Netherlands, Norway, and Israel


STUDY POPULATION
- Total population (Total no. of persons in cohort from which the subjects were drawn): Not reported
- Selection criteria: Cases were selected based on death from lung cancer during the study period. Controls were randomly selected based on matching criteria (age and country) and were free of respiratory illness and ill-defined cancer.
- Total number of subjects participating in study: 2638
- Sex/age/race: Subjects were males 75 years old or younger
- Smoker/non-smoker: Both smokers and non-smokers
- Total number of subjects at end of study: 1686
- Matching criteria: age and country


COMPARISON POPULATION
- Type: Control or reference group
- Details: Controls were cohort members who were alive at the date of the death or diagnosis of the case, who were matched to cases (3:1 ratio) on year of birth (± 3 years) and country.


HEALTH EFFECTS STUDIED
- Disease(s): Lung cancer
- Diagnostic procedure: Died from lung cancer or incidence from cancer registry.


OTHER DESCRIPTIVE INFORMATION ABOUT STUDY: Estimates of exposure were derived for bitumen fume, organic vapour, bitumen derived polycyclic aromatic hydrocarbons (PAH) (inhalation exposures) and bitumen condensate (dermal exposure – this route of exposure was not included in the cohort phase of the study), as well as for asbestos, silica, diesel exhaust and coal tar (combined exposure within and outside the original asphalt companies for the latter four agents), based on company-level information gathered during the cohort phase of the study and individual-level information gathered during the case-control study. Odds ratios were estimated.
Exposure assessment:
estimated
Details on exposure:
TYPE OF EXPOSURE: Inhalation and dermal


TYPE OF EXPOSURE MEASUREMENT: other: Base estimates (for the year 1997) for a given job were adjusted for time trend according to calendar year in which that specific job was performed. In addition, the estimates were adjusted for actual work time per year. For each company, each job
class (2-digit level) and each time-period the median length of fellow-worker/living subject reported paving season was multiplied by the median length of the reported work week and the reported length of a work day. This number was divided by 480 (12 months x 5 days x 8 hours) to arrive at the work time modifier. In this calculation a work week including work on Saturdays was set at 5.6 days following discussions with country-specific experts.Dermal exposure was semi-quantitative based estimates to bitumen condensaten and were adjusted in a similar manner as the inhalation estimates.

EXPOSURE LEVELS: Cumulative exposure: 0, 0 to <3.8743, 3.8743 to < 10.0514, 10.0514 to <26.832, and 26.832 +. It is stated that the cumulative exposure was to bitumen fume. There is no indication what the dermal exposure estimates were.


EXPOSURE PERIOD: 0 to <1.7522, 1.7522 to < 4.5886, 4.5886 to < 9.8700, and 9.9700+ years



DESCRIPTION / DELINEATION OF EXPOSURE GROUPS / CATEGORIES: Ever exposed compared to never exposed.
Statistical methods:
Unconditional logistic regression models were fitted to calculate odds ratios with 95% confidence intervals.

Results and discussion

Results:
The current case-control study was conducted because a previous cohort study of European asphalt workers reported a slight increase in lung cancer mortality among workers exposed to bitumen fume. In the cohort study there was an association between lung cancer mortality and increasing average exposure to bitumen fume, but a similar association was not observed with increasing duration of exposure or with cumulative exposure. This case-control study of lung cancer was conducted nested within the original cohort to disentangle the contribution of bitumen from other agents occurring in the asphalt industry, other occupational exposures, and tobacco smoking. Cases were selected from the original cohort study and included male workers aged less than 75 years from Denmark, Finland, France, Germany, the Netherlands, Norway, and Israel, had been employed at least two full seasons in the asphalt industry, and died from (or were diagnosed with) lung cancer between 1980 and the end of follow-up (2002-2005). Controls were cohort members who were alive at the date of the death or diagnosis of the case, who were matched to cases (3:1 ratio) on year of birth (± 3 years) and country. Living workers (2% of cases, 66% of controls) or their next-of-kin (NOK 98% of cases, 34% of controls) were interviewed with respect to tobacco smoking and complete occupational history; living subjects or fellow workers were interviewed with respect to detailed working conditions within the asphalt industry. Estimates of exposure were derived for bitumen fume, organic vapour, bitumen derived polycyclic aromatic hydrocarbons (PAH) (inhalation exposures) and bitumen condensate (dermal exposure – this route of exposure was not included in the cohort phase of the study), as well as for asbestos, silica, diesel exhaust and coal tar (combined exposure within and outside the original asphalt companies for the latter four agents), based on company-level information gathered during the cohort phase of the study and individual-level information gathered during the case-control study. Odds ratios (OR) of lung cancer were estimated for ever exposure, duration of exposure, cumulative exposure and average exposure to bitumen and the other agents, after adjusting for tobacco smoking and coal tar. Additional sensitivity analyses were conducted to assess the robustness of the results.

A total of 433 cases and 1253 controls were included in the analysis (response rate 65% among cases and 58% among controls). Next of kin interviews were used for 96% of cases and 31% of controls. The OR for ever exposure to bitumen fume was 1.12 (95% confidence interval 0.84-1.49), and there was no association between lung cancer risk and duration of exposure, cumulative exposure or average exposure. Results for exposure to organic vapour and PAH were similar to those for exposure to bitumen fume. The OR for ever exposure to bitumen condensate was 1.17 (95% CI 0.88 -1.56). There was no association with duration of exposure, cumulative exposure or average exposure to bitumen condensate and lung cancer. The results were robust to sensitivity analyses (exclusion of one country at a time, restriction to good-quality interviews, to subjects with next of kin interviews, to workers employed for more than 5 years in the asphalt industry, and to complete case-control sets). The analysis on exposure to asbestos, silica and diesel exhaust did not reveal any association with lung cancer risk. Coal tar, on the other hand, was associated with lung cancer and cumulative exposure and, to a lesser extent, duration of exposure. A comparison of prevalence of smoking between living controls and individuals included in national surveys resulted in confounding OR in the range 1.07 – 1.28. OR for tobacco smoking were consistent with data from the literature. Sensitivity analyses did not suggest a bias from the use of NOK interviews for most cases and a proportion of controls.

There was no consistent evidence of an association between indicators of inhalation or dermal exposure to bitumen and lung cancer risk.
Confounding factors:
Tobacco smoking, jobs outside the asphalt industry, asbestos

Applicant's summary and conclusion

Conclusions:
There was no consistent evidence of an association between indicators of inhalation and/or dermal exposure to bitumen and lung cancer risk.
Executive summary:

The current case-control study was conducted because a previous cohort study of European asphalt workers reported a slight increase in lung cancer mortality among workers exposed to bitumen fume. In the cohort study there was an association between lung cancer mortality and increasing average exposure to bitumen fume, but a similar association was not observed with increasing duration of exposure or with cumulative exposure. This case-control study of lung cancer was conducted nested within the original cohort to disentangle the contribution of bitumen from other agents occurring in the asphalt industry, other occupational exposures, and tobacco smoking. Cases were selected from the original cohort study and included male workers aged less than 75 years from Denmark, Finland, France, Germany, the Netherlands, Norway, and Israel, had been employed at least two full seasons in the asphalt industry, and died from (or were diagnosed with) lung cancer between 1980 and the end of follow-up (2002-2005). Controls were cohort members who were alive at the date of the death or diagnosis of the case, who were matched to cases (3:1 ratio) on year of birth (± 3 years) and country. Living workers (2% of cases, 66% of controls) or their next-of-kin (NOK 98% of cases, 34% of controls) were interviewed with respect to tobacco smoking and complete occupational history; living subjects or fellow workers were interviewed with respect to detailed working conditions within the asphalt industry. Estimates of exposure were derived for bitumen fume, organic vapour, bitumen derived polycyclic aromatic hydrocarbons (PAH) (inhalation exposures) and bitumen condensate (dermal exposure – this route of exposure was not included in the cohort phase of the study), as well as for asbestos, silica, diesel exhaust and coal tar (combined exposure within and outside the original asphalt companies for the latter four agents), based on company-level information gathered during the cohort phase of the study and individual-level information gathered during the case-control study. Odds ratios (OR) of lung cancer were estimated for ever exposure, duration of exposure, cumulative exposure and average exposure to bitumen and the other agents, after adjusting for tobacco smoking and coal tar. Additional sensitivity analyses were conducted to assess the robustness of the results.

A total of 433 cases and 1253 controls were included in the analysis (response rate 65% among cases and 58% among controls). Next of kin interviews were used for 96% of cases and 31% of controls. The OR for ever exposure to bitumen fume was 1.12 (95% confidence interval 0.84-1.49), and there was no association between lung cancer risk and duration of exposure, cumulative exposure or average exposure. Results for exposure to organic vapour and PAH were similar to those for exposure to bitumen fume. The OR for ever exposure to bitumen condensate was 1.17 (95% CI 0.88 -1.56). There was no association with duration of exposure, cumulative exposure or average exposure to bitumen condensate and lung cancer. The results were robust to sensitivity analyses (exclusion of one country at a time, restriction to good-quality interviews, to subjects with next of kin interviews, to workers employed for more than 5 years in the asphalt industry, and to complete case-control sets). The analysis on exposure to asbestos, silica and diesel exhaust did not reveal any association with lung cancer risk. Coal tar, on the other hand, were associated with lung cancer and cumulative exposure and, to a lesser extent, duration of exposure. A comparison of prevalence of smoking between living controls and individuals included in national surveys resulted in confounding OR in the range 1.07 – 1.28. OR for tobacco smoking were consistent with data from the literature. Sensitivity analyses did not suggest a bias from the use of NOK interviews for most cases and a proportion of controls.

There was no consistent evidence of an association between indicators of inhalation or dermal exposure to bitumen and lung cancer risk.

This study received a Klimisch score of one and is classified as reliable without restrictions because it was an acceptable study that was well documented.This study will influence the DNEL(s).