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Toxicological information

Epidemiological data

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Administrative data

Endpoint:
epidemiological data
Type of information:
other: Epidemiological Study (Occupational)
Adequacy of study:
key study
Study period:
1928-1979
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The rationale for the reliability scoring is based upon a Lead Study Quality Assessment tool for Carcinogenicity in both the Occupational Setting and the General Population developed by the Scientific Advisory Panel assembled to provide independent academic review of the Voluntary Risk Assessment for Lead. The Occupational and General Population Assessment assessed study quality on the basis of the following major aspects of study design, data collection and analysis. Adequacy of Cohort Definition Nature and Extent of Lead Exposure Indices Examiner Training and Procedures for Data Collection and Analysis Precision of Endpoint Definition Extent of Correction for Major Confounding Variables

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1997

Materials and methods

Study type:
cohort study (retrospective)
Endpoint addressed:
carcinogenicity
Principles of method if other than guideline:
Retrospective Cohort Mortality and Morbidity Study

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
The main products of the smelter, which was started in 1928 in northern Sweden, are copper and lead. In addition, the company also recovers precious metals (eg. gold, silver, platinum), arsenic, nickel, selenium, zinc, and sulfur products from the ores.

Method

Type of population:
occupational
Ethical approval:
not applicable
Details on study design:
A cohort of 3979 workers employed for at least one year during 1928-1979 and a subcohort of 1992 workers employed in lead-exposed departments (lead only workers) was formed. The expected mortality in 1955-1987 and cancer incidence in 1958-1987 were calculated relative to the county rates, specified for cause, gender, 5-year age groups, and calendar year. A cumulative blood-lead index was used for the dose-response analyses.
Exposure assessment:
measured
Details on exposure:
Annual arithmetic mean PbB in lead workers declined from 3.0 umol/l in 1950 to 1.6 umol/l in 1987. Workers in other metal producing plants declined from 2.7 to 0.8 umol/l in the same time period. Airborne lead levels could have exceeded 1mg/m3 in lead plant during the 1940's. Arsenic levels ranged between 0.35-1.5 mg/m3 in roaster areas.

The blood-lead level (B-Pb) was analyzed by emission spectrometry from 1950 to 1969, and since 1967 atomic absorption has been used. The quality control program started already during the 1950's. Up to about 1970, a regular exchange of B-Pb samples took place; laboratories in West Germany and the United Kingdom showed mostly satisfactory results. In 1969, the quality control of B-Pb had a precision of 9% and a systematic error of
-0.05% umol/l. Thereafter, the research laboratory at the smelter has participated in a national quality control program coordinated by the National Board of Occupational Safety and Health in Stockholm, Sweden. All told, 81,051 B-Pb analyses have been performed at the smelter from 1950 to 1987. For these workers the cumulative B-Pb dose has been calculated by summing the annual mean blood values for each worker (umol/l) during their employment period. For work periods before 1950, when the B-Pb monitoring program started, each worker was assumed to have had a B-Pb level corresponding to his mean B-Pb value during the period 1950-1952. For work periods from 1950 on, the B-Pb samples were regularly obtained up to 4 to 6 times per year from the workers in the lead departments. For work periods in the other metal producing plants, the B-Pb sampling has been more sparse. The lead exposure at the smelter has decreased continuously since the start of the B-Pb registration in 1950. The annual mean (arithmetic) B-Pb value of the lead smelter workers was 3.0 umol/l in 1950 and approximately 1.6 umol/l in 1987. For the workers in the other metal-producing plants in the smelter the mean B-Pb values have decreased from 2.7 umol/l to 0.8 umol/l. The corresponding figures for other personnel at the smelter (eg. maintenance and transportation workers) were 2.6 umol/l and 0.6 umol/l, respectively. Thus the lead exposure was not only confined to the lead departments.
Statistical methods:
Information about mortality in 1955-1987 was gathered from the Cause-of-Death register at Statistics Sweden. The death certificates were coded according to the 8th revision of the International Classification of Diseases (ICD-8) Similarly, information on incident malignant tumors was based on record linkage with the national Swedish tumor register, established in 1958. The expected mortality for the period 1955-1987 was calculated with the use of mortality rates specific for calendar year, cause, gender, and 5-year age groups in the county population obtained from Statistics Sweden. Date of death, emigration, or a subject's 80th birthday were used as the individual end points, whichever occurred first. In a similar way, yearly cancer incidence rates were obtained for the period 1958-1987 from the national Swedish tumor registry. Date of death, a second tumor diagnosis, emigration, or a subject's 80th birthday were used as the individual end points, whichever occurred first. All the epidemiologic analyses were performed with the computer program EPILUND. The 95% confidence intervals (95% CI) for cause-specific standardized mortality ratios (SMR) and standardized cancer incidence ratios (SIR) were calculated according to the Poisson distribution or to the normal distribution when the expected values were greater than 15.

Results and discussion

Results:
Appeared to be a dose-dependent relationship between indexes of cumulative lead exposure and the incidence of lung cancer. Cancers of GI tract, brain, kidney and bladder were not elevated. Lung cancer SIR for total cohort was 2.8 and 3.1 for the highest exposure group. Workers hired before 1950 had an SIR of 3.6 and those hired later had an SIR of 1.3. Lead only exposed group had higher SIR of 5.1.
Confounding factors:
Workers exposed to several contaminants in workplace including As, Sb, Cd, Cr, Co, La, Se, Zn organic and inorganic carcinogens, polyaromatics, such as benzo(a)pyrene and short lived free radicals. Smoking histories were not determined. Same as reported for Gerhardsson (1986). Follow-up of Gerhardsson (1986).
Strengths and weaknesses:
Smoking is a well-known risk factor for the development of lung cancer. However, data about smoking habits are lacking in this study. The dominant exposure to lead is in the form of slowly soluble oxides and sulfides, which can be expected to have a long biological half-time in the lungs. Interactions between lead and other metals such as arsenic, smoking, and other air pollutants may be the basis for the increased lung cancer risks observed at the smelter.

Any other information on results incl. tables

Observed and Expected Lung Cancer Morbidity

 Cumulative Blood lead Index  O  E  SIR  95% CI
 0-2 umol/l  --  1.4  0.0  0.0 -2.7
 2 -10 umol/l  7  1.6  4.5  1.8 -9.3
 >10 umol/l  7  1.4  5.1  2.0 -10.5

Applicant's summary and conclusion

Conclusions:
The mortality and morbidity from lung cancer was increased in this study, particularly in highly exposed lead workers solely employed in lead-exposed departments. The workers first employed before 1950 had considerably higher risk estimates than those first employed during later periods. The elevated risk estimates cannot solely be explained by confounding from smoking. The increased relative risks are probably mainly caused by synergism between lead and other carcinogenic exposures, including arsenic. Further studies are required concerning such possible interactions before a role can be ascribed to lead in the induction of lung cancer.
Executive summary:

Objectives: The purpose of this study was to determine the mortality and cancer incidence of long-term lead smelter workers at a primary smelter.

Methods: A cohort of 3979 workers employed for at least 1 year during 1928 -1979 and a subcohort of 1992 workers employed in lead-exposed departments (lead only workers) was formed. The expected mortality in 1955 -1987 and cancer incidence in 1958 -1987 were calculated relative to the county rates, specified for cause, gender, 5 -year age groups, and calendar year. A cumulative blood-lead index was used for the dose-response analyses.

Results: The lung cancer incidence of the total cohort {standardized incidence ratio (SIR) 2.8, 95% confidence interval (95% CI) 2.1 -3.8} and the group with the highest exposure (SIR 3.1, 95% CI 2.0-4.6) was high. Similar risk estimates were observed with a latency of 15 years. The workers hired before 1950 had higher lung cancer risk estimates (SIR 3.6, 95% CI 2.6 -5.0) than the workers hired later (SIR 1.3, 95% CI 0.6 -2.6, no latency period). The risk estimates for lung cancer were further elevated in the subcohort of lead-only workers (SIR 5.1, 95% CI 2.0 -10.5) in the highest exposed subgroup; latency period of 15 years). No excesses of other malignancies were noted.

Conclusions: The increased relative risks were probably mainly due to interactions between lead and other carcinogenic exposures, including arsenic. Further study is required concerning such possible interactions before a role in the induction of lung cancer can be ascribed to lead.