Matte, nickel

Epidemiological data

Administrative data

Endpoint:

epidemiological data

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

This study had average relevance to the substance-specific CSR, sufficient cohort description, lower than average exposure data and good endpoint definition. A detailed description of the scoring criteria and results can be found attached to IUCLID Section 7.10.2-Epidemiological Data, Epidemiological Data Summary and Scoring.

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

publication

Title:

Mortality among workers in a nickel refinery and alloy manufacturing plant in West Virginia.

Author:

Enterline PE, Marsh GM

Year:

1982

Bibliographic source:

Journal of the National Cancer Institute 68(6):925-33.

Materials and methods

Study type:

cohort study (retrospective)

Endpoint addressed:

carcinogenicity

Principles of method if other than guideline:

The authors assessed cancers among workers at a nickel refinery who were exposed to copper-nickel matte through work oxidizing nickel matte in dusty environments (calcining operations) or through melting and casting. SMRs standardized to either the US male population, the male population of the State of West Virginia or the male population of the counties around the refinery were calculated for a series of causes of death for refinery workers, non refinery workers and workers who were employed at the refinery after calcining operations were discontinued.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Matte, nickel

EC Number:

273-749-6

EC Name:

Matte, nickel

Cas Number:

69012-50-6

Molecular formula:

Not applicable

IUPAC Name:

Nickel matte

Details on test material:

- Name of test material (as cited in study report): Nickel matte (low copper-nickel matte and high copper-nickel matte)

Method

Type of population:

occupational

Ethical approval:

not specified

Details on study design:

HYPOTHESIS TESTED:
To ascertain whether nickel refinery workers who were exposed to copper-nickel matte through work oxidizing nickel matte in dusty environments experienced increased rates of lung and nasal sinus cancers compared to workers who worked at the nickel alloy plant but who had never worked in the refinery or had worked in refining operations for less than one year.

METHOD OF DATA COLLECTION
- Type: Work history / other: Vital Statistics
- Details: Refinery payroll records were examined to identify the study population and define exposure to the calcining operations. The vital status of 1,657 or 89.3% of the study members was known from plant records, either because they were still employed, had died while employed, or had retired under pension plans in which they were, in effect, followed by the company. The vital status of all but 10 of the remaining study population was determined through various follow-up resources including the Social Security Administration, the U.S. Postal Service, the Veterans Administration, and direct telephone inquiries.


STUDY PERIOD: January 1, 1948, through December 31, 1977


SETTING: Nickel refinery in West Virginia


STUDY POPULATION
- Total population: 3,249 workers categorized by when hired. 1) n=1,855 hired pre-1947 Exposed workers were comprised from two groups: n=109 in calcining department >=1 year, n=157 in melting and casting >=1 year; Unexposed = 1,589 nonrefinery workers 2) n=1,394 hired during 1948-59 when calcining was eliminated. Some could have worked in melting or casting.
- Selection criteria: employed for 1 year or more in the refinery
- Total number of subjects participating in study: 3,249
- Sex/age/race: all male
- Smoker/nonsmoker: not reported


COMPARISON POPULATION
- Type: Control or reference group: Three groups used in paper: 1) US White males, 2) males in state of West Virginia, 3) males in local six-county area where refinery was locateds
- Details: Workers at the same manufacturing plant but who were not refinery workers

Three groups or workers were compared to standard population:
1) those hired pre-1947 who had worked more than 1 year in the refinery
2) those hired pre-1947 who had worked more than a year but not in refinery
3) those hired after 1946 (<1 year in refinery)


HEALTH EFFECTS STUDIED
- Disease(s): multiple: all causes of death, malignant neoplasms, stroke, heart disease, respiratory disease, other causes
- ICD No.: ICD-7
multiple causes of death examined including all causes, all neoplasms, specific neoplasms, stroke, heart attack, non-malignant respiratory disease, all extrenal causes, all other causes, unknown causes

Exposure assessment:

estimated

Details on exposure:

DETAILS ON EXPOSURE
Personnel records were used to determine work history of men at refinery. Work history was used to determine whether men were exposed to nickel matte based on department worked or location of job at refinery.

TYPE OF EXPOSURE:
1) Calcining department where exposure was to high copper-nickel matte (high nickel-copper matte was crushed, ground and oxidized in gas calciners to produce copper-nickel oxide). Concentrations of total particulates and airborne nickel were 50-500 mg/m3 and 20-350 mg Ni/m3 where the matte was crushed, ground and handled. Concentrations around the calciners were 10-20 mg/m3 and 5-15 mg Ni/m3, respectively.
2) Melting and casting where exposure to various nickel containing alloys

Nickel exposure levels were estimated based on measurements made during study period as well as historic midget impinger counts converted to gravimetric expression. Estimates represent average airborne total nickel concentrations over 8-hour shift.

Cumulative nickel exposure was categorized as follows in mg nickel/m3 /month: <10, 10-24, 25-49, 50-99, 100-199, ≥200

Statistical methods:

Ratios of observed-to-expected numbers of deaths were expressed as SMRs, comparing nickel workers compared to one of the standard populations, adjusted for age and calendar time to the person-years distribution of the employment group of interest.

Results and discussion

Results:

EXPOSURE
- Number of measurements: not reported
- Average concentrations: In refinery: concentrations of total particulates and airborne nickel were 50-500 mg/m3 and 20-350 mg Ni/m3 where the matte was crushed, ground and handled. Concentrations around the calciners were 10-20 mg/m3 and 5-15 mg Ni/m3, respectively.
- Date(s) of measurement(s): not reported; stated as current and historical


STATISTICAL RESULTS
Group 1 Refinery workers hired before 1947: SMRs were elevated among refinery workers for every cause examined except heart disease where there was a deficit.
Statistically significant excess in sinonasal cancers due to one case who worked at calciner and second who worked in melting and casting department
Increase in nonmalignant respiratory disease believed not to be related to work in refinery.
No large excess in lung cancer among refinery workers.
Group 2 Non-refinery workers hired before 1947: statistically significant deficit for all causes. SMRs for specific causes were lower than those in refinery workers. 2 cases of sinus cancer were noted but depending on ICD version would have been coded either sinonasal or bone cancers.
Group 3 Workers hired after 1946: SMRs low. No deaths observed from sinonasal cancer. Slight excess in digestive and lung cancer mortality and stroke mortality

Calculated SMRs differed in magnitude depending on what comparison population used. If local county population used, SMRs were smaller because local population was more similar to occupational cohort than national or state populations. Overall patterns similar.

Duration of employment was directly related to respiratory cancer in both refinery and non-refinery workers but results were not statistically significant.
Refinery workers that had the highest exposure level (>=200 Ni/m3/mo) had the greatest respiratory cancer excess (SMR = 187.6).
For nonrefinery workers at the highest level of exposure, there was a deficity in respiratory cancer (SMR = 79.9).
There were no observed cases of respiratory cancer among workers employed after 1946 at the highest exposure level.

Among workers 20 years after first exposure, refinery workers with the highest cumulative nickel exposure (>=200 Ni/m3/mo) had an excess in respiratory cancers (SMR = 161.2). Nonrefinery withe the highest exposure (50-199 Ni/m3/mo) also had an elevated SMR (SMR=143.1). Workers hired after 1946 did not have any observed cases at either of these two levels of cumulative nickel exposure.

Confounding factors:

Age was adjusted for in the analyses.
Co-exposures workers exposed to included chromium, iron, copper, grinding dust, solvents and acid mists. Not possible to determine components of dust or identify the nickel species.

Strengths and weaknesses:

Not Reported

Any other information on results incl. tables

Not Applicable

Applicant's summary and conclusion

Conclusions:

Findings indicated that for lung cancer, there was no marked overall excess, though the authors noted that there was some evidence of a dose-response relationship for lung cancer thus suggesting a causal relation between lung cancer and nickel exposure. The authors concluded that for both cohorts combined there were slight overall excesses in lung, stomach, and prostate cancers with some evidence of a dose-response relationship for these cancers.

Executive summary:

Enterline et al (1982) assessed cancers among workers at a nickel refinery who were exposed to copper-nickel matte through work oxidizing nickel matte in dusty environments (calcining operations) or through melting and casting at a nickel refinery in West Virginia. SMRs standardized to either the US male population, the male population of the State of West Virginia or the male population of the counties around the refinery were calculated for a series of causes of death for refinery workers, nonrefinery workers and workers who were employed at the refinery after calcining operations were discontinued. A total of 3,249 male workers were included in the study and were categorized by date of initial employment. Nickel exposure levels were estimated based on measurements made during study period as well as historic midget impinger counts converted to gravimetric expression. The authors conducted multiple evaluations of the workers and found that refinery workers hired before 1947 had elevated SMRs for every cause examined except heart disease. Statistically significant excesses in sinonasal cancers were due to one case who worked at calciner and second who worked in melting and casting department (this was believed not to be related to work in refinery). No large excesses in lung cancer were observed among refinery workers. Among non-refinery workers hired before 1947, there were statistically significant deficits for all causes. For workers hired after 1946, SMRs were low, and no deaths were observed from sinonasal cancer. Slight excesses in digestive and lung cancer mortality and stroke mortality were observed. Calculated SMRs differed in magnitude depending on what comparison population was used. Duration of employment was directly related to respiratory cancer in both refinery and non-refinery workers but results were not statistically significant. Refinery workers that had the highest exposure level (>=200 mg Ni/m3 mo) had the greatest respiratory cancer excess (SMR = 187.6). Among workers 20 years after first exposure, refinery workers with the highest cumulative nickel exposure (>=200 mg Ni/m3 mo) had an excess in respiratory cancers (SMR = 161.2). Nonrefinery workers with the highest exposure (50-199 mg Ni/m3 mo) also had an elevated SMR (SMR=143.1). Workers hired after 1946 did not have any observed cases at either of these two levels of cumulative nickel exposure.

This study was a fairly straightforward occupational epidemiologic study that used SMRs to estimate risk of the endpoint assessed from exposure. Co-exposures that could not be ruled out included chromium, iron, copper, grinding dust, solvents and acid mists. It was also not possible to determine components of dust or identify the nickel species. Findings indicated that for lung cancer, there was no marked overall excess, though the authors noted that there was some evidence of a dose-response relationship for lung cancer, thus suggesting a causal relation between lung cancer and nickel exposure. STUDY RATED BY AN INDEPENDENT REVIEWER