Dialuminium nickel tetraoxide

Epidemiological data

Administrative data

Endpoint:

epidemiological data

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Study period:

1978-1984

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

This study had medium relevance to the Hazard or Risk Assessment of NiO, medium quality of cohort definition and size, medium quality of exposure data and a medium quality of endpoint results and reporting. 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:

Determination of nickel in lung specimens of thirty-nine autopsied nickel workers

Author:

Andersen I, Svenes KB

Year:

1989

Bibliographic source:

Int Arch Occup Environ Health 61:289-295

Materials and methods

Study type:

case control study (retrospective)

Endpoint addressed:

carcinogenicity

Principles of method if other than guideline:

Lung specimens from 39 nickel refinery workers who were autopsied during the period of 1978 to
1984 were analyzed for nickel levels and evalauted relative to lung cancer diagnoses

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Nickel monoxide

EC Number:

215-215-7

EC Name:

Nickel monoxide

Cas Number:

1313-99-1

IUPAC Name:

oxonickel

Details on test material:

- Name of test material (as cited in study report): nickel-copper oxide, (Ni, CU)O

Method

Type of population:

occupational

Ethical approval:

not specified

Details on study design:

METHOD OF DATA COLLECTION
- Type: Interview / Questionnaire / Record review / Work history / Clinical tests / other: lung specimens, Employment records, medical files
- Details: lung specimens collected from 39 consecutive autopsies between 1978 and 1984. Control lung tissue was also obtained from 16 autopsied persons not connected with the refinery. Tissue was collected from the right lower lobe and place in formaldehyde with Na2HPO4. Medical files were used to determine cause and age of death as well as smoking information.
-Other: specimens from the center and periphery of each lobe were collected from a worker (not included in the 39) and analyzed to determine variations in nickel concentration in different regions of the lung.


STUDY PERIOD: workers autopsied between 1978 and 1984


SETTING: Nickel refinery in Kristiansand, Norway


STUDY POPULATION
- Total population (Total no. of persons in cohort from which the subjects were drawn): 39 workers, 16 controls
- Selection criteria: nickel refinery worker
- Total number of subjects participating in study: 39
- Sex/age/race: average age of death was 66+/- 8 years; for workers with carcinomas 64 +/- 8.
- Smoker/nonsmoker: 23 cigarette smokers, 11 other smokers (<10 cigarettes daily, former smokers, pipe smokers), 5 non-smokers
- Other: average age at start of employment for all workers was 39 +/- 11 years, for those with carcinomas of the lung 38 +/- 8 years


COMPARISON POPULATION
- Type: State registry / Regional registry / National registry / Control or reference group / Other comparison group: other
- Details: autopsied persons non connected with the refinery


HEALTH EFFECTS STUDIED
- Disease(s): lung cancer
- Other health effects: other causes of death reported but not statistically evaluated included nose, colon, kidney and malignant melanoma cancers


OTHER DESCRIPTIVE INFORMATION ABOUT STUDY:
-lung samples were analyzed for total nickel using Electrothermal Atomic Absorption Spectrometery

Exposure assessment:

not specified

Details on exposure:

DESCRIPTION / DELINEATION OF EXPOSURE GROUPS / CATEGORIES:TYPE OF EXPOSURE:
-15 workers were employed in the Roasting and Smelting Department where exposure to nickel was predominantly in the form of nickel-copper oxides, Ni3S2 and metallic dust
- 24 workers were employed in the Electrolysis Department where exposure was considered to be mostly to the water-soluble compounds, NiS04 and NiCl2, but also to a lesser degree to water-insoluble nickel compounds such as nickel-copper oxides and sulphides

Statistical methods:

Means of lung nickel concentrations were tested to see if levels differed at the 1% (P=O.Ol) or 5% (P =0.05) level of significance employing a one-way analysis of variance (the F-statistic). Sampled populations were also tested against each other with Duncan's New Multiple Range Test with unequal observations. To meet the conditions of normal distributions and comparable population variances, all statistical comparisons involved logarithms of the nickel concentrations.

Results and discussion

Results:

EXPOSURE (Lung tissue measurements)
Roast and Smelting Department (n=15)
-Arithmetic mean ± SD: 333 ± 382 µg/g dry weight
-Geometric mean: 148 µg/g dry weight with 99% CLs of 45-490 µg/g dry weight

Electrolysis Department (n=24)
-Arithmetic mean ± SD: 34 ± 48 µg/g dry weight
-Geometric mean: 16 µg/g dry weight, with 99% CLs of 8-34 microgram per gram dry weight

Reference Group (n=16)
-Arithmetic mean ± SD: 0.76 ± 0.39 µg/g dry weight
Geometric mean: 0.67 µg/g dry weight, with 99% CLs of 0.48-0.95 µg/g dry weight

INCIDENCE / CASES OF LUNG CANCER
-Roasting and Smelting Department: lung cancer present in 8 of 24 workers; F-statistic = 0.50 (not significant)
-Electrolysis Department: lung cancer present in 6 of 15 workers; F-statistic = 0.11 (not significant)
-All Workers: lung cancer present in 14 of 39 workers; F-statistic = 0.66 (not significant)

OTHER OBSERVATIONS:
-No trend observed between lung nickel content in relation to the time elapsed between retirement and death
-Lung nickel concentrations did not show any dependence on smoking habits
-One-way ANOVA showed that mean nickel concentrations in lung tissue were statistically significantly different between the three groups.

Confounding factors:

-Lung nickel concentrations did not show any dependence on smoking habits

Strengths and weaknesses:

The authors discussed the potential losses of nickel from the tissues during the storage in 4% formaldehyde and the washing protocol (dipping into deionized water), but concluded that good agreement between this study and a previous study was an indication that the loss to the storage medium is minimal.

Any other information on results incl. tables

Not Applicable

Applicant's summary and conclusion

Conclusions:

The authors concluded that (1) nickel refinery workers exhibit elevated nickel levels in lung tissues at autopsy; (2) workers of the Electrolysis Department and the Roasting and Smelting Department constitute distinct groups with respect to the accumulation of nickel in lung tissue; (3) workers who were diagnosed to have lung cancer had the same lung nickel concentrations at autopsy as those who died of other causes.

The authors also concluded that their data show that pulmonary tissue nickel concentrations may not be used as a definitive etiologic criterion, but that this did not constitute a rejection of a causal relationship between exposure to nickel compounds and respiratory cancers. It was also concluded that in addition to primary exposure to soluble nickel salts, Electrolysis Workers were also exposed to insoluble forms of nickel.

Executive summary:

Andersen and Svenes (1989) reported on the concentrations of nickel in lung tissue collected from refinery workers. The objective of evaluating the concentrations of nickel in the lung specimens was two-fold: (a) measurements would help to clarify the uncertainty in exposure histories to various types of nickel within the refinery, and (b) comparison of tissue concentrations would characterize the levels in workers with and without lung cancer. Lung tissue samples were collected from autopsied workers in the Roasting and Smelting Department (n=15), Electrolysis Department (n = 24), as well as from persons not connected with the refinery (n=16); concentrations of total nickel were determined using Electrothermal Atomic Absorption Spectrometry. Though workplace exposures were not measured in this study, the authors stated that exposure to nickel was predominantly in the form of nickel-copper oxides, Ni3S2, and metallic dust in the Roasting and Smelting Department, whereas in the Electrolysis Department, exposures were to mostly to water soluble compounds (NiSO4 and NiCl2), but also to a lesser degree to water insoluble nickel compounds such as nickel-copper oxides and sulphides. Tissue concentrations were based on samples collected from the right lower lobe; however, additional samples (n=10) collected and analyzed from the center and periphery for each lobe indicated no differences between concentrations in the center and periphery segments.

Results of statistical analyses indicated that measured levels of nickel in the three groups were clearly different; 333 ± 382 μg/g (dry weight), 34 ± 48 μg/g, and 0.76 ± 0.39 μg/g in Roast and Smelting Department workers, Electrolysis Department workers, and the reference group, respectively. When tissue concentrations were compared between individuals diagnosed with lung cancer relative to those diagnosed with other diseases, no significant difference was found. Additionally, no trends between time elapsed between retirement and death, or smoking habits, were found. However, a relationship between the number of years worked and tissue nickel levels was noted. Based on these findings, the authors concluded employment at a nickel refinery resulted in increased tissue levels of nickel in the lung at autopsy, but that these levels did not correlate with the incidence of lung cancer in workers relative to those who died of other causes. Though nickel oxide was only one of many nickel compounds to which workers were exposed, this study clearly indicates that occupational exposure in an environment where nickel-copper oxides were present resulted in higher concentrations of nickel in the lungs relative to environments without such, but that in the study population evaluated, a correlation between lung cancer and tissue concentrations of nickel in the lung was not observed. STUDY RATED BY AN INDEPENDENT REVIEWER