Nickel bis(2-ethylhexanoate)

Epidemiological data

Administrative data

Endpoint:

epidemiological data

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

not reported

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Meets generally accepted scientific standards, well documented and acceptable for assessment. Relevant exposure to submission substance, adequate information on study cohort and exposure, relevant endpoint (A detailed description of the scoring criteria can be found in the .pdf document attached to the 'Epidemiological Data Scoring Rationale Document' record at the beginning of Section 7.10.2).

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:

Exposure to different forms of nickel and risk of lung cancer.

Author:

Grimsrud TK, Berge SR, Haldorsen T, Andersen A.

Year:

2002

Bibliographic source:

Am. J. Epidemiol., 156, 1123-1132.

Materials and methods

Study type:

case control study (retrospective)

Endpoint addressed:

carcinogenicity

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

No standard guideline reported. Study details provided in the following sections

GLP compliance:

not specified

Test material

Test material information

Method

Type of population:

occupational

Ethical approval:

not applicable

Details on study design:

HYPOTHESIS TESTED: The aim of the present study was to explore the dose-related association between cumulative exposure to nickel and lung
cancer, with optimal adjustment for smoking, according to the four forms of nickel conventionally addressed: water-soluble,
sulfidic, oxidic, and metallic. Another aim was to evaluate the effect of joint exposure to nickel and tobacco smoking.

METHOD OF DATA COLLECTION
- Type: Record review / Work history
- Details: information obtained from company records, questionnaires, and The Cancer Registry of Norway

STUDY PERIOD: employment during the period of 1910 - 1994 and under observation for cancer between 1952-1995.

SETTING: evaluated men who had been employed in the nickel refinery in Kristiansand, Norway

STUDY POPULATION
- Total population (Total no. of persons in cohort from which the subjects were drawn): 5389
- Selection criteria: employment for a minimum of 12 months
- Total number of subjects participating in study: 213
- Sex/age/race: men
- Smoker/nonsmoker: smoking history was examined
- Total number of subjects at end of study: 213
- Matching criteria: none reported
- Other: none

COMPARISON POPULATION
- Type: Control or reference group
- Details: n= 525, controls were free of lung cancer and had been born within 24 months from the case’s date of birth.

HEALTH EFFECTS STUDIED
- Disease(s): lung cancer
- ICD No.: not reported
- Year of ICD revision: not reported
- Diagnostic procedure: not reported
- Other health effects: not reported

OTHER DESCRIPTIVE INFORMATION ABOUT STUDY: none

Exposure assessment:

measured

Details on exposure:

TYPE OF EXPOSURE: inhalation of nickel refinery dusts and aerosols

TYPE OF EXPOSURE MEASUREMENT: Personal sampling, nickel speciation performed with sequential extractions (Zatka et al. 1992)

EXPOSURE LEVELS: See table below

EXPOSURE PERIOD: minimum of 12 months

POSTEXPOSURE PERIOD: 10 to 20 year lag

DESCRIPTION / DELINEATION OF EXPOSURE GROUPS / CATEGORIES: evaluated by nickel species: water soluble, oxidic, sulfidic, or metallic Ni

Statistical methods:

Relative risks were estimated as odds ratios and 95 percent confidence intervals derived from conditional logistic regression models.

Results and discussion

Results:

EXPOSURE: mean cumulative exposure (mg/m3) x years of refinery workers for cases
Water soluble Ni: 2.45
Sulfidic Ni: 0.63
Oxidic Ni: 4.34
Metallic Ni: 0.92
Other exposures included: As, asbestos, mists containing sulfuric acid. Some workers were exposed to carcinogens outside the refinery. . [Exposure matrix reported in Grimsrud et al., 2000]

FINDINGS: A clear dose-related effect was seen for water-soluble nickel (odds ratio = 1.7) and lung cancer

INCIDENCE / CASES
- Number of cases for lung cancer: 213 workers, 525 controls

STATISTICAL RESULTS
- OR (Odds ratio): smoking adjusted by Ni species, high exposure
Water soluble Ni (4.93 mg/m3 x years) = 3.8
Sulfidic Ni (1.43 mg/m3 x years) = 2.8
Oxidic Ni (12.6 mg/m3 x years) = 2.2
Metallic Ni (2.32 mg/m3 x years) = 2.4
- OR (Odds ratio): for water-soluble Ni, smoking adjusted, 10-year lag = 1.7 (95% CI = 1.2-2.3)

OTHER OBSERVATIONS: The exposures to various forms of nickel were all correlated. Exposures to water-soluble nickel and metallic nickel and exposures to oxifdic and sulfidic nickel were highly correlated (r = 0.71 and 0.87, respectively). It was not possible to distinguish between the effect from metallic nickel and other forms of insoluble nickel. The exposure levels of the Cases were similar to the Controls for sulfidc and oxidic nickel but were 50% and 30% higher than Controls for soluble and metallic nickel, respectively.

Confounding factors:

effects of smoking were addressed

Strengths and weaknesses:

Strengths: Examined Ni species.
Weaknesses: There was low to moderate confounding from smoking.

Applicant's summary and conclusion

Conclusions:

A clear dose-related effect was seen for water-soluble nickel (odds ratio = 1.7) and lung cancer.

Executive summary:

STUDY RATED BY AN INDEPENDENT REVIEWER.

(A detailed description of the scoring criteria can be found in the .pdf document attached to the 'Epidemiological Data Scoring Rationale Document' record at the beginning of Section 7.10.2).