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epidemiological data
Type of information:
other: human observational study
Adequacy of study:
supporting study
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Well-documented publication which meets basic scientific principles for epidemiological research, but is lacking information on good epidemiological practices. Contributes to the available body of epidemiological evidence for iron oxide neurotoxicity.

Data source

Referenceopen allclose all

Reference Type:
Occupational exposure to manganese, copper, lead, iron, mercury and zinc and the risk of Parkinson's disease.
Gorell JM, Johnson CC, Rybicki BA, Peterson EL, Kortsha GX, Brown GG, Richardson RJ.
Bibliographic source:
Neurotoxicology 20(2-3):239-247
Reference Type:
Occupational exposures to metals as risk factors for Parkinson's disease
Gorell JM, Johnson CC, Rybicki BA, Peterson EL, Kortsha GX, Brown GG, Richardson RJ
Bibliographic source:
Neurology 48(3)650-658

Materials and methods

Study type:
case control study (prospective)
Endpoint addressed:
Test guideline
no guideline available
Principles of method if other than guideline:
Study conducted according to established standard epidemiological methodology.
GLP compliance:
not specified

Test material

Constituent 1
Chemical structure
Reference substance name:
EC Number:
EC Name:
Cas Number:
Molecular formula:
Details on test material:
- Name of test material (as cited in study report): Iron


Type of population:
Ethical approval:
not specified
Details on study design:
HYPOTHESIS TESTED (if cohort or case control study): To see whether historical occupational exposure to manganese, copper, iron, lead, mercury or zinc increased the risk of Parkinson's disease.

- Type: Interviewer-administered questionnaire / Medical record review/ staff neurologist examination
- Details: All cases and controls were persons who received their primary care at the Henry Ford Health System (HFHS) in Detroit, MI. Persons were excluded for the following reasons: 1) lack of primary care at HFHS; 2) death; 3) residence outside of the tri-county Detroit metropolitan area; 4) failure of staff neurologists to confirm and document the diagnosis of Parkinson's disease in putative cases; 5) presence of Parkinson's disease for more than 10 years in order to minimize survival bias; 6) a history of dementia; 7) other medical conditions that would preclude a reliable interview; and 8) an inability to contact study subjects. Medical records were reviewed of all potential cases and controls, with cases being examined by a staff neurologist. Information on work history came from an interviewer-administered questionnaire.


SETTING: Henry Ford Health System and the tri-county metropolitan area of Detroit

- Total population (Total no. of persons in cohort from which the subjects were drawn): 239,722
- Selection criteria: Individuals receiving primary care at HFHS with a potential diagnosis of Parkinson's disease
- Total number of subjects participating in study: 1,243
- Sex/age/race: Within 1% of the sex and race demographics of Detroit according to the 1990 US Census. Of the cases, 50.7% were White men, 31.3% were White women, 9.0% were Black men, 6.3% were Black women and 2.1% were Other men. Of the controls, 53.2% were White men, 31.9% were White women, 8.0% were Black men, 4.5% were Black women, 1.9% were Other men and 2.4% were Other women.
- Smoker/nonsmoker: none, 1 to 30 pack-years and greater than 30 pack-years
- Total number of subjects at end of study: 608 (144 Parkinson's disease cases and 464 controls)
- Matching criteria: Sex, race and age (+/- 5 years)

- Type: Other comparison group
- Details: Persons from the same health system without diagnosed Parkinson's disease

- Disease(s): Parkinson's disease
- ICD No.: 9
- Diagnostic procedure: Staff neurologist examination of person. If person exhibited 2 or more of the 4 signs (bradykinesia, muscular rigidity, resting limb tremor and loss of postural reflexes) then they were considered a case.
Details on exposure:
TYPE OF EXPOSURE: Occupational


DESCRIPTION / DELINEATION OF EXPOSURE GROUPS / CATEGORIES: Industrial hygienist blind to case-control status reviewed the questionnaires and assessed the possibility of occupational exposure to iron and the other metals.
Statistical methods:
Logistic regression was used to study the exposure of the metal (ever/never) and the risk of Parkinson's disease. An odds ratio, 95% confidence interval and p-value were all computed for these ever/never exposure scenarios. Two binary indicator exposure variables (=<20 years or >20 years) were defined and used in a logistic regression model.

Results and discussion

- Number of measurements: None


- Parameter under consideration: Odds ratio

- OR (Odds ratio): With =<20 years of exposure to iron, OR=1.02 and 95% CI=0.59-1.75. With >20 years exposure to iron, OR=1.27 and 95% CI=0.69-2.34. For the interaction between lead and iron with >20 years exposure to both, OR=2.83 and 95% CI=1.07-7.50. For the interaction between iron and copper with >20 years exposure to both, OR=3.69 and 95% CI=1.40-9.71.

Confounding factors:
The authors adjusted the results for age, race, sex and pack-years of smoking.
Strengths and weaknesses:
The cases and controls were drawn from a representative population, increasing the suitability of the control group and limiting selection bias. Miscoding errors should not have been related to the risk factors under study. The method of exposure assessment (industrial hygienist assignment) showed high variability that could affect the odds ratio.

Applicant's summary and conclusion

There is an increased risk of Parkinson's disease for subjects with more than 20 years of exposure to iron and copper together and iron and lead together. There are no increased risks for individuals exposed only to iron.
Executive summary:

A population-based case-control study was conducted at the Henry Ford Health System in Detroit, Michigan, and compared 144 cases with confirmed Parkinson's disease to 464 controls matched on age, sex and race. The cases and controls were men and women age 50 and older, and were interviewed about work history from age 18. An industrial hygienist, blinded by status, assessed the risk of exposure to iron, copper, lead, manganese, zinc and mercury from the interview results. Adjusting for age, sex and smoking status, there was no increased risk for Parkinson's disease among persons who had worked with iron for either =<20 years or >20 years. When combined with lead or copper, however, iron exposure of greater than 20 years was associated with a statistically significant increase in Parkinson's disease risk.