Manganese

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: Well documented occupational cohort study which follows good basic scientific principles

Data source

Reference

Reference Type:

publication

Title:

Focused Medical Surveillance: A Search for Subclinical Movement Disorders in a Cohort of U.S. Workers Exposed to Low Levels of Manganese Dust

Author:

Gibbs JP, Crump KS, Houck DP, Warren PA & Mosley WS

Year:

1999

Bibliographic source:

NeuroToxicology, 20(2-3): 299-314

Materials and methods

Study type:

cross sectional study

Endpoint addressed:

neurotoxicity

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Seventy-five workers with recent and/or historical exposure to manganese (Mn) at a metal producing plant in northern Mississippi were closely matched with 75 control workers who had no known history of occupational exposure to Mn. Both plants investigated were OSHA STAR work sites and share common medical, safety, and industrial hygiene services. Airborne Mn levels were assessed for each of twelve job categories at the Mn facility by collecting 63 side-by-side full-shift personal samples of both total and respirable Mn dust. Each worker’s cumulative exposure to respirable and total Mn was estimated for the preceding 30 days, preceding year, and for the worker’s entire employment history. Both Mn and control workers were administered multiple neuropsychological tests including tests of hand-eye coordination, hand steadiness, complex reaction time and rapidity of finger tapping. A questionnaire was used to evaluate a worker's neuropsychological status.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Manganese

EC Number:

231-105-1

EC Name:

Manganese

Cas Number:

7439-96-5

Molecular formula:

Mn

IUPAC Name:

manganese

Details on test material:

workers were exposed to pure manganese whilst collecting the metal from the cathodes

Method

Type of population:

occupational

Ethical approval:

not specified

Details on study design:

HYPOTHESIS TESTED: The study was undertaken to determine whether subclinical neurological deficits could be demonstrated in a population of U.S. workers with recent and historical exposure to Mn.

METHOD OF DATA COLLECTION
- Type: Interview, exposure assessment, neurobehavioural test battery,
- Details: Neurological tests based on the Movemap, EAP Orthokinesimeter and Hole Tremometer and a finger tapping test

SETTING: Occupational (2 chemical plants in North Mississippi)

STUDY POPULATION
- Total population: The larger plant employed 390 persons, and 190 employees in the smaller of the plants.
- Selection criteria: 75 workers (63 employed at the time of the study and 12 who were previously employed) were identified as being employed in the Mn process area.
- Total number of subjects participating in study: 75
- Sex/age/race: Both males and females were included (70 males, 5 females), the mean age of the workers was 39.68 years, workers were described as either black or white.
- Smoker/nonsmoker: Both were included in the study
- Matching criteria: Matching was conducted primarily on gender, race, age and pay grade (salaried or hourly). Secondary matching variables included department (operations, maintenance or other), whether a worker was engaged in shift work, and length of employment.

COMPARISON POPULATION
- Type: Control group
- Details: The selection of the control group was performed by a resident physician not familiar with any of the employees of any of the previous testing results.

HEALTH EFFECTS STUDIED
- Disease(s): Subclinical neurological disturbances

Exposure assessment:

measured

Details on exposure:

TYPE OF EXPOSURE: Inhalation

TYPE OF EXPOSURE MEASUREMENT: Area air sampling and Personal sampling
Historical 15 minute samples of total dust were collected during the more dusty operations. No 8-fur TWA dust samples for Mn until 1995. No samples were collected post 1995 until 1997, after which, samples of respirable Mn were also collected. Jobs with the potential for exposure to Mn were divided into twelve categories, each had relatively homogenous levels of airborne Mn. These categories were further defined by a total of 63 full shift side-by-side personal samples of both total and respirable Mn dust collected using SKC model 224 PCXR7 pumps with mixed cellulose ester filters (0.8 µ pore size). Respirable dust was sampled using a 37 mm SKC aluminium cyclone and a pump flow rate of 1.9 L/min while total dust was sampled using a 2.0 L/min flow rate. These samples were analysed at an AIHA accredited laboratory using inductively coupled plasma. Airborne levels of respirable and total Mn in each of the 12 homogenous job categories at the time of the study were estimated using the arithmetic mean of the personal air samples. These were adjusted to estimate exposures prior to 1997.

Statistical methods:

Statistical tests for differences in questionnaire results between Mn exposed employees and controls were conducted using a standard chi-square test. Since possible answers of all tests could be ordered, to potentially increase statistical power, a trend test was also applied.

Neurobehavioural test outcomes of Mn workers were compared to those of controls using the Wilcoxon two-sample non-parametric test. In order to take advantage of the matched design, test results in exposed and controls were also compared using the Wilcoxon one-sample non-parametric test. To utilise the advantage of the matched design, test results in exposed and controls were also compared using the Wilcoxon one-sample non-parametric test (SAS 1996). This test used the difference between the test result in the exposed employee and the matched control as the data point for a matched pair, and tested whether the distribution of these differences was centered as zero.
Ordinary multiple regressions were conducted using age and each of the following seven Mn exposure variables one-at-a-time as explanatory variables (duration of exposure, 30-day cumulative occupational exposure to either respirable or total Mn). Shift work was also used as an explanatory variable in conjunction with age and cumulative 30-day exposure to respirable or total Mn. Outliers were eliminated when performing these regressions. A test score was considered to be an outlier if the magnitude of a residual after a model fit was more than three times the standard deviation of the residuals. All reported p-values were two-sided.

Results and discussion

Results:

EXPOSURE (listed as arithmetic means)
Respirable Mn Dust:-
30 days - 11.1 mg-hr/m3 (S.D. 13.4)
1 year - 151 mg-hr/m3 (S.D. 157)
Lifetime - 2133 mg-hr/m3 (S.D. 13.4)

Total Mn Dust:-
30 days - 32.4 mg-hr/m3 (S.D. 56.3)
1 year - 454 mg-hr/m3 (S.D. 624)
Lifetime - 5887 mg-hr/m3 (S.D. 7671)
(Further exposure details are listed in table 4 in Appendix I)

FINDINGS Results from the questionnaire showed that responses of exposed and control groups did not differ significantly on any question. There were no statistically significant differences between exposed and controls on any neurological test using either the Wilcoxon one sample or two sample test. Age was found to be highly significantly correlated with reaction time and with finger tapping speed and was also significantly correlated with % precision and % imprecision in the hand eye coordination test. In each of these cases, older employees performed worse than younger ones. No respirable Mn exposure variable was a significant predictor of any neurological test results. Similar results were obtained in analyses that utilised measures of exposure to total Mn. No association between occupational Mn exposure and sub-clinical neuropsychological symptoms was noted. However airborne Mn levels measured were significantly lower than those in other occupational studies evaluated. Lifetime cumulative exposures were on the other hand similar to those reported by other authors.

Confounding factors:

Age was found to be significantly correlated with measures of hand-eye coordination, complex reaction time and tapping time. The authors conclude that age must be controlled when interpreting results. The close matching attained in the study and the attitude of the employee cooperation prevalent in the two site made it less likely that motivational state was a significant confounder. Industrial hygiene services were shared by the two plants, an onsite nurse served both plants also. There was no known occupational exposure at either plant to lead, mercury or other potentially confounding neurotoxicant.

Strengths and weaknesses:

The large number of control employees relative to the number in the Mn group made close matching possible. Matching on gender and race was 100 % and the majority of pairs were matched for shift work, department, and pay grade. Over 50 % of all pairs were matched within 1 year for age. Chi square analysis of questionnaire responses did not demonstrate any differences between the two groups regarding the use of alcohol, tobacco, caffeine or medications, solvent use, headaches, head injuries or diagnosed neurological disorders. Age and years of service were highly correlated and shift workers were younger than non-shift workers. Exposures to respirable and total dust were highly correlated. Cumulative exposures over the previous 30 days and the year were also highly correlated. The lifetime integrated average exposures did not correlate highly with either of the shorter term cumulative exposure parameters. The average exposure of the 63 workers who were currently working in the Mn area of the plant were estimated as 0.066 ± 0.59 mg/m3 respirable Mn and 0-18 ± 0.21 mg/m3 total Mn. In the questionnaire administered, the number of responses were less than 75 in some cases as the employees were given the option of not responding to a question. Two movemap data files were lost and the data sheet for one Tremometer test was lost during the course of the study.

Any other information on results incl. tables

Full tabulated results are included in the attached pdf Appendix I

Applicant's summary and conclusion

Conclusions:

The study did not find any effects of occupational exposure to low levels of pure Mn dust in measurements of hand steadiness, hand-eye coordination, complex reaction time, or finger tapping speed. Additionally, no Mn effects were apparent in symptoms of depression, anxiety, fatigue, sleep disturbance, concentration, memory, mood changes, mania, tremor or imbalance.