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Toxicological information

Epidemiological data

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Administrative data

Endpoint:
epidemiological data
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Well reported and conducted to good scientific standards. Basis for classification of MnO2 as STOT RE 2.

Data source

Reference
Reference Type:
publication
Title:
Assessment of the permissible exposure level to manganese in workers exposed to manganese dioxide dust
Author:
Roels H A, Ghyselen P, Buchet JP, Ceulemans E & Lauwerys RR
Year:
1992
Bibliographic source:
British Journal of Industrial Medicine 1992; 49: 25-34

Materials and methods

Study type:
cohort study (prospective)
Endpoint addressed:
respiratory irritation
neurotoxicity
Test guideline
Qualifier:
no guideline required
Principles of method if other than guideline:
Cohort study assessing neurofunctional effects of workers exposed to MnO2 in a dry alkaline battery factory and matched with controls in a factory with no exposure to manganese substances . The prevalence of neuropsychological and respiratory symptoms, lung ventilatory parameters, neurofunctional performances and several biological parameters were examined.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): MnO2 dust

Method

Type of population:
occupational
Ethical approval:
not specified
Details on study design:
HYPOTHESIS TESTED (if cohort or case control study): Yes

METHOD OF DATA COLLECTION
- Type: Questionnaire, interview, clinical examination
- Details: Potential confounding factors related to hobby activities, previous employment, personal habits and medical history were controlled by questionnaire and interview. Clnical examination included: lung function tests, neurofunctional examination (visual reaction time, eye-hand coordination, hand steadiness, audioverbal short term memory), blood analyses, urine analyses

SETTING: Dry battery plant

STUDY POPULATION
- Total population (Total no. of persons in cohort from which the subjects were drawn): 92
- Selection criteria: No occupational exposure to mercury, lead, cadmium, solvents, or hazards interfering with lung function. Participants should not have suffered from lung disease and their medical history should not have shown any neurological or neuropsychiatric affections or current medical treatments that might influence the results of the neurofunctional tests.
- Total number of subjects participating in study: 193 ( included 101 in control group)
- Sex/age/race:, not stated, assumed male
- Smoker/non-smoker: 55% smoked in control and 48% smoked in exposed group.
- Matching criteria: Age, height, smoker, coffee-drinking, weight, work schedule, alcohol, education, salary

COMPARISON POPULATION
- Type: Other comparison group: Workers in a factory with no neurological confounders present
- Details: polymer-processing factory located in same area, same occupational physician with similar hiring criteria

HEALTH EFFECTS STUDIED
- Disease(s): neurofunctional effects, respiratory effects
Exposure assessment:
measured
Details on exposure:
TYPE OF EXPOSURE: Inhalation

TYPE OF EXPOSURE MEASUREMENT: Personal sampling

EXPOSURE LEVELS: Respirable dust Geometric mean (GM) = 0.215 mg/m³; Total dust GM = 0.948 mg/m³

EXPOSURE PERIOD: Average of 5.3 years.

DESCRIPTION / DELINEATION OF EXPOSURE GROUPS / CATEGORIES: MnO2- exposed group and control group were young (mean age 30 yrs). Both groups were well-matched for age, height, weight, work schedule, coffee and alcohol consumption and smoking ( no statistically significant differences between exposed and control groups). A small difference in educational difference existed between the two groups (X² test, p = 0.046) due to a greater proportion of workers with a technical degree in the control plant.
Statistical methods:
Statistical analyses were performed by SAS procedures.

Results and discussion

Results:
- Internal exposure to manganese
Manganese in blood (MnB): The MnB ranged from 0.25 to 1.31 µg/100 mL in the control group and from 0.21 to 2.10 µg/100 mL in the Mn exposed group.
Manganese in urine (MnU): The MnU ranged from 0.01 to 0.49 µg/g creatinine in the control group and from 0.15 to 7.33 µg/g creatinine in the exposed workers.
The geometric means of MnB and MnU were significantly higher in the Mn exposed group than in the control group

- Relation between parameters of external and internal exposure to manganese
On an individual basis, no statistically significant correlation was found between MnB or MnU and various external exposure parameters.

- Respiratory tract effects: No statistically significant differences

- Central nervous system effects: No statistically significant difference between control and exposed for neurovegetative complaints.
The MnO2-exposed workers performed several of the neurofunctional tests less well than the control group. The exposed group had significantly longer reaction times over the whole testing period than the control group. The five eye-hand coordination parameters indicated that the fine hand-forearm movement was more erratic in the MnO2-exposed workers than the control. The relevance of abnormal values for the five eye-hand coordination parameters were significantly higher in the Mn exposed group than in the control group. The results of the hole tremometer test showed a systematic tendency towards higher mean tremor scores in the Mn exposed group as compared with the control group. The prevalences of abnormal score values were also consistently higher in the Mn group than in the control group. Although the Mn workers performed less well in the audioverbal short term memory test than the control group, the mean scores of correctly recalled or recognised words were not significantly different between both groups. The abnormal performance in simple reaction time, eye-hand coordination, and hand steadiness increased with the cumulative integrated exposure (CEI) of respirable (MnRes) and total (MnTotal) measured by personal sampling

- Biological parameters: Al the haematological measurements were in the normal range both in the control and Mn exposed workers. The erythropoietic parameters (red blood cell count, haemoglobin, mean corpuscular volume, mean corpuscular haemoglobin concentration), and serum iron concentration, however, exhibited a consistent and statistically significant trend towards lower values in the Mn exposed workers.

- Dose response: The various neurofunctional effect variables and the variables of Mn exposure did not show clear cut dose-effect relations on an individual basis.

Applicant's summary and conclusion

Conclusions:
Manganese dioxide, in this study, caused statistically significant neurobehavioural differences in exposed workers, in the absence of confounding influences.
Executive summary:

A cohort study, assessing neurofunctional effects of workers exposed to MnO2 in a dry alkaline battery factory and matched with controls in a factory with no exposure to manganese substances, was conducted . The prevalence of neuropsychological and respiratory symptoms, lung ventilatory parameters, neurofunctional performances and several biological parameters were examined.

Manganese dioxide, in this study, caused statistically significant neurobehavioural differences in exposed workers, in the absence of confounding influences.