Registration Dossier

Toxicological information

Exposure related observations in humans: other data

Administrative data

Endpoint:
exposure-related observations in humans: other data
Type of information:
experimental study
Adequacy of study:
disregarded due to major methodological deficiencies
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: no control group, only few details on subjects, exposure was determined 12 years before survey, duration of exposure not stated.

Data source

Reference
Reference Type:
publication
Title:
Chronic Manganese Poisoning in the Dry Battery Industry
Author:
Emara AM, El-Ghawabi SH, Madkour OI & El-Samra GH
Year:
1971
Bibliographic source:
Brit. J. Industr. Med., 28: 78-82

Materials and methods

Type of study / information:
An environmental study and a survey of exposed workers.
Endpoint addressed:
toxicity to reproduction / fertility
neurotoxicity
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
A survey was conducted on 36 workers in the dry battery industry exposed to dust containing 65 to 70 % manganese oxide. In addition, an environmental study was also performed to determine the concentrations of manganese in the main working areas.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material : manganese dioxide (dust present in a dry battery factory)
- Composition of test material, percentage of components: MnO2 65 to 70 %

Method

Ethical approval:
not specified
Details on study design:
A survey of 36 worker in a factory manufacturing dry batteries was conducted. In addition to the clinical examination, blood samples were taken from the 8 workers considered to have chronic manganese poisoning after they had been transferred to new jobs at the same factory with minimal exposure to manganese dust. The manganese level in the blood was determined by spectrophotometry. No measurements were made on the blood of unaffected workers who continued at work.

An environmental study at the four main areas of dust exposure was performed with a midget impinger.
Exposure assessment:
measured
Details on exposure:
TYPE OF EXPOSURE: Occupational (dry battery manufacturing)

TYPE OF EXPOSURE MEASUREMENT: Personal sampling

EXPOSURE LEVELS: Please refer to table 2 under section remarks on results including tables and figures

POSTEXPOSURE PERIOD: Variable between workers, please refer to table 1 under section remarks on results including tables and figures

Results and discussion

Results:
In the present survey eight workers exhibited various neuropsychiatric manifestations of chronic manganese poisoning (22.2 %), six of which had chronic psychosis. The most common complaint was found to be headache, often severe with no special localisation or timing. It was associated in all six cases with an inverted sleep rhythm. Sexual impotence or diminished libido was found in three of the cases. Sexual stimulation was noted in one case suffering from parkinsonism, the hypersexuality continued for one year without being followed by diminished libido.

Any other information on results incl. tables

Table 1: Findings in Workers with Clinical Evidence of Chronic Manganese Poisoning

Case no.

Age (yrs)

Occupational Exposure

Latent Period (yrs)

Mn Level in Blood (µg/100 mL)

EEG Findings

Clinical Diagnosis

1

28

Compression

16

0.03

Abnormal

Chronic psychosis

2

29

Mixing

5

0.024

Normal

Chronic psychosis

3

29

Mixing

3

1.70

Normal

Chronic psychosis

4

22

Mixing

7

0.03

Normal

Chronic psychosis

5

32

Mixing

7

0.02

Abnormal

Chronic psychosis

6

36

Compression

10

2.30

Normal

Chronic psychosis

7

30

Compression

13

0.028

Normal

Left hemiparkinsonism

8

28

Mixing

1

0.026

Normal

Left choreo-athetosis

Abnormal = few bitemporal theta waves, slightly more on the left side, and a mild generalised cerebral dysrhythmia with a background activity of 7 to 9 c/s.

 

Table 2: Dust Concentration of Main Working Areas

Area

No. of Samples

Average Concentration (mg/m3)

Rate of Deposition (mg/m3/hr)

Weight of MnO2in Samples (mg)

Unpacking

12

42.2 (36.6-45.7)

36 (32-38)

28.44

Sieving

12

42.2 (37.2-43.8)

32.7 (30-36.2)

25.26

Mixing

12

32.6 (28.9-32.8)

30 (27-34)

21.40

Compressing

12

6.8 (6.2-7.2)

6 (5.8-6.3\0

4.80

 

Case 7 and 8 were found to have physical manifestations of manganese poisoning.

 

Case 7:

A male worker aged 30, married with two children and reported as previously being an addict to cannabis and a heavy cigarette smoker (40 cigarettes/day for 10 years). Employed in compressing battery powder for 14 years without any previous occupation. Symptoms began 13 years after the start of exposure with a gradual onset of hallucinations and increased laughter. The patient was treated as a psychological case for one month but then progressed to generalised paresis and marked disturbance of speech. Sexual potency was markedly increased. The disease was progressive. On examination the patient had normal complexion, temperature 37 °C, pulse 104/min, blood pressure 130/80 mmHg. The patient had uncontrollable laughter and crying, euphoria and mild amnesia. The patient’s speech was slurred and monotonous, his face masked and he had micrographia and von Jaksch’ (Cock’s gait). The cranial nerves were intact and muscle tone was normal but muscle power on the left side was diminished with exaggerated deep reflexes and lost abdominal reflexes on the same side. He had propulsion and retropulsion but coordination was not affected.

 

Case 8:

A male worker aged 28 years, married with one child and no reported special habits. One year after exposure to manganese dust in the manual mixing of dry battery powder he started to have painful involuntary movements in the left upper limb followed by the left lower limb. He was treated with anti-parkinsonism drugs without improvement. Five months later involuntary movements in the tongue developed. The movements disturbed sleep. He could keep balance and had no sphincteric disturbances, dysphagia or regurgitation of food. There was no family history of a similar condition, nor any history of rheumatic fever, encephalitis or head injury. On examination he was of normal intelligence, no masked facial expression, however he had involuntary movements in the left upper limb when resting. The movements were athetoid with flexion of the wrist, hyperextension of the metacarpophalangeal joints, pronation of the forearm and contractions in the shoulder muscles followed by the finger and wrist with supination of the forearm. The left foot showed flexion and extension movements in the toes (particularly the big toe). The tongue showed mild spontaneous movements on protrusion. There was no rigidity. The fundi, cranial nerves, motor power, sensations, reflexes, chest, heart and abdomen were normal. The movements stopped almost completely following right stereotactic thalamic thermocoagulation (he was then discharged and given benzhexol (Artane), 2 g three times a day).

Applicant's summary and conclusion

Conclusions:
Many of the workers had been exposed for 10 years or more without developing chronic manganese poisoning whereas other exposed for only a few years developed manganism. The shortest latent period observed in the study was one year. The author concludes that individuals susceptibility is important in manganism. Although the study is deemed unreliable in itself, it does support Roels et al in indicating neurological effects from MnO2 exposure.
Executive summary:

A survey was conducted on 36 workers in the dry battery industry exposed to dust containing 65 to 70 % manganese oxide. In addition, an environmental study was also performed to determine the concentrations of manganese in the main working areas.

The main scope of the study is not reproductive toxicity; only the symptom “impotence” was extracted from the 13 cases of “chronic manganese poisoning” described. Among the 13 cases of chronic manganese poisoning, 8 out of 12 individuals described impotence among other symptoms indicative of neurotoxicity.

The number of cases is too small to conclude, exposure is not described. It remains unclear whether impotence is a symptom of manganism or a separate disorder.