Manganese dinitrate

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: see 'Remark'

Remarks:

well-documented study, non-audited, no history on wives; parity not taken into account. Read-across from manganese sulphate to manganese nitrateis justified based on having both high water solubility and structural similarities. Specifically, both substances have anions containing multiple oxygens. In addition the percentage contribution of Mn2+ in both substances is comparable.

Data source

Reference

Reference Type:

publication

Title:

Fertility of male workers exposed to mercury vapor or to manganese dust: A questionnaire study

Author:

Lauwerys R, Roels H, Genet P, Toussaint G, Bouckaert A & de Cooman S

Year:

1985

Bibliographic source:

American Journal of Industrial Medicine, 7:171-176

Materials and methods

Study type:

cohort study (prospective)

Endpoint addressed:

toxicity to reproduction / fertility

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The fertility of male workers exposed to manganese dust was assessed with the use of questionnaire. A fertility questionnaire was applied to the total male work force of a manganese salts and oxides factory and two control plants with comparable workload characteristics.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Manganese dust (dioxide, carbonate, sulphate or manganese ore itself)

IUPAC Name:

Manganese dust (dioxide, carbonate, sulphate or manganese ore itself)

Details on test material:

Name of test material (as cited in study report): Manganese dusts (dioxide, carbonate, sulphate) including manganese ore
Other: The concentration of manganese was measured as total dust

Method

Type of population:

occupational

Ethical approval:

not specified

Details on study design:

HYPOTHESIS TESTED : The possible interference of manganese on the reproductive system in male workers occupationally exposed.


METHOD OF DATA COLLECTION
- Type: Questionnaire and Clinical examinations.
- Details: The questionnaire contained questions on fertility along with questions on duration of employment, residence and smoking and drinking habits. Samples of blood and urine were collected for the determination of manganese.


SETTING: Occupational, the manganese exposed group were recruited from a factory producing manganese salts from concentrated ores


STUDY POPULATION
- Selection criteria: Only Belgian subjects were included, who had been married once. Subjects were excluded in they were widowed, divorced, separated or never married.
- Total number of subjects participating in study: 85 workers exposed to manganese, 81 control workers.
- Sex/age/race: All workers were male and Belgian
- Smoker/nonsmoker: Both were included in the study


COMPARISON POPULATION
- Type: Control or reference group
- Details: The control workers had never been occupationally exposed to manganese.


HEALTH EFFECTS STUDIED
- Disease(s): Fertility problems

Exposure assessment:

not specified

Details on exposure:

TYPE OF EXPOSURE: Occupational


TYPE OF EXPOSURE MEASUREMENT: Personal sampling. Personal samplers were employed to measure total dust during the whole shift.


EXPOSURE LEVELS: Total dust levels over the entire shift ranged from 0.07 to 8.61 mg/m^3 (N = 80) with a median value of 0.97 µg/m^3 (overall arithmetic and geometric mean values, 1.33 and 0.94 mg/m^3 respectively).


EXPOSURE PERIOD: 7.9 ± 5.5 years average

Statistical methods:

Results were analysed for statistical significance using a χ² test or the Student’s t-test.

Results and discussion

Results:

EXPOSURE
- Number of measurements: 80
- Average concentrations: 0.07 to 8.61 mg/m3
- Arithmetic mean: 1.33 mg/m3
- Geometric mean: 0.94 mg/m3
- Median: 0.97 µg/m3


FINDINGS

Please refer to section Remarks on results including tables and figures for full tabulated results.

The matching between the exposed and controls in regard to age of the subject and their wives, age of wife at marriage, age difference between husband and wide, duration of employment in the factory, smoking habits, alcohol consumption, educational level and professional activity of spouse. Very few differences between the groups reached statistical significance. Manganese levels in the urine fluctuated much more than levels in the blood. The median values in the control and exposed groups were 0.16 and 1.17 µg/g creatinine respectively. During the period of exposure to the metal, the number of observed children in the age groups 16-25 and 26-35 was significantly lower than the expected number. The sex ratio was not found to be significantly different. The was no indication that other factors might account for the marked observed fertility difference between the control and the manganese-exposed group. No difference between the wife’s occupations were detected. The proportion of wives performing clerical or manual work was not significantly different. The only statistically significant difference between the group characteristics that might have an influence on fertility (i,e, educational levels of the wives) would tend to decrease the fertility of the control group in comparison to that of the exposed group.

Confounding factors:

Past exposure to manganese may have been lower than the levels of the study as there was a higher volume of production during the study compared to past years. The only statistically significant difference between the group characteristics that might have an influence on fertility (i.e. educational levels of wives) would tend to decrease the fertility of the control group by comparison to that of the manganese group. This may have masked the effect of manganese on fertility.

Strengths and weaknesses:

No extensive monitoring data were available to assess past exposure to manganese. However the same production process had been used for at least 15 years.

Any other information on results incl. tables

Table 1: Characteristics of Control and Manganese-Exposed Male Workers

 

	Control		Exposed		P
Number of subjects	81		85
Age (years)	39.5 ± 10.9^a	(21-58)	37.4 ± 9.3	(21-59)	NS^c
Age of wife (years)	38.0 ± 1.6	(17-61)	35.9 ± 9.4	(19-58)	NS^c
Age of wife at marriage (years)	22.4 ± 3.5	(16-34)	21.4 ± 3.6	(17-33)	NS^c
Duration of employment in the factory (years)	13.4 ± 10.8	(1-40)	8.1 ± 5.6	(1-19)	<0.001^c
Years of exposure to manganese	-	-	7.9 ± 5.5	(1-19)
Percent smokers	73		86		NS^d
Alcohol consumption
Yes (% of subjects)	73		79		NS^d
Glasses of beer/week	18.2 ± 13.9		22.4 ± 20		NS^c
Educational level
Primary and junior high school (%)	57		72		NS^d
Senior high school and university (%)	43		28
Educational level of wife
Primary and junior high school (%)	54		75		<0.02^d
Senior high school and university (%)	46		26
Wife with a job (%)	37		35		NS^d
Percent desiring a child	27		25		NS^d
Mn-B (µg/100 mL)	0.57 ± 0.26	(0.04-1.31)	1.29 ± 0.53	(0.10-3.30)
Mn-U (µg/g creatinine)	0.27 ± 0.31 (0.16)^b	(0.1-2.00)	4.37 ± 15.65 (1.17)^b	(0.09-140.6)
^aMean ± SD (range) ^bMedian ^cStudent’s t-test ^dx2 test NS: Statistically not significant.

 

Table 2: Fertility of Male Workers Exposed to Manganese Dusts

 

Age groups	Exposure	Number of years of fertility	Number of children		P
			Observed	Expected
16-25	Before	205	64	64.3	NS
	During	123	17	38.6	<0.05
26-35	Before	277	37	28.4	NS
	During	257	16	1.5	<0.05
36-45	Before	85	2	3.5	NS
	During	195	6		NS
NS: Statistically not significant (critical ratio)

Applicant's summary and conclusion

Conclusions:

Due to the presence of more than one manganese substance, including possible exposure to manganese ore, it is not possible to make a conclusion about the effect of any particular substance on fertility, or whether the effect may be due to exposure to the ore rather than a single substance. Read-across from manganese sulphate to manganese nitrateis justified based on having both high water solubility and structural similarities. Specifically, both substances have anions containing multiple oxygens. In addition the percentage contribution of Mn2+ in both substances is comparable.