Manganese sulphate

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Conducted to GLP and according to peer reviewed methods.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1993

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: NTP peer reviewed methods

Principles of method if other than guideline:

Groups of 10 male and 10 female rats were fed diets containing 0, 1600, 3130, 6250, 12500 or 25000 ppm manganese sulphate. Clinical findings were recorded weekly, feed consumption was recorded weekly by cage. Rats were weighed at the beginning of the studies and weekly thereafter. At the end of the exposure period, blood was collected for haematology analyses. A necropsy was performed on all animals and organs were weighed. A complete histopathological analysis was performed on all control and high-dose animals.

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Manganese sulphate monohydrate

IUPAC Name:

Manganese sulphate monohydrate

Details on test material:

- Name of test material (as cited in study report): manganese (II) sulphate monohydrate
- Physical state: crystalline, solid
-Appearance: white, slightly efflorescent
- Analytical purity: 97.7 ± 0.4%
- Impurities (identity and concentrations): sodium (640 ppm), potassium (120 ppm) and silicon (160 ppm).
- Stability under test conditions: No bulk stability studies were performed.
- Storage condition of test material: Bulk chemical was stored in the dark at room temperature.

Test animals

Species:

rat

Strain:

other: F344/N

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Laboratories (Stone Ridge, NY)
- Age at study initiation: 50 days

Administration / exposure

Route of administration:

oral: feed

Duration of treatment / exposure:

13 weeks

Frequency of treatment:

daily

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 1600, 3130, 6250, 12500 or 25000 which was equivalent to doses from 110 to 1700 mg/kg in males and 115 to 2000 mg/kg in females
Basis:
nominal in diet

No. of animals per sex per dose:

10 male and 10 female per dose group

Control animals:

yes

Examinations

Observations and examinations performed and frequency:

Clinical findings were recorded weekly, feed consumption was recorded weekly by cage. Rats were weighed at the beginning of the studies and weekly thereafter. At the end of the exposure period, blood was collected for haematology analyses.

Sacrifice and pathology:

A necropsy was performed on all animals and organs were weighed. A complete histopathological analysis was performed on all control and high-dose animals.

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

effects observed, treatment-related

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

not examined

Ophthalmological findings:

not examined

Haematological findings:

effects observed, treatment-related

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Gross pathological findings:

effects observed, treatment-related

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

no effects observed

Details on results:

-BODY WEIGHT AND WEIGHT GAIN: The mean bodyweight gain in males receiving 3130 ppm was marginally lower than that of the controls and was significantly lower in the three highest female dose groups than the controls.
-FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Feed consumption by exposed rats was similar to that of the controls. Females ingested an average of 20% more manganese sulphate than males in the corresponding exposure groups.
-HAEMATOLOGY: Neutrophil counts were significantly higher in all exposed male groups. Lymphocyte counts were significantly lower in the three highest dose groups.
In females: leukocyte counts were significantly lower in the three highest dose groups.
A significant increase in the percent haematocrit and erythrocyte counts occurred in males exposed to the three highest dose levels.
-ORGAN WEIGHTS: Absolute and relative liver weights of all exposed males and of the female 25000 ppm group were significantly lower than the controls.

Effect levels

1

Dose descriptor:

NOAEL

Effect level:

1 700 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male

Basis for effect level:

food consumption and compound intake

2

Dose descriptor:

NOAEL

Effect level:

2 000 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

female

Basis for effect level:

food consumption and compound intake

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

No clear relationship between observed differences and the ingestion of manganese sulphate has been defined.

Table 1.Survival, Body Weights, and Feed Consumption of Rats in the Rats in the 13-Week Feed Study of Manganese (II) Sulphate Monohydrate

 

Concentration (ppm)	Survival^a	Mean body weight and weight changes^brelative			Final Weight Feed to controls (%)	Consumption^c
		Initial	Final	Change		Week 1	Week 13
Male
0	10/10	136±5	291±4	155±4		14.9	13.1
1, 600	10/10	142±4	294±5	152±4	101	14.5	13.5
3,130	10/10	149±3	291±4	141±4	100	14.8	13.6
6, 250	10/10	148±2	294±3	146±3	101	15.0	9.6
12, 500	10/10	150±11	290±6	140±11	99	14.9	14.9
25, 000	10/10	140±4	284±6	144±4	97	14.1	14.4
Female
0	10/10	99±1	184±2	84±2		10.7	9.2
1, 600	10/10	103±1	181±2	79±2	99	10.8	9.3
3,130	10/10	96±1	175±2*	80±3	95	10.9	9.2
6, 250	10/10	101±1	176±2*	75±1**	96	10.7	14.3
12, 500	10/10	106±1**	178±1*	73±2**	97	10.7	10.5
25, 000	10/10	104±1**	174±3**	70±2**	95	12.1	10.3

* Significantly different (P≤0.05) from the control group by Williams’ or Dunnett’s test

** P≤0.01

a Number of animals surviving at 13 weeks/ number initially in group

b Weight given as mean ± standard error

c Feed consumption is expressed as grams per animal per day

 

Applicant's summary and conclusion

Conclusions:

The high level of MnSO4 consumed on a daily basis for 13 weeks in this study, without mortality, supports the lack of acute toxicity. Although some changes in lung weight and certain haematological parameters were significant compared to controls, the lack of clinical and histopathological findings despite the very high daily oral dose over a sub-chronic period, is an indication of the relatively low toxicity of MnSO4, at least for the parameters studied in this report.