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Description of key information

In an acute oral toxicity study (Smyth HF at al., American Industrial Hygiene Association Journal, 30(5): 470 (1969), Smyth HF et al., American Industrial Hygiene Association Journal 23:95 (1962)), the oral LD50 in male Carworth-Wistar rats was determined to be 3.73 g/kg bw . Manganese acetate is of low toxicity based on the LD50 in male Carworth-Wistar rats and does therefore not need to be classified according Regulation 1272/2008/EC.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non-GLP study similar to guideline with deviations, documentation on raw data missing. However, the given data indicate that the study was well-performed.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
animals are non-fasted, certain documentation is lacking
GLP compliance:
no
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
other: Carworth-Wistar
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: reared in in-house colony, Mellon Institute of Industrial Research, Pittsburgh, Pennsylvania
- Age at study initiation: 4 -5 weeks
- Weight at study initiation: 90 - 120 g
- Fasting period before study: no
- Housing: unknown
- Diet (e.g. ad libitum): Rockland rat diet
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
Gavage of solution of a concentration of 0.2 g/ml Mn(OOCH3)2*4H2O
Doses:
Arranged in a logarithmic series differing by a factor of two
No. of animals per sex per dose:
5
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: no data
Statistics:
The most probalbe LD50 value and its fiducial range are estimated b ythe method of Thompson (Thompson, W.R.: Use of moving averages and interpolation to estimate median effective dose. Bacteriol. Rev. 11:115 (June 1947)) using the tables of Weil (Weil, C.S.: Tables for convenient calculation of median-effective dose (LD50 or EC50) and instructions on their use. Biometrics 8:249 (Sept. 1952)).
Preliminary study:
no data
Dose descriptor:
LD50
Effect level:
ca. 3 730 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Single oral LD50 vary from 2680-5210 mg/kg bw, expressed as Manganese Acetate Tetrahydrate
Mortality:
no data
Clinical signs:
no data
Body weight:
no data
Gross pathology:
no data
Other findings:
no data
Interpretation of results:
relatively harmless
Remarks:
Migrated information Criteria used for interpretation of results: other: EU GHS
Conclusions:
Although there are some deficiencies in documentation, the given data indicate that the study was well-performed similar to OECD guideline 401. Therefore, the results can be considered as reliable and the LD50 value of 3.73 g/kg bw can be used for classification. Consequently, Manganese acetate can be stated to be relatively harmless.
Executive summary:

In an acute oral toxicity study, groups of non-fasted, 4 -5 weeks old Carworth-Wistar male rats (five rats / group) were given a single oral dose of Manganous acetate in water (0.2 g/ml) at doses arranged in a logarithmic series differing by a factor of two and were observed for 14 days. The oral LD50 in males was determined to be 3.73 g/kg bw . Manganese acetate is of low toxicity based on the LD50 in male Carworth-Wistar rats.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
3 730 mg/kg bw
Quality of whole database:
One study assessed with Klimisch 2 and two supporting studes (Klimisch 4 since only abstracts are available) are available to cover the endpoint "Acute Toxicity: oral", hence, the available information meets fully the tonnage-driven data requirements of REACH. Additionally, all available studies revealed rather equivalent results, i.e. the one of the key study is above the boundary value of 2000 mg/kg bw for classification, as well as the study Singh, when taking into account the correction for the molecular weight of Manganese acetate, and to the outcomes of the studies are consistent. Also, the results by Holbrook are rather close to the boundary value, and as a consequence no classification is needed.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In an acute oral toxicity study (Smyth HF at al., American Industrial Hygiene Association Journal, 30(5): 470 (1969), Smyth HF et al., American Industrial Hygiene Association Journal 23:95 (1962)), groups of non-fasted, 4 -5 weeks old Carworth-Wistar male rats (five rats / group) were given a single oral dose of Manganese acetate in water (0.2 g/ml) at doses arranged in a logarithmic series differing by a factor of two and were observed for 14 days. The oral LD50 in males was determined to be 3.73 g/kg bw . Manganese acetate is of low toxicity based on the LD50 in male Carworth-Wistar rats and does therefore not need to be classified according Regulation 1272/2008/EC.

Although there are some deficiencies in documentation, the given data indicate that the study was well-performed similar to OECD guideline 401, the reliability 2 was assigned and manganese (II) acetate was used as testing substance. Therefore, the results can be considered as reliable and the LD50 value of 3.73 g/kg bw can be used for classification. Consequently, Manganese (II) acetate can be stated to be relatively harmless.

This is in congruence with the data on acute oral toxicity gained from the supporting studies (Holbrook DJ, Environmental Health Perspectives Vol. 10, pp. 95-101, 1975, Singh PP, Indian J Pharmac (1991) 23: 153-159) on MnSO4, MnCl2 and Manganese acetate which are also of the magnitude of 2000 mg/kg bw indicating no hazard arising from Manganese (II) acetate.


Justification for selection of acute toxicity – oral endpoint
First, data were gained directly from manganese acetate, no read-across usually linked with uncertainties needed to be done. Second, this study was performed similar to guideline 401 with deviations, and the given data indicate that the study was well-performed. Hence, this study was assessed to be of reliability 2 and therefore is considered to be the most reliable one within the available studies.

Justification for selection of acute toxicity – inhalation endpoint
Data waiving: The test substance has a very low vapour pressure (< 10 mm Hg at 25°C), high melting point (210°C) and the particles are not of an inhalable size (median 650.6 µm), so the potential for the generation of inhalable forms is low, also the use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be unlikely to occur, and no acute inhalation test was performed.

Justification for selection of acute toxicity – dermal endpoint
Data waiving: According to REACH Annex VIII column 2 Testing by the dermal route is appropriate if (1) inhalation of the substance is unlikely and (2) skin contact in production and/or use is likely and (3) the physicochemical and toxicological properties suggest potential for a significant rate of absorption through the skin. Although inhalation of Manganese (II) acetate is unlikely, the latter two conditions do not apply. The rather high particle size of approx. 650 µm minimizes absorption due to the limited contact surface related to the substance' total amount. Consequently, no additional testing is required.

Justification for classification or non-classification

Manganese (II) acetate does not need to be classified according to Regulation 1272/2008/EC, because the LD50 of the most reliable study (Key, Reliability 2, on Manganese (II) acetate, Smyth HF at al., American Industrial Hygiene Association Journal, 30(5): 470 (1969), Smyth HF et al., American Industrial Hygiene Association Journal 23:95 (1962)) was determined to be 3730 mg/kg bw in male Carworth-Wistar rats. This value is above the boundary value of 2000 mg/kg bw triggering classification as acute toxic Cat. 4 and does therefore not need to be classified. Additionally, the less reliable LD50 values obtained from supporting studies on MnSO4, MnCl2 and Mn(OOOCCH3)2 are also of the magnitude of 2000 mg/kg bw indicating no hazard arising from Manganese (II) acetate.

Furthermore, the testing for acute toxicity via inhalation and dermal route was waived due to the physico-chemical properties (vapour pressure, particle size, melting point) resulting in low resorption. Consequently, the LD50 values via these routes can be exspected to be even much higher and would consequently also not trigger classification.