Manganese-(II)-hexacyanomanganate (II) sodium salts

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

30 March 2020 - 08 July 2020

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2020

Report date:

2020

Materials and methods

Test guideline

Test guideline 1

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Version / remarks:

17 December 2001

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

December 2002

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries, Test Data for Registration of Agricultural Chemicals, Acute oral toxicity (2-1-1), 12 Nousan No 8147,

Version / remarks:

November 24, 2000.

Deviations:

no

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Manganese-(II)-hexacyanomanganate (II) sodium salts

EC Number:

847-971-4

Cas Number:

2363126-59-2

Molecular formula:

NaxMny[Mn(CN)6]z X = 1.2-1.4; Y = 1.0; Z = 0.8-0.85

IUPAC Name:

Manganese-(II)-hexacyanomanganate (II) sodium salts

impurity 1

Reference substance name:

Water

EC Number:

231-791-2

EC Name:

Water

Cas Number:

7732-18-5

Molecular formula:

H2O

IUPAC Name:

Oxidane

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

See description in the test substance section

Test animals

Species:

rat

Strain:

other: RccHan™:WIST albino

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Rationale for alternative/additional species to rat (if applicable): not applicable
- Source: Envigo RMS (UK) Ltd
- Females (if applicable) nulliparous and non-pregnant: [yes]
- Rationale for use of males (if applicable): not applicable
- Age at study initiation: eight to twelve weeks of age
- Weight at study initiation: 154 to 181 g
- Fasting period before study: overnight prior to dosing
- Housing: solid bottomed polycarbonate cages with a stainless steel mesh lid. Each cage contained a quantity of autoclaved softwood bark-free fiber bedding. Cages, food hoppers, water bottles and bedding were changed at appropriate intervals.
- Diet (e.g. ad libitum): ad libitum, Teklad 2014C Diet
- Water (e.g. ad libitum): ad libitum, Potable water taken from the public supply
- Acclimation period: not specified
- Microbiological status when known: not specified
- Method of randomisation in assigning animals to test and control groups: not specified

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 24°C
- Humidity (%): 40 to 70%
- Air changes (per hr): not specified
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: Sighting study: 300 - 50 - 5 mg/kg anhydrous test substance in Corn Oil; Main study: 5 mg/kg anhydrous test substance in Corn Oil
- Amount of vehicle (if gavage): 10 mL/kg
- Justification for choice of vehicle:
- Lot/batch no. (if required):
- Purity:

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

DOSAGE PREPARATION (if unusual):not applicable

Doses:

Range finder: 300 - 50 - 5 mg/kg
Main study: 5 mg/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days (or other?) 14 d
- Frequency of observations and weighing: d 0, 1, 8 and 15
- Necropsy of survivors performed: yes : Subcutaneous tissue, Brain, Heart, Lungs and bronchi, Liver, Spleen, Kidneys, Stomach, Duodenum, Small Intestines, Large Intestines, Cecum, Urinary Bladder
- Clinical signs including body weight: Unsteady gait, Decreased activity, Irregular breathing, Convulsion, Flattened posture, Rapid breathing, Shallow breathing, Prostrate posture, Unresponsive behavior
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: yes

Results and discussion

Preliminary study:

The female (number 61) dosed at 347 mg/kg in the sighting study died approximately nine minutes after dosing and the females (animal number 62) dosed at 57.8 mg/kg was killed approximately 50 minutes after dosing.

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 5 mg/kg bw

Based on:

test mat.

Remarks:

(anhydrous content)

Mortality:

The female (number 61) dosed at 347 mg/kg in the sighting study died approximately nine minutes after dosing and the females (animal number 62) dosed at 57.8 mg/kg was killed approximately 50 minutes after dosing.
Clinical signs prior to death for female 61 (dosed at 347 mg/kg) comprised unsteady gait, decreased activity, irregular breathing, convulsion and flattened posture. These signs were seen from approximately five minutes after dosing. Macroscopic examination of this animal revealed a congestion (darkened tissue/organ) of the liver, blue fluid with blue flecks in the stomach, small and large intestines, and in the cecum. Also, a fluid with blue flecks was observed in the duodenum.
Clinical signs prior to death for female 62 (dosed at 57.8 mg/kg) comprised rapid breathing, decreased activity, shallow breathing, prostrate posture and unresponsive behavior. These signs were seen from approximately 30 minutes after dosing. Macroscopic examination of this animal revealed congestion (darkened tissue/organ) of the liver and lungs and bronchi. In addition, a fluid with blue flecks was observed in the stomach.

Clinical signs:

other: No clinical signs were observed in any animal dosed at 5.78 mg/kg in the sighting study or main study.

Gross pathology:

No abnormalities were noted in any animal dosed at 5.78 mg/kg at the macroscopic examination at study termination on Day 15.

Other findings:

not reported

Any other information on results incl. tables

Dose (mg/kg)	No. of deaths	Day^@
		1		2 to 15
		<9m	<50	a	b
Sighting study
347*	1/1F	1	-	-	-
57.8**	1/1F	0	1	-	-
5.78***	0/1F	0	0	0	0
Main study
5.78***	0/4F	0	0	0	0
*      347 mg/kg was the test item as supplied which was equivalent to 300 mg/kg of the anhydrous test item. **    57.8 mg/kg was the test item as supplied which was equivalent to 50 mg/kg of the anhydrous test item. *** 5.78 mg/kg was the test item as supplied which was equivalent to 5 mg/kg of the anhydrous test item.   @ The day/time indicated is the time that the animal was found dead/killed for humane reasons F   Female m Minutes a   First observation b   Second observation -    Not applicable

Applicant's summary and conclusion

Interpretation of results:

Category 2 based on GHS criteria

Conclusions:

The acute median lethal oral dose (LD50) to rats of the test item was demonstrated to be between 5.78 and 57.8 mg/kg body weight (equivalent to 5 and 50 mg/kg anhydrous test item).
Accordingly the test item is included in Category 2, according to the Globally Harmonised System (GHS).

Executive summary:

The study was performed to assess the acute oral toxicity of the test item, an industrial chemical, to the rat.

Fasted female rats received a single oral gavage dose of the test item, formulated in dried corn oil, at the following dose levels:

- Sighting investigations: 347*, 57.8** and 5.78*** mg/kg body weight

- Main study: Based on the results of the sighting investigations a further four fasted females were similarly dosed at 5.78*** mg/kg body weight.

* 347 mg/kg was the test item as supplied which was equivalent to 300 mg/kg of the anhydrous test item.

** 57.8 mg/kg was the test item as supplied which was equivalent to 50 mg/kg of the anhydrous test item.

*** 5.78 mg/kg was the test item as supplied which was equivalent to 5 mg/kg of the anhydrous test item.

During the study, clinical condition, body weight and macropathology investigations were undertaken.

Results

The female (number 61) dosed at 347 mg/kg in the sighting study died approximately nine minutes after dosing and the females (animal number 62) dosed at 57.8 mg/kg was killed approximately 50 minutes after dosing.

Clinical signs prior to death for female 61 (dosed at 347 mg/kg) comprised unsteady gait, decreased activity, irregular breathing, convulsion and flattened posture. These signs were seen from approximately five minutes after dosing. Macroscopic examination of this animal revealed a congestion (darkened tissue/organ) of the liver, blue fluid with blue flecks in the stomach, small and large intestines, and in the cecum. Also, a fluid with blue flecks was observed in the duodenum.

Clinical signs prior to death for female 62 (dosed at 57.8 mg/kg) comprised rapid breathing, decreased activity, shallow breathing, prostrate posture and unresponsive behavior. These signs were seen from approximately 30 minutes after dosing. Macroscopic examination of this animal revealed congestion (darkened tissue/organ) of the liver and lungs and bronchi. In addition, a fluid with blue flecks was observed in the stomach.

No clinical signs were observed in any animal dosed at 5.78 mg/kg in the sighting study or main study.

All surviving animals were considered to have achieved satisfactory body weight gains throughout the study.

No abnormalities were noted in any animal dosed at 5.78 mg/kg at the macroscopic examination at study termination on Day 15.