Iron(III) manganese(II) hexacyanoferrate(II) sodium salts

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

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:

according 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:

712-C-02-190. 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:

Iron(III) manganese(II) hexacyanoferrate(II) sodium salts

EC Number:

847-973-5

Cas Number:

2363126-51-4

Molecular formula:

NaxMny1Fey2[Fe(CN)6]z X = 1-2; Y1 = 0.5-0.9; Y2 = 0.1-0.5; Z = 0.67-1.0

IUPAC Name:

Iron(III) manganese(II) hexacyanoferrate(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:

Water

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

See section "Test material information""

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 + 2497 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 mg/kg
Main study: 2000 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:

There were no deaths during the study.

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks:

anhydrous content

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

There were no deaths during the study.

Clinical signs:

other: Black feces were observed in all females dosed at 2000 mg/kg in the main study. This sign was observed on Day 2 of the study. Recovery of this clinical sign, as judged by external appearance and behaviour, was complete by Day 3. No clinical signs were see

Gross pathology:

No abnormalities were noted in any animal at the macroscopic examination at study termination on Day 15.

Other findings:

not reported

Applicant's summary and conclusion

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

The acute median lethal oral dose (LD50) to rats of the test item was demonstrated to be greater than 2497 mg/kg body weight (equivalent to 2000 mg/kg anhydrous test item).
The test item is therefore included in Category 5, 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 corn oil, at the following dose levels:

- Sighting investigations: 375* and 2497** mg/kg body weight.

- Main study: Based on the results of the sighting investigations a further four fasted females were similarly dosed at 2497** mg/kg body weight.

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

** 2497 mg/kg was the test item as supplied which was equivalent to 2000 mg/kg of the anhydrous test item.

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

Results

There were no deaths during the study.

Black feces were observed in all females dosed at 2497 mg/kg in the main study. This sign was observed on Day 2 of the study. Recovery of this clinical sign, as judged by external appearance and behaviour, was complete by Day 3. No clinical signs were seen in any other animal dosed at 375 mg/kg (sighting study 1) or 2497 mg/kg (sighting study 2).

A low body weight gain was observed on Day 8 to 15 for female number 82 dosed at 2497 mg/kg in sighting study 2 and female number 83 dosed in the main study at 2497 mg/kg. All other animals were considered to have achieved satisfactory body weight gains throughout the study.

No abnormalities were noted in any animal at the macroscopic examination at study termination on Day 15