Sodium bis(trifluoromethylsulfonyl)imide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

August 2021

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2021

Report date:

2021

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

yes

Remarks:

Due to technical error, temperature values (maximum of 25.9°C) outside the expected range of 19-25°C was recorded occasionally in the animal rooms during the study. These deviations have no effect on the outcome of the study.

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

sodium trifluoro[(trifluoromethanesulfonylazanidyl)sulfonyl]methane

EC Number:

804-361-2

Cas Number:

91742-21-1

Molecular formula:

C2F6NO4S2.Na

IUPAC Name:

sodium trifluoro[(trifluoromethanesulfonylazanidyl)sulfonyl]methane

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

Purity: 99%

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH (Address: Sandhofer Weg 7, D-97633 Sulzfeld, Germany)
- Females: nulliparous and non-pregnant
- Age at study initiation: Young adult rats, 8 weeks old- Weight at study initiation:
- Fasting period before study: The night before treatment
- Housing: Group caging (3 animals/cage)
- Diet: Animals received ssniff SM R/M "Autoclavable complete diet for rats and mice – breeding and maintenance" produced by ssniff Spezialdiäten GmbH (Address: D-59494 Soest, Germany) ad libitum. The food was considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study. The supplier provided an analytical certificate for the batch used.
- Water: Animals received tap water from the municipal supply, as for human consumption from a 500 mL bottle, ad libitum. Water was considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study.
Water quality control analysis is performed once every three months and microbiological assessment is performed monthly, by Veszprém County Institute of State Public Health and Medical Officer Service (H-8200 Veszprém, József Attila u. 36., Hungary). The quality control results are retained in the Archives of Test Facility.
- Acclimation period: 5 days. During the acclimation period of at least 5 days, the animals were kept under the same controlled environment conditions as during the experimental period. Only animals without any visible signs of illness were used for the study.
- Microbiological status when known : The health status of the animals assigned to study was verified by the clinical Veterinarian.
- Method of randomisation in assigning animals to test and control groups: The animals were selected by hand at time of delivery. It was checked that all animals were within 20% of the overall mean at the start of the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.3 – 25.9°C
- Humidity (%): 32 - 69%
- Air changes (per hr): 15-20 air exchanges/hour
- Photoperiod (hrs dark / hrs light): 12 hours daily, from 6.00 a.m. to 6.00 p.m.

Administration / exposure

Route of administration:

oral: gavage

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

CLASS METHOD
- Rationale for the selection of the starting dose: Initially, three females (Group 1) were treated at a dose level of 300 mg/kg bw. All animals died on the day of treatment (Day 0). Therefore, one group (Group 2) was treated at the dose level of 50 mg/kg bw. As no mortality was observed, a confirmatory group (Group 3) was treated at the same dose level. No mortality was observed in this group; therefore, no further testing was required according to OECD 423 and Commission Regulation (EC) No 440/2008 of 2008, B.1.tris.

Doses:

300 and 50 mg/kg bw

No. of animals per sex per dose:

3

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: at least on Days -1 (prior to removal of food), 0 (prior to administration), 7 and 14 with a precision of 1 g.
- Necropsy of survivors performed: yes
- Clinical signs including body weight: Any clinical sign noted during dosing or at any other occasions was recorded at the time seen.

Statistics:

No statistical evaluation was performed in this study.

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 50 - < 300 mg/kg bw

Based on:

test mat.

Effect levels 2

Sex:

female

Dose descriptor:

LD0

Effect level:

50 mg/kg bw

Based on:

test mat.

Effect levels 3

Sex:

female

Dose descriptor:

LD100

Effect level:

300 mg/kg bw

Based on:

test mat.

Mortality:

All animals died at the dose level of 300 mg/kg bw on Day 0.
No mortality occurred in the study during the 14-day observation period at the dose level of 50 mg/kg bw.

Clinical signs:

convulsions

irregular respiration

other: activity, recumbency, hunched back, piloerection, red discharge

Body weight:

other body weight observations

Remarks:

There were no test item related body weight changes. Body weights were within the range commonly recorded for this strain and age.

Any other information on results incl. tables

INDIVIDUAL BODY WEIGHT AND BODY WEIGHT GAIN

Applicant's summary and conclusion

Interpretation of results:

Category 3 based on GHS criteria

Remarks:

According to the Globally Harmonised System (GHS) criteria, sodium bis(trifluoromethane)sulfonimide can be ranked as "Category 3" for acute oral exposure. According to the Classification, Labelling and Packaging (CLP) criteria, sodium bis(trifluoromethane)sulfonimide can be ranked as "Category 3" for acute oral exposure.

Conclusions:

Under the conditions of this study, the acute oral LD50 value of the test item sodium bis(trifluoromethane)sulfonimide was found to be between 50 and 300 mg/kg bw in female Crl:WI rats.

Executive summary:

The single-dose oral toxicity study of sodium bis(trifluoromethane)sulfonimide in rats was performed according to the acute toxic class method (OECD 423 and Commission Regulation (EC) No 440/2008 of 30 May 2008, B.1.Tris) in Crl:WI Wistar rats.

Three groups of three female Crl:WI rats were treated with the test item at dose levels of 300 mg/kg body weight (bw) (Group 1) and 50 mg/kg bw (Group 2 and Group 3).

A single oral treatment was carried out by gavage for each animal after an overnight food withdrawal. Food was made available again 3 hours after the treatment. The test item was administered at the dose levels of 300 and 50 mg/kg bw.

Initially, three females (Group 1) were treated at a dose level of 300 mg/kg bw. All animals died on the day of treatment (Day 0). Therefore, one group (Group 2) was treated at the dose level of 50 mg/kg bw. As no mortality was observed, a confirmatory group (Group 3) was treated at the same dose level. No mortality was observed in this group; therefore, no further testing was required according to OECD 423 and Commission Regulation (EC) No 440/2008 of 2008, B.1.tris.

Clinical observations were performed immediately after treatment and/or at 30 minutes, 1, 2, 3, 4 and 6 hours after dosing and daily for 14 days thereafter. Body weight was measured on Days -1, 0, 7 and before necropsy (Day 14). All animals were subjected to a necropsy and a macroscopic examination.

The results of the study were summarized as follows:

Mortality

All animals died at the dose level of 300 mg/kg bw on Day 0. No mortality occurred in the study during the 14-day observation period at the dose level of 50 mg/kg bw.

Clinical Observations

After treatment at 300 mg/kg bw, decreased activity (moderate) (3/3 animals), recumbency (3/3 animals), hunched back (3/3 animals), clonic / tonic convulsion (whole body) (3/3 animals), laboured respiration (3/3 animals), piloerection (3/3 animals) and red discharge (right eye) (1/3 animals) were observed prior to death. All animals at dose level of 300 mg/kg bw died on Day 0.

Animals at dose level of 50 mg/kg bw, slightly decreased activity (6/6 animals), hunched back (6/6 animals) and slight ataxia (1/6 animals) were observed on Day 0. Slightly decreased activity (3/6 animals) was observed on Day 1. All animals were symptom-free from Day 2.

Body Weight and Body Weight Gain

There were no test item related body weight changes. Body weights were within the range commonly recorded for this strain and age.

Under the conditions of this study, the acute oral LD50 value of the test item sodium bis(trifluoromethane)sulfonimide was found to be between 50 and 300 mg/kg bw in female Crl:WI rats.