bis(trifluoromethylsulfonyl)azanide;1-ethyl-3-methylimidazol-3-ium

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

June 2017 - 10 November 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

17 December 2001

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

Council regulation No. 440/2008

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Test material

Test material information

Constituent 1

Reference substance name:

1-ethyl-3-methyl-1H-imidazol-3-ium; trifluoro[(trifluoromethanesulfonylazanidyl)sulfonyl]methane

EC Number:

700-235-5

Cas Number:

174899-82-2

Molecular formula:

C8H11F6N3O4S2

IUPAC Name:

1-ethyl-3-methyl-1H-imidazol-3-ium; trifluoro[(trifluoromethanesulfonylazanidyl)sulfonyl]methane

Test material form:

liquid

Details on test material:

clear liquid, colorless

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: proionic GmbH; 25PI208_12; PA 177
- Expiration date of the lot/batch: May 2019
- Purity test date: > 99%w


STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Elevage JANVIER LABS (53940 Le Genest St Isle - France)
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 8 weeks
- Weight at study initiation: ~ 200 grams
- Housing: solid-bottomed clear polycarbonate cages with a stainless stell mesh lid; sawdust bedding
- Diet (e.g. ad libitum): foodstuff (ENVIGO - 2016)
- Water (e.g. ad libitum): tap-water from public distribution system
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19°C - 25°C
- Humidity (%): 30 to 70
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:

other: administered under a volume of 1.32 mL/kg body weight using a suitable syrine graduated with an oesophageal metal canula

Vehicle:

DMSO

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 0.20 mL test item in 1.12 mL DMSO (corresponding to 300 mg)
0.033 mL test item in 1.287 mL DMSO (corresponding to 50 mg)
0.066 mL test item in 2.574 mL DMSO (corresponding to 100 mg)
- Justification for choice of vehicle: most suitable formulation possible



MAXIMUM DOSE VOLUME APPLIED: each preparation was administered under a volume of 1.32 mL/kg body weight

Doses:

50 mg/kg and 300 mg/kg

No. of animals per sex per dose:

Group treated (300 mg/kg): 3 female rats Rf1622 to Rf1624 (Step 1)
3 female rats Rf1638 to Rf1640 (Step 2)

Group treated (50 mg/kg): 3 female rats Rf1648 to Rf1650 (Step 3)
3 female rats Rf1662 to Rf1664 (Step 4)

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 30 min, 1h, 3h, 4h, 24h, 48 h after administration of the test item and continued daily during 14 days; The animals were weighted on day D0 (just before administering the test item) then on day 2, day 7 and day 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical observations; body weight evolution; macroscopic examinations

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 50 - < 300 mg/kg bw

Based on:

test mat.

Mortality:

3 mortalities at the dose of 300 mg/kg body weight

Clinical signs:

other: absence in spontaneous activity, muscle tones, righting reflex, Preyer´s reflex, chronic convulsion, associated with an increase of and salivation, mydriasis, dyspnea or polypnea

Applicant's summary and conclusion

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

The LD50 of the test item 1-Ethyl-3-methylimidazolium bis (trifluoromethylsulfony)imide is higher than 50 mg/kg and lower than 300 mg/kg by oral route in the rat.
In accordance with the O.E.C.D Test Guideline No. 423, the LD50-cut-off of the test item may be considered as 300 mg/kg body weight by oral route in the rat.
According to the criteria for classification, packaging and labelling of dangerous substances and preperations in accordance with the regulation EC No. 1272/2008, the test item 1-Ethyl-3-methylimidazolium bis (trifluoromethylsulfonyl)imide has to be classified in the category 3. The signal word "DANGER" and hazard statement H301 "Toxic if swallowed" are required

Executive summary:

The test item 1 -Ethyl-3 -methylimidazolium bis(trifluoromethylsulfonyl)imide was administered to a group of 6 female Spreque Dawley rats at the dose of 300 mg/kg body weight and the to a group of 6 female Spraque Dawley rats at the dose of 50 mg/kg body weight. The experimental protocol was established according to the official method as defined in the O.E.C.D Test Guideline No. 423 dated December 17th, 2001 and the test method B.1tris of the Council regulation No. 440/2008.

Three mortalities were noted in animals treated at the dose of 300 mg/kg body weight, one at 3 hours post dose during the 1st step and two at 24 hours post dose during the 2nd step.

The mortalities were preceded by an absence in spontaneous activity, muscle tones, righting reflex, Preyer´s reflex, chronic convulsion, associated with an increase of and salivation, mydriasis, dyspnea or polypnea.

Rigor mortis (1/3) were noted before the necropsy.

The macroscopic examination of these animals revealed a colorless liquid inside the stomach (1/3). No other change was noted.

In the surviving animals (3/6), a decrease or absence in spontaneaous activity, muscle tones, righting reflex, chronic convulsion, Preyer´s reflex, associated with an increase of salivation, mydriasis or myosis, and eyes partially / totally closed were noted at 30 minutes pot dose. The animal recovered a normal activity on day 2.

An asence of body weight gain was noted on day 2 versus day 0. Then, the body weight evolution of the animals remained normal.

The macroscopic examination of the animals at the end of the study did not reveal treatment related changes.

No mortality was noted in the animals treated at the dose of 50 mg/kg body weight.

No clinical signs related to the administration of the test item were observed during the study.

The body weight evolution of the animals treated at the dose of 50 mg/kg body weight remained normal during the study.

The macroscopic examination of the animals treated at the dose of 50 mg/kg body weight at the end of the study did not reveal treatment related changes.

In conclusion, the LD50 of the test item 1-Ethyl-3-methylimidazolium bis (trifluoromethylsulfony)imide is higher than 50 mg/kg and lower than 300 mg/kg by oral route in the rat.

In accordance with the O.E.C.D Test Guideline No. 423, the LD50-cut-off of the test item may be considered as 300 mg/kg body weight by oral route in the rat.

According to the criteria for classification, packaging and labelling of dangerous substances and preperations in accordance with the regulation EC No. 1272/2008, the test item 1-Ethyl-3-methylimidazolium bis (trifluoromethylsulfonyl)imide has to be classified in the category 3. The signal word "DANGER" and hazard statement H301 "Toxic if swallowed" are required