Lithium bis(trifluoromethylsulfonyl)imide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Report date: 2002-04-19

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study performed according to OECD Guideline and EU Method and according to GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Report date:

2002

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Test material form:

solid: particulate/powder

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, L'Arbresle, France
- Age / weight at study initiation: On the day of treatment, the animals were approximately 6 weeks old, and had a mean body weight ± standard deviation of 182 ± 5 g for the males and 150 ± 9 g for the females. Females were nulliparous and non pregnant.
- Fasting period before study: The animals were fasted for an overnight period of approximately 18 hours before dosing, but had free access to water. Food was given back approximately 4 hours after administration of the test item.
- Housing: The animals were housed in polycarbonate cages with stainless steel lid (48 cm x 27 cm x 20 cm). Each cage contained one to seven animals of the same sex during the acclimation period and three rats of the same sex and group during the treatment period.
Each cage contained autoclaved sawdust (SICSA, Alfortville, France).
- Diet (e.g. ad libitum): All the animals had free access to A04 C pelleted diet (UAR, Villemoisson, Epinay-sur-Orge, France).
- Water (e.g. ad libitum): Drinking water filtered by a FG Millipore membrane (0.22 micron) was provided ad libitum.
- Acclimation period: At least 5 days before the beginning of the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2°C
- Humidity (%): 30 to 70%
- Air changes (per hr): Approximately 12 cycles/hour of filtered, non-recycled air.
- Photoperiod (hrs dark / hrs light): 12 h/12 h
The temperature and relative humidity were under continuous control and recording. The records were checked daily and filed. In addition to these daily checks, the housing conditions and corresponding instrumentation and equipment are verified and calibrated at regular intervals.

IN-LIFE DATES: From: 6 December 2001 To: 17 january 2002

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: purified water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 20 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg
- Justification for choice of vehicle: no data available

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

DOSAGE PREPARATION: On the day of treatment, the test item, at the chosen concentration, was incorporated in the vehicle. Each test item preparation was made freshly on the morning of administration by the CIT Pharmacy and any unused material was discarded that same day.

CLASS METHOD
- Rationale for the selection of the starting dose: Three animals of one sex were used for each step. Males were used in the initial step.
The dose-level used as the starting dose was selected from one of three fixed levels, 25, 200 or 2000 mg/kg body weight.
As no information on the toxic potential of the test item was available, for animal welfare reasons, the starting dose-level of 200 mg/kg was chosen.
After the first assay, as 2/3 males died, another assay was carried out on three males at the next lower dose-level (25 mg/kg).
After the second assay, as no mortality occurred, the results were confirmed in three females at the dose-level 25 mg/kg.
At the request of the Sponsor, another assay was performed at the dose-level of 200 mg/kg in three females.

Doses:

25 and 200 mg/kg bw

No. of animals per sex per dose:

3 per group

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality of each animal were observed frequently during the hours following administration of the test item, for detection of possible treatment-related clinical signs. Thereafter, observation of the animals was made at least once a day. Time of death was recorded individually, in terms of the number of hours or days after dosing. The animals were weighed individually just before administration of the test item on day 1 and then on days 8 and 15.
- Necropsy of survivors performed: Yes
- Other examinations performed: Clinical signs (Type, time of onset and duration of clinical signs were recorded for each animal individually.), Macroscopic post-mortem examination (All study animals were subjected to a macroscopic examination as soon as possible after death. After opening the thoracic and abdominal cavities, a macroscopic examination of the main organs (digestive tract, heart, kidneys, liver, lungs, pancreas, spleen and any other organs with obvious abnormalities) was performed.).

Statistics:

Not applicable

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 200 mg/kg bw

Mortality:

At the 25 mg/kg dose-level, no deaths occurred.
At the 200 mg/kg dose-level, mortality was 2/6 animals (two males 4h15 after treatment).

Clinical signs:

other: At the 25 mg/kg dose-level: Dyspnea and piloerection were noted in all males one hour after treatment. No other clinical signs were observed during the observation period. At the 200 mg/kg dose-level: - On day 1, hypoactivity then sedation, dyspnea, tonic

Gross pathology:

Macroscopic examination of the main organs of the animals revealed no apparent abnormalities.

Applicant's summary and conclusion

Interpretation of results:

toxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under these experimental conditions, the oral LD50 of the test item BIS TRIFLUOROMETHANESULFONIMIDE LITHIUM is higher than 200 mg/kg in rats.

Executive summary:

An acute oral toxicity study was performed with the test item Bis trifluoromethanesulfonimide lithium (TFSILi) in rats, in compliance with OECD Guideline n°423, under GLP conditions. The test item was prepared in purified water and was administered by oral route (gavage), under a volume of 10 mL/kg, to groups of fasted Sprague-Dawley rats.

The study design was as follows:

Dose (mg/kg)	Vehicle	Volume (mL/kg)	Male	Female
200	Purified water	10	3	-
25	Purified water	10	3	-
25	Purified water	10	-	3
200	Purified water	10	-	3

 

Clinical signs, mortality and body weight gain were checked for a period of up to 14 days following the single administration of the test item.

All animals were subjected to necropsy.

At the 25 mg/kg dose-level, no deaths occurred. Dyspnea and piloerection were noted in all males one hour after treatment. No other clinical signs were observed during the observation period.

At the 200 mg/kg dose-level, mortality was 2/6 animals (two males 4h15 after treatment). On day 1, hypoactivity then sedation, dyspnea, tonic-clonic convulsions, hypersalivation and piloerection were the clinical signs observed in all the animals. On day 2, hypoactivity and piloerection were noted in the surviving male; no clinical signs persisted in females. From day 3 until the end of the observation period, no clinical signs were recorded.

The body weight gain of the animals given 25 or 200 mg/kg was not affected by treatment with the test item.

At necropsy, no apparent abnormalities were observed in any animal.

The oral LD50 of the test item Bis trifluoromethanesulfonimide lithium in Sprague-Dawley rats was established to be higher than 200 mg/kg.