Lithium bis(trifluoromethylsulfonyl)imide

Endpoint summary

Description of key information

Bis trifluoromethanesulfonimide lithium (TFSILi) was found corrosive to skin and highly irritating to eyes.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

May - August 1988

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study according to the OECD 404 guideline but not GLP.

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hazleton Research Products, Inc., Denver PA
- Age at study initiation: young adults
- Weight at study initiation: Three acclimated animals weighing from 2334 to 2670 g were chosen at random for the test.
- Housing: maintained individually in screen-bottom cages in temperature and humidity-controlled quarters.
- Diet: measured amount of High Fiber Rabbit Chow 5326, Purina Mills, Inc., ad libitum
- Water: ad libitum)
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): controlled
- Humidity (%): controlled

IN-LIFE DATES: From: 07/06/1988 To: 21/06/1988

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

The test material was applied to the intact skin of each rabbit in the amount of 0.5 ml.

Duration of treatment / exposure:

4 hours

Observation period:

14 days
Observations: After the exposure period, the bandages were removed and the test sites were washed using lukewarm tap water and disposable paper towels. The test material was removed from the test sites as thoroughly as possible without irritating the skin. Thirty minutes following removal of the test material, the degree of erythema and edema was read according to the Draize technique. Subsequent examinations were made at 24, 4B, 72 and 96 hours and at 7 and 14 days after patch removal.

Number of animals:

3

Details on study design:

TEST SITE
The treated area was covered with a 2.5 x 2.5cm gauze patch secured with paper tape and overwrapped with Saran Wrap and Elastoplast tape to provide a semi-occlusive dressing.
Collars were applied to restrain the test animals for the 4-hour exposure period.

REMOVAL OF TEST SUBSTANCE
After the exposure period, the bandages were removed and the test sites were washed using lukewarm tap water and disposable paper towels. The test material was removed from the test sites as thoroughly as possible without irritating the skin. Thirty minutes following removal of the test material, the degree of erythema and edema was read according to the Draize technique. Subsequent examinations were made at 24, 48, 72 and 96 hours and at 7 and 14 days after patch removal.

SCORING SYSTEM: Draize system

Individual body weights were taken just prior to study initiation and at Days 7 and 14.
Pathology: At study termination, all animals were euthanatized and discarded.

Irritation parameter:

erythema score

Basis:

mean

Remarks:

on 3 animals

Time point:

other: at 24, 48 and 72 hours

Score:

3

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: Necrosis

Irritation parameter:

edema score

Basis:

mean

Remarks:

on 3 animals

Time point:

other: at 24, 48 and 72 hours

Score:

2.33

Max. score:

4

Reversibility:

not reversible

Table of results:

		Hours					Days
		4	24	48	72	96	7	14
Erythema	Animal 1	3AB	3N	3N	3N	3N	3N	3N
	Animal 2	3N	3N	3N	3N	3N	3N	4N
	Animal 3	3AB	3N	3N	3N	4N	4N	4N
Edema	Animal 1	4	2	2	2	2	2	2
	Animal 2	4	3	3	3	2	2	3
	Animal 3	4	2	2	2	2	2	2

A - Subcutaneous hemorrhage

B - Blanching

N - Possible necrotic area

Interpretation of results:

corrosive

Conclusions:

TFSILi is corrosive to skin.

Executive summary:

An skin irritation study was performed with the test item Bis trifluoromethanesulfonimide (TFSILi) in rabbits, in compliance with OECD Guideline n°404, but not under GLP conditions. The test item was applied on clipped skin for 4 hours under semi-occlusive coverage.

After the exposure period, the bandages were removed and the test sites were washed using lukewarm tap water and disposable paper towels. The test material was removed from the test sites as thoroughly as possible without irritating the skin. Thirty minutes following removal of the test material, the degree of erythema and edema was read according to the Draize technique. Subsequent examinations were made at 24, 48, 72 and 96 hours and at 7 and 14 days after patch removal. For erythema score, the mean on 3 animals at 24, 48 and 72 hours was 3 with necrosis, and the edema score was 2.33. In these conditions, TFSILi is considered corrosive to skin and should be classified H314 according to the CLP 1272/2008 criteria.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: CEGAV, Saint Mars d'Egrenne, France
- Age at study initiation: No data available
- Weight at study initiation: The animals had a mean body weight ± standard deviation of 3.0 ± 0.3 kg.
- Housing: The animals were housed individually in polystyrene cages (48.2 cm x 58 cm x 36.5 cm).
- Diet (e.g. ad libitum): The animals had free access to 110 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): 18 ± 3°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

IN-LIFE DATES: From: 18 December 2001 To: 18 January 2002

Vehicle:

unchanged (no vehicle)

Controls:

other: the right eye, which remained untreated, served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg introduced into the conjunctival sac of the left eye
- Concentration (if solution): Not applicable
- pH: The pH of the test item at the concentration of 10% in purified water, measured at CIT, was approximately 6.

Duration of treatment / exposure:

Single conjunctival instillation

Observation period (in vivo):

The eyes were examined approximately 1 hour, 24, 48 and 72 hours after administration of the test item.
Following the OECD and EC guidelines, since there was persistent ocular reactions at 72 hours, the observation period was extended. In the absence of complete reversibility of ocular reactions on day 22, the study was ended.

Number of animals or in vitro replicates:

3 males

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The eyes were not rinsed after administration of the test item.

SCORING SYSTEM: Ocular reactions were scored according to the numerical scale below.

TOOL USED TO ASSESS SCORE: The eyes were examined under a UV lamp after instillation of one or two drops of 0.5% sodium fluorescein solution (a clear fluorescence is visible in the areas of opacification).

ADMINISTRATION: As possible irritant effects were anticipated, the test item was administered to a single animal in the first instance. Since the test item was not severely irritant on this first animal, it was then evaluated on two other animals.

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #1

Remarks:

(mean score 1)

Time point:

other: overall at 24, 48 and 72 h

Score:

2.3

Max. score:

3

Reversibility:

not fully reversible within: 22 days

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #2

Remarks:

(mean score 2)

Time point:

other: overall at 24, 48 and 72 h

Score:

3

Max. score:

3

Reversibility:

fully reversible within: 20 days

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #3

Remarks:

(mean score 3)

Time point:

other: overall at 24, 48 and 72 h

Score:

2.7

Max. score:

3

Reversibility:

fully reversible within: 15 days

Irritation parameter:

chemosis score

Basis:

animal #1

Remarks:

(mean score 1)

Time point:

other: overall at 24, 48 and 72 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 22 days

Irritation parameter:

chemosis score

Basis:

animal #2

Remarks:

(mean score 2)

Time point:

other: overall at 24, 48 and 72 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 22 days

Irritation parameter:

chemosis score

Basis:

animal #3

Remarks:

(mean score 3)

Time point:

other: overall at 24, 48 and 72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 15 days

Irritation parameter:

cornea opacity score

Basis:

animal #1

Remarks:

(mean score 1)

Time point:

other: overall at 24, 48 and 72 h

Score:

1.7

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

cornea opacity score

Basis:

animal #2

Remarks:

(mean score 2)

Time point:

other: overall at 24, 48 and 72 h

Score:

1.3

Max. score:

4

Reversibility:

fully reversible within: 9 days

Irritation parameter:

cornea opacity score

Basis:

animal #3

Remarks:

(mean score 3)

Time point:

other: overall at 24, 48 and 72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 5 days

Irritation parameter:

iris score

Basis:

animal #1

Remarks:

(mean score 1)

Time point:

other: overall at 24, 48 and 72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 8 days

Irritation parameter:

iris score

Basis:

animal #2

Remarks:

(mean score 2)

Time point:

other: overall at 24, 48 and 72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 8 days

Irritation parameter:

iris score

Basis:

animal #3

Remarks:

(mean score 3)

Time point:

other: overall at 24, 48 and 72 h

Score:

0.3

Max. score:

2

Reversibility:

fully reversible within: 2 days

Irritant / corrosive response data:

Very slight to marked conjunctival reactions were observed in all animals from day 1: a very slight to marked chemosis (grades 1 to 3), a very slight to marked redness of the conjunctiva (grades 1 to 3) and a clear to whitish purulent discharge were recorded; some of these reactions persisted up to the end of the observation period (day 22) in 2/3 animals.

A brownish area on the conjunctivae was noted in one animal from day 6 to day 14 and a whitish area on the conjunctivae was also recorded in another animal on days 8 and 9.

A slight iritis (grade 1) was noted in all animals from day 1 or 2; it persisted up to day 7 in
2/3 animals.

A slight corneal opacity (grade 1 or 2) was recorded in all animals on day 2; it persisted up to day 4, 6 or 8.

Interpretation of results:

Category 1 (irreversible effects on the eye)

Conclusions:

Under these experimental conditions, the test item BIS TRIFLUOROMETHANESULFONIMIDE LITHIUM is severely irritant when administered by ocular route to rabbits.

Executive summary:

An acute eye irritation study was performed with the test item Bis trifluoromethanesulfonimide (TFSILi) in rabbits, in compliance with OECD Guideline n°405, under GLP conditions.

As possible irritant effects were anticipated, the test item was administered to a single male New Zealand White rabbit in the first instance. Since the test item was not severely irritant on this first animal, it was then evaluated in two other animals.

A single dose of 100 mg of the test item in its original form was introduced into the left conjunctival sac. The right eye was not treated and served as control. The eyes were not rinsed after administration of thes test item.

Ocular reactions were observed approximately 1 hour, 24, 48 and 72 hours after the administration and then daily until the end of the observation period (22 days) at the latest. The mean values of the scores for chemosis, redness of the conjunctiva, iris lesions and corneal opacity were calculated for each animal.

Very slight to marked conjunctival reactions (very slight to marked chemosis, very slight to marked redness of the conjunctiva and clear to whitish purulent discharge) were observed in all animals from day 1; some of these reactions persisted up to the end of the observation period (day 22) in 2/3 animals. A brownish area on the conjunctivae was noted in one animal from day 6 to day 14 and a whitish area on the conjunctivae was also recorded in another animal on days 8 and 9. A slight iritis was noted in all animals from day 1 or 2; it persisted up to day 7 in 2/3 animals. A slight corneal opacity was recored in all animals on day 2, it persisted up to day 4, 6 or 8. Mean scores calculated for each animal over 24, 48 and 72 hours were 3.0, 3.0 and 2.0 for chemosis, 2.3, 3.0 and 2.7 for redness of the conjunctiva, 1.0, 1.0 and 0.3 for iris lesions and 1.7, 1.3 and 1.0 for corneal opacity.

Under these experimental conditions, the test item BIS TRIFLUOROMETANESULFONIMIDE LITHIUM is severely irritant when administered by ocular route to rabbits.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

Three reliable studies are available for skin irritation/corrosion. Two studies of reliability 1 were considered as the key studies (Pelcot, 2002c and Glaza, 1988b) and one screening study of reliability 2 was selected as supporting study (Prinsen, 1997).

In the key studies, TFSILI was found to be irritating to corrosive to skin, and in the screening study, TFSILi was found to be not irritating. Taking into account the experimental results, a classification as corrosive to skin is proposed based on a precautionary principle. This is in accordance with the harmonized EU classification according to Annex VI 3.1 and 3.2 in which TFSILi is classified as skin corr. cat. 1B "H314 Causes severe skin burns and eye damage".

Eye irritation

Three reliable studies are available for eye irration. Two studies of reliability 1 were selected as key studies (Pelcot, 2002d and Glaza, 1988c) and the other study of reliability 2 was selected as supporting study (Prinsen, 1997).

Based on the results of the three studies, TFSILi is considered as highly irritating to eyes. Therefore, the classification "Eye damage 1 (H318)" is warranted according to Regulation (EC) 1272/2008.

Justification for classification or non-classification

Based on the experimental data, bis trifluoromethanesulfonimide lithium is classified as "Corrosive to skin" (Category 1, H314) and "Highly irritating to eyes" (Category 1, H318) according to the CLP regulation 1272/2008.