Lithium bis(trifluoromethylsulfonyl)imide

Eye irritation

Administrative data

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.

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 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Test material form:

solid: particulate/powder

Test animals / tissue source

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

Test system

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.

Results and discussion

In vivo

Results

Results 1

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

Results 2

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

Results 3

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

Results 4

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

Results 5

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

Results 6

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

Results 7

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

Results 8

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

Results 9

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

Results 10

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

Results 11

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

Results 12

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.

Applicant's summary and conclusion

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.