1H-Imidazole-4,5-dicarbonitrile, 2-(trifluoromethyl)-, lithium salt (1:1)

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

24 February 2014 -- 11 April 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

lithium(1+) 4,5-dicyano-2-(trifluoromethyl)-1H-imidazol-1-ide

EC Number:

691-963-1

Cas Number:

761441-54-7

Molecular formula:

C6 F3 N4. Li

IUPAC Name:

lithium(1+) 4,5-dicyano-2-(trifluoromethyl)-1H-imidazol-1-ide

Test material form:

other: white powder

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: breeder: CEGAV, Argenvilliers, France
- Age at study initiation: 2 to 4 months old on the day of treatment
- Fasting period before study: no
- Housing: noryl cages
- Diet: 110 pelleted diet (free access)
- Water: tap water filtered with a 0.22 µm filter (free access)
- Acclimation period: at least 5 days before the beginning of the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3°C
- Humidity (%): 50 ± 20%
- 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: 25 March 2014 to 11 April 2014

Test system

Type of coverage:

semiocclusive

Preparation of test site:

other: clipped

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.5 g/flank

Duration of treatment / exposure:

3 min, 1 h, 4 h.

Observation period:

1, 24, 48 and 72 h after removal of the dressing; if relevant, daily until reversibility of reactions

Number of animals:

Three males

Details on study design:

TEST SITE
- Area of exposure: on the day before treatment, two or four areas of skin (3.5 cm x 5 cm) were closely clipped using electric clippers on the right and left anterior and/or posterior flanks of animals
- Coverage: 6 cm2
- Type of wrap if used: gauze pad held in place by a non-irritation semi-occlusive dressing and a restraining bandage.

REMOVAL OF TEST SUBSTANCE
- Washing: using a dry cotton pad
- Time after start of exposure: at removal of each dressing (see Duration of exposure)

SCORING SYSTEM:

- Erythema and eschar formation:
0 no erythema
1 very slight erythema (barely perceptible)
2 well-defined erythema
3 moderate to severe erythema
4 severe erythema (beet redness) to slight eschar formation (injuries in depth)

- Edema formation:
0 no edema
1 very slight edema (barely perceptible)
2 slight edema (edges of area well-defined by definite raising)
3 moderate edema (raised approximately 1 millimeter)
4 severe edema (raised more than 1 millimeter and extending beyond area of exposure)

- Any other lesions were noted

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

no data

Results 2

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

no data

Results 3

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

1

Reversibility:

fully reversible within: day 2

Results 4

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

no data

Results 5

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.7

Max. score:

1

Reversibility:

fully reversible within: day 4

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

no data

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the experimental conditions of this study, the test item was very slightly irritant when applied topically to rabbits.

Therefore, the test item should not be classified as irritating to skin according to the criteria of CLP/GHS Regulation.

Executive summary:

The potential irritant properties of Lithium 4,5-dicyano 2-(trifluomethyl) imidazolate was evaluated following dermal application on rabbits. This study was conducted in compliance with the OECD Guideline No. 404 and the principles of Good Laboratory Practice. The test item was first applied for periods of 3 minutes, 1 hour and 4 hours to a single male New Zealand White rabbit. After the 4-hour application, since the mean value from grading at 24, 48 and 72 hours after patch removal was < 2.3 for erythema and for edema, the test item was applied on the skin of two other animals for 4 hours. A quantity of 0.5 g/flank was used. The test item was placed on a gauze pad, moistened with drinking water treated by reverses osmosis, which was then applied to a skin area of approximately 6 cm2. The gauze pad was held in place by a non-irritation semi-occlusive dressing and a restraining bandage. After required period of contact with the skin, the dressing was removed. Each animal was observed once a day for mortality and clinical signs. For each exposure period, cutaneous reactions were evaluated approximately 1, 24, 48 and 72 hours after removal of the dressing and then daily until the reversibility of cutaneous reactions. The mean values of the scores for erythema and edema were calculated for each animal. Body weight was recorded on the day of treatment and at the end of the evaluation of cutaneous reactions. On completion of the observation period, the animals were sacrificed then discarded without macroscopic post-mortem examination.

No unscheduled deaths occurred during the study and no clinical signs were noted in any animals. The body weight of the animals was unaffected by the test item treatment. After a 4-hour exposure, no skin reaction was observed in 1/3 animal and a very slight erythema was noted in 2/3 animals on Day 1, persisting until Day 3 in one of them. Dryness of the skin was recorded in one animal from Day 4 until Day 10. Mean scores calculated for each animal over 24, 48 and 72 hours were as follows:

- erythema: 0.0, 0.0, 0.7; showing no significant inflammation,

- edema: 0.0, 0.0, 0.0; showing no significant inflammation.

Under the experimental conditions of this study, Lithium 4,5-dicyano 2-(trifluomethyl) imidazolate was very slightly irritant when applied topically to rabbits.