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

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

22 April 2014 -- 27 May 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 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

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:

rat

Strain:

Sprague-Dawley

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: breeder: Janvier, Le Genest-Saint-Isle, France
- Age/Mean body weight at study initiation: on the day of treatment, the animals were approximately 8 (groups 1 and 3) or 9 (group 2) weeks. The males had a mean body weight of 370 g (range: 354 g to 380 g) and the females had a mean body weight of 215.4 g (range: 206 g to 230 g).
- Fasting period before study: yes, during the night before treatment
- Housing: polycarbonate cages
- Diet: SSNIFF R/M-H 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): 22 ± 2°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: 23 April 2014 to 27 May 2014

Administration / exposure

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: 10% of body surface, dorsal site
- Type of wrap if used: hydrophilic gauze pad + adhesive hypoallergenic aerated semi-occlusive dressing + restraining bandage

REMOVAL OF TEST SUBSTANCE
- Removal of dressing: 24h post-exposure
- Washing: at 24h post-exposure, with a moistened cotton pad with water for injection (only in females)

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg
- Constant volume: no

Doses:

2000 mg/kg

No. of animals per sex per dose:

Ten Sprague-Dawley rats (five males and five nulliparous and non pregnant females)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Clinical observations: frequently during the hours following treatment; then, at least once a day.
- Body weight: just before treatment, on day 1; then on days 8 and 15.
- Necropsy of survivors performed: yes (macroscopic).

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD0

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No unscheduled deaths occurred during the study.

Clinical signs:

other: No clinical signs indicative of systemic toxicity were observed in any animals and no cutaneous reactions were observed in males. An erythema was noted in all females from Day 2 or 3 until Day 7 at the latest or on Day 7 only and was associated with dryne

Gross pathology:

There were no macroscopic findings at necropsy.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the experimental conditions of this study, the dermal LD50 of the test item was higher than 2000 mg/kg in rats. Since there was no mortality in the study, the dermal LD0, was also higher than 2000 mg/kg in rats.

Therefore, the test item should not be classified for the acute dermal toxicity according to the criteria of CLP Regulation.

Executive summary:

The objective of this study was to evaluate the potential toxicity of Lithium 4,5-dicyano 2-(trifluomethyl) imidazolate following a single dermal application to rats. This study was conducted in compliance with OECD Guideline No. 402 and the principles of Good Laboratory Practices. The test item was applied in its original form to the skin of one female in the first instance, after four female then five male Sprague-Dawley rats at the dose-level of 2000 mg/kg. The application site was covered by a semi-occlusive dressing for 24 hours. Each animal was observed at least once a day for mortality and clinical signs for 15 days. From Day 2, any local reactions at the treatment site were also noted. Body weight was recorded on Day 1 and then on Days 8 and 15. On completion of the observation period, the animals were sacrificed and then submitted for a macroscopic post-mortem examination. No tissues were preserved.

No unscheduled deaths occurred during the study. No clinical signs indicative of systemic toxicity were observed in any animals. No cutaneous reactions and no body weight changes were observed in males. An erythema was noted in all females from Day 2 until Day 7 at the latest. This was associated with dryness from Day 3 until Day 15 at the latest. On Day 15, a lower body weight and a lower body weight gain between Day 1 and Day 15 were noted in females. The test item did not induce any macroscopic findings at necropsy.

Under the experimental conditions of this study, the dermal LD50 of Lithium 4,5-dicyano 2-(trifluomethyl) imidazolate was higher than 2000 mg/kg in rats. Since there was no mortality in the study, the dermal LD0, was also higher than 2000 mg/kg in rats.