Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report date:
2010

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Reference substance name:
1H-imidazolium, 1-ethyl-3-methyl-, acetate
Cas Number:
143314-17-4
Molecular formula:
C6 H11 N2 .C2 H3 02
IUPAC Name:
1H-imidazolium, 1-ethyl-3-methyl-, acetate
Test material form:
liquid
Details on test material:
- Name of test material (as cited in study report): 1-Ethyl-3-methylimidazolium acetate
- Physical state: liquid
- Analytical purity: 95 %
- Lot/batch No.: 08-009; PSN 06/0363-2
- Expiration date of the lot/batch: Stability under storage conditions over test period was guaranteed by the sponsor.
- Storage condition of test material: Room temperature
- Other: color: brown, clear

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Sulzfeld, Germany
- Age at study initiation: about 8 (males) and 12 (females) weeks old
- Weight at study initiation: mean for high dose: 236.4 g (male), 205.4 g (female) and for low dose: 260.4 g (male), 205.0 (female)
- Housing: Makrolon cage, type III; single housing
- Diet: VRF1(p); SDS Special Diet Services, Altrip, germany; ad libitum
- Water: Tap water ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C +/- 3°C
- Humidity (%): 30-70%
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:
semiocclusive
Details on dermal exposure:
TEST SITE
- Area of exposure: 40 cm2
- % coverage: at least 10 % of the body surface
- Type of wrap if used: semiocculsive dressing for 24 h

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with warm water
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 5000 mg/kg bw (4.5 ml/kg bw); 2000 mg/kg bw (1.80 ml/kg bw)
- Concentration (if solution): undiluted
- Constant concentration used: yes

VEHICLE
no vehicle
Duration of exposure:
24 h
Doses:
5000 and 2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily for mortality; clinical observations: several times at day of administration and at least once daily thereafter each working day; scoring of skin findings: 30-60 min after removal of the semiocclusive dressing (day 1), weekly thereafter; bw: weekly
- Necropsy of survivors performed: yes

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 - < 5 000 mg/kg bw
Based on:
test mat.
Sex:
male
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 - < 5 000 mg/kg bw
Based on:
test mat.
Mortality:
- 5000 mg/kg bw test group: 5/5 females and 1/5 males were found dead within 1h after application.
- 2000 mg/kg bw test group: 1/5 females was found dead directly after application, no mortality among the males
Clinical signs:
SYSTEMIC EFFECTS:
- 5000 mg/kg bw test group: no clinical observation of the females (died within first hour); one male that died: poor general state, gasping, twitching, clonic convulsions; surviving males: impaired and poor general state, dyspnoea, gasping, chromodacryorrhea and lateral position from hour 1-5 after administration
- 2000 mg/kg bw: one female that died: impaired general state; among all others: impaired and poor general state, dyspnoea, staggering, chromodacryorrhea, abdominal position and flat respiration from hour 0 - to 5 after administration

LOCAL EFFECTS:
- 5000 mg/kg bw: 4 surviving males: erythema (grade 1-3), edema (grade 1-4), incurstations and scaling (partial severe) were observered on study day 1 until day 8. 5 females and 1 male that died: erythema (grade 2-4) and edema (grade 2-3) during necropsy 1h after application
- 2000 mg/kg bw: erythema (grade 1-3), edema (grade (1-2), incrustations and scaling from study day 1 to 10 after application. 1 female that diesd: erythema (grade 3) and edema (grade 1) during necropsy.
Body weight:
BW of the survining animals increased throughout the study period within normal range.
Gross pathology:
- 5000 mg/kg bw test group: Animals that died (1 male, 5 females) showed no macroscopic pathologic abnormalities.
- 2000 mg/kg bw test group: 1 female that died showed yelloish discoloration of content in the small intestine.
No macroscopic pathologic abnormalities were noted in the animals examined at the end of the study.

Applicant's summary and conclusion

Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
Due to the LD50 (dermal, rat) >2000 and <5000 mg/kg bw no classification is required according to Annex VI of Directive 67/548/EWG (DSD) or Annex I of Directive 1272/2008 (EU-GHS).
Executive summary:

In the GLP, OECD402 study (BASF SE, 2010) Wistar rats were exposed once to 2000 and 5000 mg/kg bw of the test substance and observed for 14 days. 5/5 females and 1/5 male died in the high dose group and 1/5 females and 0/5 males died in the low dose group. The following clinical observations were found in the surviving animals: impaired and poor general state, dyspnoea, gasping, chromodacryorrhea and lateral position from hour 1-5 after administration in the high dose group; impaired and poor general state, dyspnoea, staggering, chromodacryorrhea, abdominal position and flat respiration from hour 0 - to 5 after administration in the low dose group. Local effects such as erythema, edema and parital severe incrustations and scaling were found in all groups but reversed within observation time. Macroscopic pathological abnormalities were found only in the one female exposed to 2000 mg/kg bw yellowish discoloration of content in the small intestine. BW of the survining animals increased throughout the study period within normal range. The dermal LD50 in rats (both sexes combined) was <2000 and < 5000 mg/kg bw.