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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
16. Feb. 2005 - 02. Mar. 2005
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2005
Report Date:
2005

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
Species : Rat, Wistar strain, Crl:WI (outbred, SPF-Quality). Recognised by international guidelines as the recommended test system (e.g. OECD, EG).
Source : Charles River Deutschland, Germany.
Number of animals : 5 males and 5 females (females were nulliparous and nonpregnant).
Age and body weight : Young adult animals (approx. 10 weeks old) were selected. Body weight variation did not exceed +/- 20% of the sex mean.
Identification : Earmark
Conditions : Animals were housed in a controlled environment, in which optimal conditions were considered to be approximately 15 air changes per hour, a temperature of 21.0 ± 3.0°C (actual range:19,3 -21.3°C), a relative humidity of 30-70% (actual range: 25 - 68%) and 12 hours artificial
fluorescent light and 12 hours darkness per day.
Accommodation : Individually housed in labelled Macrolon cages (type III, height 15 cm.) containing sterilised sawdust as bedding material (Woody-Clean type 3/4; Tecnilab-BMI BV, Someren , The Netherlands) and paper as cage-enrichment (Enviro-dri, BMI, Helmond, The Netherlands).
Acclimatisation period was at least 5 days before start of treatment under laboratory conditions.
Diet : Free access to standard pelleted laboratory animal diet (from Altromin (code VRF 1), Lage, Germany).
Water : Free access to tap water.

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Method : Dermal application.
Clipping : One day before exposure (day -1) an area of approximately 5x7 cm on the back of the animal was clipped.
Application : The test substance was applied in an area of approx. 10% of the total body surface, ie. approx. 25 cm2 for males and 18 cm2 for
females. The test substance was held in contact with the skin with a dressing, consisting of a surgical gauze (Surgy 1 D)*, successively covered with aluminium foil and Coban elastic bandage. A piece of Micropore tape' was additionally used for fixation of the bandages in females only.
* Manufacturers: Laboratoires Stella s.a., Liege, Belgium (surgical gauze) and 3M, St Paul, Minnesota, U.SA (Coban & Micropore).
Frequency : Single dosage, on day 1.
Dose level (volume) : 2000 mg/kg (1.63 ml/kg) body weight. Dose volume calculated as follows: dose level: specific gravity.
Application period : 24 hours, after which dressings were removed and the skin cleaned of residual test substance using water.
Duration of exposure:
24 hours
Doses:
2000 mg/kg b.w.
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
Observations:
Mortality/Viability : Twice daily.
Body weights : Days 1 (pre-administration), 8 and 15.
Clinical signs : At periodic intervals on the day of dosing (day 1) and once daily thereafter, until day 15. The time of onset, degree and duration
were recorded and the symptoms graded according to fixed scales: Maximum grade 4: grading slight (1) to very severe (4) Maximum grade 3: grading slight (1) to severe (3) Maximum grade 1: presence is scored (1).
Necropsy : At the end of the observation period, all animals were sacrificed by asphyxiation using an oxygen/carbon dioxide procedure and
subjected to necropsy. Descriptions of ali internal macroscopic abnormalities were recorded.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
Flat and/or hunched posture, chromodacryorrhoea, lethargy and/or ptosis were shown by most animals on days 1 and/or 2.
Scales were seen in the treated skin-area of one male and two females between days 3 and 9.
Body weight:
The changes noted in body weight gain in males and females were within the range expected for rats used in this type of study and were therefore considered not indicative of toxicity.
Gross pathology:
No test substance related abnormalities were found at macroscopic post mortem examination of the animals. A reduced size of the testes and epididymis was noted in one animal, which is occasionally noted among rats of this age and strain and was therefore considered not toxicologically
significant.

Any other information on results incl. tables

BODY WEIGHTS (GRAM):

 

Sex/dose level

animal

Day 1

Day 8

Day 15

Males 2000 mg/kg

1

368

386

414

 

2

366

363

403

 

3

365

395

438

 

4

327

341

372

 

5

336

354

386

 

Mean

352

368

403

 

St Dev

19

22

25

 

N

5

5

5

Females 2000 mg/kg

6

228

238

251

 

7

216

227

233

 

8

224

224

231

 

9

229

257

294

 

10

240

252

268

 

Mean

227

240

255

 

St Dev

9

15

26

 

N

5

5

5

 

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The dermal LD50 value of 1-ETHYL-3-METHYL IMIDAZOLIUM ETHYLSULFATE (EMIM ES) in Wistar rats was established to exceed 2000 mg/kg body weight. Based on these results 1-ETHYL-3-METHYL IMIDAZOLIUM ETHYLSULFATE (EMIM ES) does not have to be classified and has no obligatory labelling requirement for dermal toxicity according to the OECD Harmonized Integrated Hazard Classification System for Human Health
and Environmental Effects of Chemical Substances (OECD, 1998) and EC criteria for classification and labelling requirements for dangerous substance and preparations (Council Directive 67/548/EEC).
Executive summary:

Assessment of acute dermal toxicity with 1-ETHYL-3-METHYL IMIDAZOLIUM ETHYLSULFATE in the rat. The study was carried out based on the guidelines described in: OECD No402 (1987) "Acute Toxicity-Dermal" EC, Council Directive 67/548/EEC, Annex V, B.3 (1992) "Acute Dermal Toxicity" EPA, OPPTS 870.1200 (1998), "Acute Dermal Toxicity" JMAFF Guidelines (2000) including the most recent revisions. 1-ETHYL-3-METHYL IMIDAZOLIUM ETHYLSULFATE was administered to five Wi star rats of each sex by dermal application at 2000 mg/kg body weight for 24 hours. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (day 15). No mortality occurred. Flat and/or hunched posture, chromodacryorrhoea, lethargy and/or ptosis were shown by most animals on days 1 and/or 2. Scales were seen in the treated skin area of one male and two females between days 3 and 9. The mean body weight gain during the observation period was within the range expected for rats used in this type of study. No test substance related abnormalities were found at macroscopic post mortem examination of the animals. The dermal LD50 value of 1-ETHYL-3-METHYL IMIDAZOLIUM ETHYLSULFATE in Wistar rats was established to exceed 2000 mg/kg body weight.

Based on these results 1-ETHYL-3-METHYL IMIDAZOLIUM ETHYLSULFATE does not have to be classified and has no obligatory labelling requirement for dermal toxicity according to the OECD Harmonized Integrated Hazard Classification System for Human Health and Environmental Effects of Chemical Substances (OECD, 1998) and EC criteria for classification and labelling requirements for dangerous substance and preparations (Council Directive 67/548/EEC).