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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
21. Sep. 2004 - 07. Oct. 2004
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2004
Report date:
2004

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method

Test material

Constituent 1
Chemical structure
Reference substance name:
-
EC Number:
460-100-9
EC Name:
-
Cas Number:
342573-75-5
Molecular formula:
Hill formula: C8H16N2O4S CAS formula: C6H11N2.C2H5O4S
IUPAC Name:
3-ethyl-1-methyl-1H-imidazol-3-ium ethyl sulfate

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
Species : Rat, Wistar strain Crl:(WI) BR (outbred, SPF-Quality). Recognised by international guidelines as the recommended test system (e.g. OECD, EC).
Source : Charles River Deutschland, Sulzfeld, Germany.
Number of animals : 6 Females (nulliparous and non-pregnant). Each dose group consisted of 3 animals.
Age and body weight : Young adult animals (approx. 8 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: 17.2- 22.5°C), a relative humidity of 30-70% (actual range: 38· 68%) and 12 hours artificial
fluorescent light and 12 hours darkness per day.
Accommodation : Group housing of 3 animals per sex per cage in labelled Macrolon cages (type IV; height 18 cm.) containing sterilised sawdust as bedding material (Woody Clean bedding (Woody-Clean type 3/4; Tecnilab-BMI BV, Someren, The Netherlands) and paper as cage-enrichment (Envirodri, BMI, Helmond, The Netherlands). Certificates of analysis were examined and then retained in the NOTOX archives. 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). Certificates of analysis were examined and then retained in the NOTOX archives.
Water : Free access to tap-water. Certificates of quarterly analysis were examined and then retained in the NOTOX archives.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
Method : Oral gavage, using a stainless steel stomach tube.
Fasting : Food was withheld overnight (for a maximum of 20 hours) prior to dosing until 3-4 hours after administration of the test substance.
Frequency : Single dosage, on day 1.
Dose level (volume) : 2000 mg/kg (1.626 mllkg) body weight. Dose volume calculated as dose level: specific gravity.
Doses:
2000 mg/kg b.w.
No. of animals per sex per dose:
3
Control animals:
no
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 symptoms were graded according to
fixed scales and the time of onset, degree and duration were ,recorded:
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 all internal macroscopic abnormalities were recorded.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
On day 1, hunched posture was noted in all females and piloerection was noted in one female.
Body weight:
The mean body weight gain shown by the animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain. The incidence of slight body weight loss during the second week post treatment in one individual animal was considered not indicative of toxicity, based on the absence of any corroborative findings.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals,

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The oral LD50 value of 1-ETHYL-3-METHYL IMIDAZOLIUM ETHYLSULFATE in Wistar rats was established to exceed 2000 mg/kg body weight. According to the OECD 423 test guideline the LD50 cut-off value was considered to exceed 5000 mg/kg body weight.
Based on these results 1-ETHYL-3-METHYL IMIDAZOLIUM ETHYLSULFATE does not have to be classified and has no obligatory labeling requirement for oral 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 labeling requirements for dangerous substances and preparations (Council Directive 67/548/EEC).
Executive summary:

Assessment of acute oral toxicity with 1-ETHYL-3-METHYL IMIDAZOLIUM ETHYLSULFATE in the rat (Acute Toxic Class Method).

The study was carried out based on the guidelines described in: "Acute Toxicity-Oral, Acute Toxic Class Method", OECD No.423 (2001); "Acute Oral Toxicity"; EC Council Directive 67/548/EEC, Annex V, B.1 tris (2004); Environmental Protection Agency (EPA): Health Effects Test Guidelines OPPTS 870.1100 (2002), "Acute Oral Toxicity - Acute Toxic Class Method" and JMAFF Japanese test guidelines (2000). 1-ETHYL-3-METHYL IMIDAZOLIUM ETHYLSULFATE was administered by oral gavage to two subsequent groups of three female Wistar rats at 2000 mg/kg body weight. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (day 15). No mortality occurred. On day 1, hunched posture was noted in all females and piloerection was noted in one female. The mean body weight gain shown by the animals over the study period was considered to be normal. No abnormalities were found at macroscopic post mortem examination of the animals. The oral LD50value of 1-ETHYL-3-METHYL IMIDAZOLIUM ETHYLSULFATE in Wistar rats was established to exceed 2000 mg/kg body weight. According to the OECD 423 test guideline the LD50 cut-off value was considered to exceed 5000 mg/kg body weight. Based on these results 1-ETHYL-3-METHYL IMIDAZOLIUM ETHYLSULFATE does not have to be classified and has no obligatory labeling requirement for oral 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 labeling requirements for dangerous substances and preparations (Council Directive 67/548/EEC).