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Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Remarks:
This study was available at the time of registration and is submitted as part of an obligation to submit all relevant information on the substance. The study was not commisioned for REACH registration purposes.
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study was conducted by a GLP accredited laboratory using a method eqiuivalent to OECD Testing Guideline 407.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report date:
2013

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
Deviations:
no
GLP compliance:
yes
Limit test:
no

Test material

Constituent 1
Reference substance name:
1H-Imidazolium, 3-ethyl-1-methyl-, C9-14-branched alkylbenzenesulfonates
IUPAC Name:
1H-Imidazolium, 3-ethyl-1-methyl-, C9-14-branched alkylbenzenesulfonates
Constituent 2
Reference substance name:
EMI-DBS
IUPAC Name:
EMI-DBS
Constituent 3
Reference substance name:
1065642-34-3
Cas Number:
1065642-34-3
IUPAC Name:
1065642-34-3
Test material form:
semi-solid (amorphous): gel
Remarks:
migrated information: paste
Details on test material:
Name of test material (as cited in study report):1H-imidazolium, 3-ethyl-1-methyl-, C9-14-branched alkylbenzenesulfonates

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Beijing Vital River Laboratories
- Weight at study initiation: 121-160 g
- Fasting period before study: 5 days
- Housing: SPF

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-25
- Humidity (%): 40-70

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: Male: 160, 53.4, 17.8, 1.8 mg/ml ; Female: 136.8, 45.6, 15.2, 1.6 mg/ml
- Amount of vehicle (if gavage): 0.5 ml/100 g/BW
- Lot/batch no. (if required): GF1121085
- Purity: 100%
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
28 days
Frequency of treatment:
Daily
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0
Basis:
actual ingested
Remarks:
Doses / Concentrations:
Male: 9 mg/kg; Female: 8 mg/kg
Basis:
actual ingested
Remarks:
Doses / Concentrations:
Male: 89 mg/kg; Female: 76 mg/kg
Basis:
actual ingested
Remarks:
Doses / Concentrations:
Male: 267 mg/kg; Female: 228 mg/kg
Basis:
actual ingested
Remarks:
Doses / Concentrations:
Male: 800 mg/kg; Female: 684 mg/kg
Basis:
actual ingested
No. of animals per sex per dose:
10 males and 10 females per group
Control animals:
yes, concurrent no treatment
Details on study design:
Repeated dose oral toxicity, including recovery groups.
Positive control:
No

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Daily


DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Daily

BODY WEIGHT: Yes
- Time schedule for examinations: per week

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data

FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: Yes

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data

OPHTHALMOSCOPIC EXAMINATION: No data

HAEMATOLOGY: Yes
- Time schedule for collection of blood: 28 days
- Anaesthetic used for blood collection: Yes (identity)
- Animals fasted: Yes
- How many animals: 40

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: 28 days
- Animals fasted: Yes
- How many animals: 140
- Parameters checked in table [No.?] were examined.

URINALYSIS: Yes
- Time schedule for collection of urine: 28 days
- Metabolism cages used for collection of urine: No
- Animals fasted: Yes

NEUROBEHAVIOURAL EXAMINATION: No
Sacrifice and pathology:
GROSS PATHOLOGY: No data
HISTOPATHOLOGY: Yes
Statistics:
F-test, X2-test

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
no effects observed
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
effects observed, treatment-related
Description (incidence and severity):
some changes at 76mg/kg bw (female)
Clinical biochemistry findings:
effects observed, treatment-related
Description (incidence and severity):
some changes at 76 mg/kg bw (female)
Urinalysis findings:
effects observed, treatment-related
Description (incidence and severity):
some changes at 89 mg/kg bw (male)
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
no effects observed

Effect levels

open allclose all
Key result
Dose descriptor:
NOAEL
Effect level:
> 76 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
female
Basis for effect level:
haematology
Key result
Dose descriptor:
NOAEL
Effect level:
> 89 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male
Basis for effect level:
urinalysis

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

Haematology, Clinical chemical change at 76 mg/kg bw (female) .Urinalysis changes at 89 mg/kg bw (male). However, these finding were absent in the recovery group mantained for 2 week post dosing and these suggested the effect to be transient.

Applicant's summary and conclusion

Conclusions:
A NOAEL is proposed to be 76 mg/kg bw (female) and 89 mg/kg bw (male). No classification is proposed
Executive summary:

The subacute toxicity of the test substance EMI-DBS was determined in a 28-day repeated dose oral toxicity study on male and female Wistar rats. Haematology, Clinical chemical change at 76 mg/kg bw (female). Urinalysis changes at 89 mg/kg bw (male). However, these finding were absent in the recovery group miantained for 2 week post dosing and these suggested the effect to be transient.

The effects do note seem to be dose related and failed to get more significant at higher doses.  This suggests adaptive metabolic changes rather toxicological ones.

A NOAEL is proposed to be 76 mg/kg bw (female) and 89 mg/kg bw (male).