Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
12 November 2013 to 05 December 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study conducted according to OECD test guideline method.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2014
Report date:
2014

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Deviations:
no
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
D-Glucopyranoside, methyl, mixed decanoates and octanoates and oleates
EC Number:
941-129-0
Molecular formula:
C15H28O7 - C25H46O7
IUPAC Name:
D-Glucopyranoside, methyl, mixed decanoates and octanoates and oleates
Details on test material:
- Substance type: UVCB
- Physical state: Viscous liquid
- Analytical purity: 100% as UVCB
- Storage condition of test material: Room temperature in the dark

Test animals

Species:
rat
Strain:
other: RccHan : WIST(SPF)
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories B.V. Horst, The Netherlands
- Age at study initiation: 8 to 12 weeks
- Weight at study initiation: 193.4 to 213.7g
- Fasting period before study: Overnight
- Housing: Makrolon Type 4 cages
- Diet (e.g. ad libitum): Teklad Rat-Mouse diet 2914C ad libitum
- Water (e.g. ad libitum): Tap water ad libitum
- Acclimation period: 6 to 9 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/-3 °C
- Humidity (%): >30%
- Air changes (per hr): 12 to 15
- Photoperiod (hrs dark / hrs light): 12 hours light, 12 hours dark

IN-LIFE DATES: From: 12 November 2013 To: 05 December 2013

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/ml
- Amount of vehicle (if gavage): 10 ml/kg

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: The LD50in rats is
>5000 mg/kg body weight (based on data from components or similar materials), therefore the
starting dose was set at 2000 mg/kg body weight.
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Daily during acclimatization; prior to treatment, within the first 30 minutes and approximately 1, 2, 3
and 5 hours after treatment on test day 1; once daily during test days 2 - 15. Body weights were taken at start of acclimatization, on test day 1 (prior to treatment), 8 and 15.
- Necropsy of survivors performed: yes
Statistics:
No statistical analysis was performed.

Results and discussion

Preliminary study:
A preliminary study was performed in a single animal at 2000 mg/kg body weight.
Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No intercurrent deaths occured during the course of the study.
Clinical signs:
After treatment on test day 1, 2 of 5 animals (animal nos. 2 and 3) showed ruffled fur at all observation time points (within 0.5 h and at 1, 2, 3 and 5 hours). From test day 2 onwards, no clinical signs were observed in any animal.
Body weight:
The body weight of the animals was within the range commonly recorded for this strain and age.
Gross pathology:
No macroscopic findings wererecorded at necropsy.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The median lethal dose of the test substance after single oral administration to female rats, observed over a period of 14 days, is: LD50(female rat): greater than 2000 mg/kg body weight.
Executive summary:

Test Guidance

The acute toxicity of the test substance when administered by a single oral gavage to rats was investigated according to OECD test guideline No. 420 and Commission Regulation (EC) No. 440/2008, B.1.

Method

To determine the dose level for the main study, one sighting study was conducted with one female RccHan:WIST (SPF) rat. The animal was treated with the test item at a dose level of 2000 mg/kg body weight by single oral gavage administration. The test item was formulated in Polyethylene glycol 300 (PEG 300) at a concentration of 0.2 g/mLand administered at a dosing volume of 10 mL/kg body weight. Since no mortality occurred in the animal dosed at 2000 mg/kg, four additional females were treated at this dose level in the main study. The animals were examined daily during the acclimatization period and mortality, viability and clinical signs were recorded. All animals were examined for clinical signs before treatment, within the first 30 minutes and approximately 1, 2, 3 and 5 hours after treatment on test day 1 and once daily during test days 2 - 15. Mortality/viability was recorded before treatment, within the first 30 minutes and approximately 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during testdays 2 - 15. Body weights were recorded at acclimatization start, on test day 1 (prior to administration), on test days 8 and 15. All animals were necropsied and macroscopically examined.

Results

No intercurrent deaths occurred during the course of the study. After treatment on test day 1, 2 of 5 animals showed ruffled fur at all observation time points. From test day 2 onwards, no clinical signs were observed in any animal. The body weight of the animals was within the range commonly recorded for this strain and age. No abnormal macroscopic findings were recorded at necropsy.

Conclusion

The median lethal dose of the test substance after single oral administration to female rats, observed over a period of 14 days, is: LD50(female rat): greater than 2000 mg/kg body weight.