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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:
2015-01-05 - 2015-01-27
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2015
Report date:
2015

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
no
Principles of method if other than guideline:
The test substance was administered once orally via gavage to 1 fasted female albino rat at a dose level of 300 mg/kg. No mortality was observed, and another female rat was dosed at 2000 mg/kg (limit dose). No mortality was observed, and 4 additional female animals were dosed at 2000 mg/kg.
Mortality, clinical observations, and body weight changes were evaluated over a 14-day observation period. All animals were subjected to a gross necropsy.
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Reaction product of D-Glucopyranoside, methyl; esterified with oleic acid, methyl ester
EC Number:
946-364-2
Molecular formula:
C43H78O8
IUPAC Name:
Reaction product of D-Glucopyranoside, methyl; esterified with oleic acid, methyl ester
Test material form:
liquid
Details on test material:
- State of aggregation: yellow liquid
-Others: storage at room temperature, in the dark
Specific details on test material used for the study:
The purity of the test substance was 100% (tested as formulated, 100% with no purity correction).
The test substance was stored at room temperature, protected from light, and was considered stable under these conditions. A reserve sample of the test substance was collected and stored in the WIL Research Archives.
Prior to use, the bulk test substance container was inverted and/or swirled. A sufficient amount of test substance was transferred into a storage container for dispensation.

Test animals

Species:
rat
Strain:
other: Crl: CD(SD) albino rat
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Crl:CD(SD) rats from Charles River Laboratories, Inc., Raleigh, NC
- The number of animals selected was the minimum required to satisfy regulatory guidelines (5).
- No information exists to indicate a difference in sensitivity between the sexes. Therefore, only females were used to reduce variability and as means of minimizing the number of animals used.
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8-12 weeks old
- Weight at study initiation: Approximately 170 to 300 grams at initiation of dosing, ± 20% of the mean of previously tested animals.
- Fasting period before study: fasted overnight before dosing
- Housing: individually in clean, stainless steel, wire-mesh cages suspended above cage-board
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: minimum of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 71 ± 5°F (22 ± 3°C)
- Humidity (%): 50 ± 20%
- Air changes (per hr): minimum of 10
- Photoperiod (hrs dark / hrs light): 12 hrs light and 12 hrs dark photoperiod

IN-LIFE DATES: From: 2014-12-30 To: 2015-01-27
All animals were euthanized at day 14 (end of the experimental phase).

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Remarks:
due to density of test item
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED:
Individual doses were calculated based on fasted body weights taken just prior to dosing and dose volumes of 0.31 and 2.04 mL/kg for the 300 and 2000 mg/kg groups, respectively.

The rats were fasted overnight prior to dosing. The test substance was administered orally via gavage. Food was returned approximately 4 hours after dosing.
Doses:
300 mg/kg bw
2000 mg/kg bw
No. of animals per sex per dose:
1 female at 300 mg/kg
4 females at 2000 mg/kg
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of clinical observations of mortality: ~15 minutes (± 5 minutes) and 1, 2 and 4 hours post-dosing on study day 0 and twice daily, once in the morning and once in the afternoon, thereafter for 14 days.
- Frequency of weighing: study days 0 (initiation), 7, and 14 (termination).
- Necropsy of survivors performed: yes (including major organ system of cranial, thoratic and abdominal cavities and the skin)
- Other examinations performed: clinical signs, body weight, mortality
Tissues were not collected

The test substance was administered once orally via gavage to 1 fasted female albino rat at a dose level of 300 mg/kg. No mortality was observed, and another female rat was dosed at 2000 mg/kg (limit dose). No mortality was observed, and 4 additional female animals were dosed at 2000 mg/kg.

Data Aquisition and Reporting
- Archive Management System (AMS): In-house developed application for storage, maintenance, and retrieval of information for archived materials (e.g., lab books, study data, wet tissues, slides, etc.).
- Formulations Dose Dispensing Management System (FDDMS): In-house developed system used to assign unique barcodes to formulation containers and individual containers used for dispensing dosing formulations.
- InSight® Publisher: Electronic publishing system (output is Adobe Acrobat, PDF).
- Master Schedule: Maintains the master schedule for the company.
- Metasys DDC Electronic Environmental Control System: Controls and monitors animal room environmental conditions.
- Microsoft® Office 2007 and 2010: Used in conjunction with the publishing software to generate study reports.
- Provantis Dispense™: Comprehensive system (Instem LSS Limited) to manage test materials, including receipt, formulation instructions, and accountability.
- WIL Metasys: In-house developed system used to record and report animal room environmental conditions.
- WIL Toxicology Data Management System™ (WTDMS™): In-house developed system used for collection and reporting of in-life and postmortem data.

Results and discussion

Preliminary study:
No effects at dose 300 mg/kg when administered to one female albino rat in a single dose.
Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
All animals survived to the scheduled necropsy.
Clinical signs:
There were no clinical findings observed during the study.
Body weight:
There were no remarkable body weight changes noted during the study (Table 1 - Table 4).
Gross pathology:
There were no macroscopic findings at the scheduled necropsy.
Other findings:
none

Any other information on results incl. tables

Table 1: Acute oral toxicity study in Albino rats, Summary of body weights [g]

 Day  Group  300 mg/kg Female  2000 mg/kg Females
 0

 Mean

S.D.

N

192

0.0

 199

9.2

5

 7

 Mean

S.D.

N

239

0.0

236

15.0

 14

 Mean

S.D.

N

259

0.0

251

15.1

Table 2: Acute oral toxicity study in Albino rats, Summary of bofy weight changes [g]

 Day   Group   300 mg/kg Female  2000 mg/kg Females
 0 to 7

 Mean

S.D.

N

 47

0.0

1

 37

7.1

5

 7 to 14

 Mean

S.D.

N

20

0.0

15

6.7

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Remarks:
limit dose at 2000 mg/kg
Conclusions:
Based on the results of this study, the estimated LD50 of the test item was greater than 2000 mg/kg (Unclassified for CLP) when administered once orally via gavage to fasted female albino rats.
Executive summary:

The acute oral toxicity of the test item was evaluated in this single-dose study in rats according to OECD Guideline 420 and in compliance with GLP.

The test substance was administered once orally via gavage to one fasted female albino rat at a dose level of 300 mg/kg. No mortality was observed, and another female rat was dosed at 2000 mg/kg (limit dose). No mortality was observed, and 4 additional female

animals were dosed at 2000 mg/kg.

Mortality, clinical observations, and body weight changes were evaluated over a 14-day observation period. All animals were subjected to a gross necropsy.

There were no deaths, remarkable body weight changes, or gross necropsy findings. No test substance-related clinical observations were noted.

Based on the results of this study, the estimated LD50 of the test item was greater than 2000 mg/kg (CLP Category Unclassified) when administered once orally via gavage to fasted female albino rats.