Reaction product of D-Glucopyranoside, methyl; esterified with oleic acid, methyl ester

Acute Toxicity: oral

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

Test material information

Constituent 1

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 1	199 9.2 5
7	Mean S.D. N	239 0.0 1	236 15.0 5
14	Mean S.D. N	259 0.0 1	251 15.1 5

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 1	15 6.7 5

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.