Constitutional isomers of penta-O-allyl-β-D-fructofuranosylα-D-glucopyranoside; Constitutional isomers of hexa-O-allyl-β-D-fructofuranosylα-D-glucopyranoside; Constitutional isomers of hepta-O-allyl-β-D-fructofuransoylα-D-glucopyranoside

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

19 May 2014 to 11 June 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2014

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Constitutional isomers of penta-O-allyl-β-D-fructofuranosylα-D-glucopyranoside; Constitutional isomers of hexa-O-allyl-β-D-fructofuranosylα-D-glucopyranoside; Constitutional isomers of hepta-O-allyl-β-D-fructofuransoylα-D-glucopyranoside

EC Number:

419-640-0

EC Name:

Constitutional isomers of penta-O-allyl-β-D-fructofuranosylα-D-glucopyranoside; Constitutional isomers of hexa-O-allyl-β-D-fructofuranosylα-D-glucopyranoside; Constitutional isomers of hepta-O-allyl-β-D-fructofuransoylα-D-glucopyranoside

Cas Number:

68784-14-5

Molecular formula:

C3H4O to C36H54O11

IUPAC Name:

2-{[3,4-bis(prop-2-en-1-yloxy)-2,5-bis[(prop-2-en-1-yloxy)methyl]oxolan-2-yl]oxy}-3,4,5-tris(prop-2-en-1-yloxy)-6-[(prop-2-en-1-yloxy)methyl]oxane

Test material form:

other: liquid

Details on test material:

Purity: 100%
Physical state/ Appearance: straw colored viscous liquid
Expiry date: 04 April 2016
Storage Conditions: room temperature in the dark

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

The females were nulliparous and non-pregnant.
Acclimatization period of at least five days.
housed in groups of up to four in suspended solid-floor polypropylene cages furnished with woodflakes.
With the exception of an overnight fast immediately before dosing and for approximately three to four hours after dosing, free access to mains drinking water and food was allowed throughout the study.
The temperature and relative htunidity were set to achieve limits of 19 to 25 °C and 30 to 70% respectively. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

arachis oil

Remarks:

used because the test item did not dissolvc/suspend in distilled wate

Details on oral exposure:

All animals were dosed once only by gavage, using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to the fasted body weight at the time of dosing.

Doses:

Preliminary Test
1 female - 2000 mg/kg (corresponding to 1.82 mL/kg as the gravity of the solution is 1.104)
1 female - 300 mg/kg (corresponding to 10 mL of 3g/mL per kilo)

In the absence of toxicity at 300 mg/kg, an additional group of animals was treated as follows: 300 mg/kg (corresponding to 10 mL of 3g/mL per kilo)

No. of animals per sex per dose:

A total of five females were therefore treated at a dose level of 300 mg/kg in the study.

Control animals:

no

Details on study design:

Clinical observations were made 1/2, 1, 2, and 4 hours after dosing and then daily for up to fourteen days. Morbidity and mortality checks were made twice daily.
Individual body weights were recorded on Day 0 (the day of dosing) and on Days 7 and 14 or at death.
At the end of the observation period the surviving animals were killed by cervical dislocation. All animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavitics. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Statistics:

No statistics

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

2000 mg/kg: The animal was found dead 1 day after dosing.
300 mg/kg: There were no deaths.

Clinical signs:

other: 2000 mg/kg: Body tremors were noted 4 hours after dosing. 300 mg/kg: No signs of systemic toxicity were noted during the observation period.

Gross pathology:

2000 mg/kg: Abnormalities noted at necropsy were dark liver, dark kidneys and epithelial sloughing of the gastric mucosa.
300 mg/kg: No abnormalities were noted at necropsy.

Any other information on results incl. tables

DOSE LEVEL 2000 mg/kg

- Individual clinical observations and mortality data are given in Table 1 (attached).

- Body weights on Day 0 and at death are provided in Table 2 (attached).

- Necropsy findings are given in Table 3 (attached).

DOSE LEVEL 300 mg/kg

- Individual clinical observations and mortality data are given in Table 4 (attached).

- Individual body weights and body weight changes are given in Table 5 (attached).

- Individual necropsy changes are given in Table 6 (attached).

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Remarks:

Migrated information

Conclusions:

The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was estimated to be in the range of 300 - 2000 mg/kg body weight.

Executive summary:

Introduction

The study was performed to assess the acute oral toxicity ofthe test item in the Wistar strain rat.

Methods

Following a sighting test at dose levels of 2000 mg/kg and 300 mg/kg, a further group of four fasted females was given a single oral dose of test item, as a solution in arachis oil BP, at a dose level of 300 mg/kg body weight. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy.

Results

Mortality. The animal treated at a dose level of 2000 mg/kg was found dead 1 day after dosing. There were no deaths at a dose level of 300 mg/kg.

Clinical Observations. Body tremors were noted in the animal treated at a dose level of 2000 mg/kg. There were no signs of systemic toxicity at a dose level of 300 mg/kg.

Body Weight. Surviving animals showed expected gains in body weight.

Necropsy. Abnormalities noted at necropsy of the animal treated at a dose level of 2000 mg/kg were dark liver, dark kidneys and epithelial sloughing of the gastric mucosa. No abnormalities were noted at necropsy of animals treated at a dose level of 300 mg/kg.

Conclusion

The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was estimated to be in the range of 300 - 2000 mg/kg body weight.