Methyl 5-deoxy-2,3-O-isopropylidene-β-D-ribofuranoside

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

06 December 2012 to 16 July 2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Fully GLP compliant and in accordance with current test guidelines

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Methylfuranoside

IUPAC Name:

Methylfuranoside

Constituent 2

Reference substance name:

Methyl 5-deoxy-2,3-O-isopropylidene-β-D-ribofuranoside

EC Number:

245-485-1

EC Name:

Methyl 5-deoxy-2,3-O-isopropylidene-β-D-ribofuranoside

Cas Number:

23202-81-5

Molecular formula:

C9H16O4

IUPAC Name:

methyl 5-deoxy-2,3-O-isopropylidene-beta-D-ribofuranoside

Test material form:

other: pale yellow liquid

Details on test material:

Name: Methylfuranoside
CAS number: 23202-81-5
Batch number: 201111082008
Quantity supplied: 1.5 kg
Purity: 99.7%
Expiry date: November 2013
Date of receipt: 19 November 2012
Appearance: pale yellow liquid
Storage details: stored in a sealed container, at room temperature (15 to 25°C) in the dark.

Test animals

Species:

rat

Strain:

other: HsdHan:WIST

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan UK Ltd, Bicester, UK
- Age at study initiation: 8 to 9 weeks
- Weight at study initiation: weight variation did not exceed ±20% of the mean weight.
- Fasting period before study: from the evening of the day prior to dosing (Day -1) until approximately 3 hours after dosing
- Housing: The animals were housed in groups of up to three during the acclimatisation period in cages that conform to the 'Code of Practice for the Housing and Care of Animals Used in Scientific Procedures' (Home Office, London, 1989).
- Diet (e.g. ad libitum): SQC(E) Rat and Mouse Maintenance Diet No 1, ad libitum
- Water (e.g. ad libitum): Mains water was provided, ad libitum, via cage-mounted water bottles.
- Acclimation period: 8 to 10 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 24°C
- Humidity (%): 45 to 65%, On two occasions the minimum relative humidity was 41%. These deviations were considered not to have affected the integrity or outcome of the study.
- Air changes (per hr): 15 to 20 air changes per hour
- Photoperiod (hrs dark / hrs light): illuminated by fluorescent strip-lights for twelve hours daily

IN-LIFE DATES: From: 18 December 2012 To: 04 January 2013

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

VEHICLE: Not Applicable, unchanged (no vehicle)

MAXIMUM DOSE VOLUME APPLIED: 1.80 mL/kg

DOSAGE PREPARATION: The test item was used as supplied. The specific gravity was determined and used to calculate the appropriate dose volume for the required dose level.

Doses:

2000 mg/kg (Specific gravity: 1.116 g/mL)

No. of animals per sex per dose:

3 animals per dose group, 2 dose groups

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical signs were recorded immediately post-dose, at approximately 15 and 30 minutes post-dose, hourly between 1 and 4 hours post dose (inclusive), twice daily on Days 2, 3 and 4 and once daily from the fifth to last day of the observation period. Animals 211 to 213 were also observed at 5 and 7 hours post dose on Day 1.
All animals were examined at the beginning and end of the working day throughout the acclimatisation and study periods to ensure they were in good health.
Rats were weighed on Day -1 (day before dosing) and on Days 1, 4, 8 and 15. Decedent carcass weights were also recorded prior to necropsy.
- Necropsy of survivors performed: yes
- Other examinations performed: mortality, clinical signs and body weights

Statistics:

Not applicable

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

One animal was found dead on Day 2.

Clinical signs:

other: Two animals showed piloerection only, between 1 and 3 hours after dosing. These animals appeared normal from 4 hours after dosing. Piloerection was also noted in all other animals, with additional signs of prone posture, sunken flanks, decreased breathing

Gross pathology:

No abnormalities were noted at necropsy of animals that died or were killed at the end of the study.

Applicant's summary and conclusion

Interpretation of results:

study cannot be used for classification

Remarks:

Migrated information

Conclusions:

The acute median lethal oral dose level of the test article, Methylfuranoside, was found to exceed 2000 mg/kg.
The test material was considered to have no significant acute toxic risk in respect of its acute oral toxicity and did not meet the criteria for classification according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS).

Executive summary:

This study was conducted to assess the acute toxicity of the test item, Methylfuranoside, following a single oral administration to rats.

Groups of three female fasted rats were given the test item as a single dose on Day 1 by oral gavage at dose levels of 2000 mg/kg. The test item was administered as supplied. Surviving animals were killed on Day 15. All animals underwent a full necropsy.

One animal was found dead on Day 2.

Piloerection was also noted in all animals, with additional signs of prone posture, sunken flanks, decreased breathing rate, decreased activity, hunched posture, ataxia, tremors and arched gait. These signs developed from 15 minutes after dosing and lasted up to Day 2.

All surviving rats achieved body weight gains during the first and second weeks of the study.

No abnormalities were noted at necropsy of animals that died or were killed at the end of the study.

The acute median lethal oral dose level of the test article, Methylfuranoside, was found to exceed 2000 mg/kg.

The test material was considered to have no significant acute toxic risk in respect of its acute oral toxicity and did not meet the criteria for classification according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS).