D-Glucitol, 1,5-anhydro-1-C-[3-[[5-(4-fluorophenyl)-2-thienyl]methyl]-4-methylphenyl]-, 2,3,4,6-tetraacetate, (1S)-

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from 2008-09-03 to 2008-09-26

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

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:

[(2R,3R,4R,5S,6S)-3,4,5-tris(acetyloxy)-6-(3-{[5-(4-fluorophenyl)thiophen-2-yl]methyl}-4-methylphenyl)oxan-2-yl]methyl acetate

EC Number:

617-901-5

Cas Number:

866607-35-4

Molecular formula:

C32H33FO9S

IUPAC Name:

[(2R,3R,4R,5S,6S)-3,4,5-tris(acetyloxy)-6-(3-{[5-(4-fluorophenyl)thiophen-2-yl]methyl}-4-methylphenyl)oxan-2-yl]methyl acetate

Test material form:

solid: particulate/powder

Details on test material:

- Physical state: solid
- Appearance: white powder

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: HanRcc:WIST (SPF) rat from RCC Ltd
- Age when treated: 11 weeks
- Weight when treated: 178.4 g - 205.5 g
- Fasting period before study: animals were fasted 17 to 18.5 hours prior to dosing, food was provided again approximately 3 hours after dosing
- Housing: standard laboratory conditions, in groups of 3 in Makrolon type-4 cages with wire mesh tops and standard softwood bedding
- Diet (e.g. ad libitum): ad libitum, pelleted standard diet
- Water (e.g. ad libitum): ad libitum, community tap water
- Acclimation period: under laboratory conditions, after health examination. Only animals without any visible signs of illness were used for the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3 °C
- Humidity (%): 30-70%
- Air changes (per hr): 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hrs light/12 hrs dark, automatically controlled, music during the daytime light period

IN-LIFE DATES: From: 2008-09-03 To: 2008-09-26

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Remarks:

PEG300

Details on oral exposure:

VEHICLE
- Concentration in vehicle: no data
- Amount of vehicle (if gavage): 10 ml/kg
- Justification for choice of vehicle: vehicle was chosen after a non-GLP solubility trial which was performed before the study inititation date
- Lot/batch no. (if required): 1349048
- Purity:no data

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg

DOSAGE PREPARATION (if unusual): Dose levels are in terms of the test item as supplied by the sponsor. The dose formulations were made shortly before each dosing occasion using a magnetic stirrer and a spatula as homogenizers. The test item was weighed into a tared glass beaker on a suitable precision balance and the vehicle added. Homogeneity of the test item in the vehicle was maintained during administration using a magnetic stirrer.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: no data

Doses:

2000 mg/kg

No. of animals per sex per dose:

3 females per group (6 femals in total)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: mortality/viability: daily during the acclimatization period, during the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1 (with clinical signs) and twice daily during days 2-15
- Necropsy of survivors performed: yes. All animals were killed at the end of the observation period by carbon dioxide asphyxiation and discarded after macroscopic examinations were performed. No organs or tissues were retained.
- Other examinations performed:
-clinical signs: daily during the acclimatization period, during the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1. Once daily during days 2-15. All abnormalities were recorded.
-body weight: on test days 1 (prior to administration), 8 and 15

Statistics:

No statistical analysis was used

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths occurred during the study

Clinical signs:

other: No clinical signs were observed during the course of the study.

Gross pathology:

No macroscopic findings were recorded at necropsy.

Applicant's summary and conclusion

Interpretation of results:

not classified

Conclusions:

The median lethal dose of RT003066 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.