L-gluco-Octitol, 1,5-anhydro-6,8-dideoxy-, (7.xi.)-

Acute Toxicity: other routes

Administrative data

Endpoint:

acute toxicity: other routes

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

8 - 22 April 2004

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: pH and osmolarity of the dosage form preparations were not measured

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

Groups of Sprague-Dawley rats (5/sex/dose) were administered with a single subcutaneous dose of test item at 0 (vehicle) and 2000 mg/kg bw. Animals were then observed for mortality, clinical signs and bodyweights for 14 days and were all sacrificed for macroscopic examination.

GLP compliance:

yes

Limit test:

yes

Test material

Test material information

Constituent 1

Test material form:

other: liquid

Details on test material:

- Name of test material: see confidential details on test material
- Physical state: viscous brown liquid
- Lot/batch No.: see confidential details on test material
- Date of receipt: 20 February 2004
- Storage condition of test material: Stored at at room temperature

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories France, L’Arbresle, France
- Age at study initiation: Approximately 8 weeks
- Weight at study initiation: 309 ± 11 g for the males and 206 ± 12 g for the females
- Housing: Animals were housed in polycarbonate cages with stainless steel lid. Each cage contained 1-7 rats/sex during the acclimation period and 5 rats/sex/group during the treatment period.
- Diet: A04 C pelleted diet (SAFE, Villemoisson, Epinay-sur-Orge, France), ad libitum
- Water: Drinking water filtered by a FG Millipore membrane (0.22 µm), ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 2 °C
- Humidity: 30-70 %
- Air changes: Approximately 12 cycles/h of filtered, non-recycled air
- Photoperiod: 12 h dark / 12 h light

Administration / exposure

Route of administration:

subcutaneous

Vehicle:

other: 60/40 (w/w) mixture of purified water/propylene glycol

Details on exposure:

- Approximately 24 h before administration, the back area of the animals was clipped free of hair, as close to the skin as possible, using an electric clipper.
- Dosage form preparation was administered to the animals under a volume of 2.5 mL/kg bw.
- The test item was prepared freshly after mixing with the vehicle and then sterile filtered (with a 0.22 μm filter) under a laminar air-flow cabinet. Test item administration was performed in a single dose, by subcutaneous route using a single-use needle (0.50 mm x 16 mm) fitted to a 1 mL plastic syringe (0.01 mL graduations).

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Clinical signs and mortality: Animals were observed frequently during the hours following administration of the test item, for detection of possible treatment-related clinical signs. Thereafter, observation of the animals was made at least once a day until Day 15.
Bodyweight was recorded on Days 1 (prior to dosing), 8 and 15.
- Necropsy of survivors performed: Yes; all animals were killed by carbon dioxide asphyxiation on Day 15 and all animals were subjected to a macroscopic examination.

Statistics:

None

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

other: maximal non-lethal dose

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

- No mortality was observed.

Clinical signs:

- No systemic clinical signs were observed.
- Crusts were noted on the back of 1/5 females of the control group from Days 8-15.

Body weight:

- Body weight gain of treated animals was similar to that of control animals.

Gross pathology:

- No macroscopic abnormalities were observed at necropsy.

Other findings:

None

Any other information on results incl. tables

None

Applicant's summary and conclusion

Conclusions:

Under the test conditions, the maximal non-lethal dose of test item was considered to be higher than 2000 mg/kg bw in rats.

Executive summary:

In an acute subcutaneous toxicity study performed in compliance with GLP, groups of Sprague-Dawley Crl CD® (SD) IGS BR rats (5/sex/dose) were administered with a single subcutaneous dose of test item at 0 (vehicle) and 2000 mg/kg bw as a solution in the vehicle (purified water/propylene glycol, 60/40 w/w) with the dose volume of 2.5 mL/kg bw. Animals were then observed for mortality, clinical signs and bodyweights for 14 days and were all sacrificed for macroscopic examination..

No systemic clinical signs and no deaths were observed during the study. Crusts were noted on the back of 1/5 females of the control group from Days 8 to 15. The overall body weight gain of treated animals was not affected by treatment with the test item. No apparent abnormalities were observed at necropsy in any animal.

Under the test conditions, the maximal non-lethal dose of test item was considered to be higher than 2000 mg/kg bw in rats.