Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
from December 04,2000 to December 19, 2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: In compliance with GLP and OECD guideline

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2000

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
no
Qualifier:
according to
Guideline:
other: Guideline for acute oral toxicity studies. In:Toxicological principles for the safety assessment of direct food additives used in food - Bureau of food - 1982
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Name : LAB 3085 (Isosorbide)
Order number : E0021
Reference : HW 11/10/00
Supplier : ROQUETTE - Research Dpt
Conditioning : plastic bag
Used quantity : 5.0048g
Date of reception 30.11.2000
presentation : white cristals

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
Supplier : IFFA-CREDO-69592 L'ARBRESLE - France
Number/sex : 12 males - 12 females
Age : 5 semaines when arrived at the laboratory
Weight at J0 : 146.6 - 160.9g for male animals
124.1 - 133.6g for female animals

Housing : Makrolon cages 37.5 X 23.5 X 16 cm - stainless steel grid lid - sawdust bedding - 2 animals/cage - room 14
Feed : A04C maintenance diets in pellets - UAR - 91360 VILLEMOISSON/ORGE -France - given ad libitum
Drinking : Potable water - Chateau d'eau SA - 59110 La Madeleine - France - Polypropylen bottle autoclaved 10 min 121°C - given ad libitum
Environment : Temperature : 21 +/-2°C - Relative humidity : 50 +/-10% - light/Dark cycle : 12h/d - air renewal >12h

Before the experiment, animals were kept 7 days in quarantine. They were weighted at reception and carefully observed daily from the reception the 2000/11/28 to day 2000/12/05.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
The test compound was dissolved in potable water (vehicle). It was administered by gastric intubation at 2 g/kg bwt in a volume of 10 mL/kg bwt.
Doses:
The dosage was chosen according o the OECD guidelines.
The solution was prepared the day of the test. 25mL of a 200g/L solution were prepared with potable water. The solution was gently homogenized just before administration. The solution was administered at room temperature.
Control animals:
yes
Details on study design:
Randomization in 2 groups was performed at dayy 0 using ARTEMIS II software on the basis of the weights of the animals. The 2 groups were composed of 6 male and 6 female rats.
Groups were identified by coloration of the fur picric acid and animals were differenciated by gentle ear incision. Animals were allocated to groups according the table below.

Before dosing animals were 18 h fasted. Potable water was given ad libitum. Animals were carefully observed and just after dosing (t0), 1 hour and 3 hours after administration of the products at day 0.
The day after and till day 14, animals were daily observed.
Animals were weight at day 0 and at day 3, day 7, day 10 and day 14 using a 0.1 g accuracy scale.
Water was given ad libitum during the trial. Feed was given 3 hours after treatment. To calculate feed and water cosumption, feed and water were weighted at day 0 and at day 3, day 7, day 10 and day 14 using a 0.1 g accuracy scale.
At day 14, animals were sacrified by CO2 inhilation and a necropsy of the abdominal and thoracic cavities were performed.
Treated animals were examined before the controls.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No mortality and behavior modification occured during the study following the oral administration of LAB 3085.
No abnormality was observed at necropsy.
Clinical signs:
No test item related clinical signs were observed during the study. Animal behaviour of treated animals was considered as normal.
Body weight:
Bodyweight evolution, feed and water consumption of treated animals were comparable to those of controls.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: other: CLP EC 1272/2008
Conclusions:
In the experimental conditions of this study, LAB 3085 (Isosorbide) did not induce any toxic effect following oral administration of 2 g/kg bwt on Sprague-Dawley rats.
Executive summary:

Acute oral toxicity study of LAB 3085 on Sprague-Dawley rats.

The protocol is based on the following guidelines:

- OECD Guidelines for testing of chemicals 401

Acute oral toxicity study, 1987

- OECD Guidelines for testing of chemicals 420

Acute oral toxicity study - Fixed determined dose, 1992

- Guideline for acute oral toxicity studies

In : Toxicological principles for safety assessment of direct food additives used in food

Bureau of Food - FDA - 1992

Main results:

No mortality and behavior modification occured during the study following the oral administration of LAB 3085.

No abnormality was observed at necropsy.

Bodyweight evolution, feed and water consumption of treated animals were comparable to those of controls.

Conclusion :

In the experimental conditions of this study, LAB 3085 (Isosorbide) did not induce any toxic effect following oral administration of

2 g/kg bwt on Sprague-Dawley rats.