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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
Data is from peer reviewed journal

Data source

Reference
Reference Type:
publication
Title:
Effect of Sorbitol, Fructose, Succhiate, Asportate, Glutamate and Fat on Growth and Survival Time of Biotin-deficient Rats
Author:
M. S. Patel
Year:
1996
Bibliographic source:
J. Nutrition

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: Refer below principle
Principles of method if other than guideline:
Subacute oral toxicity study was performed for the test chemical using rats.
GLP compliance:
not specified

Test material

Constituent 1
Chemical structure
Reference substance name:
Disodium succinate
EC Number:
205-778-7
EC Name:
Disodium succinate
Cas Number:
150-90-3
Molecular formula:
C4H6O4.2Na
IUPAC Name:
disodium succinate
Details on test material:
- Name of test material: Sodium succinate
- Molecular formula: C4H6O4.2Na
- Molecular weight: 162.052 g/mol
- Substance type: Organic

Test animals

Species:
rat
Strain:
Sprague-Dawley
Details on species / strain selection:
No data
Sex:
male
Details on test animals or test system and environmental conditions:
- Age at study initiation: weanling rats
- Weight at study initiation: 32-38 g
- Fasting period before study: No data available
- Housing: housed individually in metal cages with raised wire screens
- Diet (e.g. ad libitum): Basal diet ad libitum
- Water (e.g. ad libitum): Water ad libitum
- Acclimation period: No data available

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Regulated
- Humidity (%):No data available
- Air changes (per hr): No data available
- Photoperiod (hrs dark / hrs light): No data available

IN-LIFE DATES: From: To: No data available


Administration / exposure

Route of administration:
oral: feed
Details on route of administration:
No data
Vehicle:
other: Basal diet
Details on oral exposure:
PREPARATION OF DOSING SOLUTIONS: Dose was prepared by adding 5 or 10% (5000 or 10000 mg/Kg) of Sodium succinate to the basal diet at the expense of an equivalent amount of glucose.

DIET PREPARATION
- Rate of preparation of diet (frequency): No data available
- Mixing appropriate amounts with (Type of food): Basal diet
- Storage temperature of food: No data available

VEHICLE
- Justification for use and choice of vehicle (if other than water): Basal diet
- Concentration in vehicle: 0, 5 and 10 % (0, 5000 or 10000 mg/Kg)
- Amount of vehicle (if gavage): No data available
- Lot/batch no. (if required): No data available
- Purity: No data available
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
No data
Duration of treatment / exposure:
7 weeks
Frequency of treatment:
Daily
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 5 and 10 % (0, 2500 and 5000 mg/kg/day)

No. of animals per sex per dose:
Total: 30
0 % : 10 male
5 % : 10 male
10 % : 10 male
Control animals:
yes, concurrent vehicle
Details on study design:
- Dose selection rationale: No data available
- Rationale for animal assignment (if not random): Animal were assignment to group on the basis of mean body weight and a similar weight distribution in each group (RGB design).
- Rationale for selecting of satellite groups: No data available
- Post-exposure recovery period in satellite groups: No data available
- Section schedule rationale (if not random): No data available

Positive control:
No data

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
Time schedule: Daily
- Cage side observations checked in table [No.?] were included: Mortality was observed.

DETAILED CLINICAL OBSERVATIONS: No data available
- Time schedule: No data available

BODY WEIGHT: Yes
- Time schedule for examinations: Weekly intervals

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes

- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data available

FOOD EFFICIENCY: No data available
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No data available

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data No data available
- Time schedule for examinations: No data available

OPHTHALMOSCOPIC EXAMINATION: No data No data available
- Time schedule for examinations: No data available
- Dose groups that were examined: No data available

HAEMATOLOGY: No data No data available
- Time schedule for collection of blood: No data available
- Anaesthetic used for blood collection: Yes (identity) / No / No data No data available
- Animals fasted: Yes / No / No data No data available
- How many animals: No data available
- Parameters checked in table [No.?] were examined. No data available

CLINICAL CHEMISTRY: No data No data available
- Time schedule for collection of blood: No data available
- Animals fasted: Yes / No / No data No data available
- How many animals: No data available
- Parameters checked in table [No.?] were examined. No data available

URINALYSIS: No data No data available
- Time schedule for collection of urine: No data available
- Metabolism cages used for collection of urine: Yes / No / No data No data available
- Animals fasted: Yes / No / No data No data available
- Parameters checked in table [No.?] were examined. No data available

NEUROBEHAVIOURAL EXAMINATION: No data No data available
- Time schedule for examinations: No data available
- Dose groups that were examined: No data available
- Battery of functions tested: sensory activity / grip strength / motor activity / other: No data available
Sacrifice and pathology:
No data available
Other examinations:
No data available
Statistics:
No data available

Results and discussion

Results of examinations

Clinical signs:
not specified
Description (incidence and severity):
Clinical signs: No data available
Mortality:
no mortality observed
Description (incidence):
No effect were observed on survival of treated rats as compared to control.
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Slight decrease in weight gain was observed in 5 and 10 % treated rat as compared to control.
Food consumption and compound intake (if feeding study):
no effects observed
Description (incidence and severity):
No effect was observed on food consumption of treated rat as compared to control.
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
not specified
Details on results:
Although addition of 5 or 10% sodium succinate led to a slight decrease in weight gain it had no effect on survival time of the treated animals

Effect levels

Dose descriptor:
NOAEL
Effect level:
2 500 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male
Basis for effect level:
other: Slight decrease in body weight gain was observed
Remarks on result:
other: No toxic effects were observed

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
The NOAEL was considered to be 2500 mg/kg/day) when Sprague Dawley male rats were treated with test substance.
Executive summary:

Subacute oral toxicity study was performed for the test chemical using weanling male Sprague Dawley rats deficient in biotin. The test chemical was mixed with feed at dose level of 0, 5 or 10% (0, 2500 or 5000 mg/Kg). The animals were fed the diet containing the test chemical for 7 weeks. Body weights were recorded at about weekly intervals. The animals were observed for Survival time. Slight decrease in weight gain was observed in 5 and 10 % treated rat as compared to control it had no effect on survival time of the treated rats. Based on the observations made, the NOAEL for test chemical was considered to be 2500 mg/Kg/day.