Registration Dossier

Administrative data

Endpoint:
sub-chronic toxicity: other route
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
before 1944
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: Old study with methodological deficiencies.

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Injections of certain plant growth substances in rats and chick embryos.
Author:
Dye W.S.
Year:
1944
Bibliographic source:
Growth
Reference Type:
secondary source
Title:
EVALUATION OF THE HEALTH ASPECTS OF SUCCINIC ACID AS A FOOD INGREDIENT
Author:
Jackson W.L.
Year:
1975
Bibliographic source:
NTIS (National Technical Information Service)
Reference Type:
secondary source
Title:
SCIENTIFIC LITERATURE REVIEWS ON GENERALLY RECOGNIZED AS SAFE (GRAS) FOOD INGREDIENTS-SUCCINIC ACID
Author:
FDA
Year:
1973
Bibliographic source:
NTIS (National Technical Information Service)

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Albino rats, seven days old, were injected subcutaneously with 0. 5 mg of succinic acid in sesame oil, and daily thereafter with increasing doses until they were receiving 2. 0 mg per day at four weeks of age (estimated to be approximately 20 mg succinic acid per kg body weight per day); this dosage was continued until the rats were 60 days old. Control animals received similar doses of sesame oil only. All the rats were weighed and measured weekly. and the times of hair appearance, tooth eruption, eye opening, and vaginal opening were recorded.
GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Succinic acid
EC Number:
203-740-4
EC Name:
Succinic acid
Cas Number:
110-15-6
Molecular formula:
C4H6O4
IUPAC Name:
butanedioic acid
Details on test material:
Name: succinic acid

Test animals

Species:
rat
Strain:
other: "albino"
Sex:
not specified
Details on test animals or test system and environmental conditions:
no data

Administration / exposure

Route of administration:
subcutaneous
Vehicle:
other: sesame oil
Details on exposure:
Albino rats, seven days old, were injected subcutaneously with 0. 5 mg of succinic acid in sesame oil, and daily thereafter with increasing doses
until they were receiving 2. 0 mg per day at four weeks of age (estimated to be approximately 20 mg succinic acid per kg body weight per day); this
dosage was continued until the rats were 60 days old. Control animals received similar doses of sesame oil only. All the rats were weighed
and measured weekly and the times of hair appearance, tooth eruption, eye opening, and vaginal opening were recorded.
Analytical verification of doses or concentrations:
not specified
Control animals:
yes, concurrent vehicle
Details on study design:
Albino rats, seven days old, were injected subcutaneously with 0. 5 mg of succinic acid in sesame oil, and daily thereafter with increasing doses until they were receiving 2. 0 mg per day at four weeks of age (estimated to be approximately 20 mg succinic acid per kg body weight per day); this dosage was continued until the rats were 60 days old. Control animals received similar doses of sesame oil only. All the rats were weighed and measured weekly and the times of hair appearance, tooth eruption, eye opening, and vaginal opening were recorded.

Examinations

Observations and examinations performed and frequency:
All the rats were weighed and measured weekly and the times of hair appearance, tooth eruption, eye opening, and vaginal opening were recorded.

Results and discussion

Results of examinations

Details on results:
There were no significant differences between the treated and the control animals except for a possible tendency toward delayed opening of the vagina in the test rats (57. 2 days) compared with the controls (49. 4 days).

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
There were no significant differences between the treated and the control animals except for a possible tendency toward delayed opening of the vagina in the test rats (57. 2 days) compared with the controls (49. 4 days).
Executive summary:

15 rats were injected s.c. at 7 days of age with a dosage of 0.5 mg of succinic acid (in sesame oil) and daily thereafter with increasing doses until they were receiving 2.0 mg per day at tour weeks of age. This level of dosage was continued until the rats reached 60 days of age. As controls, 90 rats received similar doses of sesame oil only. The rats were weighed and measured weekly and the time of hair appearance, tooth eruption, eye opening, and vaginal opening were recorded for each rat. No significant differences between the treated and the control rats were observed, except possibly in the opening of the vagina. The average age of opening in the test rats was 57.2 days as compared to 49.4 for the controls.