Succinic acid

Repeated dose toxicity: other routes

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

Reference

Reference 1

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 2

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 3

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

Test material information

Constituent 1

Reference substance name:

Succinic acid

EC Number:

203-740-4

EC Name:

Succinic acid

Cas Number:

110-15-6

Molecular formula:

C4H6O4

IUPAC Name:

succinic 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.