Sodium benzoate

Repeated dose toxicity: oral

Administrative data

Endpoint:

chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Limited study summary. Study predates approved guidelines, minimal data provided on study design and results, no GLP.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1979

Report date:

1979

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Study predates approved guidelines.
The chronic toxicity study of the test substance was examined in Fischer 344 rats. The test substance was administered in the diet for 18 to 24 months at two dose levels.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Sodium benzoate

EC Number:

208-534-8

EC Name:

Sodium benzoate

Cas Number:

532-32-1

Molecular formula:

C7H6O2.Na

IUPAC Name:

sodium benzoate

Constituent 2

Reference substance name:

Benzoic acid, sodium salt

IUPAC Name:

Benzoic acid, sodium salt

Details on test material:

No data given

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Provided by Japan CLEA Co. Ltd.
- Age at study initiation: 4-5 weeks old
- Weight at study initiation: 110-150 g
- Housing: Five in each cage
- Diet (e.g. ad libitum): CE-2 pellets, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-23℃
- Humidity (%): 55%

No additional data

Administration / exposure

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

None stated

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

18-24 months

Frequency of treatment:

Daily

Doses / concentrations

Remarks:

Doses / Concentrations:
1 or 2%
Basis:
nominal in diet

No. of animals per sex per dose:

Test group: 50 males and 52 females per dose
Control group: 25 males and 43 females

Control animals:

yes, plain diet

Details on study design:

Both male and female rats were divided into three groups and maintained on the diet containing 2 or 1% of the test substance or basal diet for 18 to 24 months. The animals were maintained on a free choice diet, but amount of diet was adequately controlled to avoid excess. Tap water was freely offered to all animals. The rats were weighed weekly, and food intake was measured daily.

Positive control:

None stated

Examinations

Observations and examinations performed and frequency:

Mortality, growth, food intake, behavior and general status were observed in the experimental period.

Sacrifice and pathology:

In the middle of the experimental period, several animals from each groups selected at random were sacrificed for morphologic examination. All surviving animals were killed between 18 to 25 months. For morphologic examination, autopsy was carried out in all animals and paraffin sections of various organs were prepared and stained (hematoxylin and eosin).

Other examinations:

None stated

Statistics:

T-test

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

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

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

no effects observed

Details on results:

Clinical signs and mortality:
During the first 16 months of the experimental period, the average mortality rate of all animals was 14.5%. Except for myeloproliferative disorder developed in one female control rat, all the dead animals showed pneumonia with abscess. Around 100 rats including those of the control groups died after 16 months of hemorrhagic pneumonia with edema which was probably induced by mixed infection of sialodacryoadenitis and mycoplasma. However, no differences in mortality rates between treated and control groups were observed throughout the experimental course.

Body weight gain and food intake:
Nor were there any significant differences in growth and food intake between groups of rats.

Histopathology:
Most developed tumours were benign, such as interstitial cell tumour of the testes and endometrial polyp of the uterus. However, a small number of malignant neoplasms including leukemia was also observed. Differences in numbers of tumor-bearing animals and time-to-tumor development between control and treated gorups were not significant (t-test). No specific toxic effect induced by the test substance was observed.

Effect levels

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No findings of toxicological significance at 20000 mg/kg diet (equivalent to 1000 mg/kg bw)..

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

From the results of this study, it may be concluded that the test substance was not toxic for male and female Fischer 344 rats after 18 to 24-month dietary exposure.

Executive summary:

The chronic toxicity study of the test substance was examined in Fischer 344 rats. The test substance was administered in the diet for 18 to 24 months at two dose levels.

No adverse clinical signs directly attributable to the compound were observed in treated animals. Differences in the average body weight, and mortality rates between treated and control groups were negligible. The results of the statistical test for dose-related trends were significant (p<0.05). Although a variety of tumors occurred among test and control rats of each sex, tumors appearing in treated rats were similar in type and number to those in controls. It was concluded that no evidence of carcinogenicity in rats from the test substance was demonstrated.