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Toxicological information

Genetic toxicity: in vivo

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Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
other: read-across based on grouping of substances (category approach)
Remarks:
Sodium benzoate is rapidly metabolized to benzoic acid.
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study predates approved guidelines and GLP.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1974
Report Date:
1973

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)
Deviations:
yes
Remarks:
number of metaphases counted
Principles of method if other than guideline:
Study predates approved guidelines.This in vivo chromosome aberration study was conducted using rats. In acute study, animals were killed 6 hours, 24 hours and 48 hours after administration. In subacute study, five doses 24 hours apart, animals were killed 6 hours after last dose. Four hours af ter the last compound administration, and two hours prior to killing, each animal was given 4 mg/kg of colcemid. The chromosomes of bonemarrow cells were counted and only diploid cells were analyzed. Fifty metaphase spreads were scored per animal. Mitotic indices were obtained by counting at least 500 cells.
GLP compliance:
no
Type of assay:
chromosome aberration assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
No data given

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS- Source: A closed colony (random-bred)- Age at study initiation: 10 to 12 weeks old- Weight at study initiation: 280 to 350 g- Assigned to test groups randomly: yes- Fasting period before study:- Housing: Housed one to five to a cage, sanitary cages and bedding were used.- Diet (e.g. ad libitum): Commercial 4% fat diet and provided ad libitum.- Water (e.g. ad libitum): ad libitum- Acclimation period: 4-11 days

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
0.85% saline
Duration of treatment / exposure:
Acute study: ImmediatelySubacute study: 96h
Frequency of treatment:
Acute study: Single doseSubacute study: Once a day for each of five consecutive days
Post exposure period:
Acute study: 6 h, 24h and 48hSubacute study: 6h
Doses / concentrations
Remarks:
Doses / Concentrations:50, 500 and 5000 mg/kgBasis:actual ingested
No. of animals per sex per dose:
5 males
Control animals:
yes, concurrent vehicle
Positive control(s):
Triethylene Melamine- Doses / concentrations: 0.3 mg/kg

Examinations

Tissues and cell types examined:
The chromosomes of each bonemarrow cell were counted and only diploid cells were analyzed. They were scored for chromatid gaps and breaks, chromosome gaps and breaks, reunions, cells with greater than ten aberrations, polyploidy, pulverization, and any other chromosomal aberrations which were observed. Fifty metaphase spreads were scored per animal . Mitotic indices were obtained by counting at least 500 cells and the ratio of the number of cells in mitosis/the number of cells observed was expressed as the mitotic index.
Details of tissue and slide preparation:
The slides were stained using a 5% Giemsa solution (Giemsa buffer pH 7.2) for 20 minutes, rinsed in acetone, 1:1 acetone:xylene, and placed in fresh xylene for 30 minutes. The slides were then mounted using Permount (Fisher Scientific) and 24 x 50 mm coverglasses. The coverglasses were selected to be 0.17 mm±0.005 mm in thickness by use of a coverglass micrometer.
Evaluation criteria:
None stated
Statistics:
None stated

Results and discussion

Test results
Sex:
male
Genotoxicity:
negative
Toxicity:
no effects
Vehicle controls validity:
valid
Positive controls validity:
valid
Additional information on results:
Acute study:The mitotic index in treatment groups and negative controls was similar. No increase in the number of aberrations was reported in the treated groups at all time points compared to untreated controls.The positive control showed a lower mitotic index and a high incidence of chromosomal abnormalitiesSubacute study:The mitotic index in treatment groups and negative controls was similar. No increase in the number of aberrations was reported in the treated groups compared to untreated controls.No data on positive controls are available.

Any other information on results incl. tables

No report on bodyweights, clinical findings or pathology

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negativeThe test substance produced no detectable significant increase in the number of aberrations in bone marrow metaphase chromosomes of rats administered orally at the dosage levels employed in this study.Reliability of this study can be demonstrated as 2 (reliable with restrictions) due to limited data available on methods and results. Study predates approved guidelines and GLP.
Executive summary:

This in vivo chromosome aberration study was conducted using rats. In acute study, animals were killed 6 hours, 24 hours and 48 hours after administration. In subacute study, five doses 24 hours apart, animals were killed 6 hours after last dose. Four hours af ter the last compound administration, and two hours prior to killing, each animal was given 4 mg/kg of colcemid. Bonemarrow cells were harvested and the chromosomes of each cell were counted and only diploid cells were analyzed (50 metaphases per treatment).

The test substance produced no detectable significant increase in the number of aberrations in bone marrow metaphase chromosomes of rats administered orally at the dosage levels employed in this study.

Reliability of this study can be demonstrated as 2 (reliable with restrictions) due to limited data available on methods and results. Study predates approved guidelines and GLP.