6,6'-di-tert-butyl-4,4'-thiodi-m-cresol

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

key study

Study period:

December 1, 1987 - March 21, 1988

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study is performed according to the applicable OECD and EPA guidelines under GLP conditions. No deviations were reported.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.5385 (In Vivo Mammalian Cytogenetics Tests: Bone Marrow Chromosomal Analysis)

Deviations:

no

GLP compliance:

yes

Type of assay:

chromosome aberration assay

Test material

Test material information

Constituent 1

Details on test material:

- Name of test material (as cited in study report): Santowhite R crystals
- Substance type: white powder
- Physical state: solid
- Analytical purity: unfortunately not readable on page 51 of report
- Storage condition of test material: room temperature

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories
- Age at study initiation: 61 days
- Weight at study initiation: males: 139 - 158 g; females: 104 - 122 g.
- Assigned to test groups randomly: yes
- Fasting period before study: 18 hr.
- Housing: individually in stainless, steel cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 4 days

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

- Vehicle(s)/solvent(s) used: corn oil

Duration of treatment / exposure:

6, 18, 30 hours

Frequency of treatment:

single dose

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 700, 1400 mg/kg bw
Basis:
actual ingested

No. of animals per sex per dose:

5

Control animals:

yes, concurrent vehicle

Positive control(s):

cyclophosphamide;
- Route of administration: oral gavage
- Doses / concentrations: 20 mg/kg bw

Examinations

Tissues and cell types examined:

bone marrow

Details of tissue and slide preparation:

DETAILS OF SLIDE PREPARATION:
Cells were resuspended in a small amount of freshly prepared fixative. Slides were prepared by dropping the cell suspension on precleaned methanol-wet glass slides followed by flaming. Slides were stained in 3% Giemsa in distilled water for 10 minutes, rinsed in distilled water and air dried. Slides were cleared in xylene and coverslips mounted with Permount.

Evaluation criteria:

Cytogenetic abnormalities were classified on a standard scoring sheet according to chromosome or chromatid aberrations and further according to type of aberration. Aberrations were classified according to the nomenclature of Buckton and Evans, 1973 and Savage, 1975.

Statistics:

Mean number of aberrations per cell per rat (50 cells per rat) were analyzed for statistically significant increases in chromosome aberration by a one-way analysis of variance (ANOVA). Each sampling time was analyzed separately as compared to its concurrent vehicle control group. The CP group was not included in the ANOVA.
Data from this group were analyzed separately by a one-tailed t test comparing CP with the 18 hour vehicle control. The mean and standard deviation of aberrations/cell were also determined for each group of rats (500 cells; 50 cells per rat). The number of aberrant metaphases was analyzed by Chi-square analysis for statistically significant increases. Statistical significance was determined at the p<= 0.05 probability level.

Results and discussion

Test results

Sex:

male/female

Genotoxicity:

negative

Toxicity:

yes

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

RESULTS OF RANGE-FINDING STUDY
- Dose range: 1500 and 2075 mg/kg bw
- Clinical signs of toxicity in test animals: severe toxicity signs at 1500 mg/kg bw and mortality at 2075 mg/kg bw

RESULTS OF DEFINITIVE STUDY
- Types of structural aberrations for significant dose levels (for Cytogenetic or SCE assay): no structural chromosomal aberrations induced by testing substance
- Appropriateness of dose levels and route: all rats dosed with 1400 mg/kg exhibited mild to severe toxicity signs at all times evaluated. Thus, the tested substance was dosed near the maximum tolerated dose.

Any other information on results incl. tables

none

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative
Male and female Fisher 344 rats received 0, 700, 1400 mg/kg Santowhite R by oral gavage. The hemopoietic cells of the bone marrow were analyzed after 6, 18, and 30 hours. No statistically significant increases in the incidence of aberrations or in the number of cells with one or more aberrations were observed in animals treated with Santowhite crystals at 700 or 1400 mg/kg at any of the three sampling times evaluated. Therefore, under the conditions of this assay, Santowhite crystals was not clastogenic to the hemopoietic cells of the rat bone marrow.