Didodecyl 3,3'-thiodipropionate

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Acceptable, well documented study which meets basic scientific principles (limited information about test item, animals were killed 2 hours instead of 3-5 h after colcemid application, only fifty metaphase spreads were scored per animal; only 3 animals in the negative control group).

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1973

Report date:

1973

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)

Deviations:

yes

Remarks:

(limited information about test item, animals were killed 2 hours instead of 3-5 h after colcemid application, only fifty metaphase spreads were scored per animal; only 3 animals in the negative control group)

GLP compliance:

no

Type of assay:

chromosome aberration assay

Test material

Test material information

Constituent 1

Reference substance name:

Didodecyl 3,3'-thiodipropionate

EC Number:

204-614-1

EC Name:

Didodecyl 3,3'-thiodipropionate

Cas Number:

123-28-4

Molecular formula:

C30H58O4S

IUPAC Name:

didodecyl 3,3'-sulfanediyldipropanoate

Details on test material:

- Name of test material (as cited in study report): FDA compound 71-40, Dilauryl Thiodipropionic Acid 10-769
No further details.

Test animals

Species:

rat

Strain:

not specified

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: obtained from a closed colony (random-bred)
- Age at study initiation: 10-12 weeks
- Weight at study initiation: 280-350 g
- Housing: groups of 5
- Diet (ad libitum): 4% fat diet
- Water (ad libitum): yes
- Acclimation period: 4-11 days

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

- Vehicle(s)/solvent(s) used: physiol. saline

Duration of treatment / exposure:

single gastric intubation

Frequency of treatment:

single

Post exposure period:

6, 24, 48 h

Doses / concentrations

Remarks:

Doses / Concentrations:
50, 500, 5000 mg/kg bw
Basis:
actual ingested

No. of animals per sex per dose:

5 (experimental groups and positive control), 3 (negative control)

Control animals:

yes, concurrent vehicle

Positive control(s):

triethylenemelamine
- Route of administration: intraperitoneal
- Doses / concentrations: 0.3 mg/kg

Examinations

Tissues and cell types examined:

cells of the bone marrow

Details of tissue and slide preparation:

CRITERIA FOR DOSE SELECTION: based on acute oral toxicity (see chapter 7.2.1.)

TREATMENT, SAMPLING TIMES and SLIDE PREPARATION:
Two hours prior to killing, each animal was given 4 mg/kg of colcemid intraperitoneal in order to arrest the bone marrow cells in C-mitosis. Animals were killed by using CO2, and the adhering muscle and epiphysis of one femur were removed. The marrow "plug" was removed with a tuberculin syringe and an 18 gauge needle, aspirated into 5 mL of Hanks' balanced salt solution (BSS) in a test tube and capped. The specimens were centrifuged at 1,500 RPM in a table-top centrifuge for 5 minutes, decanted, and 2 ml of hypotonic 0.5% KCl solution was added with gentle agitation to resuspend the cells. The specimens were then placed in a 37°C water bath for 20 minutes in order to swell the cells. Following centrifugation for 5 minutes at 1,500 RPM, the supernatant was decanted and 2 ml of fixative (3:1 absolute methanol:glacial acetic acid) was added. The cells were resuspended in the fixative with gentle agitation, capped, and placed at 4°C for 30 minutes. The specimens were again centrifuged, decanted, 2 mL of prepared fixative was added, and the cells were resuspended and placed at 4°C overnight. The following day the specimens were again centrifuged, decanted and 0.3 - 0.6 mL of freshly prepared fixative was added to obtain a suitable density. The cells were resuspended and 2 - 3 drops of the suspension were allowed to drop onto a clean, dry slide held at 15° from the horizontal. As the suspension flowed to the edge of the slide , it was ignited by an alcohol burner and allowed to flame. Following ignition, the slides were allowed to dry at room temperature overnight. Duplicate slides were prepared. 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 preparations were examined using microscopes with brightfield optics and xenon light sources. These specimens were scanned and suitable metaphase spreads that were countable were then examined critically using oil immersion flat - field apochromatic objectives. The chromosomes for each 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. They were recorded on the currently used forms and expressed as / percentages on the summary sheets. 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.
Positive controls in the acute study consisted of animals which had been given the known mutagen (Triethylene Melamine (TEM)) administered intraperitoneally at a level of 0.30 mg/kg. Negative control consisted of the vehicle in which the compound was administered.

Evaluation criteria:

no data

Statistics:

no data

Results and discussion

Test results

Sex:

male

Genotoxicity:

negative

Toxicity:

no effects

Vehicle controls validity:

valid

Negative controls validity:

not examined

Positive controls validity:

valid

Any other information on results incl. tables

Mitotic indices were normal.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative