Registration Dossier

Toxicological information

Genetic toxicity: in vivo

Currently viewing:

Administrative data

Endpoint:
in vivo mammalian cell study: DNA damage and/or repair
Remarks:
Type of genotoxicity: DNA damage and/or repair
Type of information:
experimental study
Adequacy of study:
key study
Study period:
15th August 1983 - 9th November 1983
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted in accordance with generally accepted scientific principles, possibly with incomplete reporting or methodological deficiencies, which do not affect the quality of the relevant results.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1983
Report Date:
1983

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: see below
Deviations:
not specified
Principles of method if other than guideline:
Perry, P. and H.J. Evans. 1975. Cytological detection of mutagen-carcinogen exposure by sister chromatid exchange. Nature. 258:121-125
GLP compliance:
no
Type of assay:
sister chromatid exchange assay

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
hamster, Chinese
Strain:
other: Cricetulus griseus
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: NDA
- Age at study initiation: female 6 - 10 weeks, male 4 - 9 weeks
- Weight at study initiation: female 20 - 29 g, male 22 - 28 g
- Assigned to test groups randomly: [no/yes, under following basis: ] NDA
- Fasting period before study: NDA
- Housing: individually caged
- Diet (e.g. ad libitum): NAFAG No. 924
- Water (e.g. ad libitum): ad libitum
- Acclimation period: NDA


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 - 23 ºC
- Humidity (%): 51 - 64 %
- Air changes (per hr): air conditioned room
- Photoperiod (hrs dark / hrs light): 12 hours light / day


IN-LIFE DATES: From: 15th August 1983 To: 17th August 1983

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
- Vehicle(s)/solvent(s) used: 0.5% Sodium carboxymethyl cellulose (CMC) and 0.1% Polysorbate 80 used for test substance and negative control. 0.5% Sodium carboxymethyl cellulose (CMC) alone for positive control.
- Justification for choice of solvent/vehicle: NDA
- Concentration of test material in vehicle: Various
- Amount of vehicle (if gavage or dermal): 20 ml/kg bw
Details on exposure:
The animals were treated orally by a single dose of the test material two hours after subcutaneous implantation of a 45 mg-tablet of 5-bromodeoxyuridine (BUdR) (Fa. Heinrich Mack, D-Illertissen, Germany) in the neck. 24 hours after the administration of the test material and 2 hours after intraperitoneal injection of 10 mg colcemide/kg the animals were sacrificed by dislocation of the cervical vertebrae.
Duration of treatment / exposure:
24 hours
Frequency of treatment:
Single dosage
Post exposure period:
N/A
Doses / concentrations
Remarks:
Doses / Concentrations:
1250, 2500 and 5000 mg/kg bw
Basis:
actual ingested
No. of animals per sex per dose:
4 for each dose
4 for positive control
4 for negative control
Control animals:
yes
Positive control(s):
7,12-dimethylbenzanthracene (DMBA)
- Justification for choice of positive control(s): NDA
- Route of administration: oral (gavage) in vehicle
- Doses / concentrations: 100 mg/kg bw

Examinations

Tissues and cell types examined:
Bone marrow from the shafts of both femurs.
Details of tissue and slide preparation:
Bone marrow from the shafts of both femurs was suspended in 1% sodium citrate solution for hypotonic treatment, kept in a waterbath at 4 to 6°C for 45 min and then centrifuged for 10 min at 200 x g. The pellets were then fixed in methanol-acetic acid 3:1 for a period of 30 min, resuspended, centrifuged for 5 min at 150 x g, and stored in fresh fixative overnight at 4°C. Finally the pellets again were centrifuged for 5 min at 150 x g, and resuspended in some 0.5 ml fixative in order to obtain a more concentrated cell suspension.

These specimens were pipetted onto wet slides and air-dried.

The air-dried slides then were treated with a solution of bisbenzimide (H 33258) for 15 min, rinsed in Mcllvaine-buffer pH 8.0 and irradiated in this buffer at 50°C with UV-light of 350 nm. Following the development of the fluorochrome-UV-light reaction in 60°C 2 x SSC (standard sodium citrate) for 90 min, the slides were stained in 40% Giemsa for 20-40 min, well rinsed, cleared in Xylol and mounted in Eukitt.
Evaluation criteria:
The slides of two female and two male animals each of the treatment groups and of the control groups were examined. Twenty-five differently stained metaphases of the second cell-cycle with BUdR-substitution were analysed per animal for the number of SCE's following specific criteria
Statistics:
The significance of differences of the treatment groups compared to the negative control group was assessed by t-test on the level of one percent.

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Toxicity:
not examined
Vehicle controls validity:
valid
Negative controls validity:
not examined
Positive controls validity:
valid
Additional information on results:
One male animal of the high-dose group died in the course of the experiment.

In the various dose groups no increase of the number of SCE's was found in comparison with the negative control.

The positive control group showed a highly significant increase of SCE's per cell (9.24) in comparison with the negative control (5.53 SCE's/cell).

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
The results obtained indicate that under the given experimental conditions TK 11 339 does not provoke any effect interpretable as being suggestive of a mutagenic property.
Executive summary:

A single does of TK 11 339 (Di-n-octyltindichloride) was administered orally to male ( 22 - 28 g, 4 - 9 week old) and female ( 20 - 29 g, 6 - 10 week old) Chinese hamsters (Cricetulus griseus). The experiments were performed in order to detect a possible mutagenic property of the substance, manifested in somatic cells in vivo in the form of sister chromatid exchanges.

The results obtained indicate that under the given experimental conditions TK 11 339 does not provoke any effect interpretable as being suggestive of a mutagenic property.