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Toxicological information

Genetic toxicity: in vivo

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Administrative data

Endpoint:
genetic toxicity in vivo
Remarks:
Type of genotoxicity: genome mutation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1983
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions

Data source

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

Materials and methods

GLP compliance:
no
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
hamster, Chinese
Strain:
other: Chinese hamster (Cricetulus griseus) random outbred strain
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: CIBA-GEIGY Tierfarm, Sisseln, Switzerland
- Age at study initiation: females: 6-10 weeks, males: 4-9 weeks
- Weight at study initiation: females: 20-30 g; males: 21-31 g
- Housing: individually
- Diet (e.g. ad libitum): NAFAG No.924, ad libitum
- Water (e.g. ad libitum): Tap water, ad libitum
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-23
- Humidity (%): 51-54
- Photoperiod (hrs dark / hrs light): 12 hours / 12 hours

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
0.5 % aqueous solution of sodium carboxymethylcellulose (CMC) plus 0.1 % Tween 80 (Tw 80)
Duration of treatment / exposure:
daily on 2 consecutive days
Frequency of treatment:
once a day
Post exposure period:
24 hours
Doses / concentrationsopen allclose all
Dose / conc.:
750 mg/kg bw/day (actual dose received)
Dose / conc.:
1 500 mg/kg bw/day (actual dose received)
Dose / conc.:
3 000 mg/kg bw/day (actual dose received)
No. of animals per sex per dose:
6
Control animals:
yes, concurrent vehicle
Positive control(s):
cyclophosphamide (128 mg/kg)

Examinations

Tissues and cell types examined:
bone marrow cells
Details of tissue and slide preparation:
DETAILS OF SLIDE PREPARATION: Bone marrow was harvested from the shafts of both femurs. In a siliconized pipette filled with approx. 0.5 µl rat serum the bone marrow was drawn up. In order to receive a homogeneous suspension the content of pipette was aspirated gently about three times. Small drops of the mixture were transferred on the end of a slide, spread out by pulling it behind a polished cover glass and the preparations were air-dried. Three hours later, the slides were stained in undiluted May-Gruenwald solution for 2 min then in May-Gruenwald solution/water 1/1 for
2 min and then in Giemsa's, 40 % for 20 min. After being rinsed in methanol 55 % for 5-8 sec and washed off twice in water, they were left immersed in water for approx. 2 min. After rinsing with distilled water and air-drying, the slides were cleared in Xylol and mounted in Eukitt.

METHOD OF ANALYSIS: The slides of three female and three male animals were examined. 1000 bone marrow cells each were scored per animal and the following anomalies were registered: a) Single Jolly bodies, b) fragments of nuclei in erythrocytes, c) micronuclei in erythroblasts, d) micronuclei in leucopoietic cells, e) polyploid cells.
Statistics:
The significance of difference was assessed by x²-test

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Toxicity:
not examined
Additional information on results:
RESULTS OF DEFINITIVE STUDY
- Types of structural aberrations for significant dose levels: a) Single Jolly bodies, b) fragments of nuclei in erythrocytes, c) micronuclei in erythroblasts, d) micronuclei in leucopoietic cells, e) polyploid cells
- Induction of micronuclei (for Micronucleus assay): In all dosage groups the percentage of cells displaying anomalies of nuclei did not differ significantly from the negative control.
- Statistical evaluation: The significance of difference was assessed by χ2-test

Applicant's summary and conclusion

Conclusions:
The test substance failed to induce statistically significant genome mutations under the conditions of the test.