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Toxicological information

Genetic toxicity: in vivo

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Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
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: Test procedures cannot be subsumed under testing guideline, nevertheless are well documented and scientifically acceptable.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1974
Report Date:
1974

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
GLP compliance:
no
Remarks:
Pre GLP.
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
hamster, Chinese
Strain:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Tierzuchtinstitut of the University of Zuerich.
- Weight at study initiation: 20 -30 g.
- Water: ad libitum.

ENVIRONMENTAL CONDITIONS
- Temperature: 23 ± 1 °C
- Humidity: 55 ± 5 %
- Photoperiod: 12/12 hrs dark / hrs light.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
- Vehicle used: CMC (carboxymethyl cellulose).
Duration of treatment / exposure:
2 days
Frequency of treatment:
Daily.
Post exposure period:
24 hours.
Doses / concentrations
Remarks:
Doses / Concentrations:
1250, 2500, 5000 mg/kg
Basis:
actual ingested
No. of animals per sex per dose:
6 animals per dose.
Control animals:
yes, concurrent vehicle
Positive control(s):
Cyclophosphamide
- Route of administration: oral: gavage.
- Doses / concentrations: 128 mg/kg in 20 ml/kg 0.5 % CMC solution.

Examinations

Tissues and cell types examined:
Bone marrow cells.
Details of tissue and slide preparation:
DETAILS OF SLIDE PREPARATION
Small drops of the homogeneous suspension were transferred on the end of a slide, spread out by pulling it behind a polished cover glass and the preparations were air-dried. On the next day the slides were stained in undiluted May-Gruenwald solution for 2 min and subsequently with Giemsa solution (5 %) 9 min. After rinsing with distilled water and air-drying the slides were cleared in Xylol and mounted in Eukitt.


METHOD OF ANALYSIS
1000 bone marrow cells were scored from each 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) bizarre forms of nuclei
f) polyploid cells
g) necrobiotic cells.
Statistics:
The significance of difference was assessed by x(square) -test.

Results and discussion

Test results
Sex:
male/female
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

In all dosage groups the percentage of cells displaying anomalies of nuclei did not differ significantly from the negative control. By contrast, the positive control (cyclophosphamide, 128 mg/kg) yielded a marked increase of the percentage of cells with anomalies. Here the mean percentage of anomalies was 10.8, whereas the negative control yielded a percentage of 0.15. The difference is highly significant (p < 0.01).

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
Not mutagenic.
Executive summary:

Method

Nucleus Anomaly Test on Somatic Interphase Nuclei was conducted in Chinese Hamster in order to evaluate the mutagenic effects on bone marrow cells. Doses of 1250, 2500, 5000 mg/kg were given by oral gavage .

Results

In all dosage groups the percentage of cells displaying anomalies of nuclei did not differ significantly from the negative control. By contrast, the positive control (cyclophosphamide, 128 mg/kg) yielded a marked increase of the percentage of cells with anomalies. Here the mean percentage of anomalies was 10.8, whereas the negative control yielded a percentage of 0.15. The difference is highly significant (p< 0.01).