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Diss Factsheets

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:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study according OECD guideline.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1997
Report date:
1997

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of assay:
micronucleus assay

Test material

Constituent 1
Chemical structure
Reference substance name:
-
EC Number:
427-720-1
EC Name:
-
Cas Number:
26364-65-8
Molecular formula:
C4H5N3S
IUPAC Name:
[(1,3-thiazolidin-2-ylidene)amino]formonitrile
Details on test material:
name: Cyanamide, (4,5-dihydroxy-2-thiazolyl)-
molecular formula: C4 H5 N3 S
molecular weight: 127.2
physical state: solid
analytical purity: 96.7 %

Test animals

Species:
mouse
Strain:
NMRI
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan Winkelmann GmbH, Borchen
- Age at study initiation: 6 to 12 weeks
- Weight at study initiation: 36-43 g (male) and 29-35 g (female)
- Housing: type I cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: least five days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23°C
- Humidity (%): 55-85% mean relative humidity
- Air changes (per hr): about ten times per hour
- Photoperiod (hrs dark / hrs light): twelve hours of electrical lighting daily (6.00 hours to 18.00 hours, about 500 lux)

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
- Vehicle(s)/solvent(s) used: 0.5 % aqueous Cremophor
Duration of treatment / exposure:
1 injection
Control animals:
yes, historical
Positive control(s):
cyclophosphamide
- Justification for choice of positive control(s): This is a proven cytostatic agent and known clastogen with bifunctional alkylation action.

Examinations

Details of tissue and slide preparation:
according to Schmid:
- SCHMID, W., The Micronucleus Test., Mutation Res. 31, 9-15, 1975
- SCHMID, W., Der Mikrokerntest., Deutsche Forschungsgemeinschaft. Koramission fur Mutagenitatsfragen. Mitteilung III, 53-61, 1975

Results and discussion

Test results
Genotoxicity:
negative
Toxicity:
yes
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
Based on the findings of this study the substance is considerd to be not clastogenic.
Executive summary:

The micronucleus test was employed to investigate CIT in male and female mice for a possible clastogenic effect on the chromosomes of bone-marrow erythroblasts. The known clastogen and cytostatic agent, cyclophosphamide, served as positive control. The treated animals received a single intraperitoneal administration of either CIT or cyclophosphamide. The femoral marrow of groups treated with CIT was prepared 16, 24 and 48 hours after administration. All negative and positive control animals were sacrificed after 24 hours. The doses of CIT and the positive control, cyclophosphamide, were 250 and 20 mg/kg body weight, respectively. The animals treated with CIT showed symptoms of toxicity after administration. However, all animals survived until the end of the test. There was no altered ratio between polychromatic and normochromatic erythrocytes. No indications of a clastogenic effect of CIT were found after a single intraperitoneal treatment with 250 mg/kg. Cyclophosphamide, the positive control, had a clear clastogenic effect, as is shown by the biologically relevant increase in polychromatic erythrocytes with micronuclei. The ratio of polychrom polychromatic to normochromatic erythrocytes was not altered.