2-thiazolidinylidenecyanamide

Genetic toxicity: in vivo

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

Test material information

Constituent 1

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.