5,5-Dimethylimidazolidine-2,4-dione, reaction products with oxirane

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Type of information:

experimental study

Adequacy of study:

key study

Study period:

27 August 2013 to 16 October 2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Deviations:

yes

Remarks:

On occassions the relative humidity was outside the target range of 30-70%. The animals in the main test, with the exception of the positive control group were housed in groups of seven.

GLP compliance:

yes

Type of assay:

other: Mammalian Erythrocyte Micronucleus Test

Test material

Test material information

Constituent 1

Reference substance name:

1,3-bis(2-hydroxyethyl)-5,5-dimethylimidazolidine-2,4-dione

EC Number:

701-388-0

Cas Number:

26850-24-8

IUPAC Name:

1,3-bis(2-hydroxyethyl)-5,5-dimethylimidazolidine-2,4-dione

Test material form:

other: pale yellow solid block

Details on test material:

- Name of test material (as cited in study report): Dantocol DHE
- Physical state: pale yellow solid block
- Lot/batch No.: M5469330
- Storage condition of test material: room temperature in the dark

Test animals

Species:

mouse

Strain:

ICR

Details on species / strain selection:

Sufficient albino Hsd: ICR (CD-1)

Sex:

male/female

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

Phoshate Buffered Saline (PBS)

Duration of treatment / exposure:

Once.

Frequency of treatment:

Once.

Post exposure period:

24 hours (500, 1000 or 2000 mg/kg bw) and 48 hours (2000 mg/kg bw group) post-treatment.

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

500 mg/kg bw/day (nominal)

Doses / concentrations 2

Dose / conc.:

1 000 mg/kg bw/day (nominal)

Doses / concentrations 3

Dose / conc.:

2 000 mg/kg bw/day (nominal)

No. of animals per sex per dose:

Seven/dose group

Control animals:

yes, concurrent vehicle

Positive control(s):

Cyclophosphamide (50 mg/kg bw)

Examinations

Tissues and cell types examined:

Bone marrow smears prepared and polychromatic erythrocytes per animal was scored. The number of normochromatic erythrocytes were also counted and scored for incidence of micronuclei.

Evaluation criteria:

Micronuclei are cicular, but occassionally may be oval or half-moon shaped and have a sharp contour with even staining.

Statistics:

The ratio of polychromatic to normochromtic erythrocytes was calculated together with appropriate group of mean values and standard deviations.
A positive mutagenic response was demoinstrated when a statistically significant, dose-responsive, toixicologically relevant increase in the number of micronucleated polychromatic erythrocytes was observed for iether the 24 or 48-hour kill times compared to their corresponding control group.

Results and discussion

Test results

Key result

Sex:

male/female

Genotoxicity:

negative

Toxicity:

no effects

Remarks:

No premature deaths or clinical signs of toxicity observed in any of the animals dosed.

Vehicle controls validity:

valid

Negative controls validity:

not applicable

Positive controls validity:

valid

Applicant's summary and conclusion

Conclusions:

The test item was considered to be non-genotoxic under the conditions of the test.

Executive summary:

An in vivo gentoxicity assay was conducted on the substance according to OECD Guideline 474. The results of the test indicates that the substance is non-genotoxic in vivo under the conditions of the study.