3-(dimethylamino)propylurea

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:

1986

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1986

Report date:

1986

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

GLP compliance:

yes

Type of assay:

mammalian erythrocyte micronucleus test

Test material

Test material information

Constituent 1

Reference substance name:

3-(dimethylamino)propylurea

EC Number:

401-950-2

EC Name:

3-(dimethylamino)propylurea

Cas Number:

31506-43-1

Molecular formula:

C6H15N3O

IUPAC Name:

[3-(dimethylamino)propyl]urea

Test material form:

liquid: viscous

Test animals

Species:

mouse

Strain:

other: Bor: NMRI (SPF Han)

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Duration of treatment / exposure:

1 off

Frequency of treatment:

1 time

Post exposure period:

24 h
48 h
72 h

Doses / concentrations

Dose / conc.:

5 000 mg/kg bw (total dose)

No. of animals per sex per dose:

5 males and 5 females

Control animals:

yes, concurrent no treatment

yes, concurrent vehicle

Results and discussion

Test results

Key result

Sex:

male/female

Genotoxicity:

negative

Toxicity:

yes

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Applicant's summary and conclusion

Conclusions:

After one-off oral applications of single doses of test material (5000 mg/kg b.w.) it leads to the conclusion that the test material fails to induce a significant response in the invivo clastogenicy study, similar to OECD 474.

Executive summary:

Using the micronucleus test, 3-(Dimethylamino)propylurea was investigated in male and female mice for a possible clastogenic effect on the chromosomes or bone marrow erythroblasts. The known clastogen and cytostatic agent cyclophosphamide served as a positive control.

The animals received a single oral administration at a dose of 5000 mg/kg and 20 mg/kg of body weight for 3-(Dimethy1amino)propylurea and the positive control (cyclophosphamide), respectively. The femoral

marrow of the 3-(Dimethylarnino)propylurea - groups was prepared 24, 48, and 72 hours after the administration. Negative and positive controls were sacrificed after 24 hours only.

The animals treated with 3-(Dimethylamino)propylurea showed symptoms of toxicity lasting up to 24 hours after the administration. This effect was more pronounced in females than in males. 8 of 20 females but

none of the males died during the test.

Erythrocyte formation, as measured by the ratio of polychromatic to normochromatic erythrocytes, was clearly inhibited. Cyclophosphamide, the positive control, had a clear clastogenic effect, as can be seen from the biologically relevant increase in polychromatic erythrocytes with micronuclei. An inhibition of erythropoiesis was not found here.

After oral application of single doses of test material (5000 mg/kg b.w.) it leads to the conclusion that the test material fails to induce a significant response in the invivo clastogenicy study, similar to OECD 474.