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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
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Basic data given

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1985
Report date:
1985

Materials and methods

Principles of method if other than guideline:
According to Schmid, W., The Micranucleus Test, in A. Hollaender (ed.): Chemical Mutagens, Vol. 4, plenum Press, New York - London, pp. 31-53, 1976.
GLP compliance:
no
Type of assay:
micronucleus assay

Test material

Constituent 1
Reference substance name:
DMPU
IUPAC Name:
DMPU
Test material form:
other: liquid
Details on test material:
- Name of test material (as cited in study report): DMPU (Tetrahydro-1.3-dimethyl-2(1H)-pyrimidinone)
- Lot/batch No.: 32569/2 283

Test animals

Species:
mouse
Strain:
not specified
Sex:
male/female

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
DMSO
Duration of treatment / exposure:
two single injections
Frequency of treatment:
twice with an interval of 24 hours
Post exposure period:
48 and 72 h
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0.04, 0.125 and 0.4 mL/kg bw
Basis:
nominal conc.
dose per application; dose selection based on previous toxicity study
Remarks:
Doses / Concentrations:
42.6, 133.1, 426 mg/kg bw
Basis:
nominal conc.
dose per application; dose selection based on previous toxicity study
No. of animals per sex per dose:
4 (2 male and 2 female of each dose group were killed 48 or 72 hours after the first administration)
Control animals:
yes
Positive control(s):
HMPA (hexamethylphosphoramide)

Examinations

Tissues and cell types examined:
Polychromatic erythrocytes from bone marrow smears
Details of tissue and slide preparation:
Slides were prepared from the bone marrow of femora. 1000 polychromatic eryhtrocytes (PCE) were examined per animal.

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Toxicity:
yes
Remarks:
0.8 mL/kg DMPU 100% mortality, 0.6 mL/kg DMPU 67% mortality; 0.4 mL/kg DMPU 17% mortality
Vehicle controls validity:
not examined
Negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
The mean number of micronuclei did not exceed the historical control value of 0.3% in any DMPU dose group or in any time-period. The results did not reveal any statistically significant differences compared to controls.

Any other information on results incl. tables

Results of both micronucleus tests with HMPA and DMPU:

Dose (mg/kg)a

2x i.p.

Timeb

Number of animals

Number of analyzed cells

MPEc

Mean %

0.8

HMPA

48

2

2

4000

4

15

17

3

0.98d

72

2

2

4000

1

4

3

3

0.28

0

Control

48

2

2

4000

0

0

1

3

0.10

72

2

2

4000

2

0

3

5

0.25

0.04

DMPU

48

2

2

4000

0

2

0

6

0.20

72

2

2

4000

1

1

5

5

0.30

0.125

DMPU

48

2

2

4000

3

0

1

2

0.15

72

2

2

4000

3

5

3

1

0.30

0.4

DMPU

48

2

2

4000

1

1

0

0

0.05

72

2

2

4000

3

0

0

6

0.23

a): 0.8 ml HMPA equals 820 mg; 0.4 ml DMPU equals 426 mg

b): Hours after first administration

c): MPE: Polychromatic ersthrocytes with micronuclei

d): Statistically significant compared to controls (P < 0.05)

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
DMPU has no clastogenic action in in vivo systems.

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