Tetrahydro-1,3-dimethyl-1H-pyrimidin-2-one

Genetic toxicity: in vivo

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

Test material information

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 / concentrations

Doses / concentrations 1

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

Doses / concentrations 2

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.	Time^b	Number of animals		Number of analyzed cells	MPE^c
		♂	♀		♂	♂	♀	♀	Mean %
0.8 HMPA	48	2	2	4000	4	15	17	3	0.98^d
	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.