Phenyl N-(4,6-dimethoxypyrimidin-2-yl)carbamate

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

Study period:

1991

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.12 (Mutagenicity - In Vivo Mammalian Erythrocyte Micronucleus Test)

Deviations:

no

GLP compliance:

yes

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

Phenyl N-(4,6-dimethoxypyrimidin-2-yl)carbamate

EC Number:

406-600-2

EC Name:

Phenyl N-(4,6-dimethoxypyrimidin-2-yl)carbamate

Cas Number:

89392-03-0

Molecular formula:

C13H13N3O4

IUPAC Name:

phenyl N-(4,6-dimethoxypyrimidin-2-yl)carbamate

Test material form:

solid: crystalline

Details on test material:

- Identification: IN-E6758
- Description: Off white to light blue solid
- Batch: E52691-89-3-B22
- Purity: approx. 100%
- Expiry date: not indicated
- Storage: at room temperature in a cool place in the dark (avoid high temperatures)

Test animals

Species:

mouse

Strain:

NMRI

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Species: Swiss mice, CD-1 (SPF-quality)
- Source: BRL, Switzerland
- Age at study initiation: approximately 7 weeks
- Weight at study initiation: 33.8-35.6 g males and 25.8-27.6 g females
- Housing: in groups of 5 per sex in polycarbonate cages
- Diet (e.g. ad libitum): Standard laboratory animal diet (Kliba 343 from Klingentalmuhle Ag, Kaiseraugst, Switzerland)
- Water (e.g. ad libitum): Tap water
- Acclimation period: at least 6 days under laboratory conditions

ENVIRONMENTAL CONDITIONS
- Temperature: 21°C
- Humidity: 40-70%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 hrs artiificial light

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

- Vehicle(s)/solvent(s) used: corn oil
- Dose level: 3000 mg/kg bw
- Amount of vehicle: 10 ml/kg body weight

Duration of treatment / exposure:

24, 48 and 72 hours

Frequency of treatment:

once

Doses / concentrations

Remarks:

Doses / Concentrations:
3000 mg/kg bw
Basis:
other: nominal in corn oil

No. of animals per sex per dose:

5 male and 5 female mice per treatment group.

Control animals:

yes

Positive control(s):

- Positive control: Cyclophosphamide (CAS no. 50-18-0; Endoxan, Asta-Werke, F.R.G.)
- Route of administration: oral, gavage
- Doses / concentrations: 50 mg/kg body weight dissolved in 0.9% NaCl (Herck) in Milli-RO water

Examinations

Details of tissue and slide preparation:

CRITERIA FOR DOSE SELECTION:
Selection of an adequate dose for the Micronucleus test was based on a pilot study. Depending on the available toxicity data 1 to 5 dose groups, each comprising 3 males and 3 females, received a single dose of the test substance. Generally, the study duration is 3 days, however this might be changed if considered necessary. During this period mortality and physical condition has been recorded daily.

Evaluation criteria:

A test substance is considered positive in the micronucleus test if:
a) It induced a biologically as well as a statistically significant (Wilcoxon Rank Sum Test; two-sided test at p < 0.05) increase in the frequency of aicronuclei (at any dose or at any sampling time) in the combined data for both sexes or in the data for male or female groups separately.

A test substance is considered negative in the micronucleus test if:
a) None of the tested concentrations or sampling times showed a statistically significant (P < 0.05) increase in the incidence of micronuclei neither in the combined data for both sexes nor in the data for male or female groups alone.

Statistics:

See above

Results and discussion

Test results

Sex:

male/female

Genotoxicity:

negative

Toxicity:

no effects

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative
The test item was found to be non-mutagenic in this test system

Executive summary:

The genotoxicity study in vivo was performed as Micronucleus test according to EU-method B.12. Swiss mice of strain NMRI were used at a single dose of 3000 mg/kg bw in corn oil. Sampling times were 24, 48 and 72 hours. The substance was found to be non-mutagenic in this test.