Dimethyl maleate

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, publication/study report which meets basic scientific principles, but details missing

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1982

Report date:

1982

Reference 2

Reference Type:

secondary source

Title:

Maleic acid dimethylester: evaluation of dermal toxicity and genotoxicity

Author:

Heimann KG, Jung R, Kieczka H

Year:

1991

Bibliographic source:

Fd Chem Toxic Vol 29 No 8 pp 575-578

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Deviations:

not specified

GLP compliance:

yes

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

Dimethyl maleate

EC Number:

210-848-5

EC Name:

Dimethyl maleate

Cas Number:

624-48-6

Molecular formula:

C6H8O4

IUPAC Name:

dimethyl (Z)-but-2-enedioate

Test animals

Species:

mouse

Strain:

NMRI

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 12 weeks
- Weight at study initiation: 27-38 g

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

maize oil

Details on exposure:

PREPARATION OF DOSING SOLUTIONS:
- prepared in 10 mL maize oil/kg body weight

Frequency of treatment:

once

Post exposure period:

24, 48 and 72 hrs

Doses / concentrations

Remarks:

Doses / Concentrations:
1000 mg/kg body weight
Basis:
actual ingested

No. of animals per sex per dose:

5

Control animals:

yes, concurrent vehicle

Positive control(s):

- cyclophosphamide
- Route of administration: oral (gavage)
- Doses / concentrations: 60 mg/kg bw

Examinations

Tissues and cell types examined:

bone marrow

Evaluation criteria:

1000 polychromatic erythrocytes per animal were examined for micronuclei
normochromatic erythrocyte swer also counted

Results and discussion

Test results

Sex:

male/female

Genotoxicity:

negative

Toxicity:

yes

Vehicle controls validity:

not specified

Negative controls validity:

not specified

Positive controls validity:

not specified

Any other information on results incl. tables

Slight cytotoxicity was observed (shift in relation normochromatic/polychromatic erythrocytes).

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative
The results demonstrated that the test substance did not have a clastogenic potential in mice.

Executive summary:

The test substance was dissolved in maize oil and was adminsitered orally to 5 male and 5 female NMRI mice per group. The dose was 1000 mg/kg body weight, the dose volume was 10 ml/kg bw. Negative (vehicle) and positive (cyclophosphamide, 60 mg/kg bw) control groups were included in the study design. Bone marrow was prepared 24, 48 and 72 hours after administration.

No increase in the percentage of polychromatic micronucleated erythrocytes was found and it was concluded that the test susbtance had no clastogenic potential in mice. A shift in the relation of normochromatic to polychromatic erythrocytes indicating slight cytotoxicity proved the bioavailability of the test substance.