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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

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1982
Report date:
1982
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

Constituent 1
Chemical structure
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.

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