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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Cross-reference
Reason / purpose for cross-reference:
reference to same study

Data source

Reference
Reference Type:
publication
Title:
Maleic acid dimethlyester: evaluation of dermal toxicity and genotoxicity.
Author:
Heimann KG, Jung R, and Kieczka H
Year:
1991
Bibliographic source:
Fd. Chem . Toxic. 29, 8, 575-578.

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)
Deviations:
yes
Remarks:
method shortly described; no analytical purity reported.
Principles of method if other than guideline:
The micronucleus test was performed according to Schmidt (1975), Mutation Research 31, 9-15; and Heddle (1973, Mutation Research 18, 187-190, with slight modifications.
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
Details on test material:
- Name of test material (as cited in study report): Maleic acid dimethylester
- Analytical purity: not reported

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 old.
- Weight at study initiation: 27-28 g.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
- Vehicle(s)/solvent(s) used: maize oil.
Details on exposure:
PREPARATION OF DOSING SOLUTIONS:
The dosing solutions were prepared in 10 mL maize oil/kg body weight, or maize oil alone.
Duration of treatment / exposure:
Animals were killed 24, 48, and 72 hours after treatment.
Frequency of treatment:
single exposure.
Post exposure period:
no
Doses / concentrations
Remarks:
Doses / Concentrations:
1000 mg/kg bw
Basis:
actual ingested
No. of animals per sex per dose:
5
Control animals:
yes, concurrent vehicle
Positive control(s):
cyclophosphamide
- Doses / concentrations: 60 mg.

Examinations

Tissues and cell types examined:
Bone-marrow.
Details of tissue and slide preparation:
Bone-marrow smears were prepared, stained and 1000 polychromatic erythrocytes/mouse were examined for micronuclei.
Evaluation criteria:
no data
Statistics:
no data

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Toxicity:
yes
Remarks:
A shift from polychromatic to monochromatic erythrocytes was observed, indicating a toxic influence on bone marrow cell proliferation.
Vehicle controls validity:
not specified
Negative controls validity:
not specified
Positive controls validity:
valid
Additional information on results:
No induction of micronuclei was found after oral application of 1000 mg maleic acid dimethylester/kg body weight in mice. A shift from polychromatic to monochromatic erythrocytes was observed, indicating a toxic influence on bone marrow cell proliferation. Cyclophosphamide showed the expected induction of micronuclei and thus confirmed the sensitivity of the test system. The results demonstrate that maleic acid dimethylester does not have a clastogenic potential im mice.

Applicant's summary and conclusion

Conclusions:
Interpretation of results: negative