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EC number: 210-848-5 | CAS number: 624-48-6
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Repeated dose toxicity: dermal
Administrative data
- Endpoint:
- short-term repeated dose toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- other information
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- documentation insufficient for assessment
Cross-reference
- Reason / purpose for cross-reference:
- reference to same study
Data source
Reference
- Reference Type:
- publication
- Title:
- Maleic acid dimethylester: evaluation of dermal toxicity and genotoxicity
- Author:
- Heimann KG, Jung R, and Kieczka H
- Year:
- 1 991
- Bibliographic source:
- Fd. Chem. Toxic. 29, 575-578
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 410 (Repeated Dose Dermal Toxicity: 21/28-Day Study)
- Deviations:
- yes
- Remarks:
- Method shortly described; analytical purity not reported.
- GLP compliance:
- yes
- Limit test:
- no
Test material
- 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
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Age at study initiation: 9-11 weeks old.
- Weight at study initiation: 216-238 g (male), 183-215 g (female).
Administration / exposure
- Type of coverage:
- occlusive
- Vehicle:
- olive oil
- Details on exposure:
- Route of Administration: dermal.
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 28d
- Frequency of treatment:
- 6h/d, 5d/w for a total of 20 applications.
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 60, 170, 500 mg/kg bw
Basis:
nominal per unit body weight
- No. of animals per sex per dose:
- 5
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- no data
Examinations
- Observations and examinations performed and frequency:
- Feed consumption and body weight determination, haematology, clinical chemistry, urinalysis (carried out as described in OECD guideline 410).
- Sacrifice and pathology:
- HISTOPATHOLOGY: Yes. Carried out as described in OECD guideline 410.
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Dermal irritation:
- effects observed, treatment-related
- Description (incidence and severity):
- dose related
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- effects observed, treatment-related
- Clinical biochemistry findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Some variations in the high-dose group were observed, but they were not considered to be of no major toxicological relevance.
- Urinalysis findings:
- no effects observed
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- minimal to slight dermatitis, acanthosis and hyperkeratosis.
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- not examined
- Details on results:
- No compound-related mortality and systemic clinical symptoms occurred. Clear, dose-related local effects, ranging from slight erythema and scaling in the lowest dose group up to severe erythema, slight-to-moderate oedema and scaling and slight to severe necrosis in the highest dose group, were observed. Significantly reduced feed consumption and body-weight gain occurred only in male rats of the middle- and high-dose groups.
The haematological investigation revealed slight leucocytosis (increased of about 56%), accompanied by a slight increase of neutrophilic granulocytes (factor 2) and a decrease (27%) of lymphocytes in rats of the high-dose group. The main effects of the clinical chemistry analysis were a 35% depletion of oxidized hepatic glutathione (GSSG) and corresponding 37% decrease in the total hepatic glutathione (reduced glutathione and GSSG) level in the high-dose group. Some variations in the haematological and clinico-chemical parameters (thromboplastin, partial thromboplastin time, electrolytes, glucose, urea, transferases) of the high-dose group were observed.
Urinalysis did not reveal any treatment-related changes. Absolute and relative organ weights of liver kidneys, heart, brain and adrenal glands were not significantly affected by treatment with dimethyl maleate.
The histopathological examination did not reveal any treatment-related changes in the liver and kidney. In correlation with the macroscopic findings, some rats in the middle-dose group showed minimal to slight dermatitis, acanthosis and hyperkeratosis. Moderate dermatitis and moderate-to-marked necrosis were detected in all rats in the high-dose group.
Effect levels
- Dose descriptor:
- NOEL
- Effect level:
- 60 mg/kg bw/day
- Sex:
- male/female
- Basis for effect level:
- other: body weight; haematology; foof consumption; clinical chemistry; gross pathology; organ weights.
Target system / organ toxicity
- Critical effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- Assessment not possible due to lack of reporting details.
- Executive summary:
Heimann (1991)
Dimethyl maleate was applied to 5 male and 5 female rats in each group on the shaved back.
They received dimethyl maleate for 6 hours daily, 5 days/week, for a total of 20 applications.
In an application volume of 2 mL/kg body weight (vehicle: olive oil) the following dose levels were given 0 (vehicle control), 60, 170 or 500 mg/kg body weight. The application area was about 10 % f the body surface and was covered by an occlusive dressing. Feed consumption and body weight determination, haematology, clinical chemistry, urinalysis and histopathology were carried out as described in OECD guideline 410.
No compound-related mortality and systemic clinical symptoms occurred. Clear, dose-related local effects, ranging from slight erythema and scaling in the lowest dose group up to severe erythema, slight-to-moderate oedema and scaling and slight to severe necrosis in the highest dose group, were observed. Significantly reduced feed consumption and body-weight gain occurred only in male rats of the middle- and high-dose groups.
The haematological investigation revealed slight leucocytosis (increased of about 56%), accompanied by a slight increase of neutrophilic granulocytes (factor 2) and a decrease (27%) of lymphocytes in rats of the high-dose group. The main effects of the clinical chemistry analysis were a 35% depletion of oxidized hepatic glutathione (GSSG) and corresponding 37% decrease in the total hepatic glutathione (reduced glutathione and GSSG) level in the high-dose group. Some variations in the haematological and clinico-chemical parameters (thromboplastin, partial thromboplastin time, electrolytes, glucose, urea, transferases) of the high-dose group were observed.
Urinalysis did not reveal any treatment-related changes. Absolute and relative organ weights of liver kidneys, heart, brain and adrenal glands were not significantly affected by treatment with dimethyl maleate.
The histopathological examination did not reveal any treatment-related changes in the liver and kidney. In correlation with the macroscopic findings, some rats in the middle-dose group showed minimal to slight dermatitis, acanthosis and hyperkeratosis. Moderate dermatitis and moderate-to-marked necrosis were detected in all rats in the high-dose group.
60 mg dimethyl maleate/kg body weight can be regarded as the systemic no-effect level for repeated dermal exposure of rats.
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