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EC number: 203-571-6 | CAS number: 108-31-6
- 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
Developmental toxicity / teratogenicity
Administrative data
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
Data source
Referenceopen allclose all
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 979
- Report date:
- 1979
- Reference Type:
- publication
- Title:
- Teratology and multigeneration reproduction studies with maleic anhydride in rats
- Author:
- Short R.D. et al
- Year:
- 1 986
- Bibliographic source:
- Fundamental and Applied Toxicology 7, 359-66
- Reference Type:
- review article or handbook
- Title:
- Maleic Anhydride and Maleic Acid, SIDS Initial Assessment Report For SIAM 18
- Author:
- OECD SIDS
- Year:
- 2 004
- Bibliographic source:
- OECD SIDS Initial Assessment Report For SIAM 18, Paris, France, 20-23 April 2004
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Deviations:
- yes
- Remarks:
- (administered volume in the control and high dose group is higher (1.4 ml/100 g bw) than the advised maximum volume in the guideline (0.4 ml/100 g bw))
- GLP compliance:
- no
- Limit test:
- no
Test material
- Reference substance name:
- Maleic anhydride
- EC Number:
- 203-571-6
- EC Name:
- Maleic anhydride
- Cas Number:
- 108-31-6
- Molecular formula:
- C4H2O3
- IUPAC Name:
- 2,5-dihydrofuran-2,5-dione
- Details on test material:
- - Name of test material (as cited in study report): maleic anhydride
- Physical state: white briquettes
- Analytical purity: > 99%
Constituent 1
Test animals
- Species:
- rat
- Strain:
- other: Charles River CD rats
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Age at study initiation: 12 weeks
- Housing: individually housed, except during mating
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 10 days
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on exposure:
- VEHICLE
- Concentration in vehicle: 1% (w/v)
- Amount of vehicle (if gavage): 0.3-1.4 ml/100g bw - Details on mating procedure:
- - Impregnation procedure: cohoused
- If cohoused:
- M/F ratio per cage: 1/1
- Proof of pregnancy: vaginal plug in vaginal smear referred to as day 0 of pregnancy - Duration of treatment / exposure:
- from gestation day 6 through day 15
- Frequency of treatment:
- daily
- Duration of test:
- day 20 of gestation
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 30 mg/kg bw/day (actual dose received)
- Remarks:
- low dose
- Dose / conc.:
- 90 mg/kg bw/day (actual dose received)
- Remarks:
- mid dose
- Dose / conc.:
- 140 mg/kg bw/day (actual dose received)
- Remarks:
- high dose
- No. of animals per sex per dose:
- 25
- Control animals:
- yes, concurrent vehicle
Examinations
- Maternal examinations:
- DETAILED CLINICAL OBSERVATIONS: Yes
BODY WEIGHT: Yes
- Time schedule for examinations: gestation days 0, 6, 9, 12, 15, and 20 - Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes
- Other: fetal swellings, number of viable and nonviable fetuses - Fetal examinations:
- - External examinations: Yes: [all per litter]
- Soft tissue examinations: Yes: [1/3 per litter ]
- Skeletal examinations: Yes: [2/3 per litter ] - Statistics:
- All statistical analyses compared the treatment groups with the control group, with the level of significance at p<0.05. Male to female fetal sex ratio and number of litters with anomalies were compared using the Chi-square test criterion with Yates correction for 2 x 2 contingency tables and/or Fisher's exact probability test as described by Siegel to Judge significance of differences. The proportion of lite resorbed fetuses and postimplantation losses were compared by the Mann-Whitney U-test as described by Siegel and Weil to judge significance of differences. Mean number of corpora lutes, total implantations and viable fetuses were compared by analysis of variance (one-way classification), Bartlett's test for homogeneity of variances and the appropriate t-test (for equal or unequal variances) as described by Steel and Torrie using Dunnett's multiple comparison table to judge significance of differences. Fetal body weights were compared by analysis of variance (hierarchal classification) and t-test as described by Steel and Torri using Dunnett's multiple comparison tables to judge significance of differences.
Results and discussion
Results: maternal animals
General toxicity (maternal animals)
- Clinical signs:
- no effects observed
- Dermal irritation (if dermal study):
- not examined
- Mortality:
- mortality observed, non-treatment-related
- Description (incidence):
- For further details see section "Details on results" below.
- Body weight and weight changes:
- effects observed, non-treatment-related
- Description (incidence and severity):
- For further details see section "Details on results" below.
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- no effects observed
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- not examined
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- not examined
- Histopathological findings: neoplastic:
- not examined
- Other effects:
- not examined
Maternal developmental toxicity
- Number of abortions:
- no effects observed
- Pre- and post-implantation loss:
- no effects observed
- Total litter losses by resorption:
- not examined
- Early or late resorptions:
- no effects observed
- Dead fetuses:
- no effects observed
- Changes in pregnancy duration:
- not examined
- Changes in number of pregnant:
- no effects observed
- Details on maternal toxic effects:
- Maternal toxic effects:no effects
Details on maternal toxic effects:
Respiratory involvement and red nasal discharge were observed in all dosage groups. The incidence of these was higher in the treated groups, though not in a dose-related pattern. No treatment-related deaths (one rat in each dosage group died during the first part of treatment; the cause of death was not determined) nor abnormal behavior was observed in any of the maleic anhydride treated groups. Mean body weight gain was reduced in the 30 mg/kg/day dosage group for the first three days of treatment. There was a slight mean body weight loss in the 90 and 140 mg/kg/day dosage groups for the first three days of treatment. These reductions in weight gains resulted in reduced mean body weight gains over the entire treatment period in all treatment groups compared to the control (however, mean weight of all groups was within 5% of control on days 15 and 20. No biologically meaningful differences in the mean number of viable fetuses, implantations, post implantation losses, corpora lutea, or in the male to female sex ratio between any of the maleic anhydride treated groups and the control group. The general appearance and behavior of rats were not affected by treatment.
Effect levels (maternal animals)
- Dose descriptor:
- NOAEL
- Effect level:
- >= 140 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Basis for effect level:
- body weight and weight gain
- Remarks on result:
- other: Only slight effects on the body weight in the 90 and 140 mg/kg treatment groups. These effect were reversible, and there were no statistically significant effects on body weight at any of the times examined.
Maternal abnormalities
- Abnormalities:
- no effects observed
Results (fetuses)
- Fetal body weight changes:
- effects observed, non-treatment-related
- Description (incidence and severity):
- For further details see section "Details on results" below.
- Reduction in number of live offspring:
- not examined
- Changes in sex ratio:
- not examined
- Changes in litter size and weights:
- not examined
- Changes in postnatal survival:
- not examined
- External malformations:
- effects observed, non-treatment-related
- Description (incidence and severity):
- For further details see section "Details on resutls" below.
- Skeletal malformations:
- no effects observed
- Visceral malformations:
- no effects observed
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:no effects
Details on embryotoxic / teratogenic effects:
Mean fetal body weights were lower in the treatment groups than in the control group. This was not considered compound related due to the unusually high mean fetal body weight in this concurrent control group (mean: 4 g). External evaluation, internal examination, and skeletal observations of fetuses from all three treatment groups showed no anomalies in fetal development which could be attributed to maleic anhydride (slight increase in fetal malformations in the 30 (2/23 litters) and 140 mg/kg/day dosage group (3/21 litters) when compared to the control group (1/23 litters) is considered due to random occurrence due to the variety of abnomalities observed).
Effect levels (fetuses)
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- >= 140 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Basis for effect level:
- other: teratogenicity
- Dose descriptor:
- NOAEL
- Effect level:
- >= 140 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Basis for effect level:
- other: fetotoxicity
Fetal abnormalities
- Abnormalities:
- no effects observed
Overall developmental toxicity
- Developmental effects observed:
- no
Applicant's summary and conclusion
- Conclusions:
- In developmental toxicity study (equivalent to OECD 414) maleic anhydride (>99% purity) was administered to 25 female Wistar rats/dose in corn oil at dose levels of 0, 30, 90 or 140 mg/kg bw/day from days 6 through 15 of gestation. On day 20 of gestation the animals were sacrificed. Based on the results, the NOAEL for both maternal toxicity and fetal toxicity of maleic anhydride in this study is considered to be higher or equal to 140 mg/kg bw/day.
- Executive summary:
In a developmental toxicity study (equivalent to OECD 414) maleic anhydride (>99% purtiy.) was administered to 25, rats/dose by gavage at dose levels of 0, 30, 90 or 140 mg/kg bw/day from days 6 through 15 of gestation.
There were no changes in appearance or behavior attributable to treatment with maleic Anhydride at dosage levels of 30, 90 and 140 mg/kg bw/day. Respiratory involvement and red nasal discharge were observed in all dosage groups. The incidence of these was higher in the treated groups, though not in a dose-related pattern. One rat in each dosage group dl.dd during the first part of treatment. The cause of death was not determined. There were reduced mean maternal body weight gains during the first three days of treatment in the 30 mg/kg bw/day dosage group when compared to the control group. In the 90 and 140 mg/kg bw/day dosage groups mean body weight losses were observed for the first 3 days of treatment. These reductions in weight gains resulted in reduced mean weight gains over the entire treatment period in all treatment groups when compared to the control group. There were no biologically meaningful differences in the mean number of viable fetuses, implantations, post implantation losses, corpora lutea or in the male to female sex ratio between any of the maleic anhydride treated groups and the control group. Based on the results, the NOAEL for maternal toxicity is considered to be higher than 140 mg/kg bw/day.
There were no treatment-related effects in developmental parameters. Therefore, based on the result the developmental NOAEL is also considered to be higher or equal to 140 mg/kg bw/day.
The developmental toxicity study in the rat is classified acceptable and satisfies the guideline requirement for a developmental toxicity study (OECD 414) in rats.
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