Registration Dossier
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 203-570-0 | CAS number: 108-30-5
- 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
- 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:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
Data source
Reference
- Reference Type:
- publication
- Title:
- Teratology and multigeneration reproduction studies with maleic anhydride in rats
- Author:
- Short RD, Johannsen FR, Levinskas GJ, Rodwell DE, and Schardein JL.
- Year:
- 1 986
- Bibliographic source:
- Fundamental and Applied Toxicology 7: 359-66
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- GLP compliance:
- not specified
- Limit test:
- no
Test material
Reference
- Name:
- Unnamed
- Type:
- Constituent
- Details on test material:
- White briquettes with a purity of greater than 99%
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Details on test animals and environmental conditions:
- Weanling rats were acclimated to the laboratory for at least 10 days prior to study initiation. Rats were individually housed, except during mating and lactation, in wire mesh cages or plastic cages with corn-cob bedding. All animals were maintained in environmentally controlled rooms with 12-hr photoperiods and given free access to feed (Purina Rodent Chow) and water.
Administration / exposure
- Route of administration:
- oral: unspecified
- Vehicle:
- corn oil
- Details on exposure:
- Briquettes of maleic anhydride were finely ground with a mortar and pestle and suspended in corn oil with the aid of a tissue homogenizer. All doses were prepared daily in corn oil in order to minimize problems with stability. The concentration of maleic anhydride was varied so that the desired dose could be administered orally in a volume of 10 mL/kg.
- Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- Not applicable
- Duration of treatment / exposure:
- Each generation was dosed a minimum of 80 days with maleic anhydride before its members were mated.Rats in groups of 10 males and 20 females were treated at 0, 20, 55 or 150 mg/kg bw/day (F0), Treatment began when the F0 rats were 5-6 weeks old, continued for at least 80 days prior to mating and continued to termination. For the F1 animals treatment began on Day 22, continued for at least 80 days prior to mating and then continued to termination
- Frequency of treatment:
- Daily
- Duration of test:
- Each generation was dosed a minimum of 80 days with maleic anhydride before its members were mated.Rats in groups of 10 males and 20 females were treated at 0, 20, 55 or 150 mg/kg bw/day (F0), Treatment began when the F0 rats were 5-6 weeks old, continued for at least 80 days prior to mating and continued to termination. For the F1 animals treatment began on Day 22, continued for at least 80 days prior to mating and then continued to termination
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 mg/kg bw/day (nominal)
- Remarks:
- control
- Dose / conc.:
- 30 mg/kg bw/day (nominal)
- Remarks:
- low dose
- Dose / conc.:
- 90 mg/kg bw/day (nominal)
- Remarks:
- mid dose
- Dose / conc.:
- 140 mg/kg bw/day (nominal)
- Remarks:
- high dose
- No. of animals per sex per dose:
- 25 mated females per group
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- No further information
Examinations
- Maternal examinations:
- no details
- Ovaries and uterine content:
- no details
- Fetal examinations:
- no details
- Statistics:
- no details
- Indices:
- no details
- Historical control data:
- no details
Results and discussion
Results: maternal animals
Maternal developmental toxicity
- Details on maternal toxic effects:
- The general appearance and behavior of rats were not altered by treatment. While one adult died in each of the experimental groups, the overall survival in these groups was 96%. Dams in the experimental groups either failed to gain weight or lost weight between Days 6 and 9 of gestation. However, this effect was reversible, and there were no statistically significant effects on body weight at any of the times examined.
Effect levels (maternal animals)
- Dose descriptor:
- NOAEL
- Effect level:
- 140 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- other: no adverse effects observed
Maternal abnormalities
- Abnormalities:
- no effects observed
Results (fetuses)
- Details on embryotoxic / teratogenic effects:
- Dams from all test groups produced normal-sized litters, and there was no evidence of postimplantation loss. Compared with concurrent controls, fetal body weights were slightly reduced for all test groups, but the reductions were statistically significant only in the low- and high-dose groups, However, this is not considered to be compound-related, because fetal weights for were slightly greater than the values for historical controls. Malformations were observed in one fetus (one litter) from the con-
trol group, two fetuses (two litters) from the low-dose group, and three fetuses (three litters) from the high-dose group. Since each malformation was a single occurrence and the malformations differed among the various groups, there was no evidence of a dose-related increase in any specific malformation. The fetal variations were comparable both in type and frequency in the control and treated groups.
Effect levels (fetuses)
- Dose descriptor:
- NOAEL
- Effect level:
- 140 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: no adverse effects were observed
Fetal abnormalities
- Abnormalities:
- not specified
Overall developmental toxicity
- Developmental effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- In the teratology study, pregnant rats received 0, 30, 90, or 140 mg/kg/day maleic anhydride in corn oil orally from Days 6-15 of gestation and fetuses were examined for gross soft tissue and skeletal defects. Based on the result, the maternal and developmental NOAEL can be considered to be 140 mg/kg bw.
- Executive summary:
In a developmental toxicity study (equivalent to OECD 414), CD rats (25 mated females/group) were treated orally with 30, 90, or 140 mg/kg/day of maleic anhydride from Day 6 through Day 15 of gestation. Mated females in the control group were treated in a similar manner with 14 mL/kg of corn oil. All females were sacrificed with carbon dioxide on Day 20 of gestation, and the fetuses were delivered by cesar-
ean section. All fetuses were weighed and examined for external abnormalities. Approximately one-third of the fetuses were placed in Bouin’s fixative and examined for soft tissue abnormalities (Wilson, 1965). The remaining fetuses were fixed in alcohol, cleared with potassium hy-droxide, stained with Alizarin Red S (Dawson, 1926), and examined for skeletal abnormalities.
Results showed, that the general appearance and behavior of rats were not altered by treatment. While one adult died in each of the experimental groups, the overall survival in these groups was 96%. Dams in the experimental groups either failed to gain weight or lost weight between Days 6 and 9 of gestation. However, this effect was reversible, and there were no statistically significant effects on body weight at any of the times examined.
Dams from all test groups produced normal-sized litters, and there was no evidence of postimplantation loss. Compared with concurrent controls, fetal body weights were slightly reduced for all test groups, but the reductions were statistically significant only in the low- and high-dose groups, However, this is not considered to be compound-related, because fetal weights for were slightly greater than the values for historical controls. Malformations were observed in one fetus (one litter) from the control group, two fetuses (two litters) from the low-dose group, and three fetuses (three litters) from the high-dose group. Since each malformation was a single occurrence and the malformations differed among the various groups, there was no evidence of a dose-related increase in any specific malformation. The fetal variations were comparable both in type and frequency in the control and treated groups.
Based on the results obtained, the maternal and developmental NOAEL can be considered to be 140 mg/kg bw/day.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.

Route: .live1