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EC number: 203-328-4 | CAS number: 105-76-0
- 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
Toxicity to reproduction
Administrative data
- Endpoint:
- screening for reproductive / developmental toxicity
- Remarks:
- based on test type (migrated information)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: This is a GLP study conducted according to OECD guideline 422.
Cross-reference
- Reason / purpose for cross-reference:
- reference to other study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 993
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
- Deviations:
- not specified
- GLP compliance:
- yes (incl. QA statement)
- Limit test:
- yes
Test material
- Reference substance name:
- Dibutyl maleate
- EC Number:
- 203-328-4
- EC Name:
- Dibutyl maleate
- Cas Number:
- 105-76-0
- Molecular formula:
- C12H20O4
- IUPAC Name:
- dibutyl but-2-enedioate
- Details on test material:
- No data available
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- rats: Wistar, CRL:(WI)BR
Supplier: Charles River WIGA, D8741 Sulzfeld
Body weight: (M) mean 365 and (F) mean 245
Age: about 11 weeks
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- arachis oil
- Details on exposure:
- Doses for the combined test: 0 (control; treated with vehicle), 30, 95, and 300 mg/kg/day.
Dose range finding: 0, 100, 316, and 1000 mg/kg. - Details on mating procedure:
- Mating was performed on an 1:1 base after 2 weeks of pre-mating period. Couples were separated after successful mating response at the end of a 10-days mating perido.
- Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- No data available
- Duration of treatment / exposure:
- Dosing of both sexes was started at beginning of pre-mating period and continued daily until the end of the study
- Frequency of treatment:
- Daily
- Details on study schedule:
- Day -10: receipt of animals
Day 1: First administration of the test substance
Day 15: Start of mating period
Day 16: First proven mating
Day 26: End of mating period
Day 37: First parturition
Day 41: Sacrifice of all males
Day 46: Last sacrifice
- No. of animals per sex per dose:
- 12 female and 12 male Winstar rats per dose.
- Details on study design:
- Dams were allowed to litter normally and were sacrificed together with their offspring on day 4 of lactation. All males were necropsied together with the first dams.
- Positive control:
- no available
Examinations
- Parental animals: Observations and examinations:
- Clinical signs, body weight, feed consumption, mating results, time of parturition, hematology and clinical chemistry in males, necropry, organ weight analysis, histopathology examination.
- Oestrous cyclicity (parental animals):
- No data availabe
- Sperm parameters (parental animals):
- No data available
- Litter observations:
- Clinical signs, litter weight, number, sex and viability, necropsy.
- Postmortem examinations (parental animals):
- Histopathology of selected tissues.
- Postmortem examinations (offspring):
- No data
- Statistics:
- No specified
- Reproductive indices:
- Number of pregnancies, gestation length, number of implantations, copora lutea, and litter size.
- Offspring viability indices:
- Number of live births and post implantation loss, and number of pups with grossly visible abnormalities.
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- Albumin, total protein and bilirubin were significantly higher at teh high dose and urea lower in tyhe low and mid-dose groups.
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- some renal changes at high dose but were not assumed to be test substncace realated due to their low incidence. One animal was severely affected in several organs.
- Other effects:
- no effects observed
Reproductive function / performance (P0)
- Reproductive function: oestrous cycle:
- no effects observed
- Description (incidence and severity):
- Number of pregnant females 11/11 control, 9/11 at 30 mg/kg/day; 10/10 at 95 mg/kg/day and 10/10 at 300 mg/kg/day.
- Reproductive function: sperm measures:
- not specified
- Reproductive performance:
- no effects observed
Details on results (P0)
Effect levels (P0)
- Dose descriptor:
- NOEL
- Effect level:
- 95 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- body weight and weight gain
- clinical biochemistry
- organ weights and organ / body weight ratios
Results: F1 generation
General toxicity (F1)
- Clinical signs:
- no effects observed
- Mortality / viability:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Sexual maturation:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- no effects observed
- Histopathological findings:
- not specified
Details on results (F1)
Effect levels (F1)
- Dose descriptor:
- NOEL
- Generation:
- F1
- Effect level:
- 95 mg/kg bw/day
- Sex:
- male/female
- Basis for effect level:
- other: Based on the lack of adverse effect in the mid-dose group of the study.
Overall reproductive toxicity
- Reproductive effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- No adverse on reproductive performance were identified, therefore, it can be concluded that dibutyl maleate is neither a developmental nor reproductive toxicant.
- Executive summary:
In a combined repeated-dose and reproductive/developmental screening study, dibutyl maleate was administered in arachis oil via gavage to Wistar rats (12/sex/dose) at 0, 30, 95 and 300 mg/kg BW/day during the premating (2weeks) and mating perids (10 days). Females delivered the litters normally and were sacrified with the offspring on day 4 of lactation. Males were also necropsied. Parental toxicity evaluation included clinical signs, body weight, feed consumption, mating results, time parturition; hematology and clinical chemistry in males, necropsy, organ weights, and histopathology of selected tissues. Offspring toxicity evaluation included clinical signs, litter weight, number, sex and viability and necropsy. At the high-dose (300 mg/kg), female and male rats showed unspecific signs of "reduce well-being" and increased absolute and/or relative liver and kidney weights. Also, male rats showed a higher incidence of dermal hyperremia, lower body weights, higher albumin, total protein, and bilirubin; and decreased mean corpuscular hemoglobin and renal tubular lesions including dilation, epithelial basophila, and epithelial proliferation and karyomegaly. A single female rat from the high-dose group lost its whole litter due to lacking nursing behavior. Limited information is available to assess the significance of the number of pup deaths in the mid and high-doses. The NOEL (reproductive toxicity) was determined to be 95 mg/kgBW/day. No adverse effects on reproductive performance were identified.
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