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EC number: 604-075-6 | CAS number: 138401-24-8
- 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: oral
Administrative data
- Endpoint:
- short-term repeated dose toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 30 July 1996 to December 1996
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Guideline study. GLP compliance
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 996
- Report date:
- 1996
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.7 (Repeated Dose (28 Days) Toxicity (Oral))
- GLP compliance:
- yes
Test material
- Reference substance name:
- [1,1’-Biphenyl]-2-carbonitrile, 4’-[(2-butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-
- IUPAC Name:
- [1,1’-Biphenyl]-2-carbonitrile, 4’-[(2-butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-
- Reference substance name:
- 4'-((2-butyl-4-oxo-1,3-diazaspiro[4.4]non-1-ene-3-yl)methyl)(1,1'-biphenyl)-2-carbonitrile
- EC Number:
- 604-075-6
- Cas Number:
- 138401-24-8
- Molecular formula:
- C25H27N3O
- IUPAC Name:
- 4'-((2-butyl-4-oxo-1,3-diazaspiro[4.4]non-1-ene-3-yl)methyl)(1,1'-biphenyl)-2-carbonitrile
- Details on test material:
- - Name of test material (as cited in study report): SR 47563
- Lot/batch No.: 6R00003
- purity: considered as 100% for dose calculation
- storage: at room temperature
Constituent 1
Constituent 2
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- other: 0.5% methylcellulose aqueous solution
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 28 consecutive days
- Frequency of treatment:
- Daily
Doses / concentrations
- Remarks:
- Doses / Concentrations:
100, 300 and 600 mg/kg/day (volume injected was 5 ml/kg of preparations at 20, 60 and 120 mg/mL, once daily)
Basis:
actual ingested
- No. of animals per sex per dose:
- 5 males and 5 females per group
- Control animals:
- yes
Results and discussion
Effect levels
open allclose all
- Dose descriptor:
- LOAEL
- Effect level:
- 100 mg/kg bw/day (actual dose received)
- Sex:
- male/female
- Basis for effect level:
- other: microscopic examinations
- Dose descriptor:
- NOAEL
- Basis for effect level:
- other: The authors claim that it has not been possible to establish a NOEL in this study, probably based on the significant hepatocellular hypertrophy recorded in all treated groups.
- Remarks on result:
- not determinable
- Remarks:
- no NOAEL identified
- Dose descriptor:
- NOEL
- Remarks:
- (Indicated in the study as no toxic effect level)
- Effect level:
- 100 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: mortality, body weight, food consumption, organ weight, clinical signs, blood chemistry, heamatology, coagulation, macroscopic examination
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
No dose-related body weight decrease was observed in all treated groups throughout the treatment period.
No mortality was observed at 0, 300 and 600 mg/kg. At 100 mg/kg, one female was found dead on day 7. This death was related to incorrect intubation and not to treatment.
No abdormal clinical sign related to treatment was observed in all groups.
Blood clinical biochemistry showed an increase in total protein and globulin in all treated groups, an increase of albumin in males (300 mg/kg) and in females (300 and 600 mg/kg), an increase of total cholesterol in females (300 and 600 mg/kg), a decrease of ASAT in males (300 and 600 mg/kg) and in females (600 mg/kg), an increase of creatinine in females (600 mg/kg), an increase of calcium (300 and 600 mg/kg), a decrease of potassium in females (300 and 600 mg/kg).
Most red blood cell parameters were affected in females (300 and 600 mg/kg): decrease of red blood cell count, haemoglobin, packed cell volume, mean cell haemoglobin and mean cell haemoglobin concentration.
Activated partial thromboplastin time was increased as a function of the dose levels in males (300 and 600 mg/kg) and females (all treated groups).
Absolute and relative weights of liver were markedly increased as a function of the dose level. This increase was significant in 300 and 600 mg/kg. Hepatic enlargement was the only significant macroscopic change observed during necropsy. This increase was due to hepatocellular hypertrophy. This hypertrophy was dose related.
Applicant's summary and conclusion
- Conclusions:
- The test substance administrated at the dose levels of 100, 300 and 600 mg/kg/day was associated with slight hepatotoxicity. SR 47563 induced a dose-related hepatocellular hypertrophy. No significant macroscopic effects were recorded at 100 mg/kg/day (indicated as no toxic effect level).
The authors further claim that it has not been possible to establish a NOEL in this study. This is probably based on the observed hystopathological finding of significant hepatocellular hypertrophy in all treated groups. Therefore, the lowest dose group is indicated here as a LOAEL.
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