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EC number: 402-130-7 | CAS number: 106246-33-7
- 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
Genetic toxicity: in vivo
Administrative data
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- October - December 1995
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 996
- Report date:
- 1996
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- Deviations:
- no
- GLP compliance:
- yes
- Type of assay:
- micronucleus assay
Test material
- Reference substance name:
- -
- EC Number:
- 402-130-7
- EC Name:
- -
- Cas Number:
- 106246-33-7
- Molecular formula:
- C21 H28 Cl2 N2
- IUPAC Name:
- 4-[(4-amino-2-chloro-3,5-diethylphenyl)methyl]-3-chloro-2,6-diethylaniline
- Test material form:
- solid: crystalline
- Details on test material:
- - Name: LONZACURE® M-CDEA
- Internal substance code: P5367
- Storage: Keep container tightly closed. Keep in a dry, cool and well-ventilated place.
- Aggregate state/appearance: Crystalline solid
- Colour: white to off-white
- Odour: Odourless
Constituent 1
Test animals
- Species:
- mouse
- Strain:
- CD-1
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River UK Limited, Margate, Kent, England
- Age at study initiation: approximately 35 days
- Weight at study initiation: between 22 and 24 grams
- Assigned to test groups randomly: yes
- Housing: each group was kept, with the sexes separated, in plastic disposable cages
- Diet (e.g. ad libitum): pelleted Biosure LAD 1 rodent diet
- Water (e.g. ad libitum): tap water
- Acclimation period: yes
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C
- Humidity (%): 55%
- Air changes (per hr): 20 changes/h
- Photoperiod (hrs dark / hrs light): artificial light 12 h/day
Administration / exposure
- Route of administration:
- intraperitoneal
- Vehicle:
- 1% aqueous methylcellulose; suspensions ofthe test item were prepared in CMC (obtained from Courtaulds, batch number T32397) on the morning of the test at the concentrations shown overleaf
- Details on exposure:
- All animals in all groups were dosed with the standard volume of 20 ml/kg bodyweight. The test substance and negative control were dosed by intraperitoneal injection, and mitomycin C, the positive control compound, orally by intragastric gavage. The animals in the positive control group were deprived of diet overnight prior to and for two hours after dosing.
- Duration of treatment / exposure:
- 24 and 48 hours
- Frequency of treatment:
- Once
Doses / concentrationsopen allclose all
- Dose / conc.:
- 2 000 mg/kg bw/day (nominal)
- Remarks:
- pretest; 2000 mg/kg = 100 mg/ml
- Dose / conc.:
- 0 mg/kg bw/day (nominal)
- Remarks:
- main study; vehicle control
- Dose / conc.:
- 500 mg/kg bw/day (nominal)
- Remarks:
- main study; 500 mg/kg = 25 mg/ml
- Dose / conc.:
- 1 000 mg/kg bw/day (nominal)
- Remarks:
- main study; 1000 mg/kg = 50 mg/ml
- Dose / conc.:
- 2 000 mg/kg bw/day (nominal)
- Remarks:
- main study; 2000 mg/kg = 100 mg/ml
- No. of animals per sex per dose:
- Males:
- 0 mg/kg; No. of animals: 5; Sacrifice time: 24 hours
- 0 mg/kg; No. of animals: 5; Sacrifice time: 48 hours
- 500 mg/kg; No. of animals: 5; Sacrifice time: 24 hours
- 1000 mg/kg; No. of animals: 5; Sacrifice time: 24 hours
- 2000 mg/kg; No. of animals: 5; Sacrifice time: 24 hours
- 2000 mg/kg; No. of animals: 5; Sacrifice time: 48 hours
Females:
- 0 mg/kg; No. of animals: 5; Sacrifice times: 24 hours
- 0 mg/kg; No. of animals: 5; Sacrifice times: 48 hours
- 500 mg/kg; No. of animals: 5; Sacrifice times: 24 hours
- 1000 mg/kg; No. of animals: 5; Sacrifice times: 24 hours
- 2000 mg/kg; No. of animals: 5; Sacrifice times: 24 hours
- 2000 mg/kg; No. of animals: 5; Sacrifice times: 48 hours - Control animals:
- yes
- Positive control(s):
- A positive control group was dosed orally, by intragastric gavage, with mitomycin C at 12 mg/kg bodyweight.
Examinations
- Tissues and cell types examined:
- Bone marrow smears were obtained from 5 male and 5 female animals in the negative control, test substance groups and the positive control group 24 hours after dosing. Bone marrow smears were also taken from 5 male and 5 female animals from the negative control and high dose level groups 48 hours after treatment. One smear from each animal was examined for the presence of micronuclei in 1000 polychromatic erythrocytes. The ratio of polychromatic to normochromatic erythrocytes was assessed by examination of at least 1000 erythrocytes from each animal. A record of the incidence of micro nucleated normochromatic erythrocytes was also kept.
- Evaluation criteria:
- A positive response is normally indicated by a substantial, statistically significant increase (p < 0.01) in the incidence of micronucleated polychromatic erythrocytes compared to the incidence for the concurrent vehicle control group for at least one of the sampling times~ individual and/or group mean values should exceed the laboratory historical control range.
- Statistics:
- Non-parametric statistical methods, based on rank are chosen for analysis of results because:
- They are suited to analysis of data consisting of discrete/integer values such as the incidence of micronucleated polychromatic erythrocytes.
- 'Outliers' are frequently found in the polychromatic erythrocyte to normochromatic erythrocyte ratios for both control and
- The methods make few assumptions about the underlying distribution of data and therefore the values do not require transformation to fit a theoretical distribution (where data can be approximately fitted to a normal distribution, the results of non-parametric analysis and classical analysis of variance are very similar).
Results and discussion
Test results
- Key result
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- yes
- Remarks:
- Toxic signs were only observed in the high dose group after dosing. Thes signs included lethargy, hunched posture, piloerection and altered gait. The ratio of polychromatic to normochromatic erythrocytes was unaltered by treatment.
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- Treatment with the test substance did not result in any increase in the number of miconucleated polychromatic erythrocytes.
Any other information on results incl. tables
Only minor clinical signs and no mortalities were obtained in the preliminary toxicity test at a dose level of 2000 mg/kg. Dose levels of 500, 1000 and 2000 mg/kg were therefore selected for use in the micronucleus test. The high dose level of 2000 mg/kg is the standard limit dose for the micronucleus test and we therefore consider it to be an appropriate maximum.
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results: negative
The test substance was found to be non-mutagenic in this test system. - Executive summary:
The study was performed 1996 as GLP-test following OECD test method 474 using bone marrow cells of CD-1 mice. The test item was dissolved in 1% CMC and tested at concentrations of 500 - 2000 ug/ml. Toxic signs were only observed in the high dose group after dosing. Treatment with the test substance did not result in any increase in the number of miconucleated polychromatic erythrocytes. In conclusion, the substance is not mutagenic under the conditions of this test.
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