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EC number: 217-168-8 | CAS number: 1761-71-3
- 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:
- 2.11.1983- 27.01.1984
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Study was performed according to accepted but older guidelines and under GLP.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 984
- Report date:
- 1984
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.12 (Mutagenicity - In Vivo Mammalian Erythrocyte Micronucleus Test)
- Version / remarks:
- Cited as Directive 84/449/EEC, B.12
- GLP compliance:
- yes
- Type of assay:
- micronucleus assay
Test material
- Reference substance name:
- 4,4'-methylenebis(cyclohexylamine)
- EC Number:
- 217-168-8
- EC Name:
- 4,4'-methylenebis(cyclohexylamine)
- Cas Number:
- 1761-71-3
- Molecular formula:
- C13H26N2
- IUPAC Name:
- 4,4'-methylenedicyclohexanamine
- Details on test material:
- CAS 1761-71-3 (cyclohexylamine,4,4'-methylenebis-), purity not indicated ("rein")
Constituent 1
Test animals
- Species:
- mouse
- Strain:
- NMRI
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS:
- Source: Lippische Versuchstierzucht, Extertal, Germany
- Strain: NMRI-SPF (HAN/Bö)
- Sex: male and female
- Age: 7 to 8 weeks
- Weight at study initiation: 33-40 g (males) & 30-35 g (females)
- Housing: Makrolon cages
- Acclimation period: 10 days
- Diet and water ad libitum
ENVIRONMENTAL CONDITIONS
- Temperature: 22 °C
- Relative humidity: 45-55 %
- Light: 12 hour light/ dark cycle
Administration / exposure
- Route of administration:
- intraperitoneal
- Vehicle:
- DMSO
- Details on exposure:
- TEST GROUP
- The animals received a single intraperitoneal injection of the test substance dissolved in DMSO (stock solution: 50 mg of the test item + 1 mL DMSO + 9 mL NaCl-solution (0,9%))
- The dose level of 50 mg/ kg used as the test dose was selcted to produce mortality of about 10% (based on preliminary LD50 study)
- Volume injected: 0.1 mL/10 g bw
NEGATIVE CONTROL GROUP
- The animals received a single intraperitoneal injection of DMSO (stock solution: 1 mL DMSO + 9 mL NaCl-solution (0,9%))
- Volume injected: 0.1 mL/10 g bw
POSITIVE CONTROL GROUP
- The animals received a single intraperitoneal injection of Cyclophosphamide in DMSO (stock solution: 20 mg Cyclophosphamide + 1 mL DMSO + 9 mL NaCL-solution (0,9%))
- Volume injected: 0.1 mL/10 g bw - Duration of treatment / exposure:
- single application
- Frequency of treatment:
- once
- Post exposure period:
- 24, 48 and 72 h after administration, 6 animals of each group were sacrificed, after 24 h animals from the positive control group were sacrificed
Doses / concentrations
- Dose / conc.:
- 50 other: mg/ kg
- No. of animals per sex per dose:
- negative control group: 20
positive control group: 8
test group: 22 - Control animals:
- yes, concurrent vehicle
- Positive control(s):
- Cyclophosphamide (20 mg/kg)
Examinations
- Tissues and cell types examined:
- femoral bone marrow smears
- Details of tissue and slide preparation:
- DETAILS OF SLIDE PREPARATION
- The bone marrow preparations were prepared, stained and evaluated based on the method of Schmid
- The two femora were excised from the test animals, the attached tissue was removed and the femora were dissected at the condyles
- The bone marrow was rinsed with fetal calf serum by means of a syringe and cannula and transferred to a centrifuge tube with 4 mL calf serum
- The cell suspension was centrifuged at 100 g for 5 minutes, and the serum was sucked off except for a small amount
- The cells were resuspended by careful pipetting, dropped onto clean microscopic slides and smeared
METHOD OF ANALYSIS
- After one day, the microscopic slide preparations were stained with May-Gruenwald and Giemsa solution, rinsed in distilled water, dried and mounted in DePeX via xylene
- The coded preparations were evaluated under the microscope at a 500 fold enlargement
- 1000 erythrocytes were counted and differentiated according to polychromatic (young) and normochromatic (old) erythrocytes
- The fraction of polychromatic cells indicates the function of erythropoiesis and allows detecting possible cytostatic or cytotoxic effects of the test substance
- The proportion of cells carrying miconuclei was determined in 2000 polychromatic erythrocytes
- The mean and standard deviation were calculated from the individual values of the 6 animals of each group - Evaluation criteria:
- CRITERIA FOR EVALUATING RESULTS:
- Significant increase in the incidence of micronucleated polychromatic erythrocytes in the bone marrow of male and female mice - Statistics:
- - The test group and control group were investigated for differences by means of the U-test.
Results and discussion
Test results
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- yes
- Vehicle controls validity:
- valid
- Negative controls validity:
- not examined
- Positive controls validity:
- valid
- Additional information on results:
- TOXIC RESPONSE/EFFECTS BY DOSE LEVEL:
- Mortality : Male: 2 out of 22, Female: 3 out of 22
- Clinical signs: slight to moderate convulsion and piloerection
STATISTICAL RESULTS:
% PCE and %PCE with micronucleus were not increased in males or females at 24, 48, and 72 hours after treatment.
EFFECT ON PCE/NCE RATIO (%PCE):
Males
- Control group: 52.9, 53.3, 51.8 at 24, 48 and 72 hours, respectively
- Treatment group: 50.4, 48.4, 53.6 at 24, 48 and 72 hours, respectively
- Positive control: 52.2 at 24 hours
Females
- Control group: 53.4, 51.9, 52.2 at 24, 48 and 72 hours, respectively
- Treatment group: 53.0, 53.2, 54.1 at 24, 48 and 72 hours, respectively
- Positive control: 51.7 at 24 hours
GENOTOXIC EFFECTS:
Mean number of micronucleated PCE:
Males
- Control group: 0.16, 0.27, 0.21 at 24, 48 and 72 hours, respectively
- Treatment group: 0.26, 0.24, 0.20 at 24, 48 and 72 hours, respectively
- Positive control: 1.40 at 24 hours
Females
- Control group: 0.13, 0.25, 0.19 at 24, 48 and 72 hours, respectively
- Treatment group: 0.17, 0.22, 0.21 at 24, 48 and 72 hours, respectively
- Positive control: 1.39 at 24 hours
Applicant's summary and conclusion
- Conclusions:
- Under the experimental conditions chosen here, the test substance has no chromosome damaging (clastogenic) effect nor does it lead to any impairment of chromosome distribution in the course of mitosis.
- Executive summary:
According to the test results available, there are thus no significant differences in the frequency of erythrocytes containing micronuclei either between the solvent control and the dose group (50 mg/ kg body weight) or between the different sacrifice intervals (24, 48 and 72 hours). Thus, under the experimental conditions chosen here, the test substance has no chromosome damaging (clastogenic) effect nor does it lead to any impairment of chromosome distribution in the course of mitosis. The positive control is valid.
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