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EC number: 406-530-2 | CAS number: - MDI
- 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
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 21 May 1990 - 22 August 1990
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 990
- Report date:
- 1990
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- Version / remarks:
- 26 May 1983
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: EPA, Code of Federal Regulations, Title 40, Subpart F-Genetic Toxicity, "In vivo mammalian bone marrow cytogenetics tests: Micronucleus assay."
- Version / remarks:
- 01 July 1986
- GLP compliance:
- yes
- Type of assay:
- mammalian erythrocyte micronucleus test
Test material
- Reference substance name:
- 1‐cyclohexyl‐3‐[4‐({4‐[(octadecylcarbamoyl)amino]phenyl}methyl)phenyl]urea
- EC Number:
- 604-940-8
- Cas Number:
- 154099-21-5
- Molecular formula:
- C39 H62 N4 O2
- IUPAC Name:
- 1‐cyclohexyl‐3‐[4‐({4‐[(octadecylcarbamoyl)amino]phenyl}methyl)phenyl]urea
- Reference substance name:
- 3,3'-dicyclohexyl-1,1'-methylenebis(4,1-phenylene)diurea
- EC Number:
- 406-370-3
- EC Name:
- 3,3'-dicyclohexyl-1,1'-methylenebis(4,1-phenylene)diurea
- Cas Number:
- 58890-25-8
- Molecular formula:
- C27 H36 N4 O2
- IUPAC Name:
- 3‐cyclohexyl‐1‐[4‐({4‐[(cyclohexylcarbamoyl)amino]phenyl}methyl)phenyl]urea
- Reference substance name:
- 3,3'-dioctadecyl-1,1'-methylenebis(4,1-phenylene)diurea
- EC Number:
- 406-690-3
- EC Name:
- 3,3'-dioctadecyl-1,1'-methylenebis(4,1-phenylene)diurea
- Cas Number:
- 43136-14-7
- Molecular formula:
- C51 H88 N4 O2
- IUPAC Name:
- 3‐octadecyl‐1‐[4‐({4‐[(octadecylcarbamoyl)amino]phenyl}methyl)phenyl]urea
- Test material form:
- solid
- Details on test material:
- Appearance: White yellowish solid
Storage conditions: At room temperature in the dark
The data on the individual constituents CHA/MDI/CHA (EC 406-370-3) and ODA/MDI/ODA (EC 406-690-3) for physicochemical, environmental fate, ecotoxicological and mammalian toxicological endpoints are very similar to the data available for the different compositions of the multi-constituent or represent the outer boundaries of the data on the multi-constituent. Hence, they confirm that the different compositions are expected to have similar properties for physicochemical, environmental fate, ecotoxicological and mammalian toxicological endpoints.
Constituent 1
Constituent 2
Constituent 3
Test animals
- Species:
- mouse
- Strain:
- NMRI
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: BRL Tierfarm Füllinsdorf, Füllingsdorf/Basel, Switzerland
- Age at study initiation: 11 weeks
- Weight at study initiation: approximately 30 g
- Assigned to test groups randomly: yes
- Fasting period before study: 18 h before treatment, water ad libitum
- Housing: Individually housed in Makrolon cages.
- Diet: free access pelleted standard diet (ALTROMIN, D-4937 Lage/Lippe, F.R.G.)
- Water: free access to tap water
- Acclimation period: minimum 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 3
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- oral: unspecified
- Vehicle:
- - Vehicle used:corn oil
- Justification for choice of vehicle: The test substance was suspended in corn oil. The vehicle was chosen for its nontoxicity in animals. - Details on exposure:
- PREPARATION OF DOSING SOLUTIONS: On the day of experiment, the test substance was suspended in corn oil.
MAXIMUM DOSE VOLUME APPLIED: 20 mL/kg bw. - Frequency of treatment:
- Single dose.
- Post exposure period:
- Sampling of the bone marrow was done 24, 48 and 72 h after treatment
Doses / concentrations
- Dose / conc.:
- 5 000 mg/kg bw (total dose)
- No. of animals per sex per dose:
- 12 (6 males/6 females)
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- cyclophosphamide
- Route of administration: oral (single dose)
- Doses / concentrations: 40 mg/kg bw
- Volume applied: 10 mL/kg bw.
- sampling 24 h after treatment
Examinations
- Tissues and cell types examined:
- Bone marrow
Micronuclei in polychromatic erythrocytes (PCE) and relationship PCE / normochromatic erythrocytes (NCE) - Details of tissue and slide preparation:
- CRITERIA FOR DOSE SELECTION:
It is generally recommended to use the maximum tolerated dose, which was determined to be the dose that caused toxic reactions without having major effects on survival within 72 h.
TREATMENT AND SAMPLING TIMES:
Sampling of the bone marrow was done 24, 48 and 72 h after treatment.
DETAILS OF SLIDE PREPARATION:
Epiphyses were cut off the femore and the marrow was flushed out with fetal calf serum. The cell suspension was centrifuged at 1500 rpm for 5 minutes and the supernatant discarded. A small drop of the resuspended cell pellet was spread on a slide, air-dried and stained with May-Grünwald/Giemsa. Cover slips were mounted wit EUKITT.
METHOD OF ANALYSIS:
Evaluation was performed using NIKON microscopes with 100x oil immersion objectives. 1000 polychromatic erythrocytes (PCE) were analysed per animal for micronuclei. To describe a cytotoxic effect the ratio between PCEs and normochromatic erythrocytes (NCEs) was determined in same sample and expressed in the number of NCEs per 1000 PCEs. The analysis was performed with coded slides.
Five animals per sex and group were evaluated as described. The remaining animal of each test group was evaluated in case an animal had died in its test group.
- Evaluation criteria:
- A test article is classified as mutagenic if it induces either a statistically significant dose-related increase in the number of micronucleated polychromatic erythrocytes or a reproducible statistically significant positive response for at least one of the test points.
A test article producing neither a statistically significant dose-related increase in the number of micronucleated polychromatic erythrocytes nor a statitically significant and reproducible positive response at anyone of the test points is considered non-mutagenic in this system. - Statistics:
- nonparametric Mann-Whitney test
Results and discussion
Test results
- Key result
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- yes
- Remarks:
- Animals expressed slight toxic reactions, no cytotoxicity observed
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- RESULTS OF RANGE-FINDING STUDY
- 4 animals (2 males/2 females) received orally a single dose of 5000 mg/kg bw MDI/CHA/ODA.
- All treated animals expressed slight toxic reactions: reduction of spontaneous activity. Additionally two males and one female expressed apathy.
- Higher dosing was not attainable: Appropriate suspensions could be obtained only up to 250 mg/mL and application volumes higher than 20 mL/kg bw were not justifiable for the rodents used.
RESULTS OF DEFINITIVE STUDY
- Induction of micronuclei: no significant enhancement in the frequency of the detected micronuclei at 24 h, 48 h or 72 h.
- Ratio of PCE/NCE: no increase after treatment with the test substance indicating that the test substance had no cytotoxic properties.
- Positive control: showed distinct increase of induced micronucleus frequency (mean 12 per 1000 PCE vs. mean 0.4 per 1000 PCE in vehicle control)
Applicant's summary and conclusion
- Conclusions:
- In a micronucleus assay in the bone marrow of the mouse, performed according to OECD 474 guideline and GLP principles, MDI/CHA/ODA was found not to be mutagenic.
- Executive summary:
A micronucleus assay in the bone marrow of male and female mouse with MDI/CHA/ODA was performed according to OECD 474 guideline and GLP principles. Bone marrow cells were collected for micronuclei analysis 24 h, 48 h and 72 h after a single application of 5000 mg/kg bw of the test article. In a pre-experiment, this dose was determined to be the maximum attainable dose. The animals expressed slight toxic reactions (apathy and reduction of spontaneous activity).
After treatment with the test substance the ratio between polychromatic erythrocytes and normochromatic erythrocytes was not affected indicating no cytotoxic effects. There was no significant enhancement in the frequency of detected micronuclei at any preparation interval. Appropriate negative and positive controls were included.
Based on the results of this study it is concluded that MDI/CHA/ODA is not clastogenic in the micronucleus assay in the bone marrow of the mouse.
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