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EC number: 449-410-5 | CAS number: 18084-64-5
- 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:
- supporting study
- Study period:
- 2003
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: well reported GLP study, comparable to guideline
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 003
- Report date:
- 2003
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- GLP compliance:
- yes
- Type of assay:
- micronucleus assay
Test material
- Reference substance name:
- -
- EC Number:
- 449-410-5
- EC Name:
- -
- Cas Number:
- 18084-64-5
- Molecular formula:
- C36H44N4
- IUPAC Name:
- 1,4,7,10-Tetrabenzyl-1,4,7,10-tetraazacyclododecane
Constituent 1
Test animals
- Species:
- mouse
- Strain:
- other: Crl: NMRI, BR mice (SPF)
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River GmbH, Sulfeld, Germany
- Age at study initiation: 8 - 9 weeks old
- Acclimation period: 13 days
Administration / exposure
- Route of administration:
- intraperitoneal
- Vehicle:
- 9 mg NaCl, 0.85 Polyoxyl-50-stearate (Myrj 52) at 1 ml Aqua p.i.
amount of drug substance per unit: 50 mg/mL - Details on exposure:
- dose-range finding experiment:
- One male and one female mice per dose were treated once intraperitoneally with doses of up to 2000 mg/kg bw. All treated animals were without clinical findings during an observation period of 48 hours after application. However, 72 hours after application both animals treated with 1500 mg/kg bw showed slight apathy. At the dose of 2000 mg/kg bw the female mouse showed slight apathy and the male mouse died. Therefore, for the bone marrow micronucleus test 2000 mg/kg bw was chosen as the high dose group. Additionally, 1000 and 500 mg/kg bw were chosen as mid and low doses. - Duration of treatment / exposure:
- single administration
- Frequency of treatment:
- single administration
- Post exposure period:
- 24 h (negative control and all treatment groups)
48 h (positive control and high-dose group)
Doses / concentrations
- Remarks:
- Doses / Concentrations:
500, 1000, and 2000 mg/kg bw
Basis:
nominal conc.
application volume: 10 to 40 ml/kg
- No. of animals per sex per dose:
- 5 per sex per dose for the 24 hour sampling time (vehicle control, 500 mg, 1000 mg, 2000 mg and positive control cyclophosphamide) plus
5 per sex per dose for the 48 hour sampling time (vehicle control, and 2000 mg/kg bw) were evaluated;
some more animals (all together 13 mice per sex) were treated in the high dose group to obtain 10 animals per sex for assessment. - Control animals:
- yes, concurrent vehicle
- Positive control(s):
- cyclophosphamide (30 mg/kg bw)
Examinations
- Tissues and cell types examined:
- Erythrocytes; femur bone marrow smears were prepared and stained using May-Gruenwald and Giemsa solutions.
- Evaluation criteria:
- - frequency of micronucleated poly- and normochromatic bone marrow erythrocytes (= genetic endpoint chromosome/genome mutations)
- ration of poly- to normochromatic erythrocytes (= indicates bone marrow cytotoxicity)
- additionally, clinical signs were examined
Results and discussion
Test results
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- yes
- Remarks:
- 2000 mg/kg bw: apathy, increasing with time; one male died; a statistically significant decrease in the ration of PCE/NCE was seen in all dose groups for the 24 h time point as well as in the high dose group for the 48h time point
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
Any other information on results incl. tables
The male and female animals in all dose groups, treated with 500, 1000, or 2000 mg/kg bw, showed neither a biologically relevant nor statistically signficant increase in micronucleated PCE and NCE as compared to the negative control at either of the two sampling times (24 and 48 hours). The decrease of the PCE/NCE ratio indicated bone marrow depression induced by the test substance. The positive control data were well in the expected historical range. However, in the vehicle control group the micronucleus frequency slightly exceeded the historical control data. But since the values are well within the published spontaneous rates (0.4 -3.8 per 1000 PCEs) this effect is considered as biological fluctuation.
Applicant's summary and conclusion
- Executive summary:
To investigate the potential of the test item to induce chromosomal breakage (structural chromosomal aberrations) or misdistribution of chromosomes (aneuploidy), a bone marrow micronucleus test was performed on mice. Ten male and ten female mice in the high dose group and 5 males/females in the mid and low dose group were treated intraperitoneally with single doses of 500, 1000, or 2000 mg/kg bw. Control animals (10 males/ 10 females) were given the vehicle (Myrj 52) in the same manner. The test item showed neither a biologically relevant nor statistically signficant increase in micronucleated polychromatic (PCE) and normochromatic erythrocytes (NCE) as compared to the negative control at either of the two sampling times (24 and 48 hours). The decrease of the PCE/NCE ratio indicated bone marrow depression induced by toxicity of the test substance. One male mouse died in the high-dose group. Thus, the test substance was negative in the mouse bone marrow micronucleus assay up to the recommended and toxic dose level of 2000 mg/kg bw.
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