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EC number: 478-270-8 | CAS number: -
- 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 vitro
Administrative data
- Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2006-11-06 to 2007-06-28
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP study performed according to OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test) and EU Method A.3 (Mutagenicity - In Vitro Mammalian Chromosome Aberration Test) without deviations.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 007
- Report date:
- 2007
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
- Deviations:
- no
- Remarks:
- The testing facility indicated that the protocol was followed without deviation.
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.10 (Mutagenicity - In Vitro Mammalian Chromosome Aberration Test)
- Deviations:
- no
- Remarks:
- The testing facility indicated that the protocol was followed without deviation.
- Principles of method if other than guideline:
- Not applicable
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- Certificate from "The Department of Health of the Government of the United Kingdom"
- Type of assay:
- in vitro mammalian chromosome aberration test
Test material
Reference
- Name:
- Unnamed
- Type:
- Constituent
- Details on test material:
- - Name of test material: VRT-753136 hcl
- Molecular formula: Not applicable
- Molecular weight: Not applicable
- Smiles notation: Not applicable
- InChl: Not applicable
- Structural formula attached as image file: Not applicable
- Substance type: active
- Physical state: white powder
- Analytical purity: 100 area %
- Impurities: 0.03 area % of unknowns
- Composition of test material, percentage of components: no data
- Isomers composition: no data
- Purity test date: 2006-05-25
- Lot/batch No.: batch 25515, lot AF6-001
- Expiration date of the lot/batch: 2008-05
- Stability under test conditions: no data
- Storage condition of test material: room temperature
- Other: no data
Method
- Target gene:
- Not applicable
Species / strain
- Species / strain / cell type:
- lymphocytes: human
- Details on mammalian cell type (if applicable):
- -Not applicable
- Additional strain / cell type characteristics:
- other: In the testing laboratory the cell cycle time for human lymphocytes in whole blood culture is approximately 13-15 hours.
- Metabolic activation:
- with and without
- Metabolic activation system:
- phenobarbital and 5,6-benzoflavone induced rat liver S9 (2 % v/v for experiment 1 and 5 % v/v for experiment 2)
- Test concentrations with justification for top dose:
- Experiment 1 and Experiment 2 with and without S9 activation- 14.55, 29.10, 58.20, 116.41, 232.81, 465.63, 931.25 and 1862.5 ug/mL (465.63, 931.25 and 1862.5 ug/mL were selected for metaphase analysis.)
Concentrations with high ionic strength and osmolality may cause chromosomal aberrations. Therefore, concentrations greater than 5000 ug/mL or 10 mM are not used in this test system. In this case, the highest final concentration used or subsequent testing was 1862.5 ug/mL (10 mM, based on a molecular weight of 186.25). - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: water
- Justification for choice of solvent/vehicle: Prior to commencing testing, the solubility of the test substance in sterile water was assessed. The test substance was found to be soluble in sterile water at 50 mg/mL.
Controlsopen allclose all
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- water
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- mitomycin C
- Remarks:
- without metabolic activation
Migrated to IUCLID6: 0.2 ug/mL (3 hour exposure) and 0.1 ug/mL (continuous exposure)
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- water
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- cyclophosphamide
- Remarks:
- with metabolic activation
Migrated to IUCLID6: 5 ug/mL
- Details on test system and experimental conditions:
- METHOD OF APPLICATION:
- In medium
DURATION
- Preincubation period: Not applicable
- Exposure duration: 3 hours (experiment 1 with and without metabolic activation and experiment 2 with metabolic activation) and 21 hours (experiment 2 without metabolic activation)
- Expression time: 16 hours (experiment 1 with and without metabolic activation and experiment 2 with metabolic activation), 0 hours (experiment 2 without metabolic activation)
- Selection time: Not applicable
- Fixation time: ~21 hours (with Colcemid present during the final 2 hours)
SELECTION AGENT :
not applicable
SPINDLE INHIBITOR:
Colcemid
STAIN:
10 % Giemsa
NUMBER OF REPLICATIONS:
2
NUMBER OF CELLS EVALUATED:
100 per replication
DETERMINATION OF CYTOTOXICITY
- Method: mitotic index
OTHER EXAMINATIONS:
- Determination of polyploidy: yes
- Determination of endoreplication: yes
- Other: no data
OTHER:
Blood collected aseptically from two healthy male non-smoking donors was pooled and diluted with RPMI 1640 culture medium supplemented with 10 % foetal calf serum, 0.2 IU/mL sodium heparin, 20 IU/mL penicillin/20 ug/mL streptomycin and 2.0 mM L-glutamine. Aliquots (0.4 mL blood: 4.5 mL medium: 0.1 mL phytohaemagglutinin) of the cell suspension were placed in sterile universal containers and incubated at 37 deg C for approximately 48 hours before treatment. The cultures were gently shaken daily to resuspend the cells. - Evaluation criteria:
- The assay was considered acceptable if the vehicle and positive control values laid within the current historical control range.
The test substance was considered to cause a positive response if the following conditions were met:
1. Statistically significant increases (p<0.01) in the frequency of metaphases with aberrant chromosomes (excluding gaps) were observed at one or more test concentrations.
2. The increases exceeded the negative control range of the laboratory, taken at the 99 % confidence limit.
3. The increases were reproducible between replicate cultures.
4. The increases were not associated with large changes in pH, osmolality of the treatment medium or extreme toxicity.
5. Evidence of a dose-relationship was considered to support the conclusion.
A negative response was claimed if no statistically significant increase in the number of aberrant cells above concurrent control frequencies was observed, at any dose level.
A further evaluation may have been carried out if the above criteria for a positive or a negative response were not met. - Statistics:
- The number of aberrant metaphase cells in each treatment group was compared with the solvent control value using the one-tailed Fisher exact test.
Results and discussion
Test results
- Species / strain:
- lymphocytes: human
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- only in experiment 2 after continuous exposure in the absence of metabolic activation
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: no data
- Effects of osmolality: no data
- Evaporation from medium: no data
- Water solubility: The test substance was soluble in water at 50 mg/mL.
- Precipitation: no data
- Other confounding effects: no data
RANGE-FINDING/SCREENING STUDIES:
A range finding test was not performed.
COMPARISON WITH HISTORICAL CONTROL DATA:
All solvent control and positive control values for cells with aberrations excluding and including gaps in the presence and absence of metabolic activation were within historical control value ranges for both tests.
1. Experiment 1- In the absence of S9 mix, the test substance caused a statistically significant increase in the proportion of cells with chromosomal aberrations at 465.63 ug/mL, including gap-type aberrations only, when compared with the solvent control (p<0.01). This increase was not dose-related and the significance of gap-type aberrations was questionable, therefore this was not considered to be biologically relevant.
In the presence of S9 mix, the test substance caused a statistically significant increase in the proportion of cells with chromosomal aberrations at 1862.5 ug/mL, including gap-type aberrations only, when compared with the solvent control (p<0.001). This increase was not considered to be biologically relevant since the significance of gap-type aberrations was questionable.
Both positive control substances caused statistically significant increases (p<0.001) in the proportion of aberrant cells. This demonstrated the efficacy of the S9 mix and the sensitivity of the test system.
2. Experiment 2-in the absence of S9 mix, following a continuous exposure, the test substance caused no statically significant increases in the proportion of cells with chromosomal aberrations at any dose level, when compared with the solvent control.
Following a three-hour exposure in the presence of S9 mix, the test substance caused no statistically significant increases in the proportion of cells with chromosomal aberrations at any dose level, when compared with the solvent control.
Both positive control substances caused statistically significant increases (p<0.001) in the proportion of aberrant cells. This demonstrated the efficacy of the S9 mix and the sensitivity of the test system.
No increases in polyploid metaphases were observed during metaphase analysis, in either test.
ADDITIONAL INFORMATION ON CYTOTOXICITY:
1. Experiment 1-Following a three-hour exposure in the absence and presence of S9 mix, the test substance did not cause a reduction in the mitotic index compared to the solvent control value at any dose level. The dose levels selected for the metaphase analysis were 465.63, 931.25 and 1862.5 ug/mL.
2. Experiment 2-Following a continuous exposure, in the absence of S9 mix, the test substance caused a reduction in the mitotic index to 45 % of the solvent control value at 1862.5 ug/mL. The dose levels selected for the metaphase analysis were 465.63, 931.25 and 1862.5 ug/mL. In the presence of S9 mix, the test substance did not cause a reduction in the mitotic index at 1862.5 ug/mL. The dose levels select for the metaphase analysis were 465.63, 931.25 and 1862.5 ug/mL. - Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
Any other information on results incl. tables
Not applicable
Applicant's summary and conclusion
- Conclusions:
- The test substance was evaluated for its ability to induce chromsomal aberration in human lymphocytes cultured in vitro in the presence and absence of metabolic activation. It was concluded that the test substance had shown no evidence of clastogenic activity in this in vitro cytogenetic test system, under the experimental conditions described.
- Executive summary:
Not applicable
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