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Diss Factsheets
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EC number: 444-000-2 | 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
![](https://echa.europa.eu/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
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:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- GLP-Guideline study, tested with the source substance 68424-31-7. According to the ECHA guidance document “Practical guide 6: How to report read-across and categories (March 2010)”, the reliability was changed from RL1 to RL2 to reflect the fact that this study was conducted on a read-across substance.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 992
- Report date:
- 1992
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:
- 68424-31-7
- Cas Number:
- 68424-31-7
- IUPAC Name:
- 68424-31-7
- Details on test material:
- - Name of test material (as cited in study report): only trade name given
- Physical state: pale yellow liquid
- Analytical purity: >98%
- Lot/batch No.: RMEST240
- Storage condition of test material: at room temperature in the dark
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 Breeding Laboratories (UK Limited, UK)
- Age at study initiation: 5-9 weeks
- Assigned to test groups randomly: yes
- Housing: animals were housed in groups of 5 per sex per cage in mobile mouse cage racks
- Diet: Porton Combined Diet, ad libitum
- Water: filtered tap water, ad libitum
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23
- Humidity (%): 40-70
- Air changes (per hr): 25
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- intraperitoneal
- Vehicle:
- - Vehicle(s)/solvent(s) used: corn oil
- Amount of vehicle: 10 mL/kg - Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
Dosing solutions of the test material were prepared in corn oil. A solution of cyclophosphamide was prepared in physiological saline. - Duration of treatment / exposure:
- not applicable
- Frequency of treatment:
- single treatment
- Post exposure period:
- 24 and 48 h after treatment
Doses / concentrations
- Remarks:
- Doses / Concentrations:
5000 mg/kg bw
Basis:
nominal conc.
- No. of animals per sex per dose:
- 5
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- cyclophosphamide
- Route of administration: intraperitoneal injection
- Doses / concentrations: 65 mg/kg bw in physiological saline
Examinations
- Tissues and cell types examined:
- Monochromatic and polychromatic erythrocytes
- Details of tissue and slide preparation:
- CRITERIA FOR DOSE SELECTION:
No deaths or severe adverse effects occurred in Phase I (range finding study) of the study with doses up to 5000 mg/kg bw. This dose was selected as maximum tolerated dose.
TREATMENT AND SAMPLING TIMES: 24 h and 48 h after dosing
DETAILS OF SLIDE PREPARATION: Bone Marrow smears were stained with polychrome methylene blue and eosin.
METHOD OF ANALYSIS: 1000 polychromatic erythrocytes were evaluated for micronuclei per slide. In addition, 1000 erythrocytes were counted to determine the percentage of polychromatic erythrocytes in the total erythrocyte population. - Evaluation criteria:
- Increase in the incidence of micronucleated polychromatic erythrocytes in any sex or at any time point.
Percentage of polychromatic erythrocytes. - Statistics:
- The incidence of micronucleated polychromatic erythrocytes and percentage of polychromatic erythrocytes in the erythrocyte sample were considered by analysis of variance regarding each combination of sampling time, dose level and sex as a separate group. Results were examined to determine whether any differences between vehicle control and test substance treated groups were consistent between sexes and across sampling times.
Each group mean was compared with the vehicle control group mean at the corresponding sampling time using a one-sided Student´s t-test based on the error mean square in the analysis.
Results and discussion
Test results
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- no effects
- Vehicle controls validity:
- valid
- Negative controls validity:
- not examined
- Positive controls validity:
- valid
- Additional information on results:
- RESULTS OF RANGE-FINDING STUDY
- Dose range: 50-5000 mg/kg bw
- Clinical signs of toxicity in test animals: no deaths or severe adverse reactions were recorded over the 4-day observation period at the high dose.
RESULTS OF DEFINITIVE STUDY
- Induction of micronuclei: No statistically or biologically significant increases in the incidence of micronucleated polychromatic erythrocytes over the vehicle control values were seen in either sex at either of the sampling times.
Comparison of the percentage of polychromatic erythrocytes showed no significant differences between the female animals treated with the vehicle control or with the test material. A small, but significant decrease was, however, noted in male mice treated with the test material at 5000 mg/kg bw. This small decrease is, however, considered not to be biologically significant compared to the concurrent control values.
The positive control induced statistically significant and biologically meaningful increases in micronucleated polychromatic erythrocytes, compared to the vehicle control values, thus demonstrating the sensitivity of the test system to a known clastogen.
Any other information on results incl. tables
Table 1. Results male animals.
Treatment group |
Dose |
Sampling time |
Mean incidence of MPE/1000 PE ± SD |
Mean [%] PE ± SD |
[mg/kg] |
[h] |
|||
Vehicle control |
0 |
24 |
0.8 ± 0.8 |
48.0 ± 5.6 |
|
0 |
48 |
1.0 ± 1,2 |
44.3 ± 7.5 |
Test substance |
5000 |
24 |
0.6 ± 0.6 |
42.2 ± 7.0* |
|
5000 |
48 |
0.4 ± 0.6 |
43.3 ± 1.9 |
Positive control (Cyclophosphamide) |
65 |
24 |
24.4 ± 6.0** |
41.4 ± 4.4* |
PE = polychromatic erythrocytes
MPE = micronucleated polychromatic erythrocytes
SD = standard deviation
*: statistically significant decrease in percentage of polychromatic erythrocytes at p<0.05 in the Students t´test (one-sided).
Table 2. Results female animals.
Treatment group |
Dose |
Sampling time |
Mean incidence of MPE/1000 PE ± SD |
Mean [%] PCE ± SD |
[mg/kg] |
[h] |
|||
Vehicle control |
0 |
24 |
0.2 ± 0.5 |
41.9 ± 4.8
|
|
0 |
48 |
1.4 ± 1.1 |
41.9 ± 1,7
|
Test substance |
5000 |
24 |
0.4 ± 0.9 |
46.5 ± 5.8
|
|
5000 |
48 |
0.4 ± 0.9 |
48.0 ± 5.2 |
Positive control (Cyclophosphamide) |
65 |
24 |
18.4 ± 7.3** |
45.9 ± 3.49 |
PE = polychromatic erythrocytes
MPE = micronucleated polychromatic erythrocytes
SD = standard deviation
**: statistically significant decrease in percentage of polychromatic erythrocytes at p<0.01 in the Students t´test (one-sided).
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information): negative
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
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