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Diss Factsheets
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EC number: 700-093-4 | CAS number: 176969-34-9
- 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
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 009
- Report date:
- 2009
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- GLP compliance:
- yes
- Type of assay:
- micronucleus assay
Test material
- Details on test material:
- - Name of test material (as cited in study report): Reg.No. 5069089
- Analytical purity: 99.2 weight% (following the Certificate of Analysis)
- Lot/batch No.: L80-68
- Physical state: Solid/pink
- Storage condition of test material: Refrigerator
- pH value: 2.5 (undiluted test substance, moistened with water)
Constituent 1
Test animals
- Species:
- mouse
- Strain:
- NMRI
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Laboratories Germany GmbH
- Age at study initiation: 5 – 8 weeks
- Mean weight at study initiation: 28.1 g
- Housing: Makrolon cages, type M I; single housing
- Diet: Standardized pelleted feed (Maus/Ratte Haltung "GLP", Provimi Kliba SA, Kaiseraugst, Switzerland)
- Water: Drinking water from bottles was available ad libitum
- Acclimation period: At least 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
The substance to be administered per kg body weight was suspended in corn oil. To achieve homogeneity of the test substance in the vehicle, the test substance preparation was stirred with a spatula and than shaken thoroughly. All test substance formulations were prepared immediately before administration. - Duration of treatment / exposure:
- The animals were treated once orally (gavage) with a volume of 10 mL/kg body weight of the
test substance and the vehicle. The animals were sacrificed 24 hours (all test substance
concentrations, vehicle, both positive controls) and 48 hours (highest test substance
concentration, vehicle) after the treatment, respectively. - Frequency of treatment:
- once
Doses / concentrations
- Remarks:
- Doses / Concentrations:
500, 1000, 2000 mg/kg bw
Basis:
actual ingested
- No. of animals per sex per dose:
- 5 males per treatment
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- Cyclophosphamide (CPP): 20 mg/kg bw
Vincristine sulfate (VCR): 0.15 mg/kg bw
Examinations
- Tissues and cell types examined:
- Bone marrow cells from the animals femora
- Details of tissue and slide preparation:
- CRITERIA FOR DOSE SELECTION:
In a pretest for the determination of the acute oral toxicity, at 2000 mg/kg bw recommended as the highest dose according to the OECD Guideline all animals (male and female) survived showing weak clinical signs. The clinical sign only observed was piloerection.
DETAILS OF SLIDE PREPARATION:
- The slides were stained with eosin and methylene blue (modified May-Gruenwald solution or Wrights solution) for about 5 minutes.
- After briefly rinsing in purified water, the preparations were soaked in purified water for about 2 - 3 minutes.
- Subsequently, the slides were stained with Giemsa solution (15 mL Giemsa plus 185 mL purified water) for about 15 minutes.
- After rinsing twice in purified water and clarifying in xylene, the preparations were mounted in Corbit-Balsam.
METHOD OF ANALYSIS:
In general, 2 000 polychromatic erythrocytes (PCE) were evaluated for the occurrence of micronuclei from each animal of every test group, so in total 10 000 PCEs were scored per test group. The normochromatic erythrocytes (= normocytes / NCE) were also scored. The following parameters were recorded:
• Number of polychromatic erythrocytes
• Number of polychromatic erythrocytes containing micronuclei
The increase in the number of micronuclei in polychromatic erythrocytes of treated animals as compared with the vehicle control group provides an index of a chromosome-breaking (clastogenic) effect or damage of the mitotic apparatus (aneugenic activity) of the test substance administered.
• Number of normochromatic erythrocytes
• Number of normochromatic erythrocytes containing micronuclei
The number of micronuclei in normochromatic erythrocytes at the early sacrifice interval shows the situation before test substance administration and may serve as a control value. A test substance induced increase in the number of micronuclei in normocytes may be found with an increase in the duration of the sacrifice interval.
• Ratio of polychromatic to normochromatic erythrocytes
An alteration of this ratio indicates that the test substance actually reached the bone marrow, means the target determined for genotoxic effects.
• Number of small micronuclei (d < D/4) and of large micronuclei (d ≥ D/4) [d = diameter of micronucleus, D = cell diameter]
The size of micronuclei may indicate the possible mode of action of the test substance ( 9), i.e. a clastogenic effect (d < D/4) or a spindle poison effect (d ≥ D/4).
Slides were coded before microscopic analysis. - Evaluation criteria:
- A finding is considered positive if the following criteria are met:
• Statistically significant and dose-related increase in the number of PCEs containing micronuclei.
• The number of PCEs containing micronuclei has to exceed both the concurrent vehicle control value and the range of the historical vehicle control data.
A test substance is considered negative if the following criteria are met:
• The number of cells containing micronuclei in the dose groups is not statistically significant increased above the concurrent vehicle control value and is within the range of the historical vehicle control data. - Statistics:
- The asymptotic U test according to MANN-WHITNEY (modified rank test according to WILCOXON) was carried out to clarify the question whether there are statistically significant differences between the untreated control group and the treated dose groups with regard to the micronucleus rate in polychromatic erythrocytes. The relative frequencies of cells containing micronuclei of each animal were used as a criterion for the rank determination for the U test. Statistical significances were identified as follows:
* p ≤ 0.05
** p ≤ 0.01
However, both biological relevance and statistical significance were considered together.
Results and discussion
Test results
- Sex:
- male
- Genotoxicity:
- negative
- Toxicity:
- no effects
- Vehicle controls validity:
- valid
- Negative controls validity:
- not examined
- Positive controls validity:
- valid
Any other information on results incl. tables
Summary of results | ||||||
Test | group | Sacrifice | Animal | Micronuclei in PCE | Number | |
interval | No. | total a | large b | of NCE c | ||
[hrs] | [‰] | [‰] | ||||
Vehicle | control | 24 | 5 | 1.2 | 0 | 3663 |
corn | oil | |||||
Test | substance | 24 | 5 | 1.0 | 0 | 5607 |
500 | mg/kg bw. | |||||
Test | substance | 24 | 5 | 0.9 | 0.1 | 5328 |
1000 | mg/kg bw. | |||||
Test | substance | 24 | 5 | 0.8 | 0.1 | 4328 |
2 | 0 | |||||
Positive | control | 24 | 5 | 14.4** | 0 | 4090 |
cyclophosphamide | ||||||
20 | mg/kg bw. | |||||
vincristine | sulfate | 24 | 5 | 60.5** | 19.2** | 5077 |
0.15 | mg/kg bw. | |||||
Vehicle | control | 48 | 5 | 0.8 | 0 | 3670 |
corn | oil | |||||
Test | substance | 48 | 5 | 1.3 | 0.1 | 5550 |
2000 | mg/kg bw. |
Applicant's summary and conclusion
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.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
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