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EC number: 400-920-6 | CAS number: 89857-06-7
- 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
- Study period:
- From March 11th to April 1st, 1985
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 985
- Report date:
- 1985
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- Version / remarks:
- adopted May 26, 1983
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.12 (Mutagenicity - In Vivo Mammalian Erythrocyte Micronucleus Test)
- Version / remarks:
- EEE Directive 84/449
- GLP compliance:
- not specified
- Remarks:
- Study procedures were periodically inspected and this report was audited by the Quality Assurance Unit.
- Type of assay:
- mammalian erythrocyte micronucleus test
Test material
- Reference substance name:
- -
- EC Number:
- 400-920-6
- EC Name:
- -
- Cas Number:
- 89857-06-7
- Molecular formula:
- C50 H53 N11 O14 S
- IUPAC Name:
- 5'-[2-(7-{2-[4-(2-{1'-[3-(dimethylazaniumyl)propyl]-6'-hydroxy-4'-methyl-2'-oxo-1',2'-dihydro-1λ⁵-[1,3'-bipyridin]-1-ylium-5'-yl}diazen-1-yl)phenyl]diazen-1-yl}-8-hydroxy-6-sulfonatonaphthalen-2-yl)diazen-1-yl]-6'-hydroxy-3,4'-dimethyl-2'-oxo-1',2'-dihydro-1λ⁵-[1,3'-bipyridin]-1-ylium bis(2-hydroxypropanoate)
Constituent 1
Test animals
- Species:
- mouse
- Strain:
- NMRI
- Remarks:
- KFM (outbred, SPF-quality)
- Details on species / strain selection:
- Mice are recommended for micronucleus assays as the international standard.
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Kleintierfarm Madoerin AG, 4414 Fuellinsdorf / Swiitzerland
- Age at study initiation: 7 and 8 weeks
- Weight at study initiation: males: 28 -37 g; females: 24-36 g
- Fasting period before study: not specified
- Housing: groups of 6 in makrolon type 3, with wire mesh top and granulated softwood bedding
- Diet: pelleted standard Kliba 343, mouse diet, ad libitum
- Water: tap water ad libitum
- Acclimation period: 7 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2 °C
- Humidity (%): 55 ± 10 %
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12 hours Iight/dark per day
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- 2% carboxymethylcellulose sodium salt
- Frequency of treatment:
- Single oral application
Doses / concentrations
- Dose / conc.:
- 5 000 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- 18
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- cyclohexylamine
- Route of administration: oral
- Doses / concentrations: 50 mg/kg bw/day dissolved in 0.9% saline solution
Examinations
- Tissues and cell types examined:
- bone marrow, polychromatic erythrocytes (PCE), normochromatic erythrocytes (NCE)
- Details of tissue and slide preparation:
- CRITERIA FOR DOSE SELECTION:
The maximum tolerated dose was based on acute oral toxicity data.
A preliminary acute oral LD50 (Iimit test; 2 doses, 3 males and 3 females per dose) performed with the same mouse species as was used in this study showed the following results after 14 days observation:
1000 mg/ks bw: 0 mortality in 6 animals
5000 mglkg bw: 0 mortality in 6 animals
The 5000 mg/kg bw dose uwas used in this study as the maximum tolerated dose.
TREATMENT AND SAMPLING TIMES ( in addition to information in specific fields):
All animals were given a single application of 20 ml/kg bw by gavage.
24, 48 and 72 hours after treatment, six mice per sex and group were sacrificed and bone marrow was removed from the femora for examination.
DETAILS OF SLIDE PREPARATION:
The femora were removed from each mouse and freed of adherent tissue. The proximal end of the femur was cut with scissors; the distal end was left intact. The needle of a plastic syringe containing 0.2 ml calf serurn was inserted into the proximal part of the marrow canaI.
The bone marrow cells were dispersed in 1.5 ml of calf serurn as a homogeneous suspension. The tube containing the bone marrow ceIIs of both femora was centrifuged at 1000 r.p.m. for 5 mlnutes.
The supernatant was removed, Ieaving a thin Iayer of serum. The cells of the sediment were suspended by aspiration in a siliconized pasteur pipette. A small drop of the marrow serum suspension was smeared on the sIide, which was identified by project code and the animal number, and allowed to dry overnight. Two slides per animal were prepared. The following day, the smears were stained using the panoptic stain method developed by Pappenheim (3).
METHOD OF ANALYSIS:
The slides were coded before microscopic analysis. If macroscopic evaluation revealed technical imperfections, the first slide was replaced by the second sIide prepared. From each animal, one thousand polychromatic erythrocytes (PCE) were scored under the microscope (magnification 1000x), for the incidence of micronuclei. Additional information could be obtained by scoring normochromatic enythrocytes for micronuclei.
The calculated ratio of polychromatic to normochromatic erythrocytes (PCE/NCE), based on 1000 enythrocytes scored per slide, measured the toxic efficacy of the test article.
- Evaluation criteria:
- The frequencies of micronuclei of the treated male and female groups were compared with those of the negative control groups at each sampling time. A regression model assuming a Poisson
distribution was applied. Estimation and testing were performed by maximum likelihood method (4). If a test article produced no statistically significant and reproducible positive response at any one of the test points, it was considered to be non-mutagenic in this system. - Statistics:
- The data were statistically analyzed by means of a regression model assuming a Poisson distribution. Estimation and testing were performed by maximum likelihood method (4).
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
Applicant's summary and conclusion
- Conclusions:
- Test article induced no chromosome mutations by chromosome-breaking activity or by damage to the mitotic apparatus.
- Executive summary:
This in vivo experiment was performed to assess the potential mutagenic activity induced by test substance through damage to the chromosomes of to the mitotic apparatus according to Schmid (1) with the modifications of Salomone et al. (2).
The experirnent was performed with three groups, each containing 18 males and 18 females, for a total of 108 mice.
The negative control groups received the test article vehicle, i.e. 2% carboxymethylcellulose sodium salt in distilled water. The test groups received 5000 mg/kg bw as the maximurn tolerated dose of the test article. The positive control groups received 50 mg/kg bw cyclophosphamlde dissolved in 0.9 % saline solution.
All animals were given a single application of 20 ml/kg bw by gavage.
24, 48 and 72 hours after treatment, six mice per sex and group were sacrificed and bone marrow was removed from the femora for examination. The first five animals were used for evaluation. One thousand polychromatic erythrocytes per animal were scored for micronuclei. The ratio of polychromatic to normochromatic erythrocytes was used to assess the toxicity of the test article by counting a total of 1000 erythrocytes.
All animals treated with the test article showed light sedation on the first day of the test. No toxic effect of the test article was observed.
After single application of the test article at 5000 mg/kg bw by gavage, no significant test article-related
increase of micronucleated polychromatic erythrocytes was observed in either male and female treated groups, when compared with corresponding negative control groups These results were found at the three examination times, 24, 48 and 72 hours post-application, respectively. The positive control groups, which received cyclophosphamide, exhibited a significant and clear increase in the number of micronucrlated polychromatic erythrocytes and thus validated the test.
In conclusion, it can be stated that under the extrerimental conditions reported, the test article induced no chromosome mutations by chromosome-breaking activity or by damage to the mitotic apparatus.
Therefore, test article is not considered to be mutagenic in this in vivo mouse micronucleus assay.
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