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EC number: 236-102-9 | CAS number: 13162-05-5
- 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:
- January 12 - July 24, 1992
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Guideline study (GLP)
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)
- GLP compliance:
- yes
- Type of assay:
- micronucleus assay
Test material
- Reference substance name:
- Reference substance 001
- Details on test material:
- - Test Article Lot No.: 12376-64 (Sample II)
- Test Article Purity: 99%
- Test Article Description: Clear, colorless liquid
- Storage Conditions: Frozen (-20+/-5°C), protected from light
Constituent 1
Test animals
- Species:
- mouse
- Strain:
- ICR
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Harlan Sprague Dawley, Inc., Frederick, MD
- Age at study initiation: 6 to 8 weeks old
- Weight at study initiation: Males: 29.7 to 37.3 g; Females: 22.3 to 27.6 g
- Assigned to test groups randomly: yes, based on distribution according to body weight
- Housing: group housing with up to five mice per cage in plastic autoclavable cages with filter tops
- Acclimation period: at least 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-27
- Humidity (%): 50±20
- Photoperiod (hrs dark / hrs light): 12 / 12
Administration / exposure
- Route of administration:
- intraperitoneal
- Vehicle:
- - Vehicle used: deionized water
- Justification for choice of vehicle: solubility
- Concentration of test material in vehicle: 1.9, 2.9, 3.8, 5.8, 7.5 and 11.5 mg/ml - Details on exposure:
- The test article-vehicle mixture, the vehicle alone, or the positive control was administered by IP injection at a constant volume of 10 ml/kg body weight. All mice in the experimental and control groups were weighed immediately prior to dose administration and the dose volume was based on individual body weights. Animals were observed after dose administration for clinical signs of chemical effect.
- Duration of treatment / exposure:
- Observation period: 7 days
- Frequency of treatment:
- single
Doses / concentrations
- Remarks:
- Doses / Concentrations:
males: 0, 19, 38, 75 mg/kg bw; females: 0, 29, 58, 115 mg/kg bw
Basis:
- No. of animals per sex per dose:
- 0 mg/kg: 5 males and 5 females per sampling time (24, 48 or 72 hours): control
19 mg/kg: 5 males per sampling time: low test dose
29 mg/kg: 5 females per sampling time: low test dose
38 mg/kg 5 males per sampling time: mid tetst dose
58 mg/kg: 5 females per sampling time: mid test dose
75 mg/kg: 5 males per sampling time: high test dose
115 mg/kg 5 females per sampling time: high test dose - Control animals:
- yes, concurrent vehicle
- Positive control(s):
- Cyclophosphamide
- Route of administration: intraperitoneal
- Dose: 30 mg/kg bw
- 5 males and 5 females, 24 hours
Examinations
- Details of tissue and slide preparation:
- CRITERIA FOR DOSE SELECTION:
The high dose levels of 75 or 115 mg/kg were calculated to be approximately 80% of the LD50 (7 days) for males or females, respectively (as determined in a pilot study).
SAMPLING TIMES:
24, 48 and 72 hours
DETAILS OF SLIDE PREPARATION:
At the scheduled sacrifice time, if available, five mice per sex were sacrificed by CO2 asphyxiation. Immediately following sacrifice, the femurs were exposed, cut just above the knee, and the bone marrow was aspirated into a syringe containing fetal bovine serum. The bone marrow cells were transferred to a capped centrifuge tube containing approximately 1 ml fetal bovine serum. The bone marrow cells were pelleted by centrifugation at approximately 100 x g for five minutes and the supernatant was drawn off, leaving a small amount of serum with the remaining cell pellet. The cells were resuspended by aspiration with a capillary pipet and a small drop of bone marrow suspension was spread onto a clean glass slide. Two to four slides were prepared from each animal. The slides were fixed in methanol, stained with May-Gruenwald-Giemsa and permanently mounted.
METHOD OF ANALYSIS:
Slides were coded using a random number table by an individual not involved with the scoring process. Using medium magnification, an area of acceptable quality was selected such that the cells were well spread and stained. Using oil immersion, 1000 polychromatic erythrocytes were scored for the presence of micronuclei which are defined as round, darkly staining nuclear fragments, having a sharp contour with diameters usually from 1/20 to 1/5 of the erythrocyte. The number of micronucleated normocytes in the field of 1000 polychromatic erythrocytes was enumerated. The proportion of polychromatic erythrocytes to total erythrocytes counted was also recorded. - Evaluation criteria:
- The incidence of micronucleated polychromatic erythrocytes per 1000 polychromatic erythrocytes was determined for each animal and treatment group. All analyses were performed separately for each sex. In order to quantify the proliferation state of the bone marrow as an indicator of bone marrow toxicity, the proportion of polychromatic erythrocytes to total erythrocytes was determined for each animal and treatment group. The test article was considered negative if no statistically significant increase in micronucleated polychromatic erythrocytes above the concurrent control was observed at any sampling time. The test article was considered to induce a positive response if a treatment-related increase in micronucleated polychromatic erythrocytes was observed relative to the vehicle control (P<=0.05). The positive response must be dose-dependent or must be observed at a single dose level at adjacent sacrifice times. If a single treatment group is significantly elevated at one sacrifice time with no evidence of a dose-response, the assay is considered a suspect or unconfirmed positive and a repeat assay will be recommended.
- Statistics:
- Statistical significance was determined using the Kastenbaum-Bowman tables which are based on the binomial distribution.
Results and discussion
Test results
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- no effects
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- Mortality occured at the high dose level in both male and female mice: 5/10, 8/10 and 6/10 animals were found dead in the 24, 48, and 72 hour sacrifices, respectively. Clinical signs of toxicity included lethargy and irregular breathing in males receiving 75 mg/kg and irregular breathing, crusty eyes, piloerection, ataxia and lethargy in females receiving 115 mg/kg. No reduction in the ratio of polychromatic erythrocytes (PCE) to total erythrocytes was observed in the test article-treated groups relative to the vehicle control suggesting that the TS did not induce bone marrow toxicity. No significant increases in micronucleated polychromatic erythrocytes were observed.
Any other information on results incl. tables
Micronucleated polychromatic erythrocytes (PCE’s) regarding 24, 48 and 72 h sacrifices:
|
Dose (mg/kg) |
Mean number per 1000 PCE’s |
||
males |
females |
|||
Solvent control |
|
0 |
0.0-0.2 |
0.0-0.4 |
Treatments |
Low test dose |
19 |
0.0 |
|
29 |
|
0.0-0.2 |
||
Mid test dose |
38 |
0.0-0.6 |
|
|
58 |
|
0.2-1.0 |
||
High test dose |
75 |
0.0-0.3 |
|
|
115 |
|
0.0 |
||
Positive control (24 hours) |
|
30 |
17.2 |
16.8 |
Result |
|
|
Negative |
Negative |
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information): negative
Under the conditions of this study, the test substance did not induce a significant increase in the incidence of micronucleated polychromatic erythrocytes in bone marrow and was concluded to be negative in the micronucleus test using male and female ICR mice. - Executive summary:
The study was conducted according to OECD Guideline 474, GLP standards were fulfilled.
Male ICR mice were exposed to 19, 38, or 75 mg/kg and female ICR mice to 29, 58, or 115 mg/kg of the test substance which was administered in a total volume of 10 ml/kg as a single i.p. injection. The high dose levels of 75 or 115 mg/kg were calculated to be approximately 80% of the LD50 (7 days) for males or females, respectively. The vehicle used to prepare test substance dosing stocks was deionized water. Mortality occured at the high dose level in both male and female mice: 5/10, 8/10 and 6/10 animals were found dead in the 24, 48, and 72 hour sacrifices, respectively. Clinical signs of toxicity included lethargy and irregular breathing in males receiving 75 mg/kg and irregular breathing, crusty eyes, piloerection, ataxia and lethargy in females receiving 115 mg/kg. No reduction in the ratio of polychromatic erythrocytes (PCE) to total erythrocytes was observed in the test article-treated groups relative to the vehicle control suggesting that the test substance did not induce bone marrow toxicity. No significant increases in micronucleated polychromatic erythrocytes were observed. The negative and positive controls fulfilled the requirements for determination of a valid test.The results of the study indicate that the test substance did not induce a significant increase in micronucleated polychromatic erythrocytes in either male or female ICR mice.
Conclusions: Under the conditions of this study, the test substance did not induce a significant increase in the incidence of micronucleated polychromatic erythrocytes in bone marrow and was concluded to be negative in the micronucleus test using male and female ICR mice.
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