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EC number: 428-310-5 | CAS number: 225789-38-8
- 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
Endpoint summary
Administrative data
Key value for chemical safety assessment
Genetic toxicity in vitro
Description of key information
The registration substance is not mutagenic in the bacterial reverse mutation assay, not clastogenic in chromosome aberration test and not mutagenic in reverse mutation test in mammalian cells.
Link to relevant study records
- Endpoint:
- in vitro gene mutation study in mammalian cells
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- Sept - Nov 2013
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.17 (Mutagenicity - In Vitro Mammalian Cell Gene Mutation Test)
- Deviations:
- no
- Principles of method if other than guideline:
- first experiment 4 hours treatment with and without metabolic activation
second experiment 24 hours treatment without metabolic activation, 4 hours treatment with metabolic activation - GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- mammalian cell gene mutation assay
- Target gene:
- HPRT
- Species / strain / cell type:
- Chinese hamster lung fibroblasts (V79)
- Details on mammalian cell type (if applicable):
- - Type and identity of media: MEM
- Periodically checked for Mycoplasma contamination: yes
- Periodically checked for karyotype stability: yes
- Periodically "cleansed" against high spontaneous background: yes - Additional strain / cell type characteristics:
- not specified
- Metabolic activation:
- with and without
- Metabolic activation system:
- Phenobarbital/Beta-Naphtoflavone induced Rat liver S9
- Test concentrations with justification for top dose:
- Experiment I:
without metabolic activation: 19.8; 59.3 (p); 177.8 (p); 533.3 (p); 1600 (p) µg/mL
with metabolic activation: 19.8; 59.3 (p); 177.8 (p); 533.3 (p); 1600 (p) µg/mL
Experiment II:
without metabolic activation: 6.6; 19.8; 59.3; 177.8 (p); 533.3 (p) µg/mL
with metabolic activation: 6.6; 19.8; 59.3 (p); 177.8 (p); 533.3 (p) µg/mL
(p) = precipitation visible to the unaided eye - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: solubility properties - Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- ethylmethanesulphonate
- Remarks:
- without metabolic activation
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 7,12-dimethylbenzanthracene
- Remarks:
- with metabolic activation
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in medium
On the day of the experiment (immediately before treatment), the test item was suspended in DMSO (purity 99.9 %). The final concentration of DMSO in the culture medium was 0.5 % (v/v).
DURATION
- Exposure duration: Experiment I: 4 hours with and without metabolic activation, Experiment II: 24 hours without metabolic activation, 4 hours with metabolic activation
- Expression time (cells in growth medium): 72 hours
- Selection time (if incubation with a selection agent): 10 days
SELECTION AGENT (mutation assays): 6-Thioguanine
NUMBER OF REPLICATIONS: 2
NUMBER OF CELLS EVALUATED: >1,5x10exp. 6
DETERMINATION OF CYTOTOXICITY
- Method: cloning efficiency - Evaluation criteria:
- A test item producing neither a concentration-related increase of the mutant frequency nor a reproducible positive response at any of the test points is considered to be non-mutagenic in this system.
A mutagenic response is described as follows:
The test item is classified as mutagenic if it induces reproducibly with one of the concentrations a mutation frequency that is three times higher than the spontaneous mutation frequency in the experiment.
The test item is classified as mutagenic if there is a reproducible concentration-related increase of the mutation frequency. Such evaluation may be considered also in the case that a threefold increase of the mutant frequency is not observed.
In a case by case evaluation this decision depends on the level of the corresponding solvent control data. - Statistics:
- A linear regression (least squares) was performed to assess a possible dose dependent increase of mutant frequencies. The number of mutant colonies obtained for the groups treated with the test item were compared to the solvent control groups. A trend is judged as significant whenever the p-value (probability value) is below 0.05. However, both, biological and statistical significance were considered together.
- Key result
- Species / strain:
- Chinese hamster lung fibroblasts (V79)
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity, but tested up to precipitating concentrations
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: Not effected (pH 7.33 in the solvent control versus pH 7.31 at 3200 µg/mL) measured in the pre-experiment
- Effects of osmolality: No relevant increase (358 in the solvent control versus 376 at 3200 µg/mL) measured in the pre-experiment
- Precipitation: Precipitation of the test item visible to the naked eye at the end of treatment was noted in the first experiment at 59.3 µg/mL and above with and without metabolic activation. In the second experiment precipitation as described above occurred at 59.3 µg/mL and above with and at 177.8 µg/mL and above without metabolic activation.
- Other confounding effects: None
RANGE-FINDING/SCREENING STUDIES:
The highest concentration used in the pre-test was 3200 µg/mL limited by the solubility of the test item in DMSO and aqueous medium. Test item concentrations between 28.0 µg/mL and 3200 µg/mL were used to evaluate toxicity in the presence (4 hours treatment) and absence (4 hours and 24 hours treatment) of metabolic activation. No relevant toxic effect occurred up to 1600 µg/mL with and without metabolic activation following 4 and 24 hours treatment.
The test medium was checked for precipitation or phase separation at the end of each treatment period (4 or 24 hours) prior to removal to the test item. Precipitation occurred after 4 hours treatment with and without metabolic activation at 25 µg/mL and above.
There was no relevant shift of pH and osmolarity of the medium even at the maximum concentration of the test item.
Based on the results of the pre-experiment, the individual concentrations of the main experiments were selected. The individual concentrations were generally spaced by a factor of 2.
COMPARISON WITH HISTORICAL CONTROL DATA: Complies
ADDITIONAL INFORMATION ON CYTOTOXICITY:
Relevant cytotoxic effect defined as a reduction of the relative cloning efficiency I and/or relative cell density to values below 50% was observed at 1600 µg/mL without metabolic activation following 4 hours of treatment. - Conclusions:
- Not mutagenic in HPRT.
- Executive summary:
The registration substance was investigated for its mutagenicity in mammalian cells according to the OECD Guideline 476 (HPRT). V79 cells were treated with the registration substance up to the concentrations causing visible precipitations. In the first experiment the incubation time of 4 hours with and without metabolic activation and in the seconed experiment 4 hours with metabolic activation and 24 hours without metabolic activation. No increase of mutation rate was found in two independent experiments. The registration substance in not mutagenic in HPRT test.
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1998
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study with acceptable restrictions
- Remarks:
- Performed using four bacterial strains.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- no
- GLP compliance:
- yes
- Type of assay:
- bacterial reverse mutation assay
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Metabolic activation:
- with and without
- Metabolic activation system:
- liver extract, S9-mix
- Test concentrations with justification for top dose:
- 4 to 5000 µg/ plate
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: DMSO;
- Positive controls:
- yes
- Positive control substance:
- sodium azide
- Remarks:
- without metabolic activation; for strain TA100 and TA 1535
- Positive controls:
- yes
- Positive control substance:
- 9-aminoacridine
- Remarks:
- without metabolic activation; for strain TA 1537
- Positive controls:
- yes
- Positive control substance:
- 2-nitrofluorene
- Remarks:
- without metabolic activation; for strain TA 98
- Positive controls:
- yes
- Positive control substance:
- other: 2-aminoanthracene
- Remarks:
- with metabolic activation; for all strains
- Evaluation criteria:
- the solvent control data are within the range of spontaneous mutant frequency; the positive controls induce increases in the mutation frequency
- Key result
- Species / strain:
- S. typhimurium TA 98
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 1535
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 1537
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
- Conclusions:
- Not mutagenic in the bacterial reverse mutation assay.
- Executive summary:
The registration substance was investigated for its mutagenicity according to the OECD Guideline 471 (Bacterial reverse mutation assay). No mutagenicity was found.
Comments on the study:
The study was performed using four bacterial strains, thus missing the investigation of mutation in E-coli. But it can be reasonably assumed that no increase of mutation will occur, because the registration substance is of limited water solubility (1.6 g/l) and not likely soluble in incubation media of Ames test. Due to the low bioavailability for the bacterial cells, no biological interaction is possible, thus no mutation is likely.
- Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1998
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
- Deviations:
- no
- GLP compliance:
- yes
- Type of assay:
- in vitro mammalian chromosome aberration test
- Target gene:
- trypsin
- Species / strain / cell type:
- Chinese hamster lung fibroblasts (V79)
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9-mix, rat liver
- Test concentrations with justification for top dose:
- 7.8, 25.0, 78.0, 250.0 and 780.0 µg/ml
- Vehicle / solvent:
- 0.2M disodium hydrogenephosphate and 0.2 M sodium dihydrogenphosphate
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- Positive controls:
- yes
- Positive control substance:
- ethylmethanesulphonate
- Remarks:
- without metabolic activation
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- Positive controls:
- yes
- Positive control substance:
- cyclophosphamide
- Remarks:
- with metabolic activation
- Details on test system and experimental conditions:
- exposure period without activation: 3 h, 20 h and with metabolic activation: 3h ; fixation time: 20 h (with and without activation);
- Evaluation criteria:
- -number of induced structural chromosome aberrations
-concentration-related increase of the number of chromosome aberrations; - Key result
- Species / strain:
- Chinese hamster lung fibroblasts (V79)
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity, but tested up to precipitating concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- strong precipitation at >78 µg/ml;
- Conclusions:
- Not clastogenic in in-vitro chromosome aberration test
- Executive summary:
The registration substance was investigated for its clastogenicity according to the OECD Guideline 473 (Chromosome aberration test). V79 cells were treated up to the concentration with visible precipitation.
In the first experiment the incubation time was 3h with and without metabolic activation. In the second experiment the incubation time was 3h with and 20h without metbolic activation. No increase of aberrant cells were found in both experiments. The registration substance is not clastogenic in in-vitro chromosome aberration test.
Referenceopen allclose all
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Description of key information
The registration substance did not induce an increase of micronuclei in bone marrow in mouse.
Link to relevant study records
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2008
- Reliability:
- 1 (reliable without restriction)
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- Deviations:
- no
- GLP compliance:
- yes
- Type of assay:
- micronucleus assay
- Species:
- mouse
- Strain:
- NMRI
- Sex:
- male/female
- Route of administration:
- oral: unspecified
- Vehicle:
- PEG 400
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS: formulated in PEG 400
- Duration of treatment / exposure:
- 24 h; 48 h
- Frequency of treatment:
- orally once
- Dose / conc.:
- 500 mg/kg bw (total dose)
- Dose / conc.:
- 1 000 mg/kg bw (total dose)
- Dose / conc.:
- 2 000 mg/kg bw (total dose)
- No. of animals per sex per dose:
- 5
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- cyclophosphamide
- Route of administration: orally
- Doses / concentrations: 40 mg/kg b.w. - Tissues and cell types examined:
- polychromatic erythrocytes (PCE)
- Details of tissue and slide preparation:
- CRITERIA FOR DOSE SELECTION:
The highest dose (2000 mg/kg) was estimated by a pre-experiment to be suitable; The animals treated with 2000 mg/kg b.w. expressed toxic reactions (ruffled fur);
- Evaluation criteria:
- the negative and positive controls are in the range of historical control data
- Key result
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- no effects
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
- Conclusions:
- The registration substance was investigated for its clastogenicity in mouse according to the OECD Guideline 474. The registration substance did not induce increase of micronuclei in bone marrow cells in mouse.
- Executive summary:
The registration substance was investigated for its clastogenicity in mouse according to the OECD Guideline 474. The registration substance was suspended in PEG and given to mouse per gavage at dose of 0, 500, 1000 and 2000 mg/kg. 24 or 48h after the treatment the bone marrow was collected and the polychromatic erythrocytes were investigated for the micronuclei. The treatment of up to the dose of 2000 mg/kg did not alter the number of polychromatic erythrocytes and the number of cells with microcleis. The registration substance did not induce increase of micronuclei in bone marrow cells in mouse.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Additional information
Comments on the bacterial reverse mutation assay:
The study was performed using four bacterial strains, thus missing the investigation of mutation in E-coli. But it can be reasonably assumed that no increase of mutation will occur, because the registration substance is of limited water solubility and not likely soluble in incubation media of Ames test. Due to the low bioavailability for the bacterial cells, no biological interaction is possible, thus no mutation is likely.
Justification for classification or non-classification
Negative results were obtained in three in-vitro assays and one in-vivo assay, indicating absence of genotoxicity of the registration substance. No classification is justified.
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.