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EC number: 419-310-6 | CAS number: 125248-71-7
- 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
Endpoint summary
Administrative data
Key value for chemical safety assessment
Genetic toxicity in vitro
Description of key information
The test item was not mutagenic in bacteria with and without addition of S9 mix in a GLP conform study according to OECD Guideline 471.
The test item did not induce strutural or numerical chromosome aberrations in mammalian cells according to OECD Guideline 473.
Link to relevant study records
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- May 10 to May 18, 1995
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Version / remarks:
- August 1983
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 472 (Genetic Toxicology: Escherichia coli, Reverse Mutation Assay)
- Version / remarks:
- August 1983
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
- Version / remarks:
- December 1992
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- bacterial reverse mutation assay
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102
- Metabolic activation:
- with and without
- Metabolic activation system:
- Liver S9-Mix from Aroclor 1254-pretreated rats
- Test concentrations with justification for top dose:
- First experiment: 0.5, 1.58, 5, 15.8, 50, 158, and 500 µg/plate
Second experiment: 5, 15.8, 50, 158, and 500 µg/plate
The highest concentration of 500 µg/plate was chosen as higher concentrations were not soluble in the solvent. - Vehicle / solvent:
- - Vehicle/solvent used: acetone
- Justification for choice of solvent/vehicle: Historical data of the laboratory and experience of other research groups (Maron et al. 1981) showed that such amounts of the selected solvents have no influence on the number of spontaneous revertants of any strain. - Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- Acetone
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 9-aminoacridine
- N-ethyl-N-nitro-N-nitrosoguanidine
- benzo(a)pyrene
- cumene hydroperoxide
- other: 2-Aminoanthracene, Daunomycin
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in agar (plate incorporation)
DURATION
- Exposure duration: 48 - 72 hours
-
NUMBER OF REPLICATIONS: three
DETERMINATION OF CYTOTOXICITY
- Method: reduction in the number of spontaneous revertants, clearing of background lawn of non-revertant bacteria
- Evaluation criteria:
- A test material is defined as non-mutagenic in this assay if
- "no" or "weak increases" occur in the first and second series of the main experiment.
("Weak increases" randomly occur due to experimental variation.)
A test material is defined as mutagenic in this assay if
- a dose-related (over at least two test material concentrations) increase in the number of revertants is induced, the maximal effect is a "clear increase", and the effects are reproduced at similar concentration levels in the same test system;
- "clear increases" occur at least at one test material concentration, higher concentrations show streng precipitation or cytotoxicity, and the effects are reproduced at the same concentration level in the same test system.
In all further cases should a third test series with the bacterial strain in question be performed. lf the criteria for a positive test result are not fulfilled in at least two out of the three series, the test material is defined as being non-mutagenic in this test system. - Key result
- Species / strain:
- S. typhimurium TA 1535
- 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:
- not examined
- 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, but tested up to precipitating concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 98
- 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:
- not examined
- 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, but tested up to precipitating concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 102
- 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:
- not examined
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: Precipitation occurred at the highest contration tested 500 µg/plate.
RANGE-FINDING/SCREENING STUDIES: The test material was investigated in the first experimental series at seven concentrations, separated by half-log intervals, ranging from 0.5 to 500 μg per plate. Higher concentrations were not soluble in the solvent used. In the second experimental series, usually 5 concentrations including at least 4 non-toxic concentrations should be tested.
- Conclusions:
- With and without addition of S9-Mix as the external metabolizing system, the test item was not mutagenic under the experimental conditions described.
- Executive summary:
The investigations for mutagenic potential were performed using Salmonella typhimurium TA 98, TA 100, TA 102, TA 1535, and TA 1537 as tester strains. The plate incorporation test with and without addition of liver S9-Mix from Aroclor 1254- pretreated rats was used.
The test material was tested in two series of experiments at concentrations ranging from 0.5 to 500 μg/plate. Higher concentrations were not soluble in the solvent used. Precipitation of the test material on the agar plates was macroscopically visible at the highest concentration used (500 μg/plate). Toxicity to the bacteria was not observed.
Daunomycin, N-ethyl-N'-nitro-N-nitrosoguanidine, 9-aminoacridine and cumene hydroperoxide served as strain specific positive control compounds in the absence of S9-Mix. 2-Aminoanthracene and benzo[a]pyrene were used for testing the bacteria and the activity of the S9-Mix. Each treatment with the substances used as positive controls led to a clear increase in revertant colonies, thus showing the expected reversion properties of all strains and good metabolic activity of the S9-Mix used. With and without addition of S9-Mix as the external metabolizing system, the test material was not mutagenic under the experimental conditions described.
- Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- July 03, 2006 - September 20, 2006
- 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)
- Version / remarks:
- 21 July 1997
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.10 (Mutagenicity - In Vitro Mammalian Chromosome Aberration Test)
- Version / remarks:
- 8 June 2000
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- in vitro mammalian chromosome aberration test
- Species / strain / cell type:
- Chinese hamster lung fibroblasts (V79)
- Details on mammalian cell type (if applicable):
- CELLS USED
- Source of cells: Hoffmann-La Rache, Pharma, Basel
- Suitability of cells: This cell line has a high proliferation rate and cloning efficiency. The cells have a stable karyotype and an aberration rate of about 0-5% of the metaphases.
- Methods for maintenance in cell culture if applicable: Large stocks of this clone are stored in liquid nitro gen allowing the repeated use ofthe same cell culture batch in different experiments.
- Modal number of chromosomes: 22 +/- 1
- Normal (negative control) cell cycle time: 23 to 28 hours corresponds to 1.5 normal cell cycle length
MEDIA USED
- Type and identity of media including CO2 concentration if applicable: The cells were cultured in supplemented Dulbecco's Minima! Essential Medium (DMEM). The DMEM was supplemented with L-glutamine (4 mM), sodium bicarbonate (0.375 %), antibiotics (neomycine 0.015 %), and 10 % fetal calf serum (FCS). All incubations were performed at +37°C in a 4-5 % carbon dioxide atmosphere (100 % humidity).
- Periodically checked for Mycoplasma contamination: yes
- Other: The cells were cloned to minimize the frequency of mutants, and to stabilize the karyotype. The cells have a spontaneous aberration rate of about 0-5 % aberrant metaphases. - Metabolic activation:
- with and without
- Metabolic activation system:
- Rat liver S9 mix induced by Aroclor 1254
- Test concentrations with justification for top dose:
- 5.0, 15.8, and 50.0 µg/mL (+/- S9 mix)
The highest concentration of the test item was chosen based on the limited solubility of the test item. - Vehicle / solvent:
- - Vehicle/solvent used: acetone
- Justification for choice of solvent/vehicle: Analysis of the historical data of our laboratory and experience of other research groups showed that such amounts of the selected solvents have no influence on the mutation frequency in this test system. - Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- Acetone
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- cyclophosphamide
- ethylmethanesulphonate
- other: Griseofulvin
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in medium
- Cell density at seeding: 100.000 cells
DURATION
- Exposure duration: 5, 25, and 35 hours (- S9 mix); 5 hours (+ S9 mix)
- Fixation time (start of exposure up to fixation or harvest of cells): 25 and 35 hours, respectively
SPINDLE INHIBITOR (cytogenetic assays): colchicine
STAIN (for cytogenetic assays): Cells were stained in aceto-orcein, immersed in xylene and made permanent with Entellan
NUMBER OF REPLICATIONS: 2 (positive and test material); 4 (solvent control)
METHODS OF SLIDE PREPARATION AND STAINING TECHNIQUE USED: The medium is replaced by KCl-solution (0.4 %) for hypotonic treatment. For fixation of cells fixative ( methanol: acetic acid, 3: 1) is added and then renewed 2 times. The slides are then stained in aceto-orcein, immersed in xylene and made permanent with Entellan®.
NUMBER OF METAPHASE SPREADS ANALYSED PER DOSE: 100
DETERMINATION OF CYTOTOXICITY
- Method: mitotic index, cell viability
OTHER EXAMINATIONS:
- Determination of polyploidy: Yes
- Determination of endoreplication: Yes
The frequnecy determinaton of polyploid cells and endoreduplications (chromosomes with 4, 8, 16 ... chromatids) is based on scoring 1000 mitoses per slide, and estimation of the mitotic index on scoring 1000 cells per slide. - Evaluation criteria:
- A test material is defined as being unambiguously negative or non-clastogenic in this test system if no statistically significant increase in the number of aberrant metaphases per 100 cells, as compared to the actual negative control, occurs at any test material concentration.
A test material is positive or clastogenic in this test system if
- a statistically significant, dose-related increase in the number of aberrant metaphases per 100 cells occurs or
- a statistically significant increase in the number of aberrant metaphases per 100 cells is reproduced at the same test material concentration in independent experiments.
In both cases, however, the number of aberrant metaphases should be above the range defined as the historical negative controls of the laboratory and the biological relevance of the results has to be discussed.
In all other cases, further decisions for testing strategies should be made following the scientific evaluation of all existing data including those of nontoxicological investigations. - Statistics:
- Descriptive statistics
For all groups, mean values were calculated for the following parameters:
• the percentage of observed aberrant metaphases/culture (gaps included),
• the percentage of observed aberrant metaphases/culture (gaps excluded),
• the number of mitoses per 1000 cells/ culture
• the number of polyploid cells per 1000 mitotic cells/culture
Statistical tests
For further statistical analysis the numbers of aberrant metaphases (gaps excluded) were used. Pairwise comparisons within each experimental series. Each treatment group was compared with the negative control. For the comparisons the Exact Fisher Test was performed against one-sided alternatives. The p-values of these comparisons are presented in the tables section. - 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:
- not examined
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: none
- Effects of osmolality: none
- Precipitation: at the highest concentration tested, i.e. 50 µg/mL
RANGE-FINDING/SCREENING STUDIES: Cytotoxicity of the test item was examined in the range of 0.05 - 50.0 g/mL with and without S9 mix. No clear reduction of mitotic index or cell viability (MTT-test) were induced by the test material. However, the highest concentration tested was in excess of the solubility limit in the culture medium. Thus, this was considered a suitable maximum concentration.
HISTORICAL CONTROL DATA (with ranges, means and standard deviation and confidence interval (e.g. 95%)
- Positive historical control data:
-S9 mix (EMS): mean: 13.3 +/- 7.9; range: 4.5 - 5.5
+S9 mix (CPA): mean: 11.7 +/- 5.2; range: 4.0 - 28.5
- Negative (solvent/vehicle) historical control data:
-S9 mix: mean: 1.4 +/- 1.0; range: 0 - 5.0
+S9 mix: mean: 1.6 +/- 1.0; range 0 - 5.0
- Other: Treatment of cultures with the test item in the absence and presence of S9 mix resulted in frequencies of cells with polyploidic metaphases that were very similar or identical to those seen in the concurrent negative controls. No endoreduplications were observed.
- Conclusions:
- In conclusion, treatment of V79 cell cultures with the test item, did not increase the proportion of cells with aberrant chromosomes.The test item was not clastogenic in this in vitro test system.
- Executive summary:
The test item was investigated in two experimental series for induction of chromosomal aberrations in V79 Chinese hamster cells in vitro according to OECD Guideline 473. This also included examinations on whether or not the test material may have the potential to induce numerical aberrations, i. e. an increase in number of polyploid cells.
Due to the solubility of the test item, the concentration ranging from 5.0, 15.8, and 50.0 µg/mL with and without S9 mix. In the absence of S9 mix, cells were exposed to the test item for 5, 25 or 35 hours, respectively. In the presence of S9 mix, cells were treated for 5 hours with the test item.
The positive control test materials, EMS and CPA, induced the expected clear increase in the proportion of cells with chromosomal aberrations. Griseofulvin induced a clear increase in the number of polyploid cells.
The test item precipitated in the culture medium at the highest concentration tested, i.e. 50.0 μg/mL. No clear cytotoxic effects, i.e. reduction in mitotic index or cell viability (MTT test), were induced by the test material.
The mean values of aberrant metaphases (gaps excluded) in the negative controls of both experiments (- and + S9 mix) ranged from 0.5 to 1.75 %.
The test item did not show any biologically nor statistically relevant increase in the number of aberrant metaphases. Furthermore, no treatment related increase of endoreduplications or polyploid cells was observed, i.e. neither structural nor numerical aberrations were detected.
In conclusion, treatment of V79 cell cultures with the test item, did not increase the proportion of cells with aberrant chromosomes. The test item was not clastogenic in this in vitro test system.
Referenceopen allclose all
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Ames test
The investigations for mutagenic potential were performed using Salmonella typhimurium TA 98, TA 100, TA 102, TA 1535, and TA 1537 as tester strains with and without S9 Mix in a GLP conform study according to OECD Guideline 471. The test material was tested in two series of experiments at concentrations ranging from 0.5 to 500 μg/plate. Higher concentrations were not soluble in the solvent used. Toxicity to bacteria was not observed. While the positive controls showed a clear increase in revertant colonies, the test material was not mutagenic with and without S9 Mix under the experimental conditions described.
In vitro chromosome aberration test
The test item was investigated in two experimental series for induction of chromosomal aberrations in V79 Chinese hamster cells in vitro according to OECD Guideline 473. This also included examinations on whether or not the test material may have the potential to induce numerical aberrations, i. e. an increase in number of polyploid cells. The test item did not show any biologically nor statistically relevant increase in the number of aberrant metaphases. Furthermore, no treatment related increase of endoreduplications or polyploid cells was observed, i.e. neither structural nor numerical aberrations were detected. The positive control test materials, EMS and CPA, induced the expected clear increase in the proportion of cells with chromosomal aberrations. Griseofulvin induced a clear increase in the number of polyploid cells. In conclusion, treatment of V79 cell cultures with the test item, did not increase the proportion of cells with aberrant chromosomes. The test item was not clastogenic in this in vitro test system.
Justification for classification or non-classification
Based on the available data, the test item is not classified and labelled for genototxicity according to Regulation (EC) No 1272/2008.
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