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EC number: 610-847-3 | CAS number: 524709-77-1
- 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
Clearly negative in vitro studies - both with and without metabolic activation.
Link to relevant study records
- Endpoint:
- in vitro gene mutation study in bacteria
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2007-02-19 to 2007-06-28
- 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:
- adopted 21 July 1997
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
- GLP compliance:
- yes
- Type of assay:
- bacterial reverse mutation assay
- Target gene:
- HIS operon (S. thyphimurium)
TRP operon (E. coli) - Species / strain / cell type:
- S. typhimurium TA 1535
- Details on mammalian cell type (if applicable):
- his G 46, uvrB, rfa
- Additional strain / cell type characteristics:
- other: mutations in the histidine operon
- Species / strain / cell type:
- S. typhimurium TA 1537
- Details on mammalian cell type (if applicable):
- his C 3076, uvrB, rfa
- Additional strain / cell type characteristics:
- other: mutations in the histidine operon
- Species / strain / cell type:
- S. typhimurium TA 98
- Details on mammalian cell type (if applicable):
- his D 3052, uvrB, rfa + R-factor
- Additional strain / cell type characteristics:
- other: mutations in the histidine operon
- Species / strain / cell type:
- S. typhimurium TA 100
- Details on mammalian cell type (if applicable):
- his G 46, uvrB, rfa + R-factor
- Additional strain / cell type characteristics:
- other: mutations in the histidine operon
- Species / strain / cell type:
- S. typhimurium TA 102
- Details on mammalian cell type (if applicable):
- his G 428, rfa + R-factor
- Additional strain / cell type characteristics:
- other: mutations in the histidine operon
- Species / strain / cell type:
- E. coli WP2
- Details on mammalian cell type (if applicable):
- uvrA pkM101
- Additional strain / cell type characteristics:
- other: mutations in the tryptophan operon
- Metabolic activation:
- with and without
- Metabolic activation system:
- liver S9 mix from Aroclor 1254-pretreated rats with standard co-factors
- Test concentrations with justification for top dose:
- The test material concentrations used were selected according to the EC and OECD guidelines for this test system and the requirements of the Labor Ministry of Japan:
1. Series: 2.81, 8.89, 28.1, 88.9, 281, 889 and 2810 μg per plate (S9 10 %)
2. Series: 2.81, 5.00, 8.89, 15.8 and 28.1 μg per plate (S9 30 %) - Vehicle / solvent:
- acetone
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Positive controls:
- yes
- Positive control substance:
- 4-nitroquinoline-N-oxide
- 9-aminoacridine
- sodium azide
- cumene hydroperoxide
- other: daunomycin
- Remarks:
- without S9
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Positive controls:
- yes
- Positive control substance:
- benzo(a)pyrene
- other: 2-aminoanthracene
- Remarks:
- with S9
- Details on test system and experimental conditions:
- The assessment of test material-induced effects is dependent on the number of spontaneous revertants of each bacterial strain (solvent controls) and the increase in the number of revertants at the test material concentration which shows the highest number of colonies. The following criteria, based upon the historical controls of the laboratory and statistical considerations, are established:
-----------------------------------------------------------------------------------------
Mean Number of Colonies Maximal Mean Number of Colonies over the Actual
(Solvent Control) Solvent Control
(Test Material)
-----------------------------------------------------------------------------------------
<=10 <=9 >=30
<=30 <=19 >=40
<=80 <=29 >=80
<=200 <=49 >=120
<=500 <=79 >=200
Assessment: No increase Clear increase
-----------------------------------------------------------------------------------------
All further results, ranging between "no" and "clear", are assessed as "weak in-creases".
Interpretations:
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 strong precipitation or cytotoxicity, and the effects are reproduced at the same concentration level in the same test system.
In all further cases, a third test series with the bacterial strain in question should be performed.
If 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. - Rationale for test conditions:
- according to Guideline
- Evaluation criteria:
- see Details on test systems and conditions
- Statistics:
- n.a.
- Key result
- Species / strain:
- S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- Positive controls validity:
- valid
- Key result
- Species / strain:
- E. coli WP2 uvr A pKM 101
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- Positive controls validity:
- valid
- Conclusions:
- 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:
- 2007-10-26 to 2008-04-09
- 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:
- adopted 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 Roche, Pharma, Basel, at May 27, 1997
- Suitability of cells: recommended for this type of assay
- Cell cycle length, doubling time or proliferation index: 16 to 17.5 hours
V79 cells have been successfully used in mutagenicity testing for many years. This cell line has a high proliferation rate and cloning efficiency. The cells have a relatively stable karyotype with a modal chromosome number of 22 ± 1, and an aberration rate of about 0-5 % of the metaphases. Since the cell line is not able to metabolize indirect mutagens to reactive forms, the test is performed both in the presence and absence of an external metabolizing system (liver S9 mix of rats pre-treated with Aroclor 1254). - Additional strain / cell type characteristics:
- not applicable
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9-mix with S9 from Aroclor 1254 induced rats
- Test concentrations with justification for top dose:
- Due to limited solubility of the test item in solvents used for this type of test, concentrations ranging from 0.281 to 88.9 µg/mL were tested. The test item precipitated in the culture medium at concentrations >=8.89 µg/mL. No clear cytotoxic effects were seen in the MTT assay. Quality control of the cell preparations did not show a relevant influence of the test item on the structure or spreading of the chromosomes in the concentration range investigated. A change in the pH or the osmotic value of the cell culture medium did not occur in the dose range tested.
For these reasons, cultures treated with the following test material concentrations were evaluated in absence and presence of S9 mix for the occurrence of chromosomal aberrations:
Experiment 1 (with and without S9 mix): 8.89, 28.1 and 88.9 µg/mL
Experiment 2 (with and without S9 mix): 8.89, 28.1 and 88.9 µg/mL - Vehicle / solvent:
- Acetone, 0.1% in the culture medium
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- ethylmethanesulphonate
- other: Griseofulvin
- Remarks:
- - S9 mix
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- cyclophosphamide
- Remarks:
- + S9 mix
- Details on test system and experimental conditions:
- No. of slides per concentration:
Solvent control: 4
Others: 2
No. of metaphases evaluated per slide: 100 (for structural aberrations);
1000 (for polyploidy)
Exposure times:
-S9 mix: 5, 25 and 35 hours
+S9 mix. 5 hours
Solvent for the test material: Acetone
Positive controls: - S9 mix: 250 or 500 µg Ethylmethansulfonat (EMS)/mL
31.6 or 88.9 µg Griseofulvin (GRIS)/mL
+S9 mix: 2.00 µg Cyclophosphamide (CPA)/mL - Rationale for test conditions:
- according to Guideline
- Evaluation criteria:
- Step 1: Evaluation of Slide Quality
Step 2: Evaluation of Chomosomal Aberrations
The decisive parameter for the evaluation of both, the treated and untreated cultures, is the number of aberrant metaphases (excluding gaps) per 100 cells. A basic prerequisite for the acceptance of a test series is (a) the correspondence of the actual negative controls with the historic negative controls of the laboratory and (b) a statistically significant and biologically relevant increase in the number of aberrant metaphases for the respective positive controls in relation to the actual negative controls. The discussion of biological relevance includes, among other things, considerations concerning the type and time dependent appearance of the observed chromosomal aberrations.
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 non toxicological investigations. - Statistics:
- Fisher’s Exact Test
- Key result
- Species / strain:
- Chinese hamster lung fibroblasts (V79)
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Conclusions:
- In conclusion, treatment of V79 cell cultures with the test materialdid not increase the proportion of cells with aberrant chromosomes in two independent experimental series in absence and presence of metabolic activation (S9 mix).the test material was, thus, not clastogenic in this in vitro test system.
- Executive summary:
The informtion for this endpoint study record was obtained from an experimental study. The OECD GLP criteria were met and the methods applied are fully compliant with OECD TG 473.
Treatment of V79 cell cultures with the test material did not increase the proportion of cells with aberrant chromosomes in two independent experimental series in absence and presence of metabolic activation (S9 mix). the test material was, thus, not clastogenic in this in vitro test system.
Referenceopen allclose all
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Description of key information
The performance of in vivo studies is not necessary.
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Justification for classification or non-classification
Based on the provided data, the test item is not classified and labelled for mutagenicity according to Regulation (EC) No 1272.
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.
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