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EC number: 608-770-5 | CAS number: 326894-55-7
- 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
OECD 471: not mutagenic in bacterial cells
OECD 473: not clastogenic in mammalian cells
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:
- Jun 21 - Dec 12, 2000
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- no
- 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: 5, 15.8, 50, 158, 500, 1580 and 5000 µg/plate (S9 10 %)
2. Series: 5, 15.8, 50, 158 and 500 µg/plate (S9 30 %) - Vehicle / solvent:
- acetone
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 9-aminoacridine
- N-ethyl-N-nitro-N-nitrosoguanidine
- cumene hydroperoxide
- other: daunomycin
- Remarks:
- without S9
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- benzo(a)pyrene
- other: 2-aminoanthracene
- Remarks:
- with S9
- Details on test system and experimental conditions:
- NUMBER OF REPLICATIONS:
- Number of independent experiments: two
METHOD OF TREATMENT/ EXPOSURE:
- Test substance added in agar (plate incorporation) - Evaluation criteria:
- Please refer to "any other information on materials and methods".
- Statistics:
- n.a.
- 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
- Untreated negative controls validity:
- not examined
- True 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
- True 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
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- True 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
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- True 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
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- True 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.
- Executive summary:
Purpose
The purpose of this assay was to provide information on possible health hazards for the test material and serve as a rational basis for risk assessment to the genotoxic potential of the test item in man.
Study Design
The investigations for the mutagenic potential of the test material were performed using Salmonella typhimurium tester strains TA 98, TA 100, TA 102, TA 1535, TA 1537 and Escherichia coli WP2 uvrA pKM101. The plate incorporation test with and without addition of liver S9 mix from Aroclor 1254-pretreated rats was used. Two independent experimental series were performed.
Results
The test material was dissolved in acetone and tested at concentrations ranging from 5 to 5000 µg/plate. Precipitation of the test material on the agar plates occurred in the concentration range between 158 and 500 µg/plate. Toxicity to the bacteria was not observed.
Each treatment with the test materials 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.
In both series of experiments, each performed with and without the addition of rat liver S9 mix as the external metabolizing system, the test material showed no increase in the number of revertants of any bacterial strain. According to the criteria for negative and positive results, the test material was not mutagenic under the described experimental conditions.
Conclusion
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
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- July 16 - November 19, 2002
- 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
- Principles of method if other than guideline:
- none
- GLP compliance:
- yes
- Type of assay:
- in vitro mammalian chromosome aberration test
- Species / strain / cell type:
- Chinese hamster Ovary (CHO)
- Details on mammalian cell type (if applicable):
- - Type and identity of media: McCoy's 5A medium including 10 % (v/v) FCS
- Properly maintained: yes
- Periodically checked for Mycoplasma contamination: yes
- Periodically checked for karyotype stability: yes - Metabolic activation:
- with and without
- Metabolic activation system:
- rat liver S9 mix (induction using Aroclor 1254)
- Test concentrations with justification for top dose:
- S9 Treatment+Recovery Vehicle Concentration
- 20+0 hours Ethanol 17.75, 20.88, and 24.57 µg/mL
- 44+0 hours Ethanol 15.09 and 17.75 µg/mL
+ 3+17 hours Ethanol 59.09, 65.61, and 81.00 µg/mL
+ 3+41 hours Ethanol 65.61, and 72.90 µg/mL - Vehicle / solvent:
- Name: DMSO
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 4-nitroquinoline-N-oxide
- cyclophosphamide
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in medium
DURATION
- Exposure duration:
Continous for 20 and 44 hours
Pulse for 3 + 17 and 3+41 hours
STAIN (for cytogenetic assays): Giemsa
NUMBER OF REPLICATIONS: Controls: 4; others: 2
NUMBER OF CELLS EVALUATED: 100 metaphases (structural abberations)
DETERMINATION OF CYTOTOXICITY
- Method: mitotic index; relative total growth
OTHER EXAMINATIONS:
- Determination of polyploidy: yes
- Determination of endoreplication: yes - Evaluation criteria:
- A test article is considered as positive in this assay if: 1. the proportions of cells with structural aberrations at one or more concentration exceeds the normal range in both replicate cultures, and 2. a statistically significant increase in the proportion of cells with structural aberrations (excluding gaps) occurs at these doses. Increased incidence of cells with gaps or increased proportions of cells with structural aberrations not exceeding the normal range or occurring only at very high or very toxic concentrations are likely to be concluded as "equivocal". Full assessment of the biological importance of such increases is likely only to be possible with reference to data from other test systems. Evidence of a dose-related effect is considered useful but not essential in the evaluation of a positive result. Cells with exchange aberrations or cells with greater than one structural aberration occur very infrequently in negative control cultures. Their appearance is therefore considered to be of particular biological significance.
- Statistics:
- Standard statistical methods have been applied for data processing.
- Key result
- Species / strain:
- Chinese hamster Ovary (CHO)
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- True negative controls validity:
- not examined
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: yes (441 µg/mL)
- Cytotoxicity: yes
- Other confounding effects:
RANGE-FINDING/SCREENING STUDIES:
COMPARISON WITH HISTORICAL CONTROL DATA:
ADDITIONAL INFORMATION ON CYTOTOXICITY:
Due to the toxicity profiles observed (reductions in cell number), it was not possible to select the same top concentrations for analysis from treatments sampled at 44 hours as those for treatments sampled at 20 hours. The pattern of toxicity for both treatments sampled at 44 hours was such that two concentration choices were possible; one inducing below 50 % cytotoxicity and one inducing 60 % (or slightly above) cytotoxicity. It was considered prudent to analyse both concentrations from both treatments. Although contrary to the protocol, this was considered to add to the
data set and as such has no adverse effect on the validity of the study. - Conclusions:
- It is concluded that the test material did not induce structural or numerical chromosome aberrations in cultured Chinese hamster ovary (CHO) cells when tested to its limit of cytotoxicity in both the absence and presence of metabolic activation (S-9).
- Executive summary:
Study Design
The test material was tested in an in vitro cytogenetics assay using duplicate cultures of Chinese hamster ovary (CHO) cells in two independent experiments. Treatments covering a broad range of doses, separated by narrow intervals, were performed both in the absence and presence of metabolic activation (S-9). The test article was dissolved in sterile ethanol (ethanol) and the highest dose level used, 400 μg/mL, was in excess of the solubility limit in culture medium. In Experiment 1, treatment in the absence and presence of S-9 was for 3 hours followed by a 17-hour recovery period prior to harvest (3+17). The S-9 used was prepared from a rat liver post-mitochondrial fraction (S-9) from Aroclor 1254 induced animals. The test article dose levels for chromosome analysis were selected by evaluating the effect of the test material on relative cell number. Chromosome aberrations were analysed at three dose levels. The highest concentrations chosen for analysis, 27.49 and 83.89 μg/mL induced approximately 58 % and 66 % reduction in cell number and 0 % and 49 % mitotic inhibition (MIH) in the absence and presence of S-9 respectively. In Experiment 2, treatment in the absence of S-9 was continuous for either 20 hours or 44 hours. Treatment in the presence of S-9 was either for 3 hours only followed by a 17-hour recovery period prior to harvest (3+17) or for 3 hours followed by a 41-hour recovery period prior to harvest (3+41). Chromosome aberrations were analysed at two or three dose levels (see overleaf) and the highest concentrations chosen for analysis, 24.57 μg/mL (20+0) or 17.75 μg/mL (44+0) in the absence of S-9 and 81.00 μg/mL (3 +17) or 72.90 μg/mL (3+41) in the presence of S-9, induced approximately 50 %, 60 %, 54 % and 62 % reduction in cell number and 81 %, 29 %, 55 % and 7 % MIH respectively. Appropriate negative (vehicle) control cultures were included in the test system in both experiments under each treatment condition. The proportion of cells with structural aberrations in these cultures fell within historical solvent control ranges. 4-Nitroquinoline 1 -oxide and cyclophosphamide were employed as positive control chemicals in the absence and presence of liver S-9 respectively. Cells receiving these were sampled in each experiment, 20 hours after the start of treatment; both compounds induced statistically significant increases in the proportion of cells with structural aberrations. Positive controls were included with both treatments in Experiment 1, but only with the 20+0 hour -S-9 and 3+17 +S-9 treatments in Experiment 2.
This study was performed according to GLP and the methods applied are fully compliant with OECD TG 473.Results
Treatment of cultures with the test material in the absence and the presence of S-9 (both experiments) resulted in frequencies of cells with structural aberrations which were similar to those observed in concurrent vehicle controls for the majority of concentrations analysed. Two exceptions to this were observed: a single culture at the intermediate concentration analysed (67.11 mg/mL) from the 3+17 hour +S-9 treatment in Experiment 1 and a single culture from the lowest concentration analysed (15.09 mg/mL) from the 44+0 hour –S-9 treatment in Experiment 2 both exhibited numbers of aberrant cells that exceeded historical negative control (normal) values. However, in both instances these increases were not observed in the replicate cultures and were not dose-related. Furthermore, the increase observed in the presence of S-9 in Experiment 1 was not observed at similar concentrations analysed in Experiment 2 (performed under identical treatment conditions). The aberrant cell frequency of all other test material treated cultures fell within normal values. It was therefore considered that the increases observed were spurious and of no biological significance. Normal frequencies of cells with numerical aberrations (within historical negative control (normal) ranges) were observed for the large majority of test material treated cultures. The only exception to this was observed in the 3+17 hour –S-9 treatment at the highest concentration tested (27.49 mg/mL) where a single replicate showed an aberrant cell frequency that exceeded the normal range. However, this increase was small and was not observed in the replicate culture. As all other cultures (for all treatments) exhibited normal frequencies of numerical aberrations, this increase was not considered of biological importance.
Conclusion
It is concluded that the test material did not induce structural or numerical chromosome aberrations in cultured Chinese hamster ovary (CHO) cells when tested to its limit of cytotoxicity in both the absence and presence of metabolic activation (S-9).
Referenceopen allclose all
see attachment
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
OECD 471:
The investigations for the mutagenic potential of the test material were performed using Salmonella typhimurium tester strains TA 98, TA 100, TA 102, TA 1535, TA 1537 and Escherichia coli WP2 uvrA pKM101. The plate incorporation test with and without addition of liver S9 mix from Aroclor 1254-pretreated rats was used. Two independent experimental series were performed. The test material was dissolved in acetone and tested at concentrations ranging from 5 to 5000 µg/plate. Precipitation of the test material on the agar plates occurred in the concentration range between 158 and 500 µg/plate. Toxicity to the bacteria was not observed. Each treatment with the test materials used as positive controls (see listed controls above) 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. In both series of experiments, each performed with and without the addition of rat liver S9 mix as the external metabolizing system, the test material showed no increase in the number of revertants of any bacterial strain. According to the criteria for negative and positive results (see "Details on test system and conditions"), the test material was not mutagenic under the described experimental conditions. With and without addition of S9 mix as the external metabolizing system, the test material was not mutagenic under the experimental conditions described.
OECD 473:
Study Design
The test material was tested in an in vitro cytogenetics assay using duplicate cultures of Chinese hamster ovary (CHO) cells in two independent experiments. Treatments covering a broad range of doses, separated by narrow intervals, were performed both in the absence and presence of metabolic activation (S-9). The test article was dissolved in sterile ethanol (ethanol) and the highest dose level used, 400 μg/mL, was in excess of the solubility limit in culture medium. In Experiment 1, treatment in the absence and presence of S-9 was for 3 hours followed by a 17-hour recovery period prior to harvest (3+17). The S-9 used was prepared from a rat liver post-mitochondrial fraction (S-9) from Aroclor 1254 induced animals. The test article dose levels for chromosome analysis were selected by evaluating the effect of the test material on relative cell number. Chromosome aberrations were analysed at three dose levels. The highest concentrations chosen for analysis, 27.49 and 83.89 μg/mL induced approximately 58% and 66% reduction in cell number and 0% and 49% mitotic inhibition (MIH) in the absence and presence of S-9 respectively. In Experiment 2, treatment in the absence of S-9 was continuous for either 20 hours or 44 hours. Treatment in the presence of S-9 was either for 3 hours only followed by a 17-hour recovery period prior to harvest (3+17) or for 3 hours followed by a 41-hour recovery period prior to harvest (3+41). Chromosome aberrations were analysed at two or three dose levels (see overleaf) and the highest concentrations chosen for analysis, 24.57 μg/mL (20+0) or 17.75 μg/mL (44+0) in the absence of S-9 and 81.00 μg/mL (3 +17) or 72.90 μg/mL (3+41) in the presence of S-9, induced approximately 50%, 60%, 54% and 62% reduction in cell number and 81%, 29%, 55% and 7% MIH respectively. Appropriate negative (vehicle) control cultures were included in the test system in both experiments under each treatment condition. The proportion of cells with structural aberrations in these cultures fell within historical solvent control ranges. 4-Nitroquinoline 1 -oxide and cyclophosphamide were employed as positive control chemicals in the absence and presence of liver S-9 respectively. Cells receiving these were sampled in each experiment, 20 hours after the start of treatment; both compounds induced statistically significant increases in the proportion of cells with structural aberrations. Positive controls were included with both treatments in Experiment 1, but only with the 20+0 hour -S-9 and 3+17 +S-9 treatments in Experiment 2. This study was performed according to GLP and the methods applied are fully compliant with OECD TG 473. Treatment of cultures with the test material in the absence and the presence of S-9 (both experiments) resulted in frequencies of cells with structural aberrations which were similar to those observed in concurrent vehicle controls for the majority of concentrations analysed. Two exceptions to this were observed: a single culture at the intermediate concentration analysed (67.11 mg/mL) from the 3+17 hour +S-9 treatment in Experiment 1 and a single culture from the lowest concentration analysed (15.09 mg/mL) from the 44+0 hour –S-9 treatment in Experiment 2 both exhibited numbers of aberrant cells that exceeded historical negative control (normal) values. However, in both instances these increases were not observed in the replicate cultures and were not dose-related. Furthermore, the increase observed in the presence of S-9 in Experiment 1 was not observed at similar concentrations analysed in Experiment 2 (performed under identical treatment conditions). The aberrant cell frequency of all other test material treated cultures fell within normal values. It was therefore considered that the increases observed were spurious and of no biological significance. Normal frequencies of cells with numerical aberrations (within historical negative control (normal) ranges) were observed for the large majority of test material treated cultures. The only exception to this was observed in the 3+17 hour –S-9 treatment at the highest concentration tested (27.49 mg/mL) where a single replicate showed an aberrant cell frequency that exceeded the normal range. However, this increase was small and was not observed in the replicate culture. As all other cultures (for all treatments) exhibited normal frequencies of numerical aberrations, this increase was not considered of biological importance. It is concluded that the test material did not induce structural or numerical chromosome aberrations in cultured Chinese hamster ovary (CHO) cells when tested to its limit of cytotoxicity in both the absence and presence of metabolic activation (S-9).
Justification for classification or non-classification
Based on the provided information there is no need for classification according to the EU Regulation (EC) No 1272/2008 on Classification, Labelling and Packaging of Substances and Mixtures.
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.