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EC number: 219-547-3 | CAS number: 2459-10-1
- 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
Bacterial reverse mutation assay - No mutagenic effects observed in Salmonella typhimurium strains TA98, TA1535, and TA1537 in the absence and presence of metabolic activation.
Ambiguous/positive results in Salmonella typhimurium strain TA100 and Escherichia coli strain WP2uvrA in the absence and presence of metabolic activation.
Mammalian cell gene mutation assay - Dose-related increases of the mutant frequency observed in the presence and absence of metabolic activation.
In-vitro mammalian chromosome aberration test - Positive for the induction of structural and numerical chromosome aberrations.
Link to relevant study records
- Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2006 - 2007
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study without detailed documentation
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
- Deviations:
- not specified
- GLP compliance:
- not specified
- Type of assay:
- in vitro mammalian chromosome aberration test
- Species / strain / cell type:
- Chinese hamster Ovary (CHO)
- Metabolic activation:
- with and without
- Metabolic activation system:
- Aroclor induced rat liver S9
- Test concentrations with justification for top dose:
- 5 - 2522 micrograms/mL
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: DMSO
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Species / strain:
- Chinese hamster Ovary (CHO)
- Metabolic activation:
- with and without
- Genotoxicity:
- positive
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Conclusions:
- A cytogenetic assay was positive for the induction of chromosome aberrations in Chinese hamster ovary cells.
- Executive summary:
A cytogenetic assay in Chinese hamster ovary cells resulted in positive findings for the induction of chromosome aberrations.
- Endpoint:
- in vitro gene mutation study in mammalian cells
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2006 - 2007
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study without detailed documentation
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
- Deviations:
- not specified
- GLP compliance:
- not specified
- Type of assay:
- in vitro mammalian cell gene mutation tests using the thymidine kinase gene
- Species / strain / cell type:
- mouse lymphoma L5178Y cells
- Metabolic activation:
- with and without
- Metabolic activation system:
- Aroclor induced rat liver S9
- Test concentrations with justification for top dose:
- 3 hours exposure with S9: 600 - 1500 microgram/mL
3 hours exposure without S9: 200 - 900 micrograms/mL
24 hours exposure without S9: 300 - 700 micrograms/mL - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: DMSO
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Details on test system and experimental conditions:
- Two assays conducted with 3 hours exposure in the presence of a metabolic activation system.
One assay conducted with 3 hours exposure in the absence of a metabolic activation system.
One assay conducted with 24 hours exposure in the absence of a metabolic activation system. - Species / strain:
- mouse lymphoma L5178Y cells
- Metabolic activation:
- with and without
- Genotoxicity:
- positive
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Remarks on result:
- other:
- Remarks:
- Statistically significant increases in mutation frequency observed at > 500 micrograms/mL
- Conclusions:
- Statistically significant increases in the mutant frequency in both the absence and presence of a metabolic activation system were observed. In the non-activated test systems, biologically significant increases were observed after 24 hours exposure at dose levels of > 500 micrograms/mL. In the presence of a metabolic activation system, increases were observed at dose levels of > 500 micrograms/mL in the first assay and > 600 micrograms/mL in the second assay.
- Executive summary:
Gene mutation in a mammalian cell line has been investigated. Statistically significant increases in the mutant frequency in both the absence and presence of a metabolic activation system were observed. In the non-activated test systems, biologically significant increases were observed after 24 hours exposure at dose levels of > 500 micrograms/mL. In the presence of a metabolic activation system, increases were observed at dose levels of > 500 micrograms/mL in the first assay and > 600 micrograms/mL in the second assay.
- 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:
- 20 May 2014 - 30 May 2014
- 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:
- 1997
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
- Version / remarks:
- 2008
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.5100 - Bacterial Reverse Mutation Test (August 1998)
- GLP compliance:
- yes
- Type of assay:
- bacterial reverse mutation assay
- Target gene:
- his operon (for S. typhimurium strains) and trp operon (for E. coli strains).
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Additional strain / cell type characteristics:
- other: The salmonella strains were checked for the following characteristics at regular intervals: deep rough character (rfa); UV sensitivity (∆ uvrB); ampicillin resistance (R factor plasmid).
- Species / strain / cell type:
- E. coli WP2 uvr A
- Additional strain / cell type characteristics:
- other: E. coli WP2 uvrA was checked for UV sensitivity.
- Metabolic activation:
- with and without
- Metabolic activation system:
- cofactors supplemented post-mitochondrial fraction (S9 mix), prepared from the livers of Wistar rats treated 80 mg/kg bw phenobarbital i.p. and β-naphthoflavone orally, each on 3 consecutive days
- Test concentrations with justification for top dose:
- 1st Experiment (all strains, standard plate test with and without S-9 mix; 3 plates/dose): 0; 33; 100; 333; 1000; 26500and 5300 µg/plate
2nd Experiment because mutagenicity was observed in the standard plate test:
(TA100 and E.coli, standard plate test with and without S-9 mix; 3 plates/dose): 0; 33; 100; 333; 1000; 2650 and 5300 µg/plate
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: Due to the insolubility of the test substance in ultrapure water DMSO was used as vehicle. - Untreated negative controls:
- yes
- Remarks:
- (sterility control)
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: with S9-mix
- Remarks:
- 2-aminoanthracene (2-AA): 2.5 µg/plate dissolved in DMSO for strains TA 1535, TA 100, TA 1537 and TA 98; 60 µg/plate dissolved in DMSO for Escherichia coli WP2 uvrA
- Positive controls:
- yes
- Positive control substance:
- other: without S9-mix
- Remarks:
- N-methyl-N'-nitro-N-nitrosoguanidine (MNNG): 5 µg/plate (DMSO), TA1535, TA100; 4-nitro-o-phenylenediamine (NOPD): 10 µg/plate (DMSO), TA98; 9-aminoacridine (AAC): 100 µg/plate (DMSO), TA1537; 4-nitroquinoline-N-oxide (4-NQO): 5 µg/plate (DMSO), E.coli
- Details on test system and experimental conditions:
- TEST DESIGN
Standard plate test (SPT) with and without metabolic activation, were performed.
Standard plate test (SPT):
The experimental procedure was based on Ames et al. (Mut. Res. 31: 347-364, 1975) and Maron & Ames (Mut. Res. 113: 173-215, 1983).
Test tubes containing 2 mL portions of soft agar [100 mL agar (0.8% [w/v] agar + 0.6% [w/v] NaCl) and 10 mL amino acid solution (minimal amino acid solution for the determination of mutants: 0.5 mM histidine + 0.5 mM biotin for S. typhimurium or 0.5 mM tryptophan for E.coli)] were kept in a water bath at about 42 - 45°C. An amount of 0.1 mL test solution or vehicle (negative control), 0.1 mL fresh bacterial culture and 0.5 mL S9 mix (in case of metabolic activation) or 0.5 mL phosphate buffer (in case of no metabolic activation) were added. After mixing, the samples were poured onto agar plates and incubated at 37°C for 48 to 72 hours in the dark. After incubation, the bacterial colonies were counted for revertants.
PARAMETERS EXAMINED
Mutagenicity:
Individual plate counts, the mean number of revertant colonies per plate and the standard deviations were given for all dose groups as well as for the positive and negative (vehicle) controls in all experiments. In general, six doses of the test substance were tested with a maximum of 5 mg/plate, and triplicate plating was used for all test groups at least in the 1st Experiment. Dose selection and evaluation as well as the number of plates used in repeat studies or further experiments were based on the findings of the 1st Experiment.
Cytotoxicity:
Toxicity was detected by (1) decrease in the number of revertants, (2) clearing or diminution of the background lawn (= reduced his- or trp- background growth) and (3) reduction in the titer. Cytotoxicity was recorded for all test groups both with and without S9 mix in all experiments.
Solubility:
Precipitation of the test item was recorded and indicated. As long as precipitation does not interfere with colony scoring, 5000 µg/plate is generally selected and analyzed (in cases of nontoxic compounds) as the maximum dose at least in the 1st Experiment even in the case of relatively insoluble test compounds to detect possible mutagenic impurities. Furthermore, doses > 5000µg/plate might also be tested in repeat experiments for further clarification/substanstiation. - Evaluation criteria:
- Acceptance criteria:
The experiment is considered valid if the following criteria are met:
- The number of revertant colonies in the negative controls is within the range of the historical negative control data for each tester strain;
- The sterility controls reveales no indication of bacterial contamination;
- The positive control substances both with and without S9 mix induce a distinct increase in number of revertant colonies within the range of the historical positive control data or above;
- The titer of viable bacteria is egal to/greater than 10E+9/mL.
Assessment criteria:
The test substance was considered positive in this assay if the following criteria were met:
A dose-related and reproducible increase in the number of revertant colonies, i.e. at least doubling (bacteria strains with high spontaneous mutation rate, like TA 98, TA 100 and E.coli WP2 uvrA) or tripling (bacteria strains with low spontaneous mutation rate, like TA 1535 and TA 1537) of the spontaneous mutation rate in at least one tester strain either without S9 mix or after adding a metabolizing system.
The test item is generally nonmutagenic if the number of revertants for all tester strains is within the historical negative control range under all experimental conditions in two experiments carried out independently of each other. - Species / strain:
- S. typhimurium, other: TA 1535; TA1537; TA98
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- positive
- Remarks:
- increases in the number of his+ revertants at 1.000, 2.650 and 5.300 µg/plate (factors 2.6 up to 8.4 respectively).
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Species / strain:
- E. coli WP2 uvr A
- Metabolic activation:
- with and without
- Genotoxicity:
- positive
- Remarks:
- 1st. Exp.:increases in the number of trp+ revertants at 1.000, 2.650 and 5.300 µg/plate (factors 2.4 to 7 respectively)
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: other: standard plate test (SPT)
- Executive summary:
According to the results of the present study led to a evident and dose-dependent increase in the number of his+ and trp+ revertants with the strains TA 100 and E. coli WP2 uvrA both with and without S9 mix. The increase of revertants was reproducible in two experiments carried out independently of each other. Based on the recent assessment criteria the test substance has to be considered positive.
Besides, the results of the negative as well as the positive controls performed in parallel corroborated the validity of this study, since the values fulfilled the acceptance criteria of this study.
In this study with and without S9 mix, the number of revertant colonies in the negative controls was within the range of the historical negative control data for each tester strain.
In addition, the positive control substances both with and without S9 mix induced a significant increase in the number of revertant colonies within or above the range of the historical positive control data or above.
Referenceopen allclose all
The highest concentrations chosen for the chromosome aberration assay were 1000 micrograms/mL for the 4 -hour exposure assay without a metabolic activation system, 2522 micrograms/mL
for the 4 hour exposure period with a metabolic activation system and 750 micrograms/mL for the 20 hour exposure period without a metabolic activation system.
A visible precipitate was observed at the beginning and end of the treatment periods at concentrations of 1000 micrograms/mL and greater.
Substantial toxicity (greater than a 50% reduction in cell growth relative to the vehicle control) was observed at the highest concentration in each test condition. The selection of doses for analysis was based on these dose concentration levels as well as precipitation. Cytogenetic evaluations were conducted at 500, 750 and 1000 microgramsg/mL for the 4 hour exposure period both with and without metabolic activation and at 100, 250 and 500 micrograms/mL for the 20 hour exposure period without metabolic activation.
The percentage of cells with structural aberrations following 4 hours exposure with metabolic activation was significantly increased above that of the vehicle control at 500, 750 and 1000 micrograms/mL. The percentage of cells with structural aberrations following 20 hours exposure without metabolic activation was also significantly increased above that of the vehicle control at 500 micrograms/mL. The observed changes were outside of the historical control range for structural aberrations, were accompanied by a concentration-related increase, and were therefore considered biologically significant. The percentage of cells with numerical aberrations following 4 hours exposure without metabolic activation showed a significant trend as compared to the vehicle control at 750 and 1000 micrograms/mL. The percentage of cells with numerical aberrations following 4 hours exposure with metabolic activation was also significantly increased above that of the vehicle control at 500, 750 and 1000 micrograms/mL. The observed changes were outside of the historical control range for numerical aberrations, and were therefore considered biologically significant.
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (positive)
Genetic toxicity in vivo
Description of key information
Mammalian erythrocyte micronucleus test in mice - Negative
In-vivo/in-vitro UDS assay in rats - Negative
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
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- data from handbook or collection of data
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- Deviations:
- not specified
- GLP compliance:
- not specified
- Type of assay:
- mammalian erythrocyte micronucleus test
- Species:
- mouse
- Strain:
- not specified
- Sex:
- male/female
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- no effects
- Conclusions:
- No toxicity nor decrease in the ratio of polychromatic erythroctes were seen up to the maximum recommended dose of 2000 g/kg bw.
- Executive summary:
A mammalian erythrocyte micronucleus test has been conducted in mice. No toxicity nor decrease in the ratio of polychromatic erythroctes were seen up to the maximum recommended dose of 2000 g/kg bw.
- Endpoint:
- in vivo mammalian cell study: DNA damage and/or repair
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- data from handbook or collection of data
- GLP compliance:
- not specified
- Type of assay:
- unscheduled DNA synthesis
- Species:
- rat
- Sex:
- male
- Sex:
- male
- Genotoxicity:
- negative
- Toxicity:
- no effects
- Conclusions:
- No indication of genotoxicity observed.
- Executive summary:
An unscheduled DNA synthesis assay has been conducted in rats. No indications of genotoxicity were observed at dose levels up to the maximum recommended for the assay, 2000 mg/kg bw.
Referenceopen allclose all
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Additional information
Justification for classification or non-classification
The genotoxic effects observed in-vitro are not expressed in-vivo and the substance is considered to be non-genotoxic in vivo. Classification is therefore not indicated.
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