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EC number: 807-560-2 | CAS number: 123944-63-8
- 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
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:
- 4 November 2004 to 10 December 2004
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Study conducted to GLP in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: USA EPS (TSCA) OPPTS harmonised guidelines
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- JAPAN: Guidelines for Screening Mutagenicity Testing Of Chemicals
- Version / remarks:
- (the method conforms with those published by METI, MHLW and MAFF)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- bacterial reverse mutation assay
- Target gene:
- Histidine locus
- 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:
- 10 % liver S9 in standard co-factors
- Test concentrations with justification for top dose:
- - Preliminary Test: 0, 0.15, 0.5, 1.5, 5, 15, 50, 150, 500, 1500 and 5000 µg/plate
- Mutation Test (experiments 1 and 2): 0, 50, 150, 500, 1500 and 5000 µg/plate - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: sterile distilled water. Formulated concentrations were adjusted to make allowances for the purity of the test material.
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- distilled water
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 4-nitroquinoline-N-oxide
- 9-aminoacridine
- N-ethyl-N-nitro-N-nitrosoguanidine
- benzo(a)pyrene
- mitomycin C
- other: 2-aminoanthracene, 1,8-dihydroxyanthraquinone
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in agar (plate incorporation);
A measured aliquot (0.1 mL) of bacterial culture was dispensed into a tube followed by 2.0 mL of molten, trace histidine-supplemented, top agar, 0.1 mL of the test material formulation, vehicle or positive control and either 0.5 mL of S9 mix or phosphate buffer. The content of the tube was dispensed onto the surface of a Vogel-Bonner minimal agar plate and incubated.
DURATION
- Exposure duration: 48 hours at 37 °C
NUMBER OF REPLICATIONS: The procedure was repeated in triplicate for each concentration in each bacterial strain for both Experiment 1 and Experiment 2.
NUMBER OF CELLS EVALUATED: The frequency of revertant colonies was assessed using a Domino colony counter. The top dose level was assessed manually due to test material-induced colouration.
DETERMINATION OF CYTOTOXICITY
- Method: Assessment of effects on the growth of the background bacterial lawn. - Evaluation criteria:
- The test material may be considered positive in this test system if the following criteria are met:
- the test material should have induced a reproducible, dose-related and statistically significant increase in the revertant count of at least one strain of bacteria. - Statistics:
- Dunnett’s method of linear regression was used to assess statistical significance.
- 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 nor precipitates, but tested up to recommended limit concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Additional information on results:
- The test material caused no visible reduction in the growth of the background bacterial lawn at any dose level. A blue colour was observed at and above 50 µg/plate, becoming darker with increasing concentration. This did not prevent scoring of revertant colonies. No test material precipitate was observed on any of the plates at any of the dose levels tested in either the presence or the absence of S9 mix.
No significant increases in the frequency of revertant colonies were recorded for any of the strains at any dose level with or without metabolic activation. - Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- Interpretation of results (migrated information):
negative with or without metabolic activation
Under the conditions of this study, the test material was found to be devoid of mutagenic activity on Salmonella typhimurium strains TA 1535, TA 1537, TA 98 TA 100 and TA 102 in the presence and absence of metabolic activation. - Executive summary:
The mutagenic potential of the test material was investigated in a bacterial reverse mutation assay which was conducted in accordance with the standardised guidelines OECD 471, EU Method B.13/14, USA EPS (TSCA) OPPTS harmonised guidelines and those published in Japan by METI, MHLW and MAFF under GLP conditions.
Salmonella typhimurium strains TA 1535, TA 1537, TA 98 TA100 and TA 102 were treated with the test material (using the Ames plate incorporation method) at dose levels of 50, 150, 500, 1500 and 5000 µg/plate in distilled water both in the presence and absence of metabolic activation (S9-mix). Concurrent solvent, negative and positive controls were run.
The tets material caused no visible reduction in the growth of the background bacterial lawn at any dose level. A blue colour was observed at and above 50 µg/plate, becoming darker with increasing concentration. This did not prevent scoring of revertant colonies. No test material precipitate was observed on any of the plates at any of the dose levels tested in either the presence or the absence of S9 mix.
No significant increases in the frequency of revertant colonies were recorded for any of the strains at any dose level with or without metabolic activation.
Under the conditions of this study, the test material was found to be devoid of mutagenic activity on Salmonella typhimurium strains TA 1535, TA 1537, TA 98 TA 100 and TA 102 in the presence and absence of metabolic activation.
Reference
Table 1: Experiment 1 Summary of Results
+/- S9 Mix |
Concentration (µg/plate) |
Mean number of colonies/plate |
||||
Base-pair Substitution Type |
Frameshift Type |
|||||
TA100 |
TA1535 |
TA102 |
TA98 |
TA1537 |
||
- - - - - - |
0 50 150 500 1500 5000 |
132 148 140 144 146 132 |
31 30 32 29 20 19 |
304 339 350 303 353 338 |
23 20 27 25 16 20 |
15 18 12 16 13 12 |
+ + + + + + |
0 50 150 500 1500 5000 |
134 120 138 132 105 125 |
16 10 10 11 12 9 |
374 377 345 283 376 374 |
37 42 44 41 28 28 |
19 17 20 19 17 18 |
Positive Controls |
||||||
- |
Name |
ENNG |
ENNG |
MMC |
4NQO |
9AA |
Concentration (µg/plate) |
3 |
5 |
0.5 |
0.2 |
80 |
|
Mean no. colonies/plate |
740 |
621 |
1213 |
164 |
629 |
|
+ |
Name |
2AA |
2AA |
DAN |
BP |
2AA |
Concentration (µg/plate) |
1 |
2 |
10 |
5 |
2 |
|
Mean no. colonies/plate |
802 |
231 |
1029 |
245 |
437 |
ENNG = N-ethyl-N’-nitro-N-nitrosoguanidine
MMC = mitomycin C
4NQO = 4-Nitroquinoline-1-oxide
9AA = 9-aminoacridine
2AA = 2-aminoanthracene
BP = benzo(a)pyrene
DAN = 1,8-dihydroxyanthraquinone
Table 2: Experiment 2 Summary of Results
+/- S9 Mix |
Concentration (µg/plate) |
Mean number of colonies/plate |
||||
Base-pair Substitution Type |
Frameshift Type |
|||||
TA100 |
TA1535 |
TA102 |
TA98 |
TA1537 |
||
- - - - - - |
0 50 150 500 1500 5000 |
88 78 86 77 90 72 |
20 19 14 17 19 15 |
371 348 364 341 258 335 |
17 15 12 17 18 12 |
14 20 15 12 10 13 |
+ + + + + + |
0 50 150 500 1500 5000 |
79 87 92 93 85 78 |
11 12 11 11 10 12 |
352 354 349 348 343 360 |
28 37 36 29 34 20 |
19 15 23 16 14 17 |
Positive Controls |
||||||
- |
Name |
ENNG |
ENNG |
MMC |
4NQO |
9AA |
Concentration (µg/plate) |
3 |
5 |
0.5 |
0.2 |
80 |
|
Mean no. colonies/plate |
338 |
465 |
1108 |
135 |
490 |
|
+ |
Name |
2AA |
2AA |
DAN |
BP |
2AA |
Concentration (µg/plate) |
1 |
2 |
10 |
5 |
2 |
|
Mean no. colonies/plate |
566 |
233 |
905 |
254 |
376 |
ENNG = N-ethyl-N’-nitro-N-nitrosoguanidine
MMC = mitomycin C
4NQO = 4-Nitroquinoline-1-oxide
9AA = 9-aminoacridine
2AA = 2-aminoanthracene
BP = benzo(a)pyrene
DAN = 1,8-dihydroxyanthraquinone
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Additional information
Bacterial Reverse Mutation Assay
The mutagenic potential of the test material was investigated in a bacterial reverse mutation assay which was conducted in accordance with the standardised guidelines OECD 471, EU Method B.13/14, USA EPS (TSCA) OPPTS harmonised guidelines and those published in Japan by METI, MHLW and MAFF under GLP conditions.
Salmonella typhimurium strains TA 1535, TA 1537, TA 98 TA100 and TA 102 were treated with the test material (using the Ames plate incorporation method) at dose levels of 50, 150, 500, 1500 and 5000 µg/plate in distilled water both in the presence and absence of metabolic activation (S9-mix). Concurrent solvent, negative and positive controls were run.
The tets material caused no visible reduction in the growth of the background bacterial lawn at any dose level. A blue colour was observed at and above 50 µg/plate, becoming darker with increasing concentration. This did not prevent scoring of revertant colonies. No test material precipitate was observed on any of the plates at any of the dose levels tested in either the presence or the absence of S9 mix.
No significant increases in the frequency of revertant colonies were recorded for any of the strains at any dose level with or without metabolic activation.
Under the conditions of this study, the test material was found to be devoid of mutagenic activity on Salmonella typhimurium strains TA 1535, TA 1537, TA 98 TA100 and TA 102 in the presence and absence of metabolic activation.
In Vitro Mammalian Cell Micronucleus Test
The test material was evaluated in an in vitro micronucleus assay using duplicate human lymphocyte cultures prepared from the pooled blood of two female donors in two main experiments in accordance with the standardised guideline OECD 487 under GLP conditions.
Cells were exposed to the test material in the 3 + 21 hour treatments (with and without metabolic activation) at concentrations of 0, 250, 500, 1000, 2000, 3000, 4000 and 5000 µg/mL. Cells were exposed to the test material in the 24 + 0 hour treatment (without metabolic activation) at concentrations of 0, 50, 100, 125, 150, 175, 200, 225, 250, 275, 300, 350, 400, 500 and 600 µg/mL.
The test material was formulated in DMSO, and appropriate solvent and positive controls were run concurrently. Treatments were conducted 48 hours following mitogen stimulation by Phytohaemagglutinin (PHA). In Experiment 1, micronuclei were analysed at three or four concentrations. The data for the 3+21 hour treatment in the presence of S-9 in Experiment 1 were considered inconclusive; therefore a further experiment was performed under these treatment conditions. In Experiment 2, micronuclei were analysed at three concentrations.
Treatment of cells with the test material for 3+21 hours and 24+0 hours in the absence of S-9 resulted in frequencies of binucleate cells with micronuclei (MNBN) that were not significantly different from those observed in concurrent vehicle controls at any concentration analysed. The MNBN cell frequency of all treated cultures fell within the normal range.
Treatment for 3+21 hours in the presence of S-9 in Experiment 1 resulted in frequencies of MNBN cells that were significantly higher (p≤0.001) than those observed in concurrent vehicle controls at the highest concentration analysed (5000 μg/mL), but not at 3000 and 4000 μg/mL. The MNBN cell frequency of treated cultures fell within the upper limit of the 95th percentile of the normal range at 3000 and 4000 μg/mL but both cultures exceeded this range at 5000 μg/mL. However, the MNBN cell frequency in one of the two cultures at 5000 μg/mL fell only marginally outside the normal range and there was marked heterogeneity. These data were considered inconclusive.
Treatment for 3+21 hours in the presence of S-9 in Experiment 2 resulted in frequencies of MNBN cells that were not significantly different from those observed in concurrent vehicle controls at all concentrations analysed (3000, 4000 and 5000 μg/mL). All MNBN cell frequencies in treated cultures fell within the normal range.
Some differences in toxicity were seen between experiments at 5000 μg/mL (41 and 11 % reductions in RI were seen in Experiments 1 and 2, respectively), but no concentration achieved 50 % toxicity in either experiment.
Overall, there was poor reproducibility between experiments at 5000 μg/mL in terms of toxicity and induction of micronuclei. Due to the lack of reproducibility between experiments, these data do not indicate evidence of micronucleus induction in the presence of S-9.
Under the conditions of this study, the test material did not induce increases in the frequency of micronuclei in the absence and presence of metabolic activation (S-9) when tested up to 5000 μg/mL.
Justification for selection of genetic toxicity endpoint
The study was conducted under GLP conditions in accordance with standardised guidelines and was awarded a reliability score of 1 in accordance with the criteria set forth by Klimisch et al. (1997). This study was selected as key on the basis that it is one of the standard information requirements for this level of notification.
Justification for classification or non-classification
In accordance with the criteria for classification as defined in Annex I, Regulation (EC) No. 1272/2008, the substance does not require classification with respect to genetic toxicity.
In accordance with the criteria for classification as defined in Annex VI, Directive 67/548/EEC (DSD), the substance does not require classification with respect to genetic toxicity.
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