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EC number: 220-389-2 | CAS number: 2749-59-9
- 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
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Endpoint summary
Administrative data
Key value for chemical safety assessment
Genetic toxicity in vitro
Description of key information
Based on the available test results from the bacterial reverse mutation assay, the test item is considered to be mutagenic to bacteria under the described study conditions
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:
- 18 July 2017 to 27 July 2017
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- JAPAN: Guidelines for Screening Mutagenicity Testing Of Chemicals
- Version / remarks:
- "Standards of Mutagenicity Tests using Microorganisms" (Notification No. 77, September 1 1988 & partial revision: Notification No. 67, June 2, 1997, Ministry of Labour, Japan and Notification No. 120, December 25, 2000, Ministry of Labour, Japan) and the "Amendment of the Reporting Form of the Results of the Mutagenicity Tests using Microorganims" (Notification No. 653, September 29, 1997, Labour Standards Bureau, Ministry of Labour, Japan)
- Qualifier:
- according to guideline
- Guideline:
- JAPAN: Guidelines for Screening Mutagenicity Testing Of Chemicals
- Version / remarks:
- Guidelines of Toxicity Testing of New Chemical substances (Notification No.7 of 0331 Pharmaceutical and Food Safety Bureau, Ministry of Health, Labour and Welfare, No. 5 of the Manufacturing Industries Bureau, Ministry of Economy and Industry, & No. 110331009 of Environmental Policy Bureau, Ministry of the Environment, Japan, 31 March 2011)
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Version / remarks:
- 21 July 1997
- GLP compliance:
- yes
- Type of assay:
- bacterial reverse mutation assay
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Source and lot No.of test material: 7E18
- Expiration date of the lot: 14 Sept. 2017
- Purity: 99.98%
- Name and concentration of impurities: Unknown: 0.02%
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature
OTHER SPECIFICS:
- Appearance: White powder - Target gene:
- his- (S. typhimurium)
trp- (E. coli) - Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Species / strain / cell type:
- E. coli WP2 uvr A
- Metabolic activation:
- with and without
- Metabolic activation system:
- Phenobarbital and 5,6-benzoflavone induced rat liver S9 mix
- Test concentrations with justification for top dose:
- Dose levels in the preliminary test (with and without S9 mix, all strains): 1.2, 4.9, 20, 78, 313, 1250 and 5000 μg/plate.
Dose levels in the 1st main test and 2nd main test
- without S9 mix, TA 100, TA 1535: 10, 20, 39, 78, 156, 313, 625, 1250, 2500, 5000 μg/plate
- without S9 mix, TA 98: 39, 78, 156, 313, 625, 1250 µg/plate
- without S9 mix, TA 1537: 10, 20, 39, 78, 156, 313 µg/plate
- without S9 mix, WP2 uvrA: 313, 625, 1250, 2500, 5000 µg/plate
- with S9 mix, all strains: 313, 625, 1250, 2500, 5000 µg/plate
Justification for the top dose:
The top doses were selected on the basis on the preliminary test in which, the growth inhibition by the test substance was observed at 313 μg/plate and more in TA100, TA1535 and TA1537 without metabolic activation, and at 1250 μg/plate and more in TA98 without metabolic activation. And an increase in the number of revertant colonies more than twice in comparison with that of the negative control was observed in TA100 and TA1535 without metabolic activation. And the precipitate of the test substance on the plates was not observed either with or without metabolic activation. Therefore, as the highest dose level of the test substance in the main tests, the 313 μg/plate dose was selected for TA1537 without metabolic activation, and the 1250 μg/plate dose was selected for TA98 without metabolic activation, and these highest doses were diluted 5 times (using a common ratio of 2) to provide a total of 6 dose levels. And the 5000 μg/plate dose was selected for WP2 uvrA without metabolic activation and all strains with metabolic activation, and this highest dose was diluted 4 times (using a common ratio of 2) to provide a total of 5 dose levels. Moreover, in order to confirm dose-related response, the 5000 µg/plate dose was selected for TA100 and TA1535 without metabolic activation, and this highest dose was diluted 9 times (using a common ratio of 2) to provide a total of 10 dose levels. - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: Water for injection (The Japanese Pharmacopoeia)
- Justification for choice of solvent/vehicle: Based on the information from the sponsor, the test substance was soluble at 1690 g/L and stable in water. Therefore water for injection was used as solvent for preparation. - Untreated negative controls:
- yes
- Remarks:
- sterility
- Negative solvent / vehicle controls:
- yes
- Remarks:
- water
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- sodium azide
- benzo(a)pyrene
- other: 2-(2-Furyl)-3-(5-nitro-2-furyl)acrylamide (AF-2), 2-Methoxy-6-chloro-943-(2-chloroethypaminopropylamino]acridine • 2HCl (ICR-191), 2-Aminoanthracene (2AA)
- Remarks:
- Positive controls were chosen in accordance with the "Standards for Mutagenicity Tests using Microorganisms," the "Guidelines for Toxicity Testings of New Chemical Substances" and the "OECD GUIDELINE FOR THE TESTING OF CHEMICALS 471."
- Details on test system and experimental conditions:
- METHOD OF APPLICATION OF 1st and 2nd MAIN TEST: in medium
DURATION
- Preincubation period: at 37°C for 20 minutes
- Exposure duration: at 37°C for 48 hours
NUMBER OF REPLICATIONS: 3
DETERMINATION OF CYTOTOXICITY
- Method:growth inhibition of the test strains was checked using a stereoscopic microscope
- Any supplementary information relevant to cytotoxicity: Sterility test was performed - Evaluation criteria:
- In the two main tests, if the number of revertant colonies on the test plates increased significantly in comparison with that on the control plates (based on twice as many as that of the negative control), and dose-response and reproducibility were also observed, the test substance was to be judged positive. The results at each concentration were demonstrated with the mean and the standard deviation.
- Statistics:
- Not specified. Mean and standard deviations of the test results were calculated
- Key result
- Species / strain:
- S. typhimurium TA 1535
- Metabolic activation:
- without
- Genotoxicity:
- positive
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 1535
- Metabolic activation:
- with
- 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, other: TA 100, TA 98, TA 1537
- Metabolic activation:
- without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium, other: TA 100, TA 98, TA 1537
- Metabolic activation:
- with
- Genotoxicity:
- negative
- 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:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
The precipitate of the test substnace on the plates was not observed iether with or without S9 mix.
PRELIMINARY TEST
An increase in the number of revertant colonies was observed in TA100 without S9 mix, and increased more than twice of the negative control
POSITIVE CONTROLS
The revertant colonies of the positive controls showed an increase of more than twice that of the negative controls and they were within limit of control (mean ± 3SD) in historical data, indicating that this study was performed correctly.
CYTOXICITY
The growth inhitition of the test strains by the test substance was observed in different strains at different dosages. See the 2 Tables in the "any other information on results incl. tables" for more information. - Remarks on result:
- other: 1st and 2nd main test
- Conclusions:
- The test item is considered to be mutagenic to bacteria under the described study conditions.
- Executive summary:
In this GLP compliant study, performed according to OECD guideline 471, the mutagenicity potential of the test item was assessed with Salmonella typhimurium TA100, TA1535, TA98, TA1537 and Escherichia coli WP2 uvrA using the bacterial reverse mutation assay. The test item was tested in doses of 10, 20, 39, 78, 156, 313, 625, 1250, 2500, 5000 µg/plate using with/without metabolic activation. For metabolic activation S9 -mix retrieved from phenobarbital and 5.6 -benzoflavone induced rat livers. In this study, a dose-dependent increase in the number of revertant colonies more than twice in comparison with that of the negative control and reproducibility were observed in S. typhimurium TA1535 without metabolic activation. The positive controls and negative controls tested showed that the study was performed correctly. From the above, it is therefore judged that the test substance is mutagenic under the described study conditions.
Reference
Table of the 1st main test results
|
Base-pair substitution type |
Frame-shift type |
||||
S9 mix |
Dose μg/plate |
TA 100 |
TA 1535 |
WP2 uvrA |
TA98 |
TA1537 |
|
Solvent control |
102 ± 5.7 * |
15 ± 1.7 |
29 ± 4.0 |
25 ± 3.2 |
9 ± 1.2 |
Without S9 |
10 |
99 ± 3.5 |
13 ± 2.0 |
NT |
NT |
9 ± 15 |
20 |
111 ± 21.1 |
16 ± 2.1 |
NT |
NT |
7 ± 1.0 |
|
39 |
100 ± 3.8 |
12 ± 1.0 |
NT |
24± 5.5 |
10 ± 1.2 |
|
78 |
106 ± 3.1 |
14 ± 2.5 |
NT |
23 ± 3.1 |
8 ± 1.5 |
|
156 |
112 ± 13.1 |
17 ± 4.0 |
NT |
24 ± 4.6 |
10 ± 0.6 |
|
313 |
138 ± 13.5 * |
14 ± 1.2 * |
24 ± 6.1 |
25 ± 4.9 |
10 ± 2.6 * |
|
625 |
176 ±17.4 * |
16 ± 2.1 * |
20 ± 1.0 |
23 ± 4.0 |
NT |
|
1250 |
181 ± 12.8 * |
46 ± 7.0 * |
25 ± 3.5 |
27 ± 4.0 * |
NT |
|
2500 |
154 ± 23.3 * |
48 ± 3.0 * |
24 ± 2.6 |
NT |
NT |
|
5000 |
117 ± 15.0 * |
20 ± 1.7 * |
21 ± 3.2 |
NT |
NT |
|
|
|
|
|
|
|
|
With S9 |
Solvent control |
108 ± 12.2 |
15± 2.1 |
28 ± 3.8 |
35 ± 3.6 |
15 ± 1.7 |
313 |
105 ± 2.9 |
14 ± 3.5 |
24 ± 1.5 |
31 ± 6.4 |
15 ± 2.1 |
|
625 |
113 ± 17.6 |
18 ± 1.0 |
24 ± 2.6 |
29 ± 0.6 |
13 ± 1.0 |
|
1250 |
109 ± 13.9 |
17 ± 0.6 |
26 ± 4.5 |
29 ± 1.5 |
13 ± 1.2 |
|
2500 |
98 ± 6.7 |
17 ± 2.6 |
24 ± 0.6 |
29 ± 3.2 |
13 ± 1.0 |
|
5000 |
147 ± 8.1 |
14 ± 3.0 |
23 ± 1.0 |
26 ± 1.2 |
13 ± 1.0 |
NT not tested
* = The growth inhibition of the tested bacterium by the test substance was observed
Table of the 2nd main test results
|
Base-pair substitution type |
Frame-shift type |
||||
S9 mix |
Dose μg/plate |
TA100 |
TA 1535 |
WP2 uvrA |
TA98 |
TA1537 |
|
Solvent control |
91 ± 8.5 |
12 ± 1.5 |
24 ± 2.6 |
33 ± 3.1 |
10 ± 1.2 |
Without S9 |
10 |
101 ± 9.3 |
11 ± 2.6 |
NT |
NT |
7 ± 0.0 |
20 |
90 ± 10.4 |
11 ± 1.5 |
NT |
NT |
9 ± 2.0 |
|
39 |
92 ± 3.2 |
11 ± 2.5 |
NT |
28 ± 2.0 |
9 ± 1.5 |
|
78 |
97 ± 13.6 |
9 ± 0.6 |
NT |
30 ± 3.1 |
7 ± 1.0 |
|
156 |
111 ± 12.3 |
11 ± 2.6 |
NT |
30 ± 2.6 |
8 ± 2.1 |
|
313 |
134 ± 12.5 * |
16 ± 1.5 * |
24 ± 1.7 |
31 ± 1.2 |
9 ± 2.5 * |
|
625 |
143 ± 11.5 * |
15 ± 2.3 * |
26 ± 2.5 |
25 ± 4.9 |
NT |
|
1250 |
153 ± 9.8 * |
29 ± 3.0 * |
22 ± 2.0 |
30 ± 5.3 * |
NT |
|
2500 |
153 ± 9.8 * |
49 ± 6.2 * |
23 ± 5.2 |
NT |
NT |
|
5000 |
98 ± 12.4 * |
11 ± 1.2 * |
26 ± 3.8 |
NT |
NT |
|
|
|
|
|
|
|
|
With S9 |
Solvent control |
119 ± 18.0 |
12 ± 1.5 |
32 ± 1.0 |
37 ± 4.6 |
18 ± 1.0 |
313 |
96 ± 6.4 |
10 ± 2.0 |
29 ± 5.8 |
35 ± 3.5 |
19 ± 1.5 |
|
625 |
108 ± 9.3 |
10 ± 2.1 |
30 ± 1.0 |
33 ± 3.0 |
17 ± 1.7 |
|
1250 |
107 ± 14.8 |
14 ± 3.1 |
31 ± 2.6 |
38 ± 3.6 |
17 ± 2.5 |
|
2500 |
143 ± 7.4 |
12 ± 1.5 |
32 ± 2.0 |
33 ± 4.9 |
16 ± 2.6 |
|
5000 |
147± 9.1 |
10 ± 0.6 |
38 ± 2.0 |
33 ± 6.2 |
15 ± 3.2 |
NT not tested
* = The growth inhibition of the tested bacterium by the test substance was observed
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (positive)
Genetic toxicity in vivo
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Ames test:
In a GLP compliant study, performed according to OECD guideline 471, the mutagenicity potential of the test item was assessed with Salmonella typhimurium TA100, TA1535, TA98, TA1537 and Escherichia coli WP2 uvrA using the bacterial reverse mutation assay. The test item was tested in doses of 10, 20, 39, 78, 156, 313, 625, 1250, 2500, 5000 µg/plate using with/without metabolic activation. For metabolic activation S9 -mix retrieved from phenobarbital and 5.6 -benzoflavone induced rat livers. In this study, a dose-dependent increase in the number of revertant colonies more than twice in comparison with that of the negative control and reproducibility were observed in S. typhimurium TA1535 without metabolic activation. The positive controls and negative controls tested showed that the study was performed correctly. From the above, it is therefore judged that the test substance is mutagenic under the described study conditions (BML INC, 2017).
Justification for classification or non-classification
As the substance was considered to be mutagenic in the Ames test, the substance has to be classified as Muta. 2, H341: Suspected of causing genetic defects in accordance with EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation No. 1272/2008.
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