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EC number: 601-325-6 | CAS number: 114772-38-2
- 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
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- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
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- 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:
- 15 Septiembre 2013 - 19 December 2013
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Test method according to OECD 471. GLP study.
- 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:
- EPA OPPTS 870.5100 - Bacterial Reverse Mutation Test (August 1998)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- bacterial reverse mutation assay
- Target gene:
- Histidine-requiring gene in Salmonella typhimurium and Tryptophan-requiring gene in the strain of Escherichia coli.
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9 mix from rat liver
- Test concentrations with justification for top dose:
- Initial Mutation Test: 5000; 2500; 1000; 316; 100; 31.6 and 10 µg test item/plate
Confirmatory Mutation Test: 5000, 1581, 500, 158.1, 50, 15.81, 5, 1.581 and 0.5 µg test item/plate - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: The solubility of the test item was examined using Distilled water, Dimethyl sulfoxide (DMSO) and N,N-dimethylformamide (DMF). The test item was insoluble in Distilled water. The formulation at 100 mg/mL concentration using DMSO or DMF as vehicle was suitable for the test. Due to the biocompatibility to the test system, DMSO was selected as vehicle of the study. - Untreated negative controls:
- yes
- Remarks:
- Untreated
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO and distilled water
- Positive controls:
- yes
- Positive control substance:
- sodium azide
- Remarks:
- TA100, TA1535 -S9 (2 µg/plate)
- Positive controls:
- yes
- Positive control substance:
- other: 4-nitro-1,2-phenylene-diamine
- Remarks:
- TA98, -S9 (4 µg/plate)
- Positive controls:
- yes
- Positive control substance:
- 9-aminoacridine
- Remarks:
- TA1537, -S9 (50 µg/plate)
- Positive controls:
- yes
- Positive control substance:
- methylmethanesulfonate
- Remarks:
- WP2 uvrA, -S9 (2 µL/plate)
- Positive controls:
- yes
- Positive control substance:
- other: 2-aminoanthracene
- Remarks:
- all Salmonella strains, +S9 (2 µg/plate) and WP2 uvrA, +S9 (50 µg/plate)
- Details on test system and experimental conditions:
- METHOD OF APPLICATION:
Plate incorporation (initial mutation test and confirmatory test):
Molten top agar was prepared and kept at 45°C. 2 mL of top agar was aliquoted into individual test tubes (3 tubes per control or concentration level). The equivalent number of minimal glucose agar plates was properly labelled. The test item and other components were prepared freshly and added to the overlay (45°C). This solution was mixed and poured on the surface of minimal agar plates. After preparation, the plates were incubated at 37°C for 48 hours.
NUMBER OF REPLICATIONS: 3 replicates per dose and controls.
EVALUATION OF EXPERIMENTAL DATA:
The colony numbers were determined by manual counting.
Visual examination of the plates was performed, precipitation or signs of growth inhibition (if any) were recorded and reported.
The mean number of revertants per plate, the standard deviation and the mutation factor values were calculated. - Evaluation criteria:
- Criteria for a Positive Response:
A test item was considered mutagenic if:
- a dose–related increase in the number of revertants occurred and/or;
- a reproducible biologically relevant positive response for at least one of the dose groups occurred in at least one strain with or without metabolic activation.
An increase was considered biologically relevant if:
- the number of reversions is more than two times higher than the reversion rate of the negative (solvent) control in Salmonella typhimurium TA98, TA100 and Escherichia coli WP2 uvrA bacterial strains;
- the number of reversions is more than three times higher than the reversion rate of the negative (solvent) control in Salmonella typhimurium TA1535 and TA1537 bacterial strains.
According to the guidelines, statistical method may be used as an aid in evaluating the test results. However, statistical significance should not be the only determining factor for a positive response.
Criteria for a Negative Response:
A test article was considered non-mutagenic if it produced neither a dose-related increase in the number of revertants nor a reproducible biologically relevant positive response at any of the dose groups, with or without metabolic activation. - Statistics:
- The mean number of revertants per plate, the standard deviation and the mutation factor values were calculated for each concentration level of the test item and for the controls using Microsoft ExcelTM software.
- Species / strain:
- S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2
- Metabolic activation:
- with and without
- Genotoxicity:
- positive
- Remarks:
- (TA98, TA100, TA1535 and WP2 uvrA, with and without metabolic activation)
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- (TA98, TA100 and TA1537, with and without metabolic activation)
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- RANGE-FINDING/SCREENING STUDIES:
Sporadically, slightly lower revertant counts compared to the solvent control were observed in the main tests at some non-cytotoxic concentrations. However, the mean number of revertant colonies were in the historical control range in all cases, thus they were considered as biological variability of the test system.
ADDITIONAL INFORMATION ON CYTOTOXICITY:
Inhibitory, cytotoxic effect of the test item (absent/reduced/slightly reduced background lawn development and / or reduced number of revertant colonies, in some cases pinpoint colonies were also detected) were observed in the Initial Mutation Test in Salmonella typhimurium TA98 strain at 5000 µg/plate without metabolic activation; in Salmonella typhimurium TA 100 strain at 5000, 1581 and 500 µg/plate concentrations with metabolic activation and in Salmonella typhimurium TA1537 strain at 5000, 1581 and 500 µg/plate concentrations with and without metabolic activation.
Similar inhibitory, cytotoxic effect of the test item were observed in the Confirmatory Mutation Test in Salmonella typhimurium TA 98 strain at 5000 and 1581 µg/plate without metabolic activation; in Salmonella typhimurium TA100 and TA1537 strains at 5000, 1581 and 500 µg/plate concentrations without metabolic activation and in Salmonella typhimurium TA100 and TA1537 strains at 5000 and 1581 µg/plate concentrations with metabolic activation. - Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- Interpretation of results (migrated information):
positive (with and without metabolic activation)
The test item had mutagenic activity in the applied bacterium tester strains under the test conditions used in this study. - Executive summary:
The test item was tested for potential mutagenic activity using the Bacterial Reverse Mutation Assay according to OECD Guideline 471 (GLP study). The experiments were carried out using Salmonella typhimurium strains TA98, TA100, TA1535 and TA1537 and Escherichia coli WP2 uvrA in the presence and absence of metabolic activation (S9 fraction prepared from the livers of rats). Based on the results of the Solubility Test, the test item was dissolved in DFMO. Concentrations of 5000; 2500; 1000; 316; 100; 31.6 and 10 μg/plate were examined in the Range Finding Test. Based on the results of the Range Finding Test, the test item concentrations in the main tests were as follows: Initial Mutation Test: 5000, 1581, 500, 158.1, 50, 15.81, 5 and 1.581 µg test item/plate and the test item concentrations. Confirmatory Mutation Test were 5000, 1581, 500, 158.1, 50, 15.81, 5, 1.581 and 0.5µg test item/plate. In the Initial Mutation Test and Confirmatory Mutation Test and Confirmatory Mutation Tests (using the plate incorporation method), a clear, reproducible positive effect was obtained in four examined bacterial strains (Salmonella typhimurium TA98, TA100, TA1535 and Escherichia coli WP2 uvrA) with and without metabolic activation as the observed revertant colony numbers were above the respective biological threshold value and dose-related trends were also observed.
Reference
Initial Mutation Test
Concentrations (µg/plate) |
Mean values of revertants /Mutation factor (MF) |
Salmonella typhimurium tester strains |
Escherichia coli |
||||||||
TA98 |
TA100 |
TA1535 |
TA1537 |
WP2 uvrA |
|||||||
-S9 |
+S9 |
-S9 |
+S9 |
-S9 |
+S9 |
-S9 |
+S9 |
-S9 |
+S9 |
||
5000 |
Mean |
482.7 |
442.7 |
101.3 |
242.0 |
100.7 |
179.0 |
0.0 |
0.3 |
120.3 |
121.0 |
MF |
20.39 |
15.81 |
1.03 |
2.70 |
7.02 |
23.35 |
0.00 |
0.05 |
3.11 |
2.81 |
|
1581 |
Mean |
456.7 |
476.7 |
124.3 |
172.0 |
73.7 |
124.0 |
2.0 |
6.0 |
101.0 |
105.7 |
MF |
19.30 |
17.02 |
1.27 |
1.92 |
5.14 |
16.17 |
0.40 |
0.86 |
2.61 |
2.46 |
|
500 |
Mean |
237.3 |
394.0 |
174.0 |
260.7 |
41.3 |
47.0 |
2.7 |
8.7 |
58.3 |
85.7 |
MF |
10.03 |
14.07 |
1.78 |
2.91 |
2.88 |
6.13 |
0.53 |
1.24 |
1.51 |
1.99 |
|
158.1 |
Mean |
206.0 |
177.3 |
238.0 |
252.3 |
24.3 |
19.7 |
8.3 |
15.7 |
41.0 |
51.0 |
MF |
8.70 |
6.33 |
2.43 |
2.81 |
1.70 |
2.57 |
1.67 |
2.24 |
1.06 |
1.19 |
|
50 |
Mean |
87.7 |
61.7 |
197.7 |
135.7 |
17.0 |
13.0 |
13.7 |
15.0 |
32.3 |
41.7 |
MF |
3.70 |
2.20 |
2.02 |
1.51 |
1.19 |
1.70 |
2.73 |
2.14 |
0.84 |
0.97 |
|
15.81 |
Mean |
49.7 |
33.3 |
130.7 |
89.0 |
15.0 |
9.7 |
15.0 |
9.3 |
39.0 |
41.3 |
MF |
2.10 |
1.19 |
1.33 |
0.99 |
1.05 |
1.26 |
3.00 |
1.33 |
1.01 |
0.96 |
|
5 |
Mean |
31.0 |
30.3 |
113.7 |
92.7 |
22.0 |
8.7 |
5.0 |
10.7 |
46.7 |
44.0 |
MF |
1.31 |
1.08 |
1.16 |
1.03 |
1.53 |
1.13 |
1.00 |
1.52 |
1.21 |
1.02 |
|
1.581 |
Mean |
23.3 |
29.0 |
107.3 |
91.3 |
11.3 |
8.7 |
7.3 |
11.0 |
42.3 |
36.7 |
MF |
0.99 |
1.04 |
1.10 |
1.02 |
0.79 |
1.13 |
1.47 |
1.57 |
1.09 |
0.85 |
Confirmatory Mutation Test
Concentrations (µg/plate) |
Mean values of revertants /Mutation factor (MF) |
Salmonella typhimurium tester strains |
Escherichia coli |
||||||||
TA98 |
TA100 |
TA1535 |
TA1537 |
WP2 uvrA |
|||||||
-S9 |
+S9 |
-S9 |
+S9 |
-S9 |
+S9 |
-S9 |
+S9 |
-S9 |
+S9 |
||
5000 |
Mean |
176.3 |
313.3 |
55.0 |
73.7 |
123.0 |
171.3 |
3.7 |
3.7 |
117.0 |
140.7 |
MF |
5.24 |
8.62 |
0.69 |
0.88 |
10.85 |
16.06 |
0.69 |
0.50 |
3.31 |
2.78 |
|
1581 |
Mean |
170.7 |
448.0 |
77.7 |
93.3 |
80.0 |
116.0 |
2.3 |
8.0 |
106.3 |
132.0 |
MF |
5.07 |
12.33 |
0.98 |
1.12 |
7.06 |
10.88 |
0.44 |
1.09 |
3.01 |
2.61 |
|
500 |
Mean |
275.7 |
296.7 |
131.0 |
147.0 |
33.3 |
49.3 |
5.3 |
11.0 |
91.7 |
154.7 |
MF |
8.19 |
8.17 |
1.65 |
1.76 |
2.94 |
4.63 |
1.00 |
1.50 |
2.59 |
3.05 |
|
158.1 |
Mean |
235.7 |
194.7 |
190.3 |
219.7 |
27.7 |
20.3 |
8.3 |
17.0 |
70.3 |
78.0 |
MF |
7.00 |
5.36 |
2.40 |
2.63 |
2.44 |
1.91 |
1.56 |
2.32 |
1.99 |
1.54 |
|
50 |
Mean |
118.0 |
77.7 |
160.7 |
140.3 |
20.3 |
14.0 |
5.7 |
6.3 |
38.0 |
46.7 |
MF |
3.50 |
2.14 |
2.03 |
1.68 |
1.79 |
1.31 |
1.06 |
0.86 |
1.08 |
0.92 |
|
15.81 |
Mean |
64.0 |
35.0 |
128.0 |
93.3 |
20.3 |
10.3 |
4.3 |
5.7 |
32.3 |
47.0 |
MF |
1.90 |
0.96 |
1.61 |
1.12 |
1.79 |
0.97 |
0.81 |
0.77 |
0.92 |
0.93 |
|
5 |
Mean |
52.0 |
32.7 |
105.7 |
81.0 |
28.7 |
6.0 |
3.0 |
6.7 |
35.7 |
37.7 |
MF |
1.54 |
0.90 |
1.33 |
0.97 |
2.53 |
0.56 |
0.56 |
0.91 |
1.01 |
0.74 |
|
1.581 |
Mean |
31.0 |
33.0 |
89.7 |
94.0 |
12.7 |
10.7 |
5.3 |
5.7 |
37.3 |
46.0 |
MF |
0.92 |
0.91 |
1.13 |
1.12 |
1.12 |
1.00 |
1.00 |
0.77 |
1.06 |
0.91 |
|
0.5 |
Mean |
26.3 |
34.7 |
98.7 |
96.3 |
14.7 |
13.0 |
3.7 |
6.7 |
38.0 |
47.7 |
MF |
0.78 |
0.95 |
1.24 |
1.15 |
1.29 |
1.22 |
0.69 |
0.91 |
1.08 |
0.94 |
In the initial mutation test, a clear positive effect of the test item was obtained in Salmonella typhimurium TA98, TA100, TA1535 and Escherichia coli WP2 uvrA bacterial strains with and without metabolic activation and in Salmonella typhimurium TA1537 strain without metabolic activation. Increased revertant counts were detected in Salmonella typhimurium TA1537 strain with metabolic activation in some cases.
The dose dependent substantial increases over the threshold limits were confirmed in the Confirmatory Mutation Test using the same experimental conditions. All the results were confirmed except for the Salmonella typhimurium TA1537 strain without metabolic activation.
Inhibitory, cytotoxic effect of the test item were observed in the Initial Mutation Test in Salmonella typhimurium TA98 strain at 5000 µg/plate without metabolic activation; in Salmonella typhimurium TA100 strain at 5000, 1581 and 500 µg/plate concentrations without metabolic concentration; in this strain at 5000 and 1581 µg/plate concentrations with metabolic activation and in Salmonella typhimurium TA1537 strain st 5000, 1581 and 500 µg/plate concentrations with and without metabolic activation.
Similar inhibitory, cytotoxic effect of the test item were observed in the Confirmatory Mutation Test in Salmonella typhimurium TA98 strain at 5000 and 1581 µg/plate without metabolic activation; in Salmonella typhimurium TA100 and TA 1537 strains at 5000, 1581 and 500µg/plate concentrations without metabolic activation and in Salmonella typhimurium TA100 and TA1537 strains at 5000 and 1581µg/plate concentrations with metabolic activation.
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (positive)
Additional information
Key study: The test item was tested for potential mutagenic activity using the Bacterial Reverse Mutation Assay according to OECD Guideline 471 (GLP study). The experiments were carried out using Salmonella typhimurium strains TA98, TA100, TA1535 and TA1537 and Escherichia coli WP2 uvrA in the presence and absence of metabolic activation (S9 fraction prepared from the livers of rats). The test item induced clear gene mutations by base pair changes or frameshifts in the genome in most of the strains used with and without metabolic activation. In conclusion, the test item had mutagenic activity in the applied bacterium tester strains under the test conditions used in this study.
Justification for selection of genetic toxicity endpoint
Only one study available.
Justification for classification or non-classification
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