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EC number: 268-040-3 | CAS number: 67990-17-4
- 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
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- Flash point
- Auto flammability
- Flammability
- Explosiveness
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- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
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- Stability: thermal, sunlight, metals
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- Dissociation constant
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- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
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- Endpoint summary
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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
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- Toxicological Summary
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- Irritation / corrosion
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- Specific investigations
- Exposure related observations in humans
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- Additional toxicological data
Endpoint summary
Administrative data
Key value for chemical safety assessment
Genetic toxicity in vitro
Description of key information
In an in vitro bacterial reverse mutation assay (Ames test) according to OECD TG 471, the test item did not induce gene mutations in the tester strains used.
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:
- March 21, 2018 - April 5, 2018
- 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:
- 21st July, 1997
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
- Version / remarks:
- May 30, 2008
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.5100 - Bacterial Reverse Mutation Test (August 1998)
- Version / remarks:
- August 1998
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: ICH Guidance S2(R1): Guidance on Genotoxicity Testing and Data Interpretation for Pharmaceuticals Intended for Human Use
- Version / remarks:
- June 2012
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- bacterial reverse mutation assay
- Target gene:
- The S. typhimurium histidine (his) reversion system measures his- to his+ reversions.
The E. coli strain WP2 uvrA detects mutagens that cause base-pair substitutions (AT to GC) resulting in trp- to trp+ reversions. - 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:
- S9 mix of phenobarbital (PB) and β-naphthoflavone (BNF) induced rat liver
- Test concentrations with justification for top dose:
- Selection of the concentrations for the initial mutation test is based on the results of the solubility test and the concentration range finding test (informatory toxicity test).
The test item concentrations for the initial and confirmatory mutation tests were as follows:
5000, 1600, 500, 160, 50 and 16 μg/plate (with and without S9 mix) - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: ultrapure water
- Justification for choice of solvent/vehicle: The test item is soluble in water. - Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: 4-Nitro-1,2-phenylenediamine, NPD
- Remarks:
- without S9 mix, TA98, 4 µg/plate
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- water
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- sodium azide
- Remarks:
- without S9 mix, TA100 and TA1535, 2 µg/plate
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 9-aminoacridine
- Remarks:
- without S9 mix, TA1537, 50 µg/plate
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- water
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- methylmethanesulfonate
- Remarks:
- Without S9 mix, E.coli, 2 µL/plate
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: 2-aminoanthracene, 2AA
- Remarks:
- with S9 mix, TA98,TA100,TA1535,TA1537 (each 2 µg/plate); E.coli (50 µg/plate)
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in agar (plate incorporation); preincubation
DURATION
- Preincubation period: 20 min at 37ºC in a shaking incubator
- Exposure duration: 48 hours
NUMBER OF REPLICATIONS: 3
DETERMINATION OF CYTOTOXICITY
- Method: revertant colony number - Evaluation criteria:
- A test item is considered mutagenic if:
- a dose-related increase in the number of revertants occurs and/or;
- a reproducible biologically relevant positive response for at least one of the dose groups occurs in at least one strain with or without metabolic activation.
An increase is considered biologically relevant if:
- in strain Salmonella typhimurium TA100 the number of reversions is at least twice as high as the reversion rate of the solvent control,
- in strain Salmonella typhimurium TA98, TA1535, TA1537 and Escherichia coli WP2 uvrA the number of reversions is at least three times higher than the reversion rate of the solvent control
Criteria for a negative response:
A test article is considered non-mutagenic if it produces 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:
- None
- 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:
- valid
- 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:
- valid
- 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:
- valid
- 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:
- valid
- Positive controls validity:
- valid
- Key result
- 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
- Water solubility: yes, clear solution up to 50 mg/mL
- Precipitation: none
RANGE-FINDING/SCREENING STUDIES
In the informatory toxicity test the revertant colony numbers of solvent control plates with and without S9 mix were in line with the corresponding historical control data ranges. The positive control treatments showed the expected biological relevant increases in induced revertant colonies in both tester strains.
In the informatory toxicity test a cytotoxic effect of the test item on the bacterial strains was not observed. The colony and background lawn development was not affected in any case. All of the observed slight revertant colony number decreases (compared to the revertant colony numbers of the solvent control) remained within the biological variability range of the applied test system. The obtained revertant colony numbers were sporadically higher than the revertant colony numbers of the solvent control; however all of the observed higher colony numbers remained within the biological variability range of the applied test system and far below the biologically relevant threshold for being positive.
Based on the results of the preliminary test, the maximum test item concentration was 5000 µg/plate (±S9 mix).
HISTORICAL CONTROL DATA
- Positive historical control data: see table 3
- Negative (solvent/vehicle) historical control data: see table 4
- Conclusions:
- The test item has no mutagenic activity on the applied bacterium tester strains under the test conditions used in this study.
- Executive summary:
A study according OECD TG 471 was performed to investigate the potential mutagenic activity of the test item using the Bacterial Reverse Mutation Assay.
The experiments were carried out using histidine-requiring auxotroph strains of Salmonella typhimurium (Salmonella typhimurium TA98, TA100, TA1535 and TA1537), and the tryptophan-requiring auxotroph strain of Escherichia coli (Escherichia coli WP2 uvrA) in the presence and absence of a post mitochondrial supernatant (S9) prepared from livers of Phenobarbital/b-naphthoflavone-induced rats.
The study included a preliminary solubility test, a preliminary concentration range finding test (informatory toxicity test), an initial mutation test (plate incorporation test), and a confirmatory mutation test (pre-incubation test).
Based on the results of the solubility test and the concentration range finding test the test item was dissolved in ultrapure water (ASTM Type I).
At the preparation of the test item stock solution any correction factor (based on its purity, constituents) was not taken into consideration.
Based on the cytotoxicity and solubility results of the preliminary concentration range finding test (informatory toxicity test) and based on the recommendations in OECD 471 guideline, the following concentrations of the test item were prepared and investigated in the initial and confirmatory mutation tests: 5000; 1600; 500; 160; 50 and 16 µg/plate.
The results of the preliminary concentration range finding test allowed the applying of the recommended maximum test concentration of 5000 µg/plate.
No precipitation of the test item was observed on the plates in the examined bacterial strains at any examined concentration level (±S9 mix) throughout the study.
The test item did not show inhibitory, cytotoxic effects in the performed experiments. The colony and background lawn development was not affected in any case; the obtained revertant colony number decreases (compared to the revertant colony numbers of the solvent control) remained within the biological variability range of the applied test system.
The revertant colony numbers of solvent control ultrapure water (ASTM Type I) plates with and without S9 mix demonstrated the characteristic mean number of spontaneous revertants that was in line with the corresponding historical control data ranges.
The reference mutagen treatments (positive controls) showed the expected, biological relevant increases (more than 3-fold increase) in induced revertant colonies and the number of revertants fell in the corresponding historical control ranges, thereby meeting the criteria for the positive control in all experimental phases, in all tester strains.
No biologically relevant increases were observed in revertant colony numbers of any of the five test strains following treatment with sodium (2-butoxyethoxy) acetate at any concentration level, either in the presence or absence of metabolic activation (S9 mix) in the performed experiments.
The reported data of this mutagenicity assay show that under the experimental conditions applied, the test item did not induce gene mutations by base pair changes or frameshifts in the genome of the strains used.
Reference
Table 1: Summary Table of the Results of the Initial Mutation Test
Initial Mutation Test (Plate Incorporation Test) |
||||||||||||||||||||
Concentrations (µg/plate) |
Salmonella typhimurium tester strains |
Escherichia coli |
||||||||||||||||||
TA 98 |
TA 100 |
TA 1535 |
TA 1537 |
WP2uvrA |
||||||||||||||||
-S9 |
+S9 |
-S9 |
+S9 |
-S9 |
+S9 |
-S9 |
+S9 |
-S9 |
+S9 |
|||||||||||
Mean values of revertants per plate Mutation rate (MR) |
Mean |
MR |
Mean |
MR |
Mean |
MR |
Mean |
MR |
Mean |
MR |
Mean |
MR |
Mean |
MR |
Mean |
MR |
Mean |
MR |
Mean |
MR |
Untreated Control |
15.0 |
0.83 |
20.7 |
0.89 |
79.0 |
1.05 |
99.7 |
0.87 |
9.7 |
1.26 |
7.0 |
0.91 |
5.7 |
1.31 |
9.0 |
1.08 |
32.0 |
0.91 |
33.3 |
0.76 |
DMSO Control |
12.0 |
1.00 |
22.0 |
1.00 |
– |
– |
114.7 |
1.00 |
– |
– |
8.7 |
1.00 |
6.0 |
1.00 |
6.0 |
1.00 |
– |
– |
41.7 |
1.00 |
Ultrapure Water Control |
18.0 |
1.00 |
23.3 |
1.00 |
75.0 |
1.00 |
115.0 |
1.00 |
7.7 |
1.00 |
7.7 |
1.00 |
4.3 |
1.00 |
8.3 |
1.00 |
35.0 |
1.00 |
44.0 |
1.00 |
5000 |
19.3 |
1.07 |
17.7 |
0.76 |
89.0 |
1.19 |
99.7 |
0.87 |
12.7 |
1.65 |
8.7 |
1.13 |
4.7 |
1.08 |
7.0 |
0.84 |
36.3 |
1.04 |
52.7 |
1.20 |
1600 |
14.3 |
0.80 |
17.3 |
0.74 |
86.0 |
1.15 |
101.0 |
0.88 |
8.3 |
1.09 |
11.0 |
1.43 |
4.0 |
0.92 |
7.3 |
0.88 |
29.0 |
0.83 |
47.3 |
1.08 |
500 |
15.7 |
0.87 |
18.7 |
0.80 |
86.0 |
1.15 |
97.3 |
0.85 |
9.0 |
1.17 |
7.3 |
0.96 |
6.7 |
1.54 |
6.3 |
0.76 |
32.3 |
0.92 |
51.0 |
1.16 |
160 |
17.3 |
0.96 |
27.0 |
1.16 |
82.7 |
1.10 |
96.0 |
0.83 |
8.0 |
1.04 |
8.7 |
1.13 |
6.0 |
1.38 |
7.0 |
0.84 |
34.7 |
0.99 |
38.0 |
0.86 |
50 |
16.7 |
0.93 |
19.3 |
0.83 |
82.7 |
1.10 |
94.3 |
0.82 |
6.3 |
0.83 |
8.3 |
1.09 |
5.7 |
1.31 |
8.0 |
0.96 |
28.7 |
0.82 |
38.7 |
0.88 |
16 |
20.0 |
1.11 |
19.0 |
0.81 |
89.3 |
1.19 |
95.0 |
0.83 |
7.3 |
0.96 |
11.3 |
1.48 |
4.3 |
1.00 |
9.7 |
1.16 |
32.0 |
0.91 |
54.0 |
1.23 |
NPD (4 µg) |
396.7 |
33.06 |
– |
– |
– |
– |
– |
– |
– |
– |
– |
– |
– |
– |
– |
– |
– |
– |
– |
– |
SAZ (2 µg) |
– |
– |
– |
– |
786.7 |
10.49 |
– |
– |
1282.7 |
167.30 |
– |
– |
– |
– |
– |
– |
– |
– |
– |
– |
9AA (50 µg) |
– |
– |
– |
– |
– |
– |
– |
– |
– |
– |
– |
– |
320.7 |
53.44 |
– |
– |
– |
– |
– |
– |
MMS (2 µL) |
– |
– |
– |
– |
– |
– |
– |
– |
– |
– |
– |
– |
– |
– |
– |
– |
768.7 |
21.96 |
– |
– |
2AA (2µg) |
– |
– |
2005.3 |
91.15 |
– |
– |
1893.3 |
16.51 |
– |
– |
223.7 |
25.81 |
– |
– |
85.0 |
14.17 |
– |
– |
– |
– |
2AA (50µg) |
– |
– |
– |
– |
– |
– |
– |
– |
– |
– |
– |
– |
– |
– |
– |
– |
– |
– |
217.0 |
5.21 |
MR: Mutation Rate; NPD: 4-Nitro-1,2-phenylenediamine; SAZ: Sodium azide; 9AA:9-Aminoacridine; MMS:Methyl methanesulfonate; 2AA: 2-aminoanthracene
Remarks: Ultrapure water was applied as solvent of the test item and the positive control substance: SAZ and MMS; the DMSO was applied as solvent for positive control substances NPD, 9AA and 2AA. The mutation rate of the test item, SAZ, MMS and untreated control is given referring to the ultrapure water; the mutation rate of NPD, 9AA and 2AA is given referring to DMSO.
Table 2: Summary Table of the Results of the Confirmatory Mutation Test
Confirmatory Mutation Test (Pre-Incubation Test) |
||||||||||||||||||||
Concentrations (µg/plate) |
Salmonella typhimurium tester strains |
Escherichia coli |
||||||||||||||||||
TA 98 |
TA 100 |
TA 1535 |
TA 1537 |
WP2uvrA |
||||||||||||||||
-S9 |
+S9 |
-S9 |
+S9 |
-S9 |
+S9 |
-S9 |
+S9 |
-S9 |
+S9 |
|||||||||||
Mean values of revertants per plate Mutation rate (MR) |
Mean |
MR |
Mean |
MR |
Mean |
MR |
Mean |
MR |
Mean |
MR |
Mean |
MR |
Mean |
MR |
Mean |
MR |
Mean |
MR |
Mean |
MR |
Untreated Control |
14.7 |
0.64 |
18.3 |
0.93 |
74.3 |
0.89 |
93.0 |
1.09 |
10.7 |
1.07 |
14.0 |
1.11 |
7.0 |
1.17 |
6.7 |
1.05 |
23.0 |
0.86 |
27.3 |
0.80 |
DMSO Control |
15.0 |
1.00 |
20.3 |
1.00 |
– |
– |
77.3 |
1.00 |
– |
– |
11.3 |
1.00 |
7.3 |
1.00 |
7.3 |
1.00 |
– |
– |
23.7 |
1.00 |
Ultrapure Water Control |
23.0 |
1.00 |
19.7 |
1.00 |
83.3 |
1.00 |
85.7 |
1.00 |
10.0 |
1.00 |
12.7 |
1.00 |
6.0 |
1.00 |
6.3 |
1.00 |
26.7 |
1.00 |
34.0 |
1.00 |
5000 |
17.0 |
0.74 |
17.3 |
0.88 |
74.0 |
0.89 |
79.0 |
0.92 |
12.3 |
1.23 |
12.0 |
0.95 |
7.3 |
1.22 |
8.0 |
1.26 |
33.7 |
1.26 |
25.3 |
0.75 |
1600 |
16.0 |
0.70 |
24.0 |
1.22 |
81.3 |
0.98 |
85.3 |
1.00 |
10.3 |
1.03 |
12.7 |
1.00 |
7.3 |
1.22 |
6.0 |
0.95 |
32.3 |
1.21 |
26.0 |
0.76 |
500 |
18.0 |
0.78 |
25.3 |
1.29 |
83.7 |
1.00 |
85.3 |
1.00 |
8.0 |
0.80 |
12.7 |
1.00 |
5.7 |
0.94 |
7.7 |
1.21 |
36.0 |
1.35 |
30.3 |
0.89 |
160 |
14.7 |
0.64 |
22.0 |
1.12 |
78.0 |
0.94 |
96.3 |
1.12 |
11.7 |
1.17 |
11.3 |
0.89 |
7.7 |
1.28 |
8.0 |
1.26 |
28.7 |
1.08 |
32.0 |
0.94 |
50 |
11.7 |
0.51 |
22.0 |
1.12 |
85.7 |
1.03 |
98.0 |
1.14 |
12.7 |
1.27 |
12.0 |
0.95 |
7.7 |
1.28 |
8.7 |
1.37 |
30.3 |
1.14 |
25.7 |
0.75 |
16 |
19.7 |
0.86 |
24.0 |
1.22 |
74.7 |
0.90 |
87.0 |
1.02 |
9.3 |
0.93 |
10.3 |
0.82 |
7.3 |
1.22 |
7.0 |
1.11 |
30.3 |
1.14 |
24.7 |
0.73 |
NPD (4 µg) |
493.3 |
32.89 |
– |
– |
– |
– |
– |
– |
– |
– |
– |
– |
– |
– |
– |
– |
– |
– |
– |
– |
SAZ (2 µg) |
– |
– |
– |
– |
828.7 |
9.94 |
– |
– |
1013.3 |
101.33 |
– |
– |
– |
– |
– |
– |
– |
– |
– |
– |
9AA (50 µg) |
– |
– |
– |
– |
– |
– |
– |
– |
– |
– |
– |
– |
549.3 |
74.91 |
– |
– |
– |
– |
– |
– |
MMS (2 µL) |
– |
– |
– |
– |
– |
– |
– |
– |
– |
– |
– |
– |
– |
– |
– |
– |
993.3 |
37.25 |
– |
– |
2AA (2 µg) |
– |
– |
1150.3 |
56.57 |
– |
– |
830.7 |
10.74 |
– |
– |
192.3 |
16.97 |
– |
– |
117.7 |
16.05 |
– |
– |
– |
– |
2AA (50 µg) |
– |
– |
– |
– |
– |
– |
– |
– |
– |
– |
– |
– |
– |
– |
– |
– |
– |
– |
174.0 |
7.35 |
MR: Mutation Rate; NPD: 4-Nitro-1,2-phenylenediamine; SAZ: Sodium azide; 9AA:9-Aminoacridine; MMS: Methyl methanesulfonate; 2AA: 2-aminoanthracene
Remarks: Ultrapure water was applied as solvent of the test item and the positive control substance: SAZ and MMS; the DMSO was applied as solvent for positive control substances NPD, 9AA and 2AA. The mutation rate of the test item, SAZ, MMS and untreated control is given referring to the ultrapure water; the mutation rate of NPD, 9AA and 2AA is given referring to DMSO.
Table 3: Historical Control Values of positive control for Revertants/Plate (for the Period of 2015-2017)
Bacterial strains |
|||||||
Historical control data of positive controls |
‑S9 |
|
TA98 |
TA100 |
TA1535 |
TA1537 |
E. coli |
Average |
285.9 |
1214.0 |
1024.3 |
594.4 |
858.4 |
||
SD |
25.5 |
80.0 |
120.3 |
36.4 |
164.7 |
||
Minimum |
152 |
609 |
407 |
136 |
330 |
||
Maximum |
598 |
2272 |
2597 |
2048 |
1760 |
||
+S9 |
|
TA98 |
TA100 |
TA1535 |
TA1537 |
E. coli |
|
Average |
1395.7 |
1727.4 |
160.7 |
145.8 |
204.9 |
||
SD |
261.4 |
244.1 |
30.0 |
18.9 |
3.9 |
||
Minimum |
286 |
712 |
91 |
70 |
133 |
||
Maximum |
3211 |
3435 |
328 |
315 |
367 |
Table 3: Historical Confor Revertants/Plate for the Period of 2015-2017)
|
Bacterial strains |
||||||
Historical control data of untreated control |
‑S9 |
|
TA98 |
TA100 |
TA1535 |
TA1537 |
E. coli |
Average |
19.7 |
94.6 |
10.9 |
8.9 |
25.2 |
||
SD |
1.7 |
2.4 |
0.4 |
1.3 |
5.2 |
||
Minimum |
8 |
67 |
4 |
3 |
11 |
||
Maximum |
40 |
133 |
21 |
20 |
52 |
||
+S9 |
|
TA98 |
TA100 |
TA1535 |
TA1537 |
E. coli |
|
Average |
24.5 |
112.9 |
11.0 |
9.2 |
31.7 |
||
SD |
1.4 |
6.1 |
0.5 |
1.2 |
6.4 |
||
Minimum |
11 |
74 |
3 |
3 |
13 |
||
Maximum |
43 |
159 |
20 |
20 |
60 |
||
|
Bacterial strains |
||||||
Historical control data of DMSO control |
‑S9 |
|
TA98 |
TA100 |
TA1535 |
TA1537 |
E. coli |
Average |
18.1 |
87.0 |
10.8 |
8.5 |
24.6 |
||
SD |
1.1 |
3.6 |
0.6 |
1.3 |
3.3 |
||
Minimum |
9 |
58 |
4 |
3 |
10 |
||
Maximum |
36 |
131 |
23 |
20 |
54 |
||
+S9 |
|
TA98 |
TA100 |
TA1535 |
TA1537 |
E. coli |
|
Average |
23.0 |
102.4 |
11.0 |
9.2 |
31.4 |
||
SD |
0.8 |
7.7 |
0.4 |
1.3 |
5.8 |
||
Minimum |
11 |
69 |
3 |
3 |
12 |
||
Maximum |
42 |
148 |
23 |
21 |
59 |
||
|
Bacterial strains |
||||||
Historical control data of Water control |
‑S9 |
|
TA98 |
TA100 |
TA1535 |
TA1537 |
E. coli |
Average |
19.5 |
92.8 |
11.3 |
9.1 |
26.6 |
||
SD |
1.4 |
5.0 |
0.5 |
1.8 |
6.6 |
||
Minimum |
12 |
62 |
4 |
3 |
10 |
||
Maximum |
30 |
139 |
22 |
18 |
52 |
||
+S9 |
|
TA98 |
TA100 |
TA1535 |
TA1537 |
E. coli |
|
Average |
24.4 |
109.9 |
11.2 |
9.5 |
34.0 |
||
SD |
1.2 |
6.7 |
0.8 |
1.9 |
6.1 |
||
Minimum |
13 |
83 |
5 |
4 |
16 |
||
Maximum |
37 |
149 |
18 |
18 |
63 |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
A study according OECD TG 471 was performed to investigate the potential mutagenic activity of the test item using the Bacterial Reverse Mutation Assay.
The experiments were carried out using histidine-requiring auxotroph strains of Salmonella typhimurium (Salmonella typhimurium TA98, TA100, TA1535 and TA1537), and the tryptophan-requiring auxotroph strain of Escherichia coli (Escherichia coli WP2 uvrA) in the presence and absence of a post mitochondrial supernatant (S9) prepared from livers of Phenobarbital/b-naphthoflavone-induced rats.
The study included a preliminary solubility test, a preliminary concentration range finding test (informatory toxicity test), an initial mutation test (plate incorporation test), and a confirmatory mutation test (pre-incubation test).
Based on the results of the solubility test and the concentration range finding test the test item was dissolved in ultrapure water (ASTM Type I).
At the preparation of the test item stock solution any correction factor (based on its purity, constituents) was not taken into consideration.
Based on the cytotoxicity and solubility results of the preliminary concentration range finding test (informatory toxicity test) and based on the recommendations in OECD 471 guideline, the following concentrations of the test item were prepared and investigated in the initial and confirmatory mutation tests: 5000; 1600; 500; 160; 50 and 16 µg/plate.
The results of the preliminary concentration range finding test allowed the applying of the recommended maximum test concentration of 5000 µg/plate.
No precipitation of the test item was observed on the plates in the examined bacterial strains at any examined concentration level (±S9 mix) throughout the study.
The test item did not show inhibitory, cytotoxic effects in the performed experiments. The colony and background lawn development was not affected in any case; the obtained revertant colony number decreases (compared to the revertant colony numbers of the solvent control) remained within the biological variability range of the applied test system.
The revertant colony numbers of solvent control ultrapure water (ASTM Type I) plates with and without S9 mix demonstrated the characteristic mean number of spontaneous revertants that was in line with the corresponding historical control data ranges.
The reference mutagen treatments (positive controls) showed the expected, biological relevant increases (more than 3-fold increase) in induced revertant colonies and the number of revertants fell in the corresponding historical control ranges, thereby meeting the criteria for the positive control in all experimental phases, in all tester strains.
No biologically relevant increases were observed in revertant colony numbers of any of the five test strains following treatment with sodium (2-butoxyethoxy) acetate at any concentration level, either in the presence or absence of metabolic activation (S9 mix) in the performed experiments.
The reported data of this mutagenicity assay show that under the experimental conditions applied, the test itemdid not induce gene mutations by base pair changes or frameshifts in the genome of the strains used.
Justification for classification or non-classification
Classification,
Labelling, and Packaging Regulation (EC) No 1272/2008
The
available information on the test item regarding genetic toxicity are
reliable and suitable for classification purposes under Regulation (EC)
No 1272/2008. Based on available experimental information, the
test substance is not classified for genetic toxicity according
to Regulation (EC) No 1272/2008 (CLP), as amended for the
twelfth time in Regulation
(EU) No 2019/521.
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