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EC number: 262-810-2 | CAS number: 61477-95-0
- 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
Genetic toxicity: in vitro
Administrative data
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- OCt 13, 2017-Jan 25, 2018
- Reliability:
- 1 (reliable without restriction)
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 018
- Report date:
- 2018
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- bacterial reverse mutation assay
Test material
- Reference substance name:
- Monalazone disodium
- EC Number:
- 262-810-2
- EC Name:
- Monalazone disodium
- Cas Number:
- 61477-95-0
- Molecular formula:
- C7H4ClNO4S.2Na
- IUPAC Name:
- disodium 4-[(chloroazanidyl)sulfonyl]benzoate
- Test material form:
- solid
Constituent 1
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 72617S
- Expiration date of the lot/batch: 26 July 2018
- Purity test date: 26 July 2017
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage conditions: The test item was stored in the laboratory No. 408 at temperature of (2– 8 °C), protected from moisture. The storage conditions are monitored and documented. The test item is stable in recommended store and handling conditions. Handling and storage conditions comply with corresponding SOPs.
- Stability under test conditions: stable
- Solubility and stability of the test substance in the solvent/vehicle: Test item is soluble in water according to the literature
Method
Species / strainopen allclose all
- Species / strain / cell type:
- S. typhimurium TA 97
- Species / strain / cell type:
- S. typhimurium TA 98
- Species / strain / cell type:
- S. typhimurium TA 100
- Species / strain / cell type:
- S. typhimurium TA 1535
- Species / strain / cell type:
- E. coli WP2 uvr A
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9 liver fraction from Sprague Dawley rats
- Test concentrations with justification for top dose:
- 0.001-0.6 mg//plate. Justification for top dose: non-toxicity.
- Vehicle / solvent:
- Deionized water
Controls
- Untreated negative controls:
- yes
- Remarks:
- DMSO
- Negative solvent / vehicle controls:
- no
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 4-nitroquinoline-N-oxide
- 9-aminoacridine
- 2-nitrofluorene
- sodium azide
- other: 2-aminoanthracene
- Details on test system and experimental conditions:
- Source and storage of test system:
The lyophilized test strains of Salmonella typhimurium were received from Czech Collection of Microorganism (CCM): TA 100 (batch No. 0102201220054), TA 97 (batch No. 1211201422026), TA1535 (batch No. 2101200916917), TA98 (batch No. 0102201220053). The test cultures were long term maintained in liquid nitrogen or frozen (-70°C); dimethyl sulfoxide (DMSO) was used as a cryoprotective agent. The lyophilized test strain of E.coli was received from Deutsche Sammlung von Mikroorganismen und Zellkulturen (DSMZ): WP2 uvr A (batch No.9495-0409-001).
Preparation of overnight culture:
The bacterial suspension for the test was prepared as an overnight culture from frozen stock culture. The tester strains were inoculated in nutrient broth and incubated at 37°C for 18-20 hours to achieve the bacterial density of 108-109/mL [SOP 1].
Formulation of the test item:
The appropriate amount of the test item for dose of 5 mg/plate was dissolved in sterile deionised water. The lower doses were prepared by dilution in sterile deionised water.
Metabolic activation:
The mammalian liver post-mitochondrial fraction (S9) used for metabolic activation was prepared from Sprague Dawley male rats (Charles River, Velaz Czech Republic) -batch A141112. Animals were pre-treated with Aroclor (administered i.p. at 500 mg/kg) 5 days prior to killing (Protocol No.2/2012). S9 fraction was prepared according to SOP [5] and stored in liquid nitrogen [SOP 6]. The activity of S9 fraction was determined in bacterial reverse gene mutation test on Salmonella typhimurium strains TA98 and TA100 [1]. The S9 homogenate was diluted with co-factors (S9-MIX): 33 mM KCl, 8 mM MgCl2, 5 mM glucose-6-phosphate, 4 mM NADP and 100 mM phosphate buffer (pH = 7.4). The S9 concentration in S9-MIX was 10% [SOP 1].
Media:
Examination of chemical components for mutagenic and carcinogenic properties minimal glucose agar for mutagenicity tests was used [SOP 1]. Top agar contained 0.6% Bacto agar and 0.5% NaCl in distilled water, which was autoclaved and stored at room temperature. Before plating, 10 mL of sterile 0.5 mM histidine/0.5 mM biotin solution was added to the molten top agar which was kept at 45°C and used as an overlay on the minimal agar plate. In the experiment with E.coli histidine was replaced by tryptophan. Nutrient broth (Tryptic Soy broth, Merck) and Nutrient agar (Tryptic Soy agar, Merck) were used for the growth of tester strains. The growth medium was stored at 2-8°C. The media were prepared according to the standard operating procedure [SOP 3]. - Evaluation criteria:
- Considering biological relevance the test item is considered positive if the assay is valid and the following conditions are met:
- concentration-related increase over the tested range and reproducible increase at one or more concentrations in the number of revertant colonies per plate in at least one strain with or without metabolic activation
- Mutation factor >2
The positive result indicates that the test item induces mutations in Salmonella typhimurium or E.coli cells.
The test item for which results do not meet the above criteria is considered non-mutagenic in this test.
Negative results indicate that under the test conditions, the test item does not produce mutations in Salmonella typhimurium/E.coli cells - Statistics:
- Unpaired T-test
Results and discussion
Test resultsopen allclose all
- 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:
- not applicable
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 97
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- 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:
- not applicable
- 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:
- not applicable
- 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:
- not applicable
- Positive controls validity:
- valid
Any other information on results incl. tables
Test without metabolic activation. TA 100
Solvent | Concentration (ug/plate) | Positive control | ||||||
1 | 3 | 10 | 30 | 100 | 300 | |||
No. of revertants per plate | 168 | 173 | 141 | 144 | 160 | 168 | 0 | 670 |
No. of revertants per plate | 170 | 178 | 176 | 168 |
162 |
142 |
0 |
520 |
No. of revertants per plate |
170 |
168 |
160 |
160 |
176 |
172 |
0 |
512 |
Average |
169 |
173 |
159 |
157 |
166 |
161 |
0 |
567 |
SD |
1 |
5 |
18 |
12 |
9 |
16 |
0 |
89 |
Mutation frequency |
- |
1,02 |
0,94 |
0,93 |
0,98 |
0,95 |
0 |
3,35 |
Test without metabolic activation. TA 1535
Solvent |
Concentration (ug/plate) |
Positive control |
||||||
1 | 3 | 10 | 30 | 100 | 300 | |||
No. of revertants per plate | 34 | 31 | 35 | 33 | 39 | 30 | 0 | 332 |
No. of revertants per plate | 43 | 36 | 42 | 32 | 39 | 32 | 0 | 360 |
No. of revertants per plate |
34 | 36 | 32 | 36 | 35 | 31 | 0 | 396 |
Average | 37 | 34 | 36 | 34 | 38 | 31 | 0 | 363 |
SD | 5 | 3 | 5 | 2 | 2 | 1 | 0 | 32 |
Mutation frequency | - | 0,93 | 0,98 | 0,91 | 1,02 | 0,84 | 0 | 9,80 |
Test without metabolic activation. TA 97
Solvent |
Concentration (ug/plate) |
Positive control |
||||||
1 | 3 | 10 | 30 | 100 | 300 | |||
No. of revertants per plate | 146 | 146 | 130 | 139 | 141 | 120 | 0 | 680 |
No. of revertants per plate | 147 | 130 | 118 | 128 | 142 | 120 | 0 | 688 |
No. of revertants per plate |
141 | 120 | 131 | 142 | 161 | 116 | 0 | 920 |
Average | 145 | 132 | 126 | 136 | 148 | 119 | 0 | 763 |
SD | 3 | 13 | 7 | 7 | 11 | 2 | 0 | 139 |
Mutation frequency | - | 0,91 | 0,87 | 0,94 | 1,02 | 0,82 | 0 | 5,27 |
Test without metabolic activation. TA 98
Solvent |
Concentration (ug/plate) |
Positive control |
||||||
1 | 3 | 10 | 30 | 100 | 300 | |||
No. of revertants per plate | 26 | 30 | 46 | 32 | 18 | 23 | 0 | 178 |
No. of revertants per plate | 28 | 52 | 84 | 34 | 33 | 28 | 0 | 178 |
No. of revertants per plate |
29 | 41 | 58 | 43 | 34 | 32 | 0 | 149 |
Average | 28 | 41 | 63 | 36 | 28 | 28 | 0 | 168 |
SD | 2 | 11 | 19 | 6 | 9 | 5 | 0 | 17 |
Mutation frequency | - | 1,48 | 2,27 | 1,31 |
1,02 | 1,00 | 0 | 6,08 |
Test without metabolic activation. WP2 uvrA
Solvent |
Concentration (ug/plate) |
Positive control |
||||||
1 | 3 | 10 | 30 | 100 | 300 | |||
No. of revertants per plate | 36 | 24 | 35 | 35 | 36 | 37 | 37 | 205 |
No. of revertants per plate | 30 | 31 | 30 | 39 | 38 | 41 | 33 | 167 |
No. of revertants per plate |
33 | 28 | 33 | 33 | 38 | 30 | 30 | 200 |
Average | 33 | 28 | 33 | 36 | 37 | 36 | 33 | 191 |
SD | 3 | 4 | 3 | 3 | 1 | 6 | 4 | 21 |
Mutation frequency | - | 0,84 | 0,99 | 1,08 |
1,13 | 1,09 | 1,01 | 5,78 |
Test with metabolic activation. TA 100
Solvent |
Concentration (ug/plate) |
Positive control |
||||||
3 | 10 | 30 | 100 | 300 | 600 | |||
No. of revertants per plate | 173 | 174 | 180 | 164 | 160 | 156 | 53 | 792 |
No. of revertants per plate | 204 | 170 | 176 | 182 | 166 | 160 | 152 | 824 |
No. of revertants per plate |
168 | 179 | 181 | 172 | 173 | 168 | 104 | 843 |
Average | 182 | 174 | 179 | 173 | 166 | 161 | 103 | 820 |
SD | 20 | 5 | 3 | 9 | 7 | 6 | 50 | 26 |
Mutation frequency | - | 0,96 | 0,99 | 0,95 |
0,92 | 0,89 | 0,57 | 4,51 |
Test with metabolic activation. TA 1535
Solvent |
Concentration (ug/plate) |
Positive control |
||||||
3 | 10 | 30 | 100 | 300 | 600 | |||
No. of revertants per plate | 20 | 25 | 27 | 26 | 24 | 27 | 10 | 171 |
No. of revertants per plate | 21 | 19 | 25 | 20 | 22 | 22 | 13 | 183 |
3 No. of revertants per plate |
24 | 22 | 20 | 23 | 21 | 20 | 11 | 178 |
Average | 22 | 22 | 24 | 23 | 22 | 23 | 11 | 177 |
SD | 2 | 3 | 4 | 3 | 2 | 4 | 2 | 7 |
Mutation frequency | - | 1,02 | 1,11 | 1,06 |
1,03 | 1,06 | 0,52 | 8,26 |
Test with metabolic activation. TA 97
Solvent |
Concentration (ug/plate) |
Positive control |
||||||
3 | 10 | 30 | 100 | 300 | 600 | |||
No. of revertants per plate | 136 | 141 | 130 | 154 | 125 | 125 | 105 | 370 |
No. of revertants per plate | 128 | 126 | 153 | 164 | 126 | 141 | 120 | 392 |
No. of revertants per plate |
118 | 141 | 143 | 150 | 129 | 132 | 116 | 435 |
Average | 127 | 136 | 142 | 156 | 127 | 133 | 114 | 399 |
SD | 9 | 9 | 12 | 7 | 2 | 8 | 8 | 33 |
Mutation frequency | - | 1,07 | 1,12 | 1,23 |
0,99 | 1,04 | 0,89 | 3,13 |
Test with metabolic activation. TA 98
Solvent |
Concentration (ug/plate) |
Positive control |
||||||
3 | 10 | 30 | 100 | 300 | 600 | |||
No. of revertants per plate | 23 | 20 | 20 | 19 | 27 | 26 | 14 | 356 |
No. of revertants per plate | 22 | 19 | 23 | 22 | 28 | 17 | 19 | 440 |
No. of revertants per plate |
23 | 22 | 21 | 24 | 22 | 18 | 16 | 408 |
Average | 23 | 20 | 21 | 22 | 26 | 20 | 16 | 401 |
SD | 1 | 2 | 2 | 3 | 3 | 5 | 3 | 42 |
Mutation frequency | - | 0,90 | 0,94 | 0,96 |
1,13 | 0,90 | 0,72 | 17,71 |
Test with metabolic activation. WPuvrA
Solvent |
Concentration (ug/plate) |
Positive control |
||||||
3 | 10 | 30 | 100 | 300 | 600 | |||
No. of revertants per plate | 31 | 46 | 46 | 40 | 40 | 47 | 47 | 396 |
No. of revertants per plate | 41 | 42 | 39 | 33 | 34 | 41 | 46 | 408 |
No. of revertants per plate |
47 | 41 | 42 | 46 | 40 | 38 | 33 | 402 |
Average | 40 | 43 | 42 | 40 | 38 | 42 | 42 | 402 |
SD | 8 | 3 | 4 | 7 | 3 | 5 | 8 | 6 |
Mutation frequency | - | 1,08 | 1,07 | 1,00 |
0,96 | 1,06 | 1,06 | 10,13 |
Applicant's summary and conclusion
- Conclusions:
- No significant increase in the mutant frequency after treatment with Monalazone disodium was observed in four tester strains of Salmonella typhimurium TA100, TA1535, TA 98 and TA 97 as well as in E.coli WP2 uvrA in the standard plate incorporation either with or without metabolic activation. It can be concluded that Monalazone disodium is not mutagenic in in vitro bacterial mutation test.
- Executive summary:
Four strains of Salmonella typhimurium TA100, TA98, TA97, TA1535 and one strain of Escherichia coli WP2 uvrA were used for evaluation of mutagenic activity of test item Monalazone disodium in Bacterial Reverse Mutation Assay (Ames test). The tests were performed according to OECD Guideline 471, in compliance with GLP rules and according to the Study Plan.Test item Monalazone disodium was tested in Dose Range Finding test without metabolic activation up to a maximal dose of 5 mg/plate. The highest dose as well as doses > 1 mg/plate inhibited test bacteria growth; therefore lower doses in the range of 0.6-0.0003 were tested in the main tests with and without metabolic activation. Adequate positive and negative controls were evaluated and showed the reliability of the test system. No significant increase in the mutant frequency after treatment with Monalazone disodium was observed in four tester strains of Salmonella typhimurium TA100, TA1535, TA 98 and TA 97 as well as in E.coli WP2 uvrA in the standard plate incorporation either with or without metabolic activation. The same holds true for the test with preincubation. It is concluded that test item Monalazone disodium did not exert mutagenic activity in strains Salmonella typhimurium TA98, TA97, TA100, TA1535 and E.coli WP2 uvrA under the conditions of the performed tests. Based on this it can be concluded that the test item is not mutagenic in in vitro bacterial gene mutation test.
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