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EC number: 485-320-2 | CAS number: 221667-31-8
- 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
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:
- 17 - 27 Nov 2006
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 006
- Report date:
- 2006
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Version / remarks:
- adopted 21 Jul 1997 (corrected 26 Jun 2020)
- Deviations:
- yes
- Remarks:
- The sole indicator of S9 efficacy was 2-aminoanthracene (2-AA). Historical control ranges are present as median values, with a semi Q-range, without 95th or 99th percentile.
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- Ministerium für Umwelt und Naturschutz, Landwirtschaft und Verbraucherschutz des Landes Nordrhein-Westfalen, Germany
- Type of assay:
- bacterial reverse mutation assay
Test material
- Reference substance name:
- -
- EC Number:
- 485-320-2
- EC Name:
- -
- Cas Number:
- 221667-31-8
- Molecular formula:
- C18H18N205S
- IUPAC Name:
- N-[4-(cyclopropylcarbamoyl)benzenesulfonyl]-2-methoxybenzamide
Constituent 1
Method
- Target gene:
- his operon
Species / strain
- 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:
- Type and composition of metabolic activation system:
Cofactor supplemented post-mitochondrial fraction (S9 mix) was prepared from the livers of at least six adult male Sprague Dawley rats, of approximately 200 to 300 g in weight. For enzyme induction, the animals received a single intraperitoneal injection of Aroclor 1254, dissolved in com oil, at a dose of 500 mg/kg body weight, five days prior to sacrifice.
The protein concentration of the S9 preparation was 37.6 mg/mL in the both experiments. 70 mL of the co-factor contained: 162.6 mg MgCI2 x 6H20, 246 mg KCI, 179.1 mg Glucose-6-phosphate, disodium salt, 315 mg NADP, disodium salt in 100 mM sodium phosphate buffer. S9 fraction was thawed and mixed with S9 cofactor solution and, if needed, 0.15 M KCI, to result in a final concentration of approx. 10% v/v in the S9 mix and approx. 1.8% in the final culture medium.
Prior to first use, each batch was checked for its metabolizing capacity by using reference mutagens; appropriate activity was demonstrated. At the beginning of each experiment four aliquots of the S9 mix were plated (0.5 ml per plate) in order to assess its sterility. This was repeated after completion of test tube plating. The sterility control plates were then incubated for 48 hours at 37°C. No indication of contamination of S9 mix was found. - Test concentrations with justification for top dose:
- First experiment: 16, 50, 158, 500, 1581 and 5000 µg/plate with and without metabolic activation
Second experiment: 16, 50, 158, 500, 1581 and 5000 µg/plate with and without metabolic activation
5000 µg/plate was selected as the highest test concentration based on the results of first experiment, which also served as the pre-test for toxicity. No significant cytotoxicity and no precipitation was observed up to and including the highest concentration. - Vehicle / solvent:
- - Vehicle/solvent used: DMSO (0.1 mL/plate)
- Justification for choice of solvent/vehicle: Solubility of the test compound
Controls
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- sodium azide
- cumene hydroperoxide
- mitomycin C
- other: Nitrofurantoin (NF): TA 100, 0.2 μg/plate in DMSO, -S9; 4-nitro-1,2-phenylene diamine (4-NPDA): TA98 0.5 µg/plate and TA1537 10 µg/plate in DMSO, -S9; 2-aminoanthracene (2-AA), TA 1535, TA 100, TA 1537, TA 98 and TA 102, 3 µg/plate in DMSO, +S9.
- Details on test system and experimental conditions:
- NUMBER OF REPLICATIONS:
- Number of cultures per concentration: Triplicate
- Number of independent experiments: 2
METHOD OF TREATMENT/ EXPOSURE:
- Test substance added in agar for plate incorporation test (experiment I) and in bacterial suspension for preincubation (experiment II).
TREATMENT AND HARVEST SCHEDULE:
- Preincubation period: 20 min
- Exposure duration/duration of treatment: 48 hours
METHODS FOR MEASUREMENT OF CYTOTOXICITY
- Method: Reduction in background growth; reduction in mutant count per plate; titer. - Evaluation criteria:
- Acceptance of an assay:
1. The negative controls had to be within the expected range, as defined by published data (e.g. Maron and Ames, 1983) and/ or the laboratories' own historical data.
2. The positive controls had to show sufficient effects, as defined by the laboratories' experience.
3. Titer determinations had to demonstrate sufficient bacterial density in the suspension.
Even if the criteria for points 1 and 2 were not met, a trial was accepted if it showed mutagenic activity of the test compound.
Criteria for a positive result:
A reproducible and dose-related increase in mutant counts of at least one strain (For TA1535, TA100 and TA98 about twice that of negative controls, for TA1537 at least threefold; for TA102 an increase of about 100 mutants should be reached). Otherwise the result is evaluated as negative. - Statistics:
- Means and standard deviation of triplicate plates were calculated.
Results and discussion
Test resultsopen allclose all
- Key result
- Species / strain:
- S. typhimurium TA 1535
- 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 examined
- True negative controls validity:
- not examined
- 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 nor precipitates, but tested up to recommended limit concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- True negative controls validity:
- not examined
- 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 nor precipitates, but tested up to recommended limit concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- True negative controls validity:
- not examined
- 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 nor precipitates, but tested up to recommended limit concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- True negative controls validity:
- not examined
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium 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 examined
- True negative controls validity:
- not examined
- Positive controls validity:
- valid
- Additional information on results:
- STUDY RESULTS
- No precipitation of the test item occurred up to the highest investigated dose in both experiments. No indication of a bacteriotoxic effect was observed at doses of up to and including 5000 µg per plate. The total bacteria counts consistently produced results comparable to the negative controls, or differed only insignificantly. No inhibition of growth was noted as well.
- None of the five strains concerned showed in the plate incorporation test a dose related and biologically relevant increase in mutant counts over those of the negative controls. This applied both to the tests with and without S9 mix and was confirmed by the results of the pre-incubation trials.
STABILITY IN VEHICLE:
- The test substance was stable in DMSO at room temperature at concentrations ranging from 0.01 mg/mL to 200 mg/mL for at least 24 hours. An interval which
covers the time range from preparation of the formulation to last treatment.
- Content as % of nominal value after storage time in hours: 0.01 mg/mL, 96% at 0 and 24 hours. 200 mg/mL, 92 and 91%, at 0 and 24 hours, respectively.
COMPARISON WITH HISTORICAL CONTROL DATA:
- The experimental data is well comparable with the provided historical control data (see Attachment 1 for historical control data).
- The positive controls sodium azide, nitrofurantoin, 4-nitro-1,2-phenylene diamine, mitomycin C, cumene hydroperoxide and 2-aminoanthracene increased mutant counts to well over those of the negative controls, and thus demonstrated the system's sensitivity and the activity of the S9 mix.
Any other information on results incl. tables
Table 1: Test results (experiment I, plate incorporation)
Without S9 |
Test substance concentration (μg/plate) |
Mean number of revertant colonies per plate (average of 3 plates) |
||||
TA 1535 |
TA 1537 |
TA 98 |
TA 100 |
TA 102 |
||
Solvent control (DMSO) |
10 ± 2 |
7± 3 |
16 ± 3 |
126 ± 6 |
217 ± 22 |
|
16 |
12 ± 3 |
6 ± 1 |
17 ± 6 |
121 ± 5 |
191 ± 26 |
|
50 |
10 ± 5 |
7 ± 1 |
16 ± 3 |
116 ± 19 |
163 ± 21 |
|
158 |
15 ± 4 |
6 ± 2 |
18 ± 4 |
115 ± 26 |
208 ± 24 |
|
500 |
15 ± 4 |
7 ± 2 |
11 ± 2 |
118 ± 12 |
175 ± 29 |
|
1581 |
13 ± 8 |
7 ± 1 |
11 ± 4 |
110 ± 12 |
147 ± 4 |
|
5000 |
10 ± 1 |
6 ± 1 |
9 ± 2 |
115 ± 11 |
154 ± 20 |
|
Positive controls (µg/plate) |
Na-azide (10) |
4-NPDA (10) |
4-NPDA (0.5) |
NF (0.2) |
MMC (0.2) |
|
Mean (No. of colonies/plate) |
407 ± 41 |
81 ± 7 |
140 ± 9 |
337 ± 14 |
428 ± 44 |
|
With S9 |
Solvent control (DMSO) |
10 ± 4 |
8 ± 2 |
21 ± 6 |
138 ± 18 |
235 ± 18 |
16 |
9 ± 3 |
7 ± 1 |
17 ± 4 |
117 ± 14 |
191 ± 43 |
|
50 |
9 ± 2 |
8 ± 2 |
14 ± 5 |
98 ± 18 |
189 ± 10 |
|
158 |
10 ± 5 |
7 ± 2 |
22 ± 4 |
142 ± 16 |
240 ± 58 |
|
500 |
9 ± 2 |
8 ± 2 |
24 ± 6 |
131 ± 15 |
261 ± 14 |
|
1581 |
11 ± 2 |
7 ± 1 |
14 ± 5 |
123 ± 9 |
234 ± 47 |
|
5000 |
7 ± 2 |
7 ± 1 |
18 ± 2 |
122 ± 16 |
205 ± 31 |
|
Positive controls (µg/plate) |
2-AA (3) |
2-AA (3) |
2-AA (3) |
2-AA (3) |
2-AA (3) |
|
Mean (No. of colonies/plate) |
105± 12 |
72 ± 8 |
556 ± 147 |
1229 ± 72 |
471 ± 35 |
2-AA: 2-Aminoanthracene
MMC: Mitomycin C
4-NPDA: 4-Nitro-1,2-phenyiene diamine
NF: Nitrofurantoin
Na-azide: Sodium azide
Table 2: Test results (experiment II, pre-incubation)
Without S9 |
Test substance concentration (μg/plate) |
Mean number of revertant colonies per plate (average of 3 plates) |
||||
TA 1535 |
TA 1537 |
TA 98 |
TA 100 |
TA 102 |
||
Solvent control (DMSO) |
26 ± 1 |
8± 1 |
14 ± 2 |
116 ± 4 |
184 ± 39 |
|
16 |
21 ± 6 |
8 ± 1 |
12 ± 2 |
114 ± 6 |
173 ± 9 |
|
50 |
26 ± 1 |
8 ± 2 |
13 ± 2 |
101 ± 5 |
158 ± 7 |
|
158 |
22 ± 6 |
9 ± 2 |
15 ± 5 |
124 ± 11 |
209 ± 21 |
|
500 |
27 ± 1 |
9 ± 2 |
13 ± 4 |
115 ± 12 |
179 ± 14 |
|
1581 |
23 ± 3 |
7 ± 0 |
16 ± 3 |
130 ± 6 |
173 ± 4 |
|
5000 |
15 ± 5 |
7 ± 2 |
15 ± 1 |
118 ± 12 |
168 ± 6 |
|
Positive controls (µg/plate) |
Na-azide (10) |
4-NPDA (10) |
4-NPDA (0.5) |
NF (0.2) |
Cumene (50) |
|
Mean (No. of colonies/plate) |
535 ± 35 |
94 ± 10 |
135 ± 3 |
428 ± 12 |
414 ± 34 |
|
With S9 |
Solvent control (DMSO) |
12 ± 4 |
8 ± 1 |
20 ± 4 |
112 ± 3 |
196 ± 9 |
16 |
14 ± 2 |
9 ± 2 |
17 ± 3 |
98 ± 8 |
207 ± 32 |
|
50 |
13 ± 1 |
7 ± 1 |
20 ± 5 |
95 ± 10 |
190 ± 15 |
|
158 |
10 ± 3 |
8 ± 1 |
22 ± 2 |
126 ± 21 |
187 ± 34 |
|
500 |
14 ± 3 |
7 ± 2 |
22 ± 2 |
105 ± 2 |
205 ± 18 |
|
1581 |
10 ± 3 |
8 ± 3 |
19 ± 5 |
96 ± 4 |
194 ± 62 |
|
5000 |
13 ± 2 |
8 ± 2 |
22 ± 5 |
118 ± 15 |
183 ± 24 |
|
Positive controls (µg/plate) |
2-AA (3) |
2-AA (3) |
2-AA (3) |
2-AA (3) |
2-AA (3) |
|
Mean (No. of colonies/plate) |
156± 18 |
210 ± 13 |
741 ± 111 |
1344 ± 64 |
405 ± 25 |
2-AA: 2-Aminoanthracene
Cumene: Cumene hydroperoxide
4-NPDA: 4-Nitro-1,2-phenyiene diamine
NF: Nitrofurantoin
Na-azide: Sodium azide
Applicant's summary and conclusion
- Conclusions:
- The study was performed according to OECD guideline 471 and compliant with GLP. Under the conditions of the assay, the test item was not mutagenic in S. typhimurium strains TA 98, TA 100, TA 1535, TA 1537 and in TA 102 with and without metabolic activation.
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