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EC number: 810-161-6 | CAS number: 1229654-66-3
- 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:
- 07 - 24 May 2013
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 013
- Report date:
- 2013
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Version / remarks:
- adopted in 1997
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
- Version / remarks:
- adopted in 2008
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.5100 - Bacterial Reverse Mutation Test (August 1998)
- Version / remarks:
- adopted in 1998
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- Hess. Ministerium für Umwelt, Energie, Landwirtschaft und Verbraucherschutz, Wiesbaden, Germany
- Type of assay:
- bacterial reverse mutation assay
Test material
- Reference substance name:
- 1-(3-chloropyridin-2-yl)-N-[4-cyano-2-methyl-6-(methylcarbamoyl)phenyl]-3-{[5-(trifluoromethyl)-2H-1,2,3,4-tetrazol-2-yl]methyl}-1H-pyrazole-5-carboxamide
- EC Number:
- 810-161-6
- Cas Number:
- 1229654-66-3
- Molecular formula:
- C22 H16 Cl F3 N10 O2
- IUPAC Name:
- 1-(3-chloropyridin-2-yl)-N-[4-cyano-2-methyl-6-(methylcarbamoyl)phenyl]-3-{[5-(trifluoromethyl)-2H-1,2,3,4-tetrazol-2-yl]methyl}-1H-pyrazole-5-carboxamide
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:
- cofactor supplemented post-mitochondrial fraction (S9 mix), prepared from the livers of rats treated with phenobarbital/beta-naphthoflavone
- Test concentrations with justification for top dose:
- Pre-experiment/Experiment I: 3, 10, 33, 100, 333, 1000, 2500 and 5000 µg/plate with and without metabolic activation
Experiment II: 10, 33, 100, 333, 1000, 2500 and 5000 µg/plate with and without metabolic activation
5000 µg/plate was chosen as maximal concentration since minor toxic effects were observed in the pre-test/experiment I. - Vehicle / solvent:
- - Vehicle/solvent used: DMSO
- Justification for choice of solvent/vehicle: The solvent DMSO was chosen because of its solubility properties and its relative nontoxicity to the bacteria.
Controls
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- sodium azide
- methylmethanesulfonate
- other: 4-nitro-o-phenylene-diamine (4-NOPD), 2-aminoanthracene (2-AA)
- Remarks:
- + S9: 2-AA (2.5 µg/plate in TA 1535, TA 1537, TA 98, TA 100; 10 µg/plate in TA 102) - S9: sodium azide (10 µg/plate in TA 1535, TA 100), 4-NOPD (10 µg/plate in TA 98; 50 µg/plate in TA 1537), methylmethanesulfonate (2.0 µL/plate in TA 102)
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in agar (plate incorporation); preincubation
DURATION
- Preincubation period: 60 min
- Exposure duration: 48 h
NUMBER OF REPLICATIONS: 3 replications each in 2 independent experiments
DETERMINATION OF CYTOTOXICITY
- Method: other: number of revertants - Evaluation criteria:
- A test item is considered as a mutagen if a biologically relevant increase in the number of revertants exceeding the threshold of twice (strains TA 98, TA 100, and TA 102) or thrice (strains TA 1535 and TA 1537) the colony count of the corresponding solvent control is observed. A dose dependent increase is considered biologically relevant if the threshold is exceeded at more than one concentration. An increase exceeding the threshold at only one concentration is judged as biologically relevant if reproduced in an independent second experiment.
A dose dependent increase in the number of revertant colonies below the threshold is regarded as an indication of a mutagenic potential if reproduced in an independent second experiment. However, whenever the colony counts remain within the historical range of negative and solvent controls such an increase is not considered biologically relevant. - Statistics:
- Mean values and standard deviation 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, but tested up to precipitating concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 1537
- Metabolic activation:
- with
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity, but tested up to precipitating concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 1537
- Metabolic activation:
- without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- 2500 and 5000 µg/plate
- 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, but tested up to precipitating concentrations
- 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, but tested up to precipitating concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- 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, but tested up to precipitating concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: In the pre-experiment/experiment 1 the test item precipitated in the overlay agar in the test tubes and on the incubated agar plates from 1000 to 5000 μg/plate. In experiment II precipitation of the test item was observed in the overlay agar in the test tubes and on the incubated agar plates from 2500 to 5000 μg/plate. The undissolved particles had no influence on the data recording.
RANGE-FINDING/SCREENING STUDIES: A pre-test (experiment I, plate incorporation method) was performed with all strains used to evaluate the toxicity of the test item and to choose a concentration range for experiment II. The test substance was tested with and without metabolic activation at eight concentrations ranging from 3 - 5000 µg/plate. A reduction in the number was observed in one strain only (TA 1537) at 2500 and 5000 µg/plate (precipitating concentrations) in the absence of metabolic activation. Thus, the same concentrations with the exception of 3 µg/plate were used in experiment II.
HISTORICAL CONTROL DATA (with ranges, means and standard deviation and confidence interval (e.g. 95%)
- Positive historical control data: The historical control data represent approximately 550 experiments for TA 1535, TA 1537, TA 98 and TA 100 and approximately 200 experiments for TA 102 (from 2011; see table 1).
- Negative (solvent/vehicle) historical control data: The historical control data represent approximately 550 experiments for TA 1535, TA 1537, TA 98 and TA 100 and approximately 200 experiments for TA 102 (from 2011; see table 1).
Any other information on results incl. tables
Table 1 Historical control data
Strain |
|
without S9 mix |
with S9 mix |
||||||
Mean |
SD |
Min |
Max |
Mean |
SD |
Min |
Max |
||
TA 1535 |
Solvent control |
14 |
2.37 |
9 |
23 |
20 |
3.75 |
11 |
35 |
Untreated control |
14 |
2.87 |
7 |
25 |
20 |
3.82 |
10 |
32 |
|
Positive control |
1751 |
226.44 |
710 |
2385 |
367 |
93.12 |
126 |
703 |
|
TA 1537 |
Solvent control |
12 |
3.31 |
5 |
26 |
16 |
4.34 |
7 |
30 |
Untreated control |
12 |
4.03 |
5 |
29 |
18 |
4.92 |
6 |
33 |
|
Positive control |
88 |
38.92 |
61 |
448 |
342 |
144.31 |
77 |
809 |
|
TA 98 |
Solvent control |
30 |
5.60 |
17 |
47 |
40 |
6.08 |
21 |
58 |
Untreated control |
31 |
6.36 |
17 |
55 |
42 |
6.83 |
24 |
68 |
|
Positive control |
372 |
78.05 |
158 |
595 |
2167 |
717.60 |
249 |
4089 |
|
TA 100 |
Solvent control |
142 |
29.42 |
86 |
243 |
156 |
29.4 |
99 |
249 |
Untreated control |
450 |
28.19 |
86 |
248 |
163 |
31.26 |
94 |
281 |
|
Positive control |
1741 |
488.75 |
569 |
3082 |
2642 |
796.59 |
825 |
4503 |
|
TA 102 |
Solvent control |
380 |
43.64 |
305 |
510 |
502 |
89.88 |
321 |
677 |
Untreated control |
372 |
41.71 |
300 |
479 |
511 |
87.27 |
315 |
659 |
|
Positive control |
2499 |
898.06 |
1080 |
4678 |
2329 |
598.00 |
1091 |
3972 |
Mean = mean value of revertants/plate; SD = standard deviation; Min = minimal value; Max = maximal value
Table 2. Test results of the pre-experiment/experiment I (plate incorporation)
With or without S9-Mix |
Test substance concentration [µg/plate] |
Mean number of revertant colonies per plate (average of 3 plates ± standard deviation) |
||||
TA 1535 |
TA 1537 |
TA 98 |
TA 100 |
TA 102 |
||
- |
0 (DMSO) |
13 ± 3 |
10 ± 4 |
33 ± 3 |
88 ± 4 |
355 ± 22 |
- |
0 |
14 ± 1 |
11 ± 2 |
37 ± 6 |
98 ± 6 |
329 ± 24 |
- |
3 |
15 ± 2 |
10 ± 5 |
34 ± 6 |
83 ± 2 |
325 ± 49 |
- |
10 |
11 ± 2 |
7 ± 2 |
30 ± 6 |
85 ± 4 |
366 ± 29 |
- |
33 |
12 ± 4 |
9 ± 1 |
24 ± 3 |
90 ± 6 |
366 ± 19 |
- |
100 |
16 ± 5 |
8 ± 0 |
35 ± 9 |
89 ± 23 |
311 ± 29 |
- |
333 |
13 ± 3 |
7 ± 2 |
30 ± 1 |
87 ± 12 |
317 ± 9 |
- |
1000 |
13 ± 8P |
8 ± 2P |
27 ± 6P |
90 ± 23P |
316 ± 2P |
- |
2500 |
11 ± 2P,M |
4 ± 2P,M |
28 ± 4P,M |
94 ± 9P,M |
224 ± 27P,M |
- |
5000 |
9 ± 2P,M |
3 ± 1P,M |
21 ± 1P,M |
92 ± 12P,M |
172 ± 9P,M |
Positive controls, - S9 |
Na-azide, 10 µg/plate |
1913 ± 54 |
|
|
1949 ± 122 |
|
4-NOPD, 10 µg/plate |
|
|
254 ± 69 |
|
|
|
4-NOPD, 50 µg/plate |
|
72 ± 6 |
|
|
|
|
MMS, 2.0 µL/plate |
|
|
|
|
3681 ± 508 |
|
+ |
0 (DMSO) |
20 ± 3 |
18 ± 4 |
29 ± 6B,M |
137 ± 10 |
484 ± 36 |
+ |
0 |
16 ± 5 |
16 ± 1 |
36 ± 6B,M |
147 ± 10 |
533 ± 17 |
+ |
3 |
19 ± 6 |
18 ± 3 |
27 ± 5B,M |
131 ± 10 |
460 ± 34 |
+ |
10 |
16 ± 4 |
16 ± 4 |
26 ± 6B,M |
137 ± 11 |
494 ± 26 |
+ |
33 |
21 ± 4 |
17 ± 5 |
23 ± 3B,M |
126 ± 8 |
512 ± 65 |
+ |
100 |
18 ± 7 |
15 ± 2 |
28 ± 4B,M |
140 ± 3 |
459 ± 47 |
+ |
333 |
17 ± 4 |
21 ± 2 |
29 ± 2B,M |
132 ± 11 |
439 ± 9 |
+ |
1000 |
18 ± 4 |
12 ± 3 |
31 ± 7B,M |
111 ± 8 |
485 ± 39 |
+ |
2500 |
16 ± 3P |
10 ± 1P,M |
31 ± 4B,P,M |
115 ± 11P |
514 ± 11P |
+ |
5000 |
12 ± 2P,M |
10 ±3P,M |
33 ± 8B,P,M |
119 ± 6P,M |
410 ± 1P,M |
Positive controls, + S9 |
2-AA, 2.5 µg/plate |
414 ± 23 |
373 ± 35 |
1905 ± 100B,M |
3106 ± 300 |
|
2-AA, 10 µg/plate |
|
|
|
|
3158 ± 70 |
Na-azide: sodium azide; 4-NOPD: 4-nitro-o-phenylene diamine; MMS: methylmethanesulfonate; 2-AA: 2-aminoanthracene
P = precipitate; M = manual count, B = extensive bacterial growth
Table 3. Test results of the experiment II (preincubation)
With or without S9-Mix |
Test substance concentration [µg/plate] |
Mean number of revertant colonies per plate (average of 3 plates ± standard deviation) |
||||
TA 1535 |
TA 1537 |
TA 98 |
TA 100 |
TA 102 |
||
- |
0 (DMSO) |
14 ± 5 |
9 ± 0 |
25 ± 9 |
90 ± 3 |
363 ± 4 |
- |
0 |
15 ± 4 |
8 ± 4 |
32 ± 12 |
98 ± 5 |
384 ± 19 |
- |
10 |
12 ± 6 |
9 ± 2 |
25 ± 7 |
101 ± 15 |
391 ± 18 |
- |
33 |
13 ± 3 |
8 ± 0 |
25 ± 4 |
81 ± 3 |
381 ± 20 |
- |
100 |
11 ± 3 |
9 ± 1 |
25 ± 3 |
98 ± 12 |
359 ± 27 |
- |
333 |
13 ± 5 |
9 ± 3 |
28 ± 2 |
85 ± 7 |
368 ± 34 |
- |
1000 |
12 ± 2 |
8 ± 1 |
22 ± 7 |
98 ± 19 |
398 ± 22 |
- |
2500 |
14 ± 1P |
8 ± 2P,M |
24 ± 6P |
87 ± 11P |
399 ± 10P |
- |
5000 |
11 ± 3P,M |
5 ± 3P,M |
20 ± 2P,M |
89 ± 11P,M |
330 ± 42P,M |
Positive controls, - S9 |
Na-azide, 10 µg/plate |
1939 ± 64 |
|
|
2144 ± 26 |
|
4-NOPD, 10 µg/plate |
|
|
342 ± 28 |
|
|
|
4-NOPD, 50 µg/plate |
|
68 ± 7 |
|
|
|
|
MMS, 2.0 µL/plate |
|
|
|
|
3761 ± 15 |
|
+ |
0 (DMSO) |
20 ± 3 |
18 ± 4 |
44 ± 8 |
129 ± 13 |
522 ± 27 |
+ |
0 |
18 ± 3 |
20 ± 5 |
45 ± 3 |
152 ± 10 |
493 ± 6 |
+ |
10 |
20 ± 4 |
17 ± 3 |
42 ± 5 |
133 ± 17 |
522 ± 25 |
+ |
33 |
22 ± 9 |
15 ± 7 |
37 ± 3 |
137 ± 21 |
527 ± 37 |
+ |
100 |
18 ± 4 |
19 ± 6 |
47 ± 15 |
137 ± 11 |
546 ± 63 |
+ |
333 |
19 ± 6 |
21 ± 2 |
41 ± 6 |
142 ± 14 |
476 ± 29 |
+ |
1000 |
23 ± 3 |
17 ± 2 |
50 ± 2 |
127 ± 9 |
509 ± 19 |
+ |
2500 |
20 ± 3P |
15 ± 5P |
61 ± 4P |
124 ± 4P |
557 ± 22P |
+ |
5000 |
13 ± 5P,M |
12 ± 4P,M |
46 ± 8P,M |
127 ± 9P,M |
534 ± 23P,M |
Positive controls, + S9 |
2-AA, 2.5 µg/plate |
415 ± 40 |
269 ± 8 |
2314 ± 458 |
3638 ± 20 |
|
2-AA, 10 µg/plate |
|
|
|
|
2217 ± 259 |
Na-azide: sodium azide; 4-NOPD: 4-nitro-o-phenylene diamine; MMS: methylmethanesulfonate; 2-AA: 2-aminoanthracene
P = precipitate; M = manual count
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