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EC number: 911-527-9 | CAS number: -
- 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
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- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
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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
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
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- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
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- Exposure related observations in humans
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- 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:
- 21 June 2017 - 13 July 2017
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 017
- Report date:
- 2018
Materials and methods
Test guidelineopen allclose all
- 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
- Qualifier:
- according to guideline
- Guideline:
- JAPAN: Guidelines for Screening Mutagenicity Testing Of Chemicals
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- bacterial reverse mutation assay
Test material
- Reference substance name:
- Reaction product of 1,5-naphthylene diisocyanate (221-641-4) and cyclohexylamine (203-629-0)
- Molecular formula:
- C24H32N4O2
- IUPAC Name:
- Reaction product of 1,5-naphthylene diisocyanate (221-641-4) and cyclohexylamine (203-629-0)
- Test material form:
- solid
Constituent 1
Method
Species / strainopen allclose all
- 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:
- S-9 mix
- Test concentrations with justification for top dose:
- The eight concentrations of the test item in experiment 1 were: 1.5, 5, 15, 50, 150, 500, 1500 and 5000 µg/plate. The maximum concentration was 5000 µg/plate, the maximum recommended dose level.
In experiment 2 concentrations were: 5, 50, 150, 500, 1500 and 5000 µg/plate. - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: Dimethyl formide (DMF)
- Justification for choice of solvent/vehicle: The test item was insoluble in sterile distilled water, dimethyl sulphoxide, dimethyl formamide and acetonitrile at 50 mg/mL, acetone at 100 mg/mL and tetrahydrofuran at 200 mg/mL in solubility checks performed in–house. The test item formed the best doseable suspension in dimethyl formamide, therefore, this solvent was selected as the vehicle.
Controls
- Untreated negative controls:
- yes
- Remarks:
- Untreated
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMF
- Positive controls:
- yes
- Positive control substance:
- 4-nitroquinoline-N-oxide
- 9-aminoacridine
- N-ethyl-N-nitro-N-nitrosoguanidine
- benzo(a)pyrene
- other: 2-Aminoanthracene (2AA); In DMSO solvent; Used in the presence of S9-mix
- Details on test system and experimental conditions:
- METHOD OF APPLICATION:
Experiment 1 in agar (plate incorporation); Experiment 2: Preincubation method
DURATION
- Preincubation period: At 37 ± 3 °C for 20 minutes (in experiment 2 only)
- Exposure duration: 48 hours
NUMBER OF REPLICATIONS: 3
- Number of independent experiments: 2 - Rationale for test conditions:
- The test method was designed to be compatible with the guidelines for bacterial mutagenicity testing published by the major Japanese Regulatory Authorities including METI, MHLW and MAFF, the OECD Guidelines for Testing of Chemicals No. 471 "Bacterial Reverse Mutation Test", Method B13/14 of Commission Regulation (EC) number 440/2008 of 30 May 2008 and the USA, EPA OCSPP harmonized guideline - Bacterial Reverse Mutation Test.
- Evaluation criteria:
- There are several criteria for determining a positive result. Any, one, or all of the following can be used to determine the overall result of the study:
1. A dose-related increase in mutant frequency over the dose range tested (De Serres and Shelby, 1979).
2. A reproducible increase at one or more concentrations.
3. Biological relevance against in-house historical control ranges.
4. Statistical analysis of data as determined by UKEMS (Mahon et al., 1989).
5. Fold increase greater than two times the concurrent solvent control for any tester strain (especially if accompanied by an out-of-historical range response (Cariello and Piegorsch, 1996)).
A test item will be considered non-mutagenic (negative) in the test system if the above criteria are not met. - Statistics:
- Statistical significance was confirmed by using Dunnetts Regression Analysis (* = p < 0.05) for those values that indicate statistically significant increases in the frequency of revertant colonies compared to the concurrent solvent control.
Results and discussion
Test resultsopen allclose all
- Species / strain:
- S. typhimurium TA 100
- Remarks:
- Plate incorporation and pre-incubation methods
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 1535
- Remarks:
- Plate incorporation and pre-incubation methods
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Species / strain:
- E. coli WP2 uvr A
- Remarks:
- Plate incorporation and pre-incubation methods
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 98
- Remarks:
- Plate incorporation and pre-incubation methods
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 1537
- Remarks:
- Plate incorporation and pre-incubation methods
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: None reported
- Effects of osmolality: None reported
- Evaporation from medium: None reported
- Water solubility: The test item was insoluble in sterile distilled water, dimethyl sulphoxide, dimethyl formamide and acetonitrile at 50 mg/mL, acetone at 100 mg/mL and tetrahydrofuran at 200 mg/mL in solubility checks performed in–house. The test item formed the best doseable suspension in dimethyl formamide, therefore, this solvent was selected as the vehicle.
- Precipitation: In Experiment 1, (plate incorporation method) a test item precipitate (greasy in appearance) was observed at and above 1500 μg/plate. In Experiment 2, (pre-incubation method) a greasy test item precipitate was again observed from 1500 μg/plate with a white particulate precipitate also noted at 5000 μg/plate. None of these observations prevented the scoring of revertant colonies.
- Other confounding effects: None reported
RANGE-FINDING/SCREENING STUDIES: The results of experiment 1 (plate incorporation method) were used to inform the dose selection for experiment 2 (pre-incubation method)
HISTORICAL CONTROL DATA (with ranges, means and standard deviation and confidence interval (e.g. 95%)
- Positive historical control data: See tables 6 and 7
- Negative (solvent/vehicle) historical control data: See tables 8 and 9
Any other information on results incl. tables
Table 2: Test Results: Experiment 1 - Without Metabolic Activation (Plate Incorporation)
Test Period |
From: 28 June 2017 |
To: 01 July 2017 |
|||||||||
S9 -Mix (-) |
Dose Level Per Plate |
Number of revertants (mean) +/- SD |
|||||||||
Base-pair substitution strains |
Frameshift strains |
||||||||||
TA100 |
TA1535 |
WP2uvrA |
TA98 |
TA1537 |
|||||||
Solvent Control (DMF) |
101 |
(94) 5.9# |
12 |
(13) 1.2 |
33 |
(35) 2.6 |
16 |
(15) 1.2 |
12 |
(11) 1.0 |
|
92 |
14 |
34 |
16 |
11 |
|||||||
90 |
14 |
38 |
14 |
10 |
|||||||
1.5 µg |
89 |
(83) 5.6 |
10 |
(12) 1.5 |
30 |
(29) 1.7 |
19 |
(16) 4.6 |
10 |
(11) 1.2 |
|
82 |
12 |
27 |
19 |
10 |
|||||||
78 |
13 |
30 |
11 |
12 |
|||||||
5 µg |
87 |
(84) 9.8 |
18 |
(15) 2.3 |
31 |
(29) 2.6 |
18 |
(14) 4.0 |
13 |
(14) 2.1 |
|
73 |
14 |
30 |
10 |
16 | |||||||
92 | 14 | 26 | 14 | 12 | |||||||
15 µg |
103 |
(92) 10.5 |
8 |
(11) 3.8 |
25 |
(27) 3.8 |
10 |
(11) 2.6 |
9 |
(10) 1.0 |
|
82 |
9 |
24 |
14 |
10 |
|||||||
91 |
15 |
31 |
9 |
11 |
|||||||
50 µg |
93 |
(95) 4.4 |
14 |
(13) 2.3 |
31 |
(30) 1.2 |
14 |
(14) 0.0 |
10 |
(13) 5.2 |
|
100 |
14 |
31 |
14 |
19 |
|||||||
92 |
10 |
29 |
14 |
10 |
|||||||
150 µg |
100 |
(95) 5.6 |
8 |
(11) 2.6 |
25 |
(24) 2.1 |
15 |
(16) 2.1 |
12 |
(12) 2.5 |
|
96 |
13 |
22 |
14 |
10 |
|||||||
89 |
12 |
26 |
18 |
15 |
|||||||
500 µg |
101 |
(89) 10.2 |
13 |
(13) 0.6 |
35 |
(30) 7.0 |
16 |
(16) 0.6 |
10 |
(11) 1.2 |
|
82 |
12 |
22 |
16 |
12 |
|||||||
85 |
13 |
33 |
15 |
10 |
|||||||
1500 µg |
92 P |
(98) 6.5 |
13 P |
(12) 0.6 |
34 P |
(31) 2.3 |
18 P |
(16) 1.5 |
10 P |
(10) 0.0 |
|
98 P |
12 P |
30 P |
16 P |
10 P |
|||||||
105 P |
12 P |
30 P |
15 P |
10 P |
|||||||
5000 µg |
102 P |
(102) 2.5 |
13 P |
(12) 1.7 |
32 P |
(32) 1.0 |
11 P |
(14) 2.9 |
12 P |
(13) 1.2 |
|
105 P |
13 P |
31 P |
16 P |
12 P |
|||||||
100 P |
10 P |
33 P |
16 P |
14 P |
|||||||
Positive controls S9 -Mix (-) |
Name |
ENNG |
ENNG |
ENNG |
4NQO |
9AA |
|||||
Dose Level |
3 µg |
5 µg |
2 µg |
0.2 µg |
80 µg |
||||||
No. of Revertants |
799 |
(820) 32.4 |
449 |
(450) 16.0 |
866 |
(878) 10.6 |
103 |
(118) 14.1 |
479 |
(495) 30.9 |
|
857 |
435 |
886 |
131 |
476 |
|||||||
803 |
467 |
882 |
120 |
531 |
ENNG N-ethyl-N'-nitro-N-nitrosoguanidine
4NQO 4-Nitroquinoline-1-oxide
9AA 9-Aminoacridine
P Test item precipitate
# Standard deviation
Table 3: Test Results: Experiment 1 - With Metabolic Acitvation (Plate Incorporation)
Test Period |
From: 28 June 2017 |
To: 01 July 2017 |
|||||||||
S9 -Mix (+) |
Dose Level Per Plate |
Number of revertants (mean) +/- SD |
|||||||||
Base-pair substitution strains |
Frameshift strains |
||||||||||
TA100 |
TA1535 |
WP2uvrA |
TA98 |
TA1537 |
|||||||
Solvent Control (DMF) |
95 |
(98) 7.9# |
11 |
(12) 1.7 |
38 |
(41) 4.6 |
18 |
(22) 4.7 |
8 |
(9) 1.2 |
|
92 |
11 |
46 |
20 |
10 |
|||||||
107 |
14 |
38 |
27 |
8 |
|||||||
1.5 µg |
84 |
(103) 16.5 |
7 |
(9) 2.9 |
48 |
(38) 9.5 |
23 |
(18) 6.1 |
14 |
(12) 2.5 |
|
114 |
12 |
37 |
11 |
9 |
|||||||
111 |
7 |
29 |
19 |
12 |
|||||||
5 µg |
100 |
(100) 3.5 |
12 |
(12) 1.0 |
37 |
(38) 2.3 |
18 |
(18) 7.0 |
10 |
(9) 1.2 |
|
97 |
13 |
41 |
25 |
10 |
|||||||
104 |
11 |
37 |
11 |
8 |
|||||||
15 µg |
102 |
(91) 14.7 |
9 |
(13) 3.5 |
37 |
(39) 4.7 |
19 |
(23) 3.8 |
8 |
(9) 0.6 |
|
74 |
16 |
44 |
25 |
9 |
|||||||
96 |
13 |
35 |
26 |
9 |
|||||||
50 µg |
96 |
(94) 16.1 |
15 |
(15) 3.0 |
41 |
(39) 2.9 |
33 |
(26) 9.9 |
11 |
(9) 1.5 |
|
109 |
12 |
41 |
31 |
9 |
|||||||
77 |
18 |
36 |
15 |
8 |
|||||||
150 µg |
104 |
(96) 12.7 |
11 |
(15) 3.6 |
38 |
(35) 3.1 |
20 |
(24) 6.4 |
9 |
(11) 1.5 |
|
81 |
18 |
32 |
31 |
12 |
|||||||
102 |
16 |
36 |
20 |
11 |
|||||||
500 µg |
102 |
(97) 7.8 |
11 |
(14) 5.8 |
40 |
(41) 1.5 |
20 |
(21) 1.0 |
8 |
(9) 1.5 |
|
101 |
11 |
43 |
22 |
9 |
|||||||
88 |
21 |
41 |
21 |
11 |
|||||||
1500 µg |
85 P |
(93) 8.5 |
15 P |
(13) 1.5 |
27 P |
(30) 9.3 |
20 P |
(20) 0.6 |
10 P |
(9) 1.2 |
|
92 P |
13 P |
40 P |
20 P |
8 P |
|||||||
102 P |
12 P |
22 P |
21 P |
8 P |
|||||||
5000 µg |
100 P |
(101) 0.6 |
13 P |
(13) 1.5 |
38 P |
(41) 4.2 |
24 P |
(22) 2.1 |
5 P |
(10) 4.6 |
|
101 P |
15 P |
46 P |
20 P |
13 P |
|||||||
101 P |
12 P |
40 P |
21 P |
13 P |
|||||||
Positive controls S9 -Mix (+) |
Name |
2AA |
2AA |
2AA |
BP |
2AA |
|||||
Dose Level |
1 µg |
2 µg |
10 µg |
5 µg |
2 µg |
||||||
No. of Revertants |
1993 |
(2032) 111.2 |
293 |
(304) 22.9 |
245 |
(243) 15.1 |
223 |
(228) 4.2 |
552 |
(532) 37.3 |
|
2157 |
330 |
257 |
229 |
555 |
|||||||
1945 |
288 |
227 |
231 |
489 |
BP Benzo(a)pyrene
2AA 2-Aminoanthracene
P Test item precipitate
# Standard deviation
Table 4: Test results; Experiment 2 - Without Metabolic Activation (Pre-Incubation)
Test Period | From: 10 July 2017 | To: 13 July 2017 | |||||||||
S9 -Mix (-) |
Dose Level Per Plate |
Number of revertants (mean) +/- SD |
|||||||||
Base-pair substitution strains |
Frameshift strains |
||||||||||
TA100 |
TA1535 |
WP2uvrA |
TA98 |
TA1537 |
|||||||
Solvent Control (DMF) |
67 |
(76) 10.5# |
9 |
(9) 2.0 |
13 |
(16) 3.1 |
11 |
(14) 3.0 |
8 |
(11) 3.0 |
|
86 |
11 |
19 |
14 |
11 |
|||||||
77 |
7 |
15 |
17 |
14 |
|||||||
15 µg |
69 |
(70) 7.5 |
16 |
(14) 2.9 |
19 |
(16) 4.4 |
14 |
(15) 0.6 |
13 |
(13) 4.5 |
|
63 |
16 |
11 |
15 |
8 |
|||||||
78 |
11 |
18 |
15 |
17 |
|||||||
50 µg |
74 |
(76) 4.9 |
7 |
(11) 4.6 |
18 |
(17) 5.6 |
19 |
(17) 8.6 |
12 |
(14) 4.7 |
|
73 |
10 |
22 |
25 |
19 |
|||||||
82 |
16 |
11 |
8 |
10 |
|||||||
150 µg |
75 |
(74) 5.1 |
10 |
(14) 7.8 |
21 |
(18) 3.5 |
20 |
(17) 3.0 |
7 |
(12) 5.0 |
|
78 |
9 |
14 |
17 |
12 |
|||||||
68 |
23 |
18 |
14 |
17 |
|||||||
500 µg |
80 |
(79) 4.2 |
9 |
(15) 7.2 |
15 |
(15) 0.6 |
13 |
(15) 3.8 |
19 |
(15) 4.5 |
|
74 |
23 |
15 |
12 |
15 |
|||||||
82 |
13 |
16 |
19 |
10 |
|||||||
1500 µg |
73 P |
(83) 9.0 |
16 P |
(15) 2.3 |
18 P |
(14) 3.5 |
10 P |
(16) 6.6 |
13 P |
(16) 3.1 |
|
88 P |
16 P |
12 P |
23 P |
19 P |
|||||||
89 P |
12 P |
12 P |
15 P |
17 P |
|||||||
5000 µg |
69 P |
(81) 10.8 |
7 P |
(8) 1.0 |
17 P |
(15) 2.1 |
13 P |
(10) 3.1 |
9 P |
(9) 1.5 |
|
86 P |
9 P |
14 P |
7 P |
8 P |
|||||||
89 P |
8 P |
13 P |
11 P |
11 P |
|||||||
Positive controls S9 -mix (-) |
Name |
ENNG |
ENNG |
ENNG |
4NQO |
9AA |
|||||
Dose Level |
3 µg |
5 µg |
2 µg |
0.2 µg |
80 µg |
||||||
No. of revertants |
872 |
(906) 72.6 |
136 |
(141) 10.1 |
647 |
(626) 20.5 |
406 |
(437) 33.7 |
202 |
(182) 30.7 |
|
989 |
135 |
626 |
433 |
198 |
|||||||
856 |
153 |
606 |
473 |
147 |
ENNG N-ethyl-N'-nitro-N-nitrosoguanidine
4NQO 4-Nitroquinoline-1-oxide
9AA 9-Aminoacridine
P Test item precipitate
# Standard deviation
Table 5: Test results; Experiment 2 - With Metabolic Activation (Pre-incubation)
Test Period | From: 10 July 2017 | To: 13 July 2017 | |||||||||
S9 -Mix (+) |
Dose Level Per Plate |
Number of revertants (mean) +/- SD |
|||||||||
Base-pair substitution strains |
Frameshift strains |
||||||||||
TA100 |
TA1535 |
WP2uvrA |
TA98 |
TA1537 |
|||||||
Solvent Control (DMF) |
82 |
(76) 7.9# |
12 |
(11) 3.2 |
16 |
(20) 3.2 |
19 |
(18) 1.2 |
14 |
(14) 1.5 |
|
67 |
7 |
22 |
17 |
12 |
|||||||
79 |
13 |
21 |
19 |
15 |
|||||||
15 µg |
75 |
(77) 8.7 |
11 |
(13) 4.7 |
20 |
(18) 4.7 |
24 |
(21) 3.5 |
13 |
(13) 0.6 |
|
87 |
9 |
22 |
17 |
13 |
|||||||
70 |
18 |
13 |
21 |
14 |
|||||||
50 µg |
75 |
(79) 8.4 |
11 |
(10) 2.6 |
23 |
(18) 5.0 |
17 |
(19) 2.1 |
13 |
(14) 2.6 |
|
89 |
12 |
17 |
21 |
17 |
|||||||
74 |
7 |
13 |
20 |
12 |
|||||||
150 µg |
80 |
(71) 8.5 |
12 |
(11) 2.1 |
13 |
(20) 9.5 |
18 |
(22) 3.5 |
16 |
(16) 2.5 |
|
71 |
13 |
31 |
22 |
14 |
|||||||
63 |
9 |
17 |
25 |
19 |
|||||||
500 µg |
95 |
(84) 10.0 |
13 |
(17) 4.7 |
15 |
(16) 1.7 |
29 |
(24) 4.7 |
13 |
(9) 3.2 |
|
76 |
22 |
18 |
22 |
8 |
|||||||
80 |
15 |
15 |
20 |
7 |
|||||||
1500 µg |
77 P |
(92) 14.2 |
13 P |
(13) 0.6 |
23 P |
(26) 2.6 |
25 P |
(21) 3.6 |
10 P |
(10) 1.5 |
|
105 P |
13 P |
28 P |
18 P |
11 P |
|||||||
95 P |
12 P |
27 P |
20 P |
8 P |
|||||||
5000 µg |
79 P |
(77) 1.7 |
11 P |
(12) 1.0 |
16 P |
(19) 5.8 |
14 P |
(14) 2.5 |
7 P |
(8) 1.5 |
|
76 P |
13 P |
16 P |
12 P |
10 P |
|||||||
76 P |
12 P |
26 P |
17 P |
8 P |
|||||||
Positive controls S9 -mix (+) |
Name |
2AA |
2AA |
2AA |
BP |
2AA |
|||||
Dose Level |
1 µg |
2 µg |
10 µg |
5 µg |
2 µg |
||||||
No. of revertants |
1839 |
(1720) 114.4 |
229 |
(238) 14.2 |
143 |
(143) 19.5 |
195 |
(175) 26.3 |
319 |
(352) 31.6 |
|
1709 |
254 |
123 |
184 |
354 |
|||||||
1611 |
230 |
162 |
145 |
382 |
2AA 2-Aminoanthracene
BP Benzo(a)pyrene
P Test item precipitate
# Standard deviation
Table 6: Positive Control Values 2015
Strain S9 -Mix | TA100 | TA1535 | TA102 | WP2uvrA | TA98 | TA1537 | WP2uvrApKM101 |
WP2pKM101 | ||||||||
-S9 | +S9 | -S9 | +S9 | -S9 | +S9 | -S9 | +S9 | -S9 | +S9 | -S9 | +S9 | -S9 | +S9 | -S9 | +S9 | |
Values* | 276 | 280 | 252 | 264 | 13 | 13 | 231 | 227 | 262 | 276 | 253 | 261 | 20 | 35 | 20 | 35 |
Min | 222 | 250 | 79 | 118 | 953 | 673 | 116 | 103 | 100 | 78 | 164 | 97 | 430 | 494 | 745 | 325 |
Max | 2266 | 2402 | 2779 | 457 | 3140 | 1655 | 2769 | 550 | 502 | 705 | 2318 | 823 | 1696 | 2264 | 3662 | 1174 |
Mean | 614 | 927 | 472 | 246 | 2303 | 1093 | 792 | 266 | 222 | 218 | 911 | 336 | 761 | 1461 | 2257 | 569 |
SD | 260.6 | 452.5 | 434.8 | 55.7 | 815.2 | 376.5 | 342.1 | 97.7 | 70.2 | 107.6 | 412.4 | 135.7 | 350.0 | 382.0 | 790.7 | 220.3 |
SD standard deviation
Min minimum value
Max maximum value
* Number of mean values used to create dataset
Table 7: Positive control values 2016
Strain S9 -Mix | TA100 | TA1535 | TA102 | WP2uvrA | TA98 | TA1537 | WP2 uvrA pKM101 |
WP2pKM101 | ||||||||
-S9 | +S9 | -S9 | +S9 | -S9 | +S9 | -S9 | +S9 | -S9 | +S9 | -S9 | +S9 | -S9 | +S9 | -S9 | +S9 | |
Values | 409 | 406 | 381 | 386 | 30 | 28 | 341 | 335 | 388 | 385 | 379 | 381 | 14 | 24 | 8 | 16 |
Min | 221 | 284 | 84 | 92 | 897 | 629 | 107 | 102 | 100 | 96 | 95 | 101 | 445 | 574 | 1674 | 372 |
Max | 2222 | 2863 | 2994 | 879 | 2326 | 2140 | 1611 | 637 | 449 | 4357 | 1413 | 639 | 1117 | 1855 | 2823 | 945 |
Mean | 724 | 1264 | 854 | 240 | 1633 | 950 | 718 | 240 | 186 | 188 | 406 | 290 | 743 | 1271 | 2379 | 535 |
SD | 320.4 | 562.9 | 664.9 | 62.1 | 564.5 | 382.7 | 338.6 | 98.2 | 49.8 | 230.8 | 227.0 | 92.7 | 214.6 | 326.5 | 426.2 | 143.3 |
Table 8: Combined Vehicle and Untreated Control Values 2015
Strain S9 -Mix | TA100 | TA1535 | TA102 | WP2uvrA | TA98 | TA1537 | WP2uvrApKM101 |
WP2pKM101 | ||||||||
-S9 | +S9 | -S9 | +S9 | -S9 | +S9 | -S9 | +S9 | -S9 | +S9 | -S9 | +S9 | -S9 | +S9 | -S9 | +S9 | |
Values | 274 | 278 | 504 | 285 | 26 | 13 | 461 | 229 | 526 | 299 | 506 | 282 | 42 | 51 | 39 | 49 |
Min | 60 | 61 | 7 | 7 | 222 | 278 | 10 | 12 | 11 | 10 | 4 | 6 | 87 | 98 | 89 | 93 |
Max | 166 | 175 | 31 | 29 | 376 | 388 | 58 | 43 | 45 | 46 | 27 | 27 | 237 | 254 | 174 | 177 |
Mean | 91 | 95 | 16 | 14 | 286 | 333 | 24 | 27 | 21 | 24 | 12 | 13 | 156 | 164 | 123 | 137 |
SD | 19.3 | 19.1 | 4.5 | 4.0 | 48.7 | 37.6 | 5.6 | 5.9 | 6.2 | 6.1 | 3.8 | 3.4 | 42.2 | 35.6 | 23.1 | 21.2 |
Table 9: Combined Vehicle and Untreated Control Values 2016
Strain S9 -Mix | TA100 | TA1535 | TA102 | WP2uvrA | TA98 | TA1537 | WP2uvrApKM101 |
WP2pKM101 | ||||||||
-S9 | +S9 | -S9 | +S9 | -S9 | +S9 | -S9 | +S9 | -S9 | +S9 | -S9 | +S9 | -S9 | +S9 | -S9 | +S9 | |
Values | 399 | 401 | 758 | 393 | 60 | 30 | 690 | 345 | 788 | 415 | 762 | 398 | 32 | 32 | 16 | 24 |
Min | 63 | 66 | 8 | 8 | 216 | 221 | 10 | 13 | 8 | 12 | 3 | 4 | 97 | 104 | 78 | 52 |
Max | 154 | 156 | 34 | 39 | 30 | 375 | 53 | 53 | 49 | 51 | 24 | 23 | 268 | 243 | 148 | 166 |
Mean | 90 | 93 | 15 | 15 | 268 | 310 | 22 | 27 | 21 | 25 | 12 | 13 | 161 | 159 | 118 | 110 |
SD | 14.5 | 14.3 | 4.5 | 5.2 | 26.4 | 31.1 | 5.8 | 6.3 | 4.8 | 5.7 | 3.5 | 3.5 | 39.2 | 32.3 | 17.0 | 29.3 |
Applicant's summary and conclusion
- Conclusions:
- For the test item there were no increases in the frequency of revertant colonies recorded for any of the bacterial strains, with any dose of the test item, either with or without metabolic activation (S9-mix) in Experiment 1 (plate incorporation method). Similarly, no increases in the frequency of revertant colonies were recorded for any of the bacterial strains, with any dose of the test item, either with or without metabolic activation (S9-mix) in Experiment 2 (pre-incubation method). R59 was considered to be non-mutagenic under the conditions of this test.
- Executive summary:
The genetic toxicity of the test item was investigated in an OECD 471, EU method B13/14 and US EPA 870.1500 guideline study. The study was conducted with two experiments, Experiment 1 was a plate incorporation method and Experiment 2 was a pre-incubation method with both experiments performed with and without metabolic activation. The study was performed at concentrations of 1.5, 5, 15, 50, 150, 500, 1500 and 5000 µg/plate and 15, 50, 150, 500 and 1500 µg/plate for experiment 1 and 2, respectively, with DMF used as the vehicle solvent. The studies without metabolic activation utilised N-ethyl-N'-nitro-N-nitrosoguanidine, 4 -Nitroquinoline-1 -oxide and 9 -Aminoacridine as positive control substances; the studies with metabolic activation utilised Benzo(a)pyrene and 2 -Aminoanthracene as positive control substances. Untreated test media was used as the negative control in all experiments.
There were no increases in the frequency of revertant colonies recorded for any of the bacterial strains, with any dose of the test item, either with or without metabolic activation (S9-mix) in Experiment 1 (plate incorporation method). Similarly, no increases in the frequency of revertant colonies were recorded for any of the bacterial strains, with any dose of the test item, either with or without metabolic activation (S9-mix) in Experiment 2 (pre-incubation method). The test item was considered to be non-mutagenic under the conditions of this test.
The study is a GLP compliant guideline experimental study, without restrictions and is fully adequate for assessment of this endpoint.
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