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EC number: 448-300-4 | CAS number: 88642-03-9
- 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:
- 2005-10-02
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 005
- Report date:
- 2005
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Version / remarks:
- 1997
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
- Version / remarks:
- 2000
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- bacterial reverse mutation assay
Test material
- Reference substance name:
- -
- EC Number:
- 448-300-4
- EC Name:
- -
- Cas Number:
- 88642-03-9
- Molecular formula:
- C16H28O
- IUPAC Name:
- (6E)-cyclohexadec-6-en-1-one; (7Z)-cyclohexadec-7-en-1-one; (8E)-cyclohexadec-8-en-1-one; (8Z)-cyclohexadec-8-en-1-one
Constituent 1
Method
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:
- source of S9 : Phenobarbital/ß-Naphthoflavone induced rat liver
- method of preparation of S9 mix: prepared from 8 - 12 weeks old male Wistar Hanlbm rats (approx. 220 - 320 g) induced by applications of 80 mg/kg b.w. Phenobarbital i.p. (Desitin; D-22335 Hamburg) and ß-Naphthoflavone p.o. (Aldrich, D-89555 Steinheim) each on three consecutive days. The livers are prepared 24 hours after the last treatment. The S9 fractions are produced by dilution of the liver homogenate with a KCI solution (1+3) followed by centrifugation at 9000 g. Aliquots of the supernatant are frozen and stored in ampoules at -80° C. Small numbers of the ampoules can be kept at -20°C for up to one week. The protein concentration in the S9 preparation was 34.5 mg/mL (lot no. R 300404) in the pre-experiment and experiment I (strains TA 98 and TA 100), and 32.8 mg/mL (lot no. R 151004) in experiment I and II.
- concentration or volume of S9 mix and S9 in the final culture medium: Before the experiment an appropriate quantity of S9 supernatant was thawed and mixed with S9 co-factor solution. The amount of S9 supernatant was 15% v/v in the S9 mix. Cofactors are added to the S9 mix to reach the following concentrations in the S9 mix:
8 mM MgCl2
33 mM KCI
5 mM Glucose-6-phosphate
5 mM NADP
in 100 mM sodium-ortho-phosphate-buffer, pH 7.4.
During the experiment the S9 mix was stored in an ice bath. The S9 mix preparation was performed according to Ames et al. - Test concentrations with justification for top dose:
- Pre-Experiment: 3; 10; 33; 100; 333; 1000; 2500; and 5000 µg/plate
Experiment I: 33; 100; 333; 1000; 2500; and 5000 µg/plate
Experiment II, Ila: 10; 33; 100; 333; 1000; 2500; and 5000 µg/plate
Concentrations applied in the main experiment (I, II and IIa) werer based on the results of the Pre-Experiment. - Vehicle / solvent:
- - Vehicle used: ethanol
- Justification for choice of solvent/vehicle: The solvent 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
- 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 medium; in agar (plate incorporation, experiment I) and preincubation (experiment II and IIa)
TREATMENT AND HARVEST SCHEDULE:
- Preincubation period: 60 min
- Exposure duration/duration of treatment: 48 h
METHODS FOR MEASUREMENT OF CYTOTOXICITY
- Method, e.g.: background growth inhibition
- Rationale for test conditions:
- according to the test guidelines
- 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:
- A statistical analysis of the data is not required.
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:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- 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:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- 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:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- 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:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- 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:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- True negative controls validity:
- not examined
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation and time of the determination: The test item precipitated weakly at different concentrations in the overlay agar. The undissolved particles of the test item had no influence on the data recording.
Ames test:
- Signs of toxicity : cytotoxicity was observed
HISTORICAL CONTROL DATA
- Positive historical control data: Please refer to "Any other information on results"
- Negative (solvent/vehicle) historical control data: Please refer to "Any other information on results"
Any other information on results incl. tables
Table 1 Summary of Results Pre-Experiment and Experiment I
Metabolic Activation |
Test Item |
Dose Level (µg/plate) |
Revertant Colony Counts (Mean ± SD) |
|
TA 98 |
TA 100 |
|||
Without Activation |
Ethanol |
|
36 ± 6 |
92 ± 14 |
Untreated |
|
26 ± 6 |
99 ± 6 |
|
Aurelione |
3 µg |
26 ± 3 |
91 ± 25 |
|
10 µg |
28 ± 4 |
83 ± 3 |
||
33 µg |
29 ± 7 |
74 ± 12 |
||
100 µg |
31 ± 7 |
86 ± 12 |
||
333 µg |
33 ± 6 |
70 ± 6 |
||
1000 µg |
33 ± 4 |
78 ± 11 |
||
2500 µg |
34 ± 7 |
79 ± 5 |
||
5000 µg |
31 ± 3 |
64 ± 7 |
||
4-NOPD |
10 µg |
376 ± 5 |
|
|
Sodium azide |
10 µg |
|
2211 ± 80 |
|
With Activation |
Ethanol |
|
49 ± 3 |
118 ± 10 |
Untreated |
|
37 ± 6 |
114 ± 5 |
|
Aurelione |
3 µg |
49 ± 6 |
93 ± 11 |
|
10 µg |
44 ± 6 |
104 ± 6 |
||
33 µg |
51 ± 5 |
112 ± 30 |
||
100 µg |
41 ± 4 |
124 ± 3 |
||
333 µg |
43 ± 9 |
96 ± 9 |
||
1000 µg |
37 ± 7 |
44 ± 2 |
||
2500 µg |
30 ± 5 |
45 ± 5 |
||
5000 µg |
32 ± 8 |
48 ± 3 |
||
2-AA |
2.5 µg |
2505 ± 191 |
2282 ± 179 |
4-NOPD 4-nitro-o-phenylene-diamine
2-AA 2-aminoanthracene
Table 2 Summary of Results Experiment I
Metabolic Activation |
Test Item |
Dose Level (µg/plate) |
Revertant Colony Counts (Mean ± SD) |
||
TA 1535 |
TA 1537 |
TA 102 |
|||
Without Activation |
Ethanol |
|
30±7 |
17±6 |
450±15 |
Untreated |
|
31±2 |
12±3 |
416±27 |
|
Aurelione |
33 µg |
33±8 |
20±7 |
439±24 |
|
|
100 µg |
31±9 |
15±6 |
453±28 |
|
|
333 µg |
39±6 |
8±3 |
365±62 |
|
|
1000 µg |
32±5 |
13±5 |
241±47 |
|
|
2500 µg |
30±15 |
10±2 |
167±25 |
|
|
5000 µg |
21±4 |
18±3 |
156±23 |
|
Sodium azide |
10 µg |
1228±152 |
|
|
|
4-NOPD |
50 µg |
|
94±12 |
|
|
MMS |
4.0 µL |
|
|
5696±196 |
|
With Activation |
Ethanol |
|
33±8 |
17±3 |
554±37 |
Untreated |
|
32±2 |
17±5 |
482±69 |
|
Aurelione |
33 µg |
35±8 |
18±1 |
520±76 |
|
|
100 µg |
32±4 |
18±3 |
529±69 |
|
|
333 µg |
32±2 |
9±4 |
498±10 |
|
|
1000 µg |
27±6 |
9±1 |
263±13 |
|
|
2500 µg |
30±12 |
14±3 |
189±13 |
|
|
5000 µg |
28±3 |
9±3 |
165±18 |
|
2-AA |
2.5 µg |
270±12 |
219±33 |
|
|
2-AA |
10.0 µg |
|
|
4004±238 |
4-NOPD 4-nitro-o-phenylene-diamine
MMS methyl methane sulfonate
2-AA 2-aminoanthracene
Table 3 Summary of Results Experiment II
Metabolic Activation |
Test Item |
Dose Level (µg/plate) |
Revertant Colony Counts (Mean ± SD) |
|||||
TA 1535 |
TA 1537 |
TA 98 |
TA 100 |
TA 102 |
||||
II |
IIa |
|||||||
Without Activation |
Ethanol |
|
24 ± 2 |
11 ± 1 |
34 ± 3 |
21 ± 2 |
132 ± 4 |
301 ± 3 |
Untreated |
|
22 ± 6 |
12 ± 3 |
35 ± 11 |
27 ± 6 |
144 ± 22 |
292 ± 14 |
|
Aurelione |
10 µg |
24 ± 8 |
9 ± 2 |
31 ± 4 |
26 ± 4 |
125 ± 14 |
325 ± 32 |
|
33 µg |
29 ± 6 |
11 ± 2 |
32 ± 12 |
24 ± 2 |
122 ± 7 |
327 ± 20 |
||
100 µg |
24 ± 7 |
8 ± 1 |
32 ± 6 |
21 ± 4 |
113 ± 13 |
305 ± 19 |
||
333 µg |
31 ± 2 |
11 ± 3 |
43 ± 5 |
7 ± 5 |
77 ± 5 |
243 ± 48 |
||
1000 µg |
23 ± 4 |
15 ± 8 |
52 ± 8 |
14 ± 5 |
72 ± 13 |
140 ± 3 |
||
2500 µg |
30 ± 6 |
9 ± 3 |
101 ± 13 |
n.a. |
63 ± 12 |
84 ± 9 |
||
5000 µg |
27 ± 9 |
12 ± 2 |
80 ± 4 |
n.a. |
56 ± 1 |
26 ± 5 |
||
Sodium azide |
10 µg |
1291 ± 46 |
|
|
|
1773 ± 102 |
|
|
4-NOPD |
10 µg |
|
|
458 ± 61 |
|
|
|
|
4-NOPD |
50 µg |
|
100 ± 7 |
|
354 ± 14 |
|
|
|
MMS |
4.0 µL |
|
|
|
|
|
1593 ± 130 |
|
With Activation |
Ethanol |
|
36 ± 7 |
31 ± 8 |
50 ± 1 |
|
151 ± 10 |
317 ± 16 |
Untreated |
|
35 ± 4 |
36 ± 5 |
60 ± 2 |
|
160 ± 17 |
402 ± 5 |
|
Aurelione |
10 µg |
37 ± 7 |
34 ± 3 |
53 ± 6 |
|
138 ± 3 |
360 ± 12 |
|
33 µg |
30 ± 3 |
31 ± 4 |
58 ± 10 |
|
142 ± 16 |
213 ± 32 |
||
100 µg |
31 ± 2 |
33 ± 3 |
49 ± 3 |
|
129 ± 5 |
141 ± 22 |
||
333 µg |
39 ± 3 |
41 ± 5 |
61 ± 2 |
|
114 ± 12 |
57 ± 13 |
||
1000 µg |
37 ± 8 |
31 ± 2 |
56 ± 6 |
|
85 ± 17 |
32 ± 13 |
||
2500 µg |
35 ± 5 |
4 ± 1 |
35 ± 5 |
|
98 ± 20 |
19 ± 7 |
||
5000 µg |
27 ± 4 |
6 ± 2 |
33 ± 3 |
|
77 ± 8 |
16 ± 2 |
||
2-AA |
2.5 µg |
376 ± 34 |
166 ± 19 |
1417 ± 81 |
|
1462 ± 127 |
|
|
2-AA |
10.0 µg |
|
|
|
|
|
1628 ± 128 |
4-NOPD 4-nitro-o-phenylene-diamine
MMS methyl methane sulfonate
2-AA 2-aminoanthracene
n.a. not analysable due to reduced background growth
Table 4 Historical Control Data
Strain |
|
Without S9 mix |
With S9 mix |
||||||
Mean |
SD |
Min |
Max |
Mean |
SD |
Min |
Max |
||
TA 1535 |
Solvent control Negative control Positive control |
20 18 3042 |
6 5 756 |
9 10 1003 |
30 29 3618 |
18 18 357 |
10 10 111 |
7 9 172 |
39 38 476 |
TA 1537 |
Solvent control Negative control Positive control |
11 12 97 |
7 6 21 |
4 5 52 |
29 29 191 |
18 18 141 |
9 6 47 |
6 8 94 |
31 29 380 |
TA 98 |
Solvent control Negative control Positive control |
24 26 379 |
9 10 98 |
14 15 137 |
58 52 976 |
37 43 1239 |
13 15 510 |
21 17 229 |
57 64 5466 |
TA 100 |
Solvent control Negative control Positive control |
121 141 2089 |
29 23 408 |
91 101 1262 |
198 189 2872 |
149 147 921 |
36 43 346 |
109 13 546 |
281 254 2589 |
TA 102 |
Solvent control Negative control Positive control |
338 326 2764 |
77 53 1479 |
242 242 1220 |
430 390 5593 |
426 450 2104 |
70 60 752 |
332 280 872 |
514 556 3052 |
Mean = mean value of revertants/plate
SD = standard deviation
Min = minimal value
Max = maximal value
Applicant's summary and conclusion
- Conclusions:
- In conclusion, it can be stated that during the described mutagenicity test and under the experimental conditions reported, the test item did not induce gene mutations by base pair changes or frameshifts in the genome of the strains used. Therefore, the test item is considered to be non-mutagenic in this Salmonella typhimurium reverse mutation assay.
- Executive summary:
This study was performed to investigate the potential of the test item to induce gene mutations according to the plate incorporation test (experiment I) and the pre-incubation test (experiment II) using the Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100, and TA 102, according to OECD 471. The assay was performed in two independent experiments both with and without liver microsomal activation. An additional experiment was performed as pre-incubation with strain TA 98 without S9, only (reported as exp. IIa). Each concentration, including the controls, was tested in triplicate. The test item was tested at the following concentrations:
Pre-Experiment: 3; 10; 33; 100; 333; 1000; 2500; and 5000 µg/plate
Experiment 1: 33; 100; 333; 1000; 2500; and 5000 µg/plate
Experiment II, Ila: 10; 33; 100; 333; 1000; 2500; and 5000 µg/plateThe plates incubated with the test item showed reduced background background growth in almost all strains with and without S9 mix. Toxic effects, evident as a reduction in the number of revertants, occurred in strains TA 100 (with S9 mix) and TA 102 (with and without S9 mix) in experiment I and in strains TA 98 (IIa), 100, and TA 102 without S9 mix and in strains TA 1537 and TA 102 with S9 mix in experiment II. A seemingly dose dependent increase in revertant colony numbers was observed following treatment with the test item in strain TA 98 without metabolic activation in experiment II. The number of colonies reached or exceeded the threshold of twice the number of the corresponding solvent control at concentrations of 2500 µg/plate and above in the absence of metabolic activation. To verify the results an additional experiment was performed as pre-incubation test with TA 98 without S9 mix (exp. IIa). In this experiment an increase of the revertant colonies was not observed. However, reduced background growth was observed from 333 µg/plate up to 5000 µg/plate. Therefore, the observed large number of very small colonies in experiment II were judged to be based upon toxicity rather than indicating a possible mutagenic potential. A major reduction of the background growth results in less bacteria competing for the traces of histidine introduced by the top agar. The traces of histidine are sufficient to allow the surviving bacteria to grow into very small colonies until the histidine is depleted. All other strains did not show any mutagenic effect of the test item up to the maximal concentration applied. Appropriate reference mutagens were used as positive controls and showed a distinct increase of induced revertant colonies.
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