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EC number: 941-893-5 | CAS number: 15229-79-5
- 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:
- 19-11-2014 to 14-01-2015
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Guideline study performed under GLP. All relevant validity criteria were met.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 014
- Report date:
- 2014
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:
- other: US EPA OCSPP harmonized guideline - Bacterial Reverse Mutation Test
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: Japanese Ministry of Economy, Trade and Industry, Japanese Ministry of Health, Labour and Welfare and Japanese Ministry of Agriculture, Forestry and Fisheries
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- inspected: July 2012 ; signature: November 2012
- Type of assay:
- bacterial reverse mutation assay
Test material
- Reference substance name:
- (3E,7E)-cyclododeca-3,7-dien-1-one; (4E,8Z)-cyclododeca-4,8-dien-1-one; (4Z,8E)-cyclododeca-4,8-dien-1-one
- EC Number:
- 941-893-5
- Cas Number:
- 15229-79-5
- Molecular formula:
- C12H18O
- IUPAC Name:
- (3E,7E)-cyclododeca-3,7-dien-1-one; (4E,8Z)-cyclododeca-4,8-dien-1-one; (4Z,8E)-cyclododeca-4,8-dien-1-one
- Test material form:
- liquid
- Details on test material:
- - Physical state: Liquid
- Storage condition of test material: Keep in the dark at 0 - 10 °C, under nitrogen
- Other: Colourless
Constituent 1
Method
- Target gene:
- histidine operon (Salmonella strains)
tryptophan operon (E.coli strain)
Species / strainopen allclose all
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Additional strain / cell type characteristics:
- not applicable
- Species / strain / cell type:
- E. coli WP2 uvr A
- Additional strain / cell type characteristics:
- not applicable
- Metabolic activation:
- with and without
- Metabolic activation system:
- phenobarbitone/β-naphthoflavone activated rat liver S9
- Test concentrations with justification for top dose:
- Experiment 1 (pre-incubation method): range-finding test: 1.5, 5, 15, 50, 150, 500, 1500, 5000 µg/plate
Experiment 2 (pre-incubation method): 0, 1.5, 5, 15, 50, 150, 500, 1500 and 5000 µg/plate
Up to eight test item dose levels were selected in Experiment 2 in order to achieve both a minimum of four non-toxic doses and the toxic/guideline limit of the test item following the change in test methodology. The dose levels were selected based on the results of Experiment 1.
TA 100 (- MA); TA 98, TA 1537 (+ MA); WP2 uvrA (+/- MA): 0.5, 1.5, 5, 15, 50, 150, 500 µg/plate
TA 98, TA 1535, TA 1537 (- MA); TA 1535, TA 100 (+ MA): 0.15, 0.5, 1.5, 5, 15, 50, 150 µg/plate - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: dimethyl sulphoxide (DMSO)
- Justification for choice of solvent/vehicle: the test item was immiscible in sterile distilled water at 50 mg/ml but was fully miscible in dimethyl sulphoxide at the same concentration, Dimethyl sulphoxide was selected as the vehicle.
Controlsopen allclose all
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- N-ethyl-N-nitro-N-nitrosoguanidine
- Remarks:
- WP2 uvrA: 2 µg/plate, TA 100: 3 µg/plate, TA 1535: 5 µg/plate (without activation)
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 9-aminoacridine
- Remarks:
- TA 1537: 80 µg/plate (without activation)
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 4-nitroquinoline-N-oxide
- Remarks:
- TA 98: 0.2 µg/plate (without activation)
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: 2-aminoanthracene
- Remarks:
- TA 100: 1 µg/plate, TA 1535 & TA 1537: 2 µg/plate, WP2 uvrA: 10 µg/plate (with activation)
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- benzo(a)pyrene
- Remarks:
- TA 98: 5 µg/plate (with activation)
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in medium; in agar (pre-incubation)
DURATION
- Exposure duration: 0.1 mL of the appropriate bacterial strain culture, 0.5 mL of phosphate buffer OR S9-mix (as appropriate) and 0.1 mL of the test item formulation, vehicle or 0.1 mL of appropriate positive control were incubated at 37 ± 3 ºC for 20 minutes (with shaking) prior to addition of 2 mL of molten amino-acid supplemented media. All of the plates were incubated at 37 ± 3 ºC for approximately 48 hours and scored for the presence of revertant colonies using an automated colony counting system. The plates were viewed microscopically for evidence of thinning (toxicity). A number of manual counts were performed, predominantly due to colonies spreading, thus distorting the actual plate count.
SELECTION AGENT (mutation assays): histidine or tryptophan deficient agar
NUMBER OF REPLICATIONS: triplicate plates, experiment repeated
NUMBER OF CELLS EVALUATED: the plates were scored for the presence of revertant colonies using an automated colony counting system. The plates were assessed microscopically for evidence of thinning (toxicity). Several manual counts were required, predominantly due to the revertant colonies spreading slightly, thus distorting the actual plate count.
DETERMINATION OF CYTOTOXICITY
- Method: relative total growth and condition of background lawn. - 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 is considered non-mutagenic (negative) in the test system if the above criteria are not met.
In instances of data prohibiting definitive judgement about test item activity are reported as equivocal. - Statistics:
- Statistical methods (Mahon, et al.); as recommended by the UKEMS Subcommittee on Guidelines for Mutagenicity Testing, Report - Part III (1989).
Results and discussion
Test resultsopen allclose all
- Species / strain:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- Reduction in background lawn from 50 µg/plate
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Species / strain:
- E. coli WP2 uvr A
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- Reduction in background lawn at 500 µg/plate
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
Any other information on results incl. tables
Table 1 : Test Results: Experiment 1 with and without metabolic activation and results of concurrent positive controls (mean, n=3 plates)
Concentration (µg/plate) |
TA 100 |
TA 1535 |
WP2 uvrA |
TA 98 |
TA 1537 |
|||||
- MA |
+ MA |
- MA |
+ MA |
- MA |
+ MA |
- MA |
+ MA |
- MA |
+ MA |
|
Solvent control |
77 |
92 |
16 |
9 |
22 |
30 |
22 |
18 |
6 |
7 |
1.5 |
73 |
78 |
14 |
12 |
20 |
23 |
17 |
21 |
6 |
6 |
5 |
72 |
87 |
18 |
12 |
16 |
26 |
26 |
15 |
11 |
8 |
15 |
68 |
81 |
9 |
9 |
19 |
28 |
23 |
19 |
12 |
11 |
50 |
79 |
86 |
12 |
11 |
24 |
27 |
17 |
20 |
13 |
8 |
150 |
61 |
78* |
11* |
12* |
22 |
22 |
19* |
19 |
5* |
10 |
500 |
48* |
76* |
11* |
0** |
14* |
23* |
9* |
23* |
7* |
4* |
1500 |
0** |
42*** |
0** |
0*** |
0** |
21* |
0*** |
8** |
0*** |
5* |
5000 |
0*** |
0*** |
0*** |
0*** |
0*** |
14** |
0*** |
0*** |
0*** |
0*** |
Positive control |
519 |
496 |
2242 |
128 |
679 |
131 |
195 |
115 |
639 |
272 |
* Sparse bacterial background lawn
** Very weak bacterial background lawn
*** Toxic, no bacterial background lawn
Table 2 : Test Results: Experiment 2 with and without metabolic activation and results of concurrent positive controls (mean, n=3 plates)
Concentration (µg/plate) |
TA 100 |
TA 1535 |
WP2 uvrA |
TA 98 |
TA 1537 |
|||||
- MA |
+ MA |
- MA |
+ MA |
- MA |
+ MA |
- MA |
+ MA |
- MA |
+ MA |
|
Solvent control |
72 |
69 |
20 |
11 |
13 |
23 |
20 |
16 |
12 |
9 |
0.15 |
NT |
71 |
9 |
11 |
NT |
NT |
16 |
NT |
6 |
NT |
0.5 |
67 |
75 |
17 |
11 |
10 |
20 |
18 |
20 |
5 |
9 |
1.5 |
78 |
75 |
15 |
12 |
10 |
18 |
19 |
12 |
7 |
9 |
5 |
70 |
67 |
15 |
9 |
13 |
20 |
19 |
18 |
9 |
9 |
15 |
74 |
67 |
11 |
9 |
15 |
22 |
15 |
20 |
10 |
7 |
50 |
57* |
78* |
7* |
8* |
12 |
19 |
14* |
17 |
9* |
7 |
150 |
58* |
56* |
7** |
7* |
11 |
12 |
16* |
13* |
8* |
8* |
500 |
44** |
NT |
NT |
NT |
9* |
15* |
NT |
14* |
NT |
5* |
Positive control |
794 |
649 |
120 |
167 |
431 |
232 |
159 |
226 |
150 |
216 |
NT not tested
* Sparse bacterial background lawn
** Very weak bacterial background lawn
Table 3. Spontaneous Mutation Rates (Concurrent Negative Controls): Experiment 1 and 2, respectively
Number of revertants (mean number of colonies per plate) |
|||||||||
Base-pair substitution type |
Frameshift type |
||||||||
TA100 |
|
TA1535 |
|
WP2urvA |
|
TA98 |
|
TA1537 |
|
82 |
|
12 |
|
20 |
|
27 |
|
13 |
|
86 |
(88) |
8 |
(9) |
19 |
(20) |
13 |
(12) |
11 |
(12) |
95 |
|
8 |
|
21 |
|
27 |
|
13 |
|
Number of revertants (mean number of colonies per plate) |
|||||||||
Base-pair substitution type |
Frameshift type |
||||||||
TA100 |
|
TA1535 |
|
WP2urvA |
|
TA98 |
|
TA1537 |
|
88 |
|
13 |
|
20 |
|
16 |
|
11 |
|
74 |
(78) |
9 |
(11) |
16 |
(18) |
18 |
(15) |
33 |
(8) |
73 |
|
12 |
|
19 |
|
10 |
|
11 |
|
|
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information):
negative
Under the conditions of this study the test item was considered to be non-mutagenic in the presence and absence of S9 activation. - Executive summary:
The study was performed to the requirements of OECD Guideline 471, EU Method B13/14 and US EPA OCSPP harmonized guideline for bacterial mutagenicity testing under GLP, to evaluate the potential mutagenicity of the test substance in a bacterial reverse mutation assay using S.typhimurium strains TA98, TA100, TA1535, TA1537 and E.coli strain WP2uvrA- in both the presence and absence of S-9 mix. The test strains were treated with the test substance using the pre incubation methods at up to eight dose levels, in triplicate, both with and without the addition of a rat liver homogenate metabolizing system (10% liver S9 in standard co-factors). The dose range for Experiment 1 was predetermined and was 1.5 to 5000 µg/plate. The experiment was repeated on a separate day using fresh cultures of the bacterial strains and fresh test item formulations. The dose range was amended following the results of the range-finding test and ranged between 0.15 and 500 μg/plate, depending on bacterial strain type and presence or absence of metabolic activation (S9-mix). Seven test item dose levels were selected in Experiment 2 in order to achieve both a minimum of four non-toxic dose levels and the toxic limit of the test item following the change in test methodology. The dose range was amended following the results of Experiment 1 and ranged between 0.15 and 500 µg/plate, depending on bacterial strain type and presence or absence of S9-mix. The vehicle (dimethyl sulphoxide) control plates gave counts of revertant colonies within the normal range. All of the positive control chemicals used in the test induced marked increases in the frequency of revertant colonies, both with or without metabolic activation. Thus, the sensitivity of the assay and the efficacy of the S9-mix were validated. The maximum dose level of the test item in the first experiment was selected as the maximum recommended dose level of 5000 μg/plate. The test item induced a visible reduction in the growth of the bacterial background lawns of all of the tester strains in the absence of S9-mix, initially from 150 μg/plate (TA1535, TA98 and TA1537) and 500 μg/plate (TA100 and WP2uvrA). In the presence of S9-mix, weakened lawns were noted from 150 μg/plate (TA100 and TA1535) and 500 μg/plate (TA98, TA1537 and WP2uvrA). Consequently, the toxic limit was employed in the second mutation test. Visible reduction in the growth of the bacterial background lawns of all of the Salmonella tester strains, initially from 50 μg/plate in the absence of S9-mix and from 50 μg/plate (TA100 and TA1535) and 150 μg/plate (TA98 and TA1537) in the presence of S9-mix. Toxicity was also noted to E.coli strain WP2uvrA at 500 μg/plate in both the absence and presence of S9-mix. No test item precipitate was observed on the plates at any of the doses tested in either the presence or absence of S9-mix. There were no significant 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). A small, statistically significant increase in TA1537 revertant colony frequency was observed in the absence of S9-mix at 50 μg/plate in the range-finding test. This increase was considered to be of no biological relevance because there was no evidence of a dose-response relationship or reproducibility. The individual revertant counts at the statistically significant level were within the historical vehicle control range for the strain and the maximum increase was only two-fold the concurrent vehicle control. It was concluded that, under the conditions of this assay, the test item gave a negative, i.e. non-mutagenic response in S.typhimurium strains TA98, TA100, TA1535, TA1537 and E.coli strain WP2uvrA- in the presence and absence of S-9 mix.
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