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EC number: 209-665-3 | CAS number: 589-92-4
- 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:
- 21 June 2016 to 08 July 2016
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 016
- Report date:
- 2016
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- no
- Principles of method if other than guideline:
- The most widely used assays for detecting gene mutations are those using bacteria. They are relatively simple and rapid to perform, and give reliable data on the ability of an agent to interact with DNA and produce mutations.
Reverse mutation assays determine the frequency with which an agent reverses or suppresses the effect of the forward mutation. The genetic target presented to an agent is therefore small, specific and selective. Several bacterial strains, or a single strain with multiple markers are necessary to assure reliable detection of mutagens that may be specific to one tester strain or locus. The reversion of bacteria from growth-dependence on a particular amino acid to growth in the absence of that amino acid (reversion from auxotrophy to prototrophy) is the most widely used marker. - GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- bacterial reverse mutation assay
Test material
- Reference substance name:
- 4-methylcyclohexanone
- EC Number:
- 209-665-3
- EC Name:
- 4-methylcyclohexanone
- Cas Number:
- 589-92-4
- Molecular formula:
- C7H12O
- IUPAC Name:
- 4-methylcyclohexan-1-one
- Test material form:
- liquid
- Details on test material:
- - Other: Colourless liquid
Constituent 1
Method
- Target gene:
- The S. typhimurium histidine (his) and the E. coli tryptophan (trp) reversion system measures his- → his+ and trp- → trp+ reversions, respectively. The S. typhimurium and Escherichia coli strains are constructed to differentiate between base pair (TA1535, TA100, WP2 uvrA pKM101, and WP2 pKM101) and frameshift (TA1537, TA98) mutations.
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
- Species / strain / cell type:
- E. coli WP2 uvr A pKM 101
- Metabolic activation:
- with and without
- Metabolic activation system:
- Phenobarbital/ß-naphthoflavone induced rat liver S9
- Test concentrations with justification for top dose:
- Pre-experiment/Experiment I: 3; 10; 33; 100; 333; 1000; 2500; and 5000 μg/plate
Expriment II: 33; 100; 333; 1000; 2500; and 5000 μg/plate
In the pre-experiment, the concentration range of the test substance was 3 - 5000 μg/plate. The pre-experiment is reported as experiment I. Since no cytotoxic effects were observed in experiment I, 5000 μg/plate was chosen as the maximal concentration for experiment II. - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: DMSO
Controlsopen allclose all
- Untreated negative controls:
- yes
- Remarks:
- untreated
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- sodium azide
- Positive controls:
- yes
- Positive control substance:
- other: 4-nitro-o-phenylene-diamine
- Positive controls:
- yes
- Positive control substance:
- methylmethanesulfonate
- Positive controls:
- yes
- Positive control substance:
- other: 2-aminoanthracene 2.5 µg/plate in DMSO for TA1535, TA1537, TA98 and TA100; 10 µg/plate in DMSO for WP2 uvrA (pKM101) and WP2 (pKM101) with S9
- Details on test system and experimental conditions:
- METHOD OF APPLICATION:in agar (plate incorporation - Expt. I); preincubation
- Expt. II
DURATION
- Preincubation period: 60 mins
- Exposure duration: 72 hours
NUMBER OF REPLICATIONS: 3
DETERMINATION OF CYTOTOXICITY
- Method: relative total growth - Evaluation criteria:
- A test substance is considered as a mutagen if a biologically relevant increase in the number of revertants exceeding the threshold of twice the colony count of the corresponding solvent control is observed.
A concentration 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 concentration 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:
- Not applicable
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
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- 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
- 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
- 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:
- cytotoxicity
- Remarks:
- at 5000 µg/plate
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- E. coli WP2 uvr A
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- E. coli WP2 uvr A pKM 101
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
Any other information on results incl. tables
Table 1: Summary of results Experiment I without S9 - Revertant Colony Counts (Mean ±SD)
Group |
Concn. (per plate) |
TA1535 |
TA1537 |
TA98 |
TA100 |
WP2 pKM101 |
WP2 uvrA pKM101 |
DMSO |
- |
11 ± 3 |
8 ± 1 |
35 ± 4 |
186 ± 13 |
217 ± 17 |
350 ± 14 |
Untreated |
- |
7 ± 3 |
14 ± 5 |
36 ± 5 |
199 ± 13 |
224 ± 21 |
362 ± 23 |
CA5110 |
3 µg |
10 ± 4 |
8 ± 2 |
25 ± 3 |
169 ± 11 |
188 ± 5 |
336 ± 14 |
CA5110 |
10 µg |
13 ± 3 |
9 ± 2 |
24 ± 7 |
167 ± 19 |
199 ± 12 |
331 ± 19 |
CA5110 |
33 µg |
10 ± 1 |
11 ± 4 |
25 ± 5 |
165 ± 13 |
198 ± 10 |
311 ± 17 |
CA5110 |
100 µg |
13 ± 3 |
8 ± 3 |
26 ± 9 |
163 ± 5 |
201 ± 9 |
337 ± 24 |
CA5110 |
333 µg |
12 ± 5 |
8 ± 2 |
29 ± 8 |
178 ± 9 |
192 ± 9 |
337 ± 8 |
CA5110 |
1000 µg |
10 ± 2 |
11 ± 5 |
35 ± 7 |
178 ± 10 |
197 ± 7 |
316 ± 15 |
CA5110 |
2500 µg |
7 ± 2 |
9 ± 2 |
35 ± 2 |
176 ± 6 |
191 ± 17 |
323 ± 23 |
CA5110 |
5000 µg |
8 ± 1 |
13 ± 5 |
39 ± 3 |
91 ± 9 |
166 ± 9 |
331 ± 7 |
NaN3 |
10 µg |
1060 ± 26 |
- |
- |
1693 ± 110 |
- |
- |
4-NOPD |
10 µg |
- |
- |
426 ± 37 |
- |
- |
- |
4-NOPD |
50 µg |
- |
63 ± 10 |
- |
- |
- |
- |
MMS |
2.0 µL |
- |
- |
- |
- |
3807 ± 415 |
3555 ± 69 |
Table 2: Summary of results Experiment I with S9 - Revertant Colony Counts (Mean ±SD)
Group |
Concn. (per plate) |
TA1535 |
TA1537 |
TA98 |
TA100 |
WP2 pKM101 |
WP2 uvrA pKM101 |
DMSO |
- |
12 ± 4 |
14 ± 3 |
34 ± 12 |
164 ± 17 |
230 ± 13 |
393 ± 10 |
Untreated |
- |
15 ± 4 |
15 ± 2 |
47 ± 6 |
192 ± 21 |
259 ± 20 |
436 ± 10 |
CA5110 |
3 µg |
11 ± 1 |
16 ± 5 |
36 ± 4 |
153 ± 23 |
229 ± 22 |
404 ± 9 |
CA5110 |
10 µg |
9 ± 3 |
18 ± 3 |
41 ± 4 |
142 ± 27 |
224 ± 16 |
401 ± 23 |
CA5110 |
33 µg |
13 ± 3 |
12 ± 2 |
40 ± 6 |
122 ± 16 |
195 ± 27 |
379 ± 24 |
CA5110 |
100 µg |
13 ± 3 |
13 ± 3 |
42 ± 6 |
150 ± 13 |
214 ± 18 |
396 ± 15 |
CA5110 |
333 µg |
12 ± 0 |
15 ± 3 |
45 ± 10 |
163 ± 20 |
225 ± 35 |
402 ± 21 |
CA5110 |
1000 µg |
10 ± 3 |
17 ± 6 |
45 ± 3 |
171 ± 9 |
208 ± 4 |
371 ± 5 |
CA5110 |
2500 µg |
14 ± 3 |
17 ± 3 |
45 ± 8 |
175 ± 11 |
198 ± 15 |
345 ± 20 |
CA5110 |
5000 µg |
12 ± 3 |
14 ± 2 |
37 ± 7 |
137 ± 8 |
170 ± 21 |
359 ± 26 |
2-AA |
2.5 µg |
381 ± 25 |
189 ± 12 |
4418 ± 246 |
4830 ± 406 |
- |
- |
2-AA |
10.0 µg |
- |
- |
- |
- |
1082 ± 26 |
2285 ± 128 |
Table 3: Summary of results Experiment II without S9 - Revertant Colony Counts (Mean ±SD)
Group |
Concn. (per plate) |
TA1535 |
TA1537 |
TA98 |
TA100 |
WP2 pKM101 |
WP2 uvrA pKM101 |
DMSO |
|
11 ± 5 |
12 ± 2 |
21 ± 5 |
158 ± 17 |
201 ± 30 |
350 ± 9 |
Untreated |
|
14 ± 3 |
13 ± 4 |
28 ± 10 |
205 ± 23 |
241 ± 21 |
369 ± 10 |
CA5110 |
33 µg |
16 ± 5 |
8 ± 3 |
20 ± 5 |
157 ± 5 |
209 ± 22 |
338 ± 10 |
CA5110 |
100 µg |
12 ± 3 |
8 ± 3 |
23 ± 2 |
139 ± 11 |
189 ± 10 |
355 ± 15 |
CA5110 |
333 µg |
16 ± 3 |
10 ± 1 |
25 ± 5 |
137 ± 16 |
200 ± 4 |
331 ± 18 |
CA5110 |
1000 µg |
17 ± 4 |
9 ± 1 |
30 ± 2 |
120 ± 15 |
211 ± 5 |
351 ± 11 |
CA5110 |
2500 µg |
16 ± 3 |
10 ± 4 |
34 ± 3 |
123 ± 8 |
199 ± 8 |
330 ± 7 |
CA5110 |
5000 µg |
14 ± 3 |
7 ± 2 |
20 ± 2 |
68 ± 10 |
110 ± 20 |
303 ± 25 |
NaN3 |
10 µg |
1053 ± 27 |
|
|
2256 ± 119 |
|
|
4-NOPD |
10 µg |
|
|
334 ± 33 |
|
|
|
4-NOPD |
50 µg |
|
81 ± 3 |
|
|
|
|
MMS |
2.0 µL |
|
|
|
|
3232 ± 332 |
2779 ± 377 |
Table 4: Summary of results Experiment II - with S9 - Revertant Colony Counts (Mean ±SD)
Group |
Concn. (per plate) |
TA1535 |
TA1537 |
TA98 |
TA100 |
WP2 pKM101 |
WP2 uvrA pKM101 |
DMSO |
|
15 ± 1 |
15 ± 6 |
45 ± 6 |
129 ± 14 |
249 ± 26 |
394 ± 10 |
Untreated |
|
12 ± 2 |
19 ± 3 |
37 ± 4 |
216 ± 12 |
296 ± 20 |
483 ± 3 |
CA5110 |
33 µg |
13 ± 2 |
11 ± 3 |
39 ± 9 |
144 ± 19 |
240 ± 38 |
396 ± 20 |
CA5110 |
100 µg |
15 ± 3 |
13 ± 3 |
36 ± 8 |
141 ± 19 |
245 ± 18 |
417 ± 16 |
CA5110 |
333 µg |
16 ± 6 |
16 ± 6 |
44 ± 15 |
135 ± 18 |
241 ± 29 |
407 ± 5 |
CA5110 |
1000 µg |
11 ± 1 |
12 ± 4 |
38 ± 9 |
113 ± 3 |
239 ± 14 |
400 ± 22 |
CA5110 |
2500 µg |
15 ± 1 |
15 ± 5 |
43 ± 11 |
87 ± 7 |
183 ± 8 |
363 ± 6 |
CA5110 |
5000 µg |
17 ± 3 |
10 ± 2 |
32 ± 10 |
53 ± 4 |
157 ± 2 |
341 ± 27 |
2 AA |
2.5 µg |
380 ± 45 |
159 ± 16 |
3865 ± 655 |
4594 ± 579 |
|
|
2 AA |
10.0 µg |
|
|
|
|
1055 ± 88 |
2035 ± 113 |
NaN3 sodium azide 2-AA 2-aminoanthracene 4-NOPD 4-nitro-o-phenylene-diamine MMS methyl methane sulfonate |
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 substance did not induce gene mutations by base pair changes or frameshifts in the genome of the strains used.
Therefore, the test substance is considered to be non-mutagenic in this Salmonella typhimurium and Escherichia coli reverse mutation assay. - Executive summary:
This study was performed to investigate the potential of the test substance to induce gene mutations in the plate incorporation test (experiment I) and the pre-incubation test (experiment II) using the Salmonella typhimurium strains TA1535, TA1537, TA98, and TA100, and the Escherichia coli strains WP2 uvrA pKM101 and WP2 pKM101.
The plates incubated with the test substance showed normal background growth up to 5000 μg/plate in all strains with and without metabolic activation.
In experiment II, cytotoxicity (evident as a reduction in the number of revertants (below the indication factor of 0.5)) was observed in strain TA100 at 5000 μg/plate both with and wihout metabolic activation. No other cytotoxic effects were observed in any other strain both with and without metabolic activation.
No increase in revertant colony numbers of any of the six tester strains was observed following treatment with the test substance at any concentration, neither in the presence nor absence of metabolic activation (S9 mix). There was also no tendency of higher mutation rates with increasing concentrations and all mutation rates were within the range of normal biological variability.
Appropriate reference mutagens were used as positive controls. They showed a distinct increase of induced revertant colonies.
In conclusion, it can be stated that during the described mutagenicity test and under the experimental conditions reported, the test substance did not induce gene mutations by base pair changes or frameshifts in the genome of the strains used. Therefore, the test substance is considered to be non-mutagenic in this Salmonella typhimurium and Escherichia coli reverse mutation assay.
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