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EC number: 232-107-5 | CAS number: 7787-20-4
Genetic toxicity: in vitro
Administrative data
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
Data source
Reference
- Reference Type:
- publication
- Title:
- A Compilation of Two Decades of Mutagenicity Test Results with the Ames Salmonella typhimurium and L5178Y Mouse Lymphoma Cell Mutation Assays
- Author:
- Seifried H E
- Year:
- 2 006
- Bibliographic source:
- Chemical Research in Toxicology, vol. 19, nº 5, pp. 627-644
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- no
- GLP compliance:
- not specified
- Type of assay:
- bacterial reverse mutation assay
Test material
- Reference substance name:
- 1,3,3-trimethylnorbornan-2-one
- EC Number:
- 232-107-5
- EC Name:
- 1,3,3-trimethylnorbornan-2-one
- Cas Number:
- 7787-20-4
- Molecular formula:
- C10H16O
- IUPAC Name:
- 1,3,3-trimethylnorbornan-2-one
Constituent 1
Method
- Target gene:
- Histidine-requiring gene in Salmonella typhimurium
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:
- Liver S9 homogenate prepared from male Sprague-Dawley rats and Syrian golden hamsters induced with Aroclor 1254.
- Test concentrations with justification for top dose:
- 0, 100, 333, 1000, 3333 and 10000 μg/plate.
These doses were selected based on the levels of cytotoxicity observed in a preliminary dose range-finding study using strain TA100. Ten dose levels, one plate per dose, were tested in both the presence and the absence of induced hamster S9. As no toxicity was observed, a total maximum dose of 10 mg per plate was used. - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: ethanol
Controls
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- no
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- not specified
- Details on test system and experimental conditions:
- METHOD OF APPLICATION:
Direct plate incorporation method: For testing in the absence of S9 mix, 100 μL of the tester strain and 50 μL of the solvent or test chemical were added to 2.5 mL of molten selective top agar at 45 ± 2 ºC. When S9 was used, 0.5 mL of S9 mix, 50 μL of tester strain, and 50 μL of solvent or test chemical were added to 2.0 mL of molten selective top agar at 45 ± 2 ºC. After it was vortexed, the mixture was overlaid onto the surface of 25 mL of minimal bottom agar. After the overlay had solidified, the plates were incubated for 48 h at 37 ± 2 ºC.
- Cell density at seeding: Cultures were grown overnight in Oxoid nutrient broth no. 2 and were removed from incubation when they reached a density of 1-2x10e9 cells/mL.
DURATION
- Exposure duration: 48h
SELECTION AGENT (mutation assays): the lack of amino-acid in the medium. Only the mutants can grow due to their capability to synthesize the essential amino acid.
NUMBER OF REPLICATIONS: 3
DETERMINATION OF CYTOTOXICITY
No toxicity was observed in a preliminary dose range-finding study using strain TA100. - Evaluation criteria:
- For the test substance to be considered positive, it had to induce at least a doubling (TA98, TA100, and TA1535) in the mean number of revertants per plate of at least one tester strain. This increase in the mean revertants per plate had to be accompanied by a dose response to increasing concentrations of the test substance. If the study showed a dose response with a less than 3-fold increase on TA1537 or TA1538, the response had to be confirmed in a repeat experiment.
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:
- not applicable
- 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:
- not applicable
- 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:
- not applicable
- 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
- Vehicle controls validity:
- not applicable
- 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
- Vehicle controls validity:
- not applicable
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- RANGE-FINDING/SCREENING STUDIES:
The doses that were tested in the mutagenicity assay were selected based on the levels of cytotoxicity observed in a preliminary dose range-finding study using strain TA100. Ten dose levels of the chemical, one plate per dose, were tested in both the presence
and the absence of induced hamster S9. As no toxicity was observed, a total maximum dose of 10 mg of test chemical per plate was used in the main study.
Any other information on results incl. tables
Table 3 Salmonella Test Data
Chemical Name |
CAS # |
Dose |
TA98 |
TA100 |
TA102 |
TA1535 |
TA1537 |
||||||||||
|
|
|
no S9 |
rat S9 |
Ham'r S9 |
no S9 |
rat S9 |
Ham'r S9 |
no S9 |
rat S9 |
Ham'r S9 |
no S9 |
rat S9 |
Ham'r S9 |
no S9 |
rat S9 |
Ham'r S9 |
(1R)-(-)-Fenchone |
7787-20-4 |
|
Negative |
Negative |
Negative |
Negative |
Negative |
Negative |
Negative |
Negative |
Negative |
Negative |
Negative |
Negative |
Negative |
Negative |
Negative |
|
|
EtOH |
17 ± 4 |
27 ± 9 |
15 ± 5 |
112 ± 19 |
127 ± 16 |
132 ± 21 |
324 ± 29 |
366 ± 13 |
324 ± 41 |
8 ± 2 |
8 ± 3 |
10 ± 2 |
4 ± 2 |
8 ± 4 |
6 ± 2 |
|
|
100ug |
16 ± 3 |
36 ± 7 |
21 ± 6 |
111 ± 4 |
109 ± 15 |
123 ± 9 |
317 ± 30 |
309 ± 13 |
355 ± 9 |
9 ± 1 |
9 ± 2 |
9 ± 1 |
4 ± 2 |
5 ± 2 |
8 ± 1 |
|
|
333ug |
16 ± 3 |
38 ± 12 |
22 ± 4 |
103 ± 12 |
126 ± 5 |
134 ± 15 |
354 ± 28 |
270 ± 47 |
368 ± 32 |
10 ± 3 |
11 ± 1 |
8 ± 3 |
4 ± 2 |
6 ± 1 |
5 ± 3 |
|
|
1000ug |
16 ± 5 |
35 ± 3 |
19 ± 4 |
101 ± 25 |
119 ± 28 |
111 ± 14 |
272 ± 34 |
333 ± 7 |
370 ± 24 |
9 ± 2 |
10 ± 4 |
9 ± 2 |
4 ± 2 |
5 ± 1 |
5 ± 3 |
|
|
3333ug |
16 ± 5 |
22 ± 4 |
23 ± 7 |
121 ± 18 |
131 ± 18 |
105 ± 12 |
312 ± 29 |
289 ± 16 |
395 ± 39 |
10 ± 1 |
9 ± 3 |
10 ± 2 |
6 ± 1 |
4 ± 2 |
7 ± 3 |
|
|
10000ug |
15 ± 3 |
27 ± 8 |
19 ± 4 |
116 ± 11 |
113 ± 9 |
104 ± 19 |
324 ± 60 |
321 ± 21 |
396 ± 34 |
12 ± 4 |
11 ± 4 |
10 ± 1 |
6 ± 2 |
4 ± 1 |
5 ± 2 |
|
|
Positive |
285 ± 57 |
470 ± 276 |
1260 ± 199 |
570 ± 72 |
792 ± 487 |
1176 ± 113 |
1189 ± 138 |
1562 ± 60 |
1056 ± 100 |
767 ± 117 |
73 ± 117 |
102 ± 14 |
2088 ± 415 |
54 ± 32 |
108 ± 44 |
Applicant's summary and conclusion
- Conclusions:
- L-fenchone was not mutagenic in all strains tested with and without metabolic activation.
- Executive summary:
L-fenchone was tested for mutagenecity on Salmonella typhimurium strains TA1535, TA1537, TA98, TA100 and TA102 with and without metabolic activation (S9 mix prepared from both rat and hamster liver). The experiment was performed using the Ames Salmonella assay for mutagenicity. In a preliminary dose range-finding study ten dose levels of the test substance, one plate per dose, were tested in both the presence and the absence of induced hamster S9 using strain TA100. As no toxicity was observed, a maximum dose of 10 mg per plate was used. Based on this preliminary study, the selected doses for the main study were 0, 100, 333, 1000, 3333 and 10000 μg/plate. Ethanol was used as solvent and tested as negative control. Under these experimental conditions, the test substance was found not mutagenic in all strains tested with and without metabolic activation.
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