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EC number: 227-231-1 | CAS number: 5726-19-2
- 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 mammalian cells
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1991
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 1 991
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
- GLP compliance:
- not specified
- Type of assay:
- mammalian cell gene mutation assay
Test material
- Reference substance name:
- Menthol
- EC Number:
- 201-939-0
- EC Name:
- Menthol
- Cas Number:
- 89-78-1
- IUPAC Name:
- 2-isopropyl-5-methylcyclohexanol
- Details on test material:
- - Name of test material (as cited in study report): dl-menthol
- Molecular formula (if other than submission substance): C10H20O
- Molecular weight (if other than submission substance): 156.26
Constituent 1
Method
Species / strain
- Species / strain / cell type:
- mouse lymphoma L5178Y cells
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9 from liver of Aroclor-induced male Sprague-Dawley rat
- Test concentrations with justification for top dose:
- + and -S9: 0, 12.5, 25, 50, 75, 100, 150, 200, and 300 ug/ml
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: ethanol
Controlsopen allclose all
- Negative solvent / vehicle controls:
- yes
- Remarks:
- (ethanol)
- Positive controls:
- yes
- Positive control substance:
- methylmethanesulfonate
- Remarks:
- (without metabolic activation)
- Positive controls:
- yes
- Positive control substance:
- 3-methylcholanthrene
- Remarks:
- (with metabolic activation)
- Details on test system and experimental conditions:
- Two trials (3 replicates/concentration) were conducted for each: non-activated cultures and activated cultures. RPMI 1640 medium used for growth, expression and cloning. Ethanol used as vehicle control.
METHOD OF APPLICATION: Mouse lymphoma L5178Y TK+/- cells were maintained at 37° C as suspension cultures in Fischer's medium supplemented with 2 mM l-glutamine, 110 ug/mL sodium pyruvate, 0.05% luronic F68, antibiotics, and heatinactivated horse serum; normal cycling time was approximately 10 hours. To reduce the number of spontaneously occurring trifluorothymidine (TFT) resistant cells, subcultures were exposed once to medium containing thymidine, hypoxanthine, methotrexate, and glycine for one day; to thymidine, hypoxanthine, and glycine for one day; and to normal medium for 3 to 5 days. For cloning, horse serum content was increased and Noble agar was added.
All treatment levels within an experiment, including concurrent positive and solvent controls, were replicated. Treated cultures contained 6 x 10 6 cells in 10 mL of medium. This volume included the S9 fraction in those experiments performed with metabolic activation. Incubation with the test chemical continued for 4 hours, at which time the medium plus chemical was removed and the cells were resuspended in 20 mL of fresh medium and incubated for an additional 2 days to express the mutant phenotype. Cell density was monitored so that log phase growth was maintained. After the 48-hour expression period, 3 x 106 cells were plated in medium and soft agar supplemented with TFT for selection of TFT-resistant cells (TK-/-) and in nonselective medium and soft agar to determine cloning efficiency. Plates were incubated at 37 C. in 5% CO2 for 10 to 12 days. At the end of incubation, colonies were counted with an automated counter. The test was initially performed without S9. If a clearly positive response was not obtained, the test was repeated using freshly prepared S9 from the livers of either Aroclor 1254-induced or non-induced male Fischer 344 rats. - Evaluation criteria:
- Trend and peak responses had to be significant (P < 0.05) for a chemical to be considered capable of inducing TFT resistance; a single significant response led to a "questionable" conclusion, and the absence of both a trend and a peak response resulted in a "negative" call.
- Statistics:
- All data were evaluated statistically for trend and peak responses.
Results and discussion
Test results
- Species / strain:
- mouse lymphoma L5178Y cells
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- (at >= 200 µg/ml)
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
Any other information on results incl. tables
Test substance was cytotoxic at 200 µg/ml and higher, with or without S9.
Without S9,
Trial 1 at 0, 12.5, 25, 50, 100, and 150 µg/ml: 37, 36, 27, 38, 29, and 33 mutant cells/10E+06 cells
Trial 2 at 0, 25, 50, 75, 100, and 150 µg/ml: 27, 30, 24, 19, 28, and 29 mutant cells/10E+06 cells
With S9,
Trial 1 at 0, 25, 50, 75, 100, 150, and 200 µg/ml: 35, 42, 43, 45, 33, 33, and 35 mutant cells/10E+06 cells
Trial 2 at 0, 25, 50, 75, 100, and 150 µg/ml: 48, 54, 58, 53, 64, and 37 mutant cells/10E+06 cells
Nonactivation Trial: 1 Experiment Call: Negative |
|||||||
|
Conc. |
Cloning |
Relative Total |
Mutant Colonies |
Mutant Frequency |
AVG Mutant Frequency |
|
µg/mL |
Efficiency |
Growth |
|||||
Vehicle Control |
Ethanol |
0 |
77 |
96 |
65 |
28 |
37 |
96 |
94 |
134 |
47 |
||||
77 |
100 |
75 |
32 |
||||
78 |
110 |
95 |
41 |
||||
Test Chemical |
DL-menthol |
12.5 |
68 |
91 |
83 |
41 |
36 |
70 |
95 |
76 |
36 |
||||
72 |
99 |
68 |
31 |
||||
25 |
68 |
27 |
51 |
25 |
27 |
||
83 |
108 |
83 |
33 |
||||
87 |
78 |
59 |
23 |
||||
50 |
74 |
71 |
74 |
33 |
38 |
||
56 |
88 |
78 |
46 |
||||
69 |
56 |
73 |
35 |
||||
100 |
100 |
67 |
87 |
29 |
29 |
||
74 |
65 |
62 |
28 |
||||
97 |
68 |
88 |
30 |
||||
150 |
68 |
25 |
59 |
29 |
33 |
||
83 |
24 |
91 |
37 |
||||
LETHAL |
|||||||
200 |
LETHAL |
|
|||||
LETHAL |
|||||||
LETHAL |
|||||||
Positive Control |
Methyl Methane Sulfonate |
5 |
40 |
34 |
480 |
400 |
488* |
33# |
29 |
467 |
472 |
||||
37 |
16 |
659 |
591 |
Nonactivation Trial: 2 Experiment Call: Negative |
|||||||
|
Conc. |
Cloning |
Relative Total |
Mutant Colonies |
Mutant Frequency |
AVG Mutant Frequency |
|
µg/mL |
Efficiency |
Growth |
|||||
Vehicle Control |
Ethanol |
0 |
61 |
82 |
45 |
24 |
27 |
97# |
105 |
80 |
27 |
||||
98 |
103 |
77 |
26 |
||||
94 |
110 |
86 |
30 |
||||
Test Chemical |
DL-menthol |
25 |
73 |
69 |
73 |
33 |
30 |
64 |
56 |
71 |
37 |
||||
76 |
84 |
44 |
19 |
||||
50 |
81 |
55 |
71 |
29 |
24 |
||
83 |
73 |
43 |
17 |
||||
78 |
71 |
60 |
26 |
||||
75 |
102 |
54 |
64 |
21 |
19 |
||
91 |
63 |
54 |
20 |
||||
82 |
28 |
39 |
16 |
||||
100 |
85 |
43 |
73 |
29 |
28 |
||
81 |
34 |
73 |
30 |
||||
88 |
54 |
70 |
26 |
||||
150 |
91 |
21 |
95 |
35 |
29 |
||
81 |
30 |
60 |
25 |
||||
89 |
29 |
76 |
29 |
||||
Positive Control |
Methyl Methane Sulfonate |
5 |
65 |
38 |
602 |
310 |
274* |
67 |
43 |
523 |
260 |
||||
77 |
53 |
576 |
251 |
Induced S9 Trial: 1 Experiment Call: Negative |
|||||||
|
Conc. |
Cloning |
Relative Total |
Mutant Colonies |
Mutant Frequency |
AVG Mutant Frequency |
|
µg/mL |
Efficiency |
Growth |
|||||
Vehicle Control |
Ethanol |
0
|
102 |
112 |
91 |
30 |
35
|
81 |
108 |
88 |
36 |
||||
71 |
95 |
62 |
29 |
||||
63 |
84 |
88 |
47 |
||||
Test Chemical |
DL-menthol |
25
|
73 |
92 |
74 |
34 |
42
|
95 |
93 |
108 |
38 |
||||
58 |
65 |
93 |
53 |
||||
50
|
73 |
71 |
111 |
50 |
43
|
||
71 |
76 |
88 |
41 |
||||
76 |
94 |
88 |
39 |
||||
75
|
76 |
68 |
109 |
48 |
45
|
||
79 |
73 |
93 |
39 |
||||
72 |
80 |
102 |
47 |
||||
100
|
75 |
82 |
87 |
39 |
33
|
||
89 |
81 |
93 |
35 |
||||
110 |
89 |
84 |
26 |
||||
150
|
75 |
71 |
78 |
35 |
33
|
||
79 |
66 |
74 |
31 |
||||
107 |
144 |
104 |
32 |
||||
200
|
95 |
52 |
122 |
43 |
35 |
||
96 |
47 |
79 |
27 |
||||
LETHAL |
|||||||
300 |
LETHAL |
|
|||||
LETHAL |
|||||||
LETHAL |
|||||||
Positive Control |
3-Methylcho-lanthrene |
2.5 |
105 |
71 |
390 |
124 |
145* |
84 |
315 |
315 |
125 |
||||
84 |
468 |
438 |
186 |
Induced S9 Trial: 2 Experiment Call: Negative |
|||||||
|
Conc. |
Cloning |
Relative Total |
Mutant Colonies |
Mutant Frequency |
AVG Mutant Frequency |
|
µg/mL |
Efficiency |
Growth |
|||||
Vehicle Control |
Ethanol |
0
|
110 |
115 |
124 |
38 |
46 |
122r |
115 |
97 |
27 |
||||
84 |
96 |
136 |
54 |
||||
84 |
88 |
113 |
45 |
||||
Test Chemical |
DL-menthol |
25
|
98 |
78 |
162 |
55 |
54 |
100 |
62 |
159 |
53 |
||||
101 |
79 |
165 |
54 |
||||
50
|
109 |
56 |
174 |
53 |
58 |
||
84 |
60 |
146 |
58 |
||||
104 |
66 |
197 |
63 |
||||
75
|
122r |
65 |
194 |
53 |
53 |
||
99 |
60 |
187 |
63 |
||||
83 |
52 |
106 |
43 |
||||
100
|
118 |
44 |
237 |
67 |
64 |
||
104 |
70 |
160 |
51 |
||||
113 |
51 |
249 |
73 |
||||
150
|
115 |
46 |
125 |
36 |
37 |
||
110 |
64 |
125 |
38 |
||||
111 |
46 |
126 |
38 |
||||
200
|
LETHAL |
|
|||||
LETHAL |
|||||||
LETHAL |
|||||||
Positive Control |
3-Methylcho-lanthrene |
2.5 |
66 |
32 |
398 |
201 |
271* |
64 |
38 |
579 |
303 |
||||
73 |
33 |
676 |
310 |
Footnotes:
Asterisks(*) indicate significant responses.
r = rejected value due to quality control criteria
# = reduced sample size because of the loss of one culture dish due to contamination
Applicant's summary and conclusion
- Conclusions:
- 2-Isopropyl-5-methylcyclohexanol did not increase mutation frequency in mouse lymphoma cells at test conditions.
- Executive summary:
A Forward mutation assay was performed in mouse lymphoma cells with 2 -isopropyl-5 -methylcyclohexanol at a concentration of 0, 12.5, 25, 50, 75, 100, 150, 200 and 300 µg/ml, with and without S9 metabolic activation. Two trials (3 replicates/concentration) were conducted for each: non-activated cultures and activated cultures. RPMI 1640 medium was used for growth, expression and cloning. Ethanol was used as vehicle control. Test substance was cytotoxic at 200 ug/ml and higher with or without S9. 2-Isopropyl-5-methylcyclohexanol did not increase mutation frequency in mouse lymphoma cells at test conditions.
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