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EC number: 460-490-0 | CAS number: 477218-42-1
- 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
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 06-05-2004 to 21-06-2004
- 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:
- 2 004
- Report date:
- 2004
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- no
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
- Deviations:
- no
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- EPA OPPTS 870.5100 - Bacterial Reverse Mutation Test (August 1998)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- inspected: June 2001; signature: January 2002
- Type of assay:
- bacterial reverse mutation assay
Test material
- Reference substance name:
- -
- EC Number:
- 460-490-0
- EC Name:
- -
- Cas Number:
- 477218-42-1
- Molecular formula:
- C18H32O3
- IUPAC Name:
- 2-[(1S)-1-[(1R)-3,3-dimethylcyclohexyl]ethoxy]-2-methylpropyl cyclopropanecarboxylate; 2-[(1S)-1-[(1S)-3,3-dimethylcyclohexyl]ethoxy]-2-methylpropyl cyclopropanecarboxylate
- Test material form:
- liquid
- Details on test material:
- Physical state: Liquid
- Storage condition of test material: at room temperature
- Other: colourless liquid
Constituent 1
Method
- Target gene:
- histidine or tryptophan locus
Species / strain
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102
- Additional strain / cell type characteristics:
- not applicable
- Metabolic activation:
- with and without
- Metabolic activation system:
- Rat liver S9
- Test concentrations with justification for top dose:
- Experiment 1 (plate incorporation method): 3, 10, 33, 100, 333, 1000, 2500 and 5000 µg/plate
Experiment 2 (pre-incubation method): 3, 10, 33, 100, 333, 1000, 2500 and 5000 µg/plate
Salmonella strain TA1537 (with and without S9-mix): 3, 10, 33, 100, 333, 1000, 2500 and 5000 µg/plate
Salmonella strain TA98 and E.coli strain WP2uvrA (with and without S9-mix): 3, 10, 33, 100, 333, 1000, 2500 and 5000 µg/plate
Salmonella strains TA100 and TA1535 (with and without S9-mix): 3, 10, 33, 100, 333, 1000, 2500 and 5000 µg/plate - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: Ethanol (purity > 99%)
- Justification for choice of solvent/vehicle: The solvent was chosen because of its solubility properties and relative nontoxicity to the bacteria.
- Other: No precipitation of the test item occurred up to the highest investigated dose.
Controls
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- sodium azide
- methylmethanesulfonate
- other: 2-Aminoanthracene (2AA) ; 4-nitro-o-phenylenediamine (4NOPD)
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: Experiment 1. in medium; in agar (plate-incorporation) ; Experiment 2. in medium; in agar (pre-incubation)
DURATION
- Exposure duration:
Experiment 1. The appropriate bacterial strain culture, with or without S9-activation mix, as applicable, the test item formulation, solvent or appropriate positive control were incubated at 37°C for 4 hours (with shaking) prior to plating. All testing for this experiment was performed in triplicate. Concurrent negative controls were dosed using the standard plate incorporation method. All of the plates were incubated at 37°C for approximately 48 hours in the dark, and scored for the presence of revertant colonies using an automated colony counting system. Due to reduced background growth, some of the plates were counted manually.
Experiment 2. The procedure for incubation and duration was the same as in Experiment 1, with the exception: In the pre-incubation assay 100 µL test solution, 500 µL S9 mix / S9 mix substitution buffer and 100 µL bacterial suspension were mixed in a test tube and incubated at 37°C for 60 minutes. After pre-incubation 2.0 ml overlay agar (45°C) was added to each tube. The mixture was poured on minimal agar plates.
NUMBER OF REPLICATIONS: 3
DETERMINATION OF CYTOTOXICITY
- Method: relative total growth - Rationale for test conditions:
- In accordance with the relevant guidelines.
- 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
4. Statistical analysis of data (as required or applicable).
5. Fold increase greater than two or three times the concurrent solvent control for respective tester strain
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:
- Not performed.
Results and discussion
Test results
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- See table 1 and 2
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: all strains/cell types tested
Any other information on results incl. tables
Table 1 : Test Results: Experiment 1 with and without metabolic activation and results of concurrent positive controls
S9-Mix (-) |
Dose Level Per Plate |
Number of revertants (mean) +/- SD |
||||
Base-pair substitution strains |
Frameshift strains |
|||||
TA100 |
TA102 |
TA1535 |
TA98 |
TA1537 |
||
Solvent Control |
150 (151) 139 13.1 165 |
111 (129) 122 21.8 153 |
18 (16) 21 6.2 9 |
14 (16) 19 2.6 15 |
6 (8) 7 3.2 12 |
|
33 µg |
137 (136) 140 4.6 131 |
99 (104) 96 10.8 116 |
18 (18) 14 4.0 22 |
15 (14) 16 3.2 10 |
6 (5) 3 1.5 5 |
|
100 µg |
141 (137) 132 4.7 139 |
71 (94) 111 20.5 99 |
15 (14) 12 1.7 15 |
17 (17) 15 1.5 18 |
8 (8) 7 0.6 8 |
|
333 µg |
122 (132) 136 9.1 139 |
112 (111) 108 2.3 112 |
19 (17) 16 2.1 15 |
16 (16) 18 2.5 13 |
7 (8) 6 2.1 10 |
|
1000 µg |
143 (134) 137 11.4 121 |
72 (86) 96 12.5 90 |
12 (14) 11 3.8 18 |
17 (16) 15 1.2 17 |
6 (6) 7 0.6 6 |
|
2500 µg |
135 (136) 143 7.0 129 |
117 (108) 114 13.7 92 |
13 (15) 19 3.8 12 |
14 (14) 12 2.0 16 |
5 (4) 2 2.1 6 |
|
5000 µg |
140 (144) 149 4.5 144 |
98 (103) 112 7.8 99 |
21 (19) 16 2.5 19 |
14 (12) 11 2.1 10 |
3 (4) 5 1.2 3 |
|
Positive controls S9-Mix (-) |
Name |
Sodium Azide |
methyl methane sulfonate |
Sodium Azide |
4-nitro-o-phenylene-idamine |
4-nitro-o-phenylene-idamine |
Dose Level |
10.0 µg/plate |
4.0 µg/plate |
10.0 µg/plate |
10.0 µg/plate |
50.0 µg/plate |
|
No. of Revertants |
632 (574) 537 50.7 554 |
530 (530) 486 44.0 574 |
296 (318) 312 26.1 347 |
124 (135) 145 10.5 136 |
68 (67) 58 8.1 74 |
|
S9-Mix (+) |
Dose Level Per Plate |
Number of revertants (mean) +/- SD |
||||
Base-pair substitution strains |
Frameshift strains |
|||||
TA100 |
TA102 |
TA1535 |
TA98 |
TA1537 |
||
Solvent Control |
166 (167) 170 3.1 164 |
120 (136) 141 13.8 146 |
20 (18) 18 2.0 16 |
17 (17) 16 1.5 19 |
16 14 13 1.7 13 |
|
33 µg |
140 (154) 163 12.3 159 |
104 (122) 118 19.8 143 |
24 (20) 15 4.6 21 |
12 (13) 13 1.5 15 |
21 (15) 8 6.5 15 |
|
100 µg |
148 (149) 152 2.6 147 |
111 (121) 128 8.9 124 |
22 (22) 24 2.5 19 |
14 (16) 18 2.1 17 |
10 (13) 21 6.7 9 |
|
333 µg |
138 (132) 121 9.8 138 |
115 (120) 132 10.8 112 |
19 (21) 23 2.0 21 |
17 (17) 14 3.0 20 |
10 (10) 10 0.6 9 |
|
1000 µg |
131 (118) 114 11.2 110 |
67 (78) 79 10.1 87 |
14 (16) 17 1.7 17 |
20 (17) 14 3.0 17 |
15 (12) 11 2.3 11 |
|
2500 µg |
102 (106) 116 9.1 99 |
61 (53) 63 16.2 34 |
5 (7) 5 2.9 10 |
21 (20) 20 0.6 20 |
16 (9) 6 6.1 5 |
|
5000 µg |
80 (90) 93 8.5 96 |
20 (24) 23 4.0 28 |
4 (2) 1 1.7 1 |
14 (16) 19 2.5 16 |
3 (3) 2 0.6 3 |
|
Positive controls S9-Mix (+) |
Name |
2-aminoanthracene |
2-aminoanthracene |
2-aminoanthracene |
2-aminoanthracene |
2-aminoanthracene |
Dose Level |
2.5 µg/plate |
10.0 µg/plate |
2.5 µg/plate |
2.5 µg/plate |
2.5 µg/plate |
|
No. of Revertants |
1224 (1179) 1206 63.0 1107 |
757 (821) 840 56.9 866 |
320 (297) 302 25.9 269 |
147 (14) 162 15.0 132 |
201 (179) 177 21.5 158 |
Table 2 : Test Results: Experiment 2 with and without metabolic activation and results of concurrent positive controls
S9-Mix (-) |
Dose Level Per Plate |
Number of revertants (mean) +/- SD |
||||
Base-pair substitution strains |
Frameshift strains |
|||||
TA100 |
TA102 |
TA1535 |
TA98 |
TA1537 |
||
Solvent Control |
81 (83) 89 5.3 79 |
142 (139) 141 4.9 133 |
23 (19) 16 3.6 18 |
27 (31) 38 5.9 29 |
6 (6) 7 1.0 5 |
|
33 µg |
85 (78) 74 5.9 76 |
94 (90) 81 7.8 95 |
15 (13) 14 2.6 10 |
18 (21) 25 3.5 21 |
4 (4) 3 1.0 5 |
|
100 µg |
84 (69) 60 5.9 63 |
88 (93) 99 5.7 91 |
12 (14) 16 2.1 15 |
23 (32) 20 1.5 21 |
3 (4) 6 1.5 4 |
|
333 µg |
73 (74) 79 5.0 69 |
38 (35) 39 6.1 28 |
9 (10) 11 1.2 9 |
25 (24) 20 3.6 27 |
5 (6) 4 2.1 8 |
|
1000 µg |
54 (57) 67 8.5 51 |
27 (23) 17 5.3 25 |
13 (12) 3 2.3 13 |
21 (22) 24 1.5 22 |
8 (8) 8 0.6 7 |
|
2500 µg |
48 (49) 54 7.0 46 |
18 (18) 20 2.5 15 |
8 (9) 9 1.5 11 |
25 (24) 28 5.1 18 |
8 (5) 4 2.3 4 |
|
5000 µg |
38 (29) 26 7.6 24 |
17 (15) 9 4.9 18 |
7 (9) 10 1.7 10 |
23 (25) 26 2.1 27 |
2 (3) 3 1.0 4 |
|
Positive controls S9-Mix (-) |
Name |
Sodium Azide |
methyl methane sulfonate |
Sodium Azide |
4-nitro-o-phenylene-idamine |
4-nitro-o-phenylene-idamine |
Dose Level |
10.0 µg/plate |
4.0 µg/plate |
10.0 µg/plate |
10.0 µg/plate |
50.0 µg/plate |
|
No. of Revertants |
559 (580) 595 18.7 586 |
801 (794) 798 10.2 782 |
1266 (1244) 1201 37.0 1264 |
297 (300) 306 5.5 296 |
103 (102) 106 4.6 97 |
|
S9-Mix (+) |
Dose Level Per Plate |
Number of revertants (mean) +/- SD |
||||
Base-pair substitution strains |
Frameshift strains |
|||||
TA100 |
TA102 |
TA1535 |
TA98 |
TA1537 |
||
Solvent Control |
101 (167) 108 5.1 98 |
161 (162) 159 3.6 166 |
24 (21) 19 2.6 20 |
29 (28) 26 1.5 28 |
11 (9) 7 2.1 10 |
|
33 µg |
114 (107) 116 13.9 91 |
101 (105) 119 12.5 95 |
13 (13) 12 1.5 15 |
28 (29) 30 1.0 29 |
11 (9) 6 2.5 9 |
|
100 µg |
86 (78) 76 7.6 71 |
99 (97) 104 7.6 89 |
12 (14) 16 2.1 13 |
22 (21) 23 3.2 17 |
11 (9) 6 2.9 11 |
|
333 µg |
57 (46) 41 9.9 39 |
29 (30) 34 4.0 26 |
15 (14) 16 2.6 11 |
25 (28) 31 3.1 27 |
7 (5) 2 3.5 n.a. |
|
1000 µg |
65 (57) 55 7.6 50 |
21 (19) 17 2.1 18 |
6 (10) 9 4.6 15 |
33 (31) 30 1.5 31 |
2 (5) 7 2.9 7 |
|
2500 µg |
51 (45) 45 6.5 38 |
10 (14) 18 5.7 n.a. |
8 (8) 5 3.0 11 |
7 (9) 11 2.1 10 |
4 (2) 0 2.8 n.a. |
|
5000 µg |
28 (35) 37 6.7 41 |
9 (9) n.a. 0.7 8 |
5 (5) 6 0.6 5 |
14 (11) 7 4.9 n.a. |
1 (1) 1 0.0 1 |
|
Positive controls S9-Mix (+) |
Name |
2-aminoanthracene |
2-aminoanthracene |
2-aminoanthracene |
2-aminoanthracene |
2-aminoanthracene |
Dose Level |
2.5 µg/plate |
10.0 µg/plate |
2.5 µg/plate |
2.5 µg/plate |
2.5 µg/plate |
|
No. of Revertants |
599 (684) 768 84.5 685 |
864 (786) 795 83.4 698 |
182 (181) 170 10.5 191 |
655 (585) 548 60.9 551 |
129 (124) 118 5.7 126 |
n.a. = not analysable (no distinction possible between colonies and reduced background growth).
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results:
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 under GLP, to evaluate the potential mutagenicity of the test item in a bacterial reverse mutation assay using S.typhimurium strains TA98, TA100, TA102, TA1535, and TA1537 in both the presence and absence of S-9 mix. The test strains were treated with the test substance using the Ames plate incorporation method (Experiment 1) and pre incubation method (Experiment 2) at up to six dose levels, in triplicate, both with and without the addition of a rat liver homogenate metabolizing system (15% liver S9 in standard co-factors). The dose range for Experiment 1 was predetermined and was 33 to 5000 µg/plate. The experiment was repeated on a separate day using fresh cultures of the bacterial strains and fresh test item formulations. Six test item dose levels were again 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 the maximum recommended dose level of 5000 μg/plate. The vehicle (ethanol) 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 (plate-incorporation) was selected as the maximum recommended dose level of 5000 μg/plate. For the second mutation test (pre-incubation) the toxic limit was employed as the maximum dose concentration. In the second experiment, reduced background growth was observed in strains TA1535, TA1537, and TA100 at 333 μg/plate and above with metabolic activation, in strains TA98 (with metabolic activation) and TA100 (without metabolic activation) at 1000 ug/plate and above, and in strain TA102 at 33 μg/plate and above with and without metabolic activation. 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) or were within the expected ranges. 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, TA102, TA1535, and TA1537 in the presence and absence of S-9 mix.
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