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EC number: 606-467-2 | CAS number: 202189-76-2
- 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
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- Nanomaterial pour density
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- 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:
- May 16, 2002 - July 5, 2002
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 002
- Report date:
- 2007
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- no
- GLP compliance:
- yes
- Type of assay:
- bacterial reverse mutation assay
Test material
- Reference substance name:
- 2-{4-[2-(4,4-dimethyl-4,5-dihydro-1,3-oxazol-2-yl)propan-2-yl]phenyl}ethyl 4-methylbenzene-1-sulfonate
- EC Number:
- 606-467-2
- Cas Number:
- 202189-76-2
- Molecular formula:
- C23H29NO4S
- IUPAC Name:
- 2-{4-[2-(4,4-dimethyl-4,5-dihydro-1,3-oxazol-2-yl)propan-2-yl]phenyl}ethyl 4-methylbenzene-1-sulfonate
- Test material form:
- solid
Constituent 1
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Source: sponsor
- Code: W-02-7046-A1
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature in darkness.
- Solubility and stability of the test substance in the solvent/vehicle: DMSO was used as a vehicle to prepare the test item concentrations. A stock concentration of 100 mg/ml was prepared from which 1:5 dilutions were carried out. The test item precipitates in contact with the phospate tampon in concentrations of 10 and 20mg/ml.
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: no
Method
- Target gene:
- Histidine
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 specified
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9
- Test concentrations with justification for top dose:
- Due to the fact that during the initial tests the concentrations of 10 and 20 mg/ml, precipitated in contact with the phosphate tampon, the following concentrations were used in successive tests: 4; 0.8; 0.16; 0.032 and 0.0064 mg/ml.
- Vehicle / solvent:
- - Vehicle/solvent used: DMSO
- Justification for choice of solvent/vehicle: Solvent is compatible with the survival of the bacteria and the S9 activity.
Controls
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 9-aminoacridine
- 2-nitrofluorene
- sodium azide
- cumene hydroperoxide
- other: 2-aminoantracene
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: Preincubation
Each point of two serioes of tubes (with and without S9) was tested in duplicate and with the following composition: phosphate buffer (or S9 mixture), 2E9 cell/ml bacterial culture and the solvent (negative control), the test item (each one of the five concentrations) or the reference item (positive control). The tubes were place in a water bath at 37ºC for 45 minutes. Then 2ml of surface agar supplemented with histidine/biotine 0.5mM was added to each tube and poured out onto a minimum agar plate. The plates were left to set for 1 hour and they were then placed in the incubator at 37ºC for 48-72 hours.
DURATION
- Preincubation period: 45 minutes
- Exposure duration:48 -72 hours
SELECTION AGENT (mutation assays): The lack of amino-acid in the medium. Only the mutants can grow due to their capability to synthesize an essential amino acid.
NUMBER OF REPLICATIONS: 2. In cases where a positive may exist the assay has been duplicated which results in 4 replicates for some concentrations.
DETERMINATION OF CYTOTOXICITY
-Method: Visual observation of the colonies.
OTHER EXAMINATIONS:
Phenotype and sterility controls were also performed.
- OTHER:
Solutions preparation: DMSO was used as a vehicle to prepare the test item concentrations. In all cases, these concentrations were prepared on the day they were used. A stock concentration of 100mg/ml was prepared from which 1:5 dilutions were carried out.
Test system: Prior to the study, the master plates for each strain were prepared. The strains were plated out in minimum enriched agar plate with Biotin 0.5 mM and Histidine 0.1 M. In the case of strains TA98 and TA100 the plates also contained ampicilyne 8 mg/ml and in the case of strain TA102 they contained tetracycline 8 mg/ml, in addition to Histidine, Biotin and Ampicilyne. The plates were cultivated for 48 hours at 37 ºC. - Rationale for test conditions:
- Due to the fact that during the initial tests the concentrations of 10 and 20 mg/ml, precipitated in contact with the phosphate tampon, the following concentrations were used in successive tests: 4; 0.8; 0.16; 0.032 and 0.0064 mg/ml.
- Evaluation criteria:
- Criteria conclusion: the result of the test is considered as positive if the test item induce an increase of colonies with respect to non-treated plates, dependent on the concentration of one, or several of the 5 strains, without and/or with metabolic activation.
Results and discussion
Test resultsopen allclose all
- Key result
- Species / strain:
- S. typhimurium TA 1535
- Metabolic activation:
- with and without
- Genotoxicity:
- positive
- 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
- Genotoxicity:
- positive
- 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:
- without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: The concentrations of 10 and 20 mg/ml, precipitated in contact with the phosphate tampon
Any other information on results incl. tables
The conditions listed below indicate that the tests are acceptable:
1. The plates show a firm uniform lawn which demonstrates there is no toxicity on the concentration taken as a reference to evaluate the mutagenic power.
2. The number of colonies on the spontaneous mutation colonies is within the normal range for each strain.
3. The positive controls induce a clear increase in the number of revertants in all cases.
4. The phenotype control plates show the expected results for each strain.
From the results expressed on the tables below it can be deduced that:
- The test item induce an increase of colonies with respect to non-treated plates, dependent on the concentration of strains TA1535 (with and without S9) and TA100 (with S9).
- The test item does not induce an increase in colonies in the rest of the strains used for this assay.
- The mutation index (MI) calculated from the average os the number of colonies counted on each plate, show values of 1.74 and 3.11 for the strain TA1535 (without and with S9) and 1.46 on the TA100 (with S9) strain.
The results described indicate that:
- The test item is not mutagenic for the strains TA98, TA102 and TA1537
- The test item is mutagenic for the strains TA1535 and TA100
Calculation of the mutation index (MI)
MI = nº. of mut. in a dose / nº. of mut. in the control
Strain TA1535 |
||||||
|
-S9 |
+S9 |
||||
|
No. Col. |
Average |
MI |
No. Col. |
Average |
MI |
Sp. Mut. |
20/28 |
24.00 |
|
19/25/18/25 |
21.75 |
|
0.00 (mg/ml) |
17/20/23/27 |
21.75 |
|
23/23/17/20 |
20.75 |
|
0.0064 (mg/ml) |
16/22 |
19.00 |
0.874 |
23/20/22 |
21.67 |
1.044 |
0.032 (mg/ml) |
16/13 |
14.50 |
0.667 |
22/23/13/19 |
19.25 |
0.928 |
0.16 (mg/ml) |
17/19 |
18.00 |
0.828 |
25/14/18/24 |
20.25 |
0.976 |
0.8 (mg/ml) |
28/22/25/32 |
26.75 |
1.230 |
47/35/30/32 |
36.00 |
1.735 |
4 (mg/ml) |
28/39/45/42 |
38.50 |
1.770 |
66/65/62/65 |
64.50 |
3.108 |
Control + |
480/470 |
475.00 |
21.839 |
134/172 |
153.00 |
7.373 |
Strain TA1000 |
||||||
|
-S9 |
+S9 |
||||
|
No. Col. |
Average |
MI |
No. Col. |
Average |
MI |
Sp. Mut. |
110/116 |
113.00 |
|
95/108 |
101.50 |
|
0.00 (mg/ml) |
89/90 |
89.50 |
|
100/138/146/80 |
116.00 |
|
0.0064 (mg/ml) |
108/99 |
103.50 |
1.156 |
132/135/134/129 |
132.50 |
1.142 |
0.032 (mg/ml) |
88/106 |
97.00 |
1.084 |
138/111/134/117 |
125.00 |
1.078 |
0.16 (mg/ml) |
102/95 |
98.50 |
1.101 |
127/124/149/132 |
133.00 |
1.147 |
0.8 (mg/ml) |
112/106 |
109.00 |
1.218 |
138/125/161/160 |
146.00 |
1.259 |
4 (mg/ml) |
124/100 |
112.00 |
1.251 |
168/144/183/182 |
169.25 |
1.459 |
Control + |
505/487 |
496.00 |
5.542 |
952/946/940/1108 |
986.50 |
8.504 |
Strain TA98 |
||||||
|
-S9 |
+S9 |
||||
|
No. Col. |
Average |
MI |
No. Col. |
Average |
MI |
Sp. Mut. |
28/28 |
28.00 |
|
36/38 |
37.00 |
|
0.00 (mg/ml) |
20/29 |
24.50 |
|
33/33 |
33.00 |
|
0.0064 (mg/ml) |
21/23 |
22.00 |
0.898 |
34/26 |
30.00 |
0.909 |
0.032 (mg/ml) |
20/27 |
23.50 |
0.959 |
33/34 |
33.50 |
1.015 |
0.16 (mg/ml) |
22/30 |
26.00 |
1.061 |
28/29 |
28.50 |
0.864 |
0.8 (mg/ml) |
28/30 |
29.00 |
1.184 |
32/29 |
30.50 |
0.924 |
4 (mg/ml) |
30/23 |
26.50 |
1082 |
38/26 |
32.00 |
0.970 |
Control + |
>1000/>1000 |
>1000 |
>40.816 |
973/965 |
969.00 |
29.364 |
Strain TA1537 |
||||||
|
-S9 |
+S9 |
||||
|
No. Col. |
Average |
MI |
No. Col. |
Average |
MI |
Sp. Mut. |
23/23 |
23.00 |
|
28/40 |
34.00 |
|
0.00 (mg/ml) |
21/18 |
19.50 |
|
26/24 |
25.00 |
|
0.0064 (mg/ml) |
20/22 |
21.00 |
1.077 |
28/24 |
26.00 |
1.040 |
0.032 (mg/ml) |
21/21 |
21.00 |
1.077 |
29/29 |
29.00 |
1.160 |
0.16 (mg/ml) |
21/21 |
21.00 |
1.077 |
30/25 |
27.50 |
1.100 |
0.8 (mg/ml) |
23/21 |
22.00 |
1.128 |
28/26 |
27.00 |
1.080 |
4 (mg/ml) |
25/19 |
22.00 |
1.128 |
28/30 |
29.00 |
1.160 |
Control + |
941/786 |
863.50 |
44.282 |
112/92 |
102.00 |
4.080 |
Strain TA102 |
||||||
|
-S9 |
+S9 |
||||
|
No. Col. |
Average |
MI |
No. Col. |
Average |
MI |
Sp. Mut. |
270/-- |
270.00 |
|
355/316 |
335.50 |
|
0.00 (mg/ml) |
261/260 |
260.50 |
|
315/295 |
305.00 |
|
0.0064 (mg/ml) |
228/239 |
233.50 |
0.896 |
250/240 |
245.00 |
0.803 |
0.032 (mg/ml) |
256/244 |
250.00 |
0.960 |
222/227 |
224.50 |
0.736 |
0.16 (mg/ml) |
200/231 |
215.50 |
0.827 |
282/286 |
284.00 |
0.931 |
0.8 (mg/ml) |
229/268 |
248.50 |
0.954 |
320/284 |
302.00 |
0.990 |
4 (mg/ml) |
250/254 |
252.00 |
0.967 |
321/282 |
301.50 |
0.989 |
Control + |
512/568 |
540.00 |
2.069 |
>1000/>1000 |
>1000 |
>3.279 |
--: It was not possible to count colonies
Results of the phenotype control
|
TA98 |
TA100 |
TA1535 |
TA1537 |
TA102 |
Ampicilyne |
Resistant |
Resistant |
Sensitive |
Sensitive |
Resistant |
Violet Crystal |
Sensitive |
Sensitive |
Sensitive |
Sensitive |
Sensitive |
UV light |
Sensitive |
Sensitive |
Sensitive |
Sensitive |
Sensitive |
Tetracycline |
- |
- |
- |
- |
Resistant |
Applicant's summary and conclusion
- Conclusions:
- The test item induce a dose-dependent increase in Salmonella typhimurium strain TA1535 (with and without S9) and TA100 (with S9). Therefore, it was considered as mutagenic under test conditions.
- Executive summary:
A Bacterial reverse mutation test was performed according OECD guideline 471 with GLP. Based on a previous toxicity test, 1-2E9 cell/mL of Salmonella typhimurium strains TA98, TA100, TA1535, TA1537 and TA102 were exposed to 0.0064, 0.032, 0.16, 0.8 and 4 mg/mL test item, solvent and positive controls with and without metabolic activation (two replicates each). The incubation mixtures were pre-incubated at 37 ºC for 45 minutes and incubated at 37 ºC for 48 -72 hours. Then, the revertant colonies were counted. Phenotype and sterility controls were also performed. The plates showed a firm, uniform lawn, which demonstrates that there was no toxicity. The number of colonies in the spontaneous mutation colonies was within the normal range for each strain. The positive controls induced a clear increase in the number of revertants in all cases and the phenotype control plates show the expected results for each strain. The test induce a dose-dependent increase in TA1535 (with and without S9) and TA100 (with S9). Therefore, the test item was determined to be mutagenic under test conditions.
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