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EC number: 946-937-7 | CAS number: -
- 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 cytogenicity / chromosome aberration study in mammalian cells
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 11 August 2009 to 21 September 2009
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study with acceptable restrictions
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 009
- Report date:
- 2009
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
- Version / remarks:
- 1997
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.5375 - In vitro Mammalian Chromosome Aberration Test
- Version / remarks:
- 1998
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: Guidelines for the testing of chemicals Section 4: Health Effects, Ministry of environmental protection of People's Republic of China, 473.
- Version / remarks:
- 2003
- Deviations:
- no
- GLP compliance:
- not specified
- Remarks:
- Not specified
- Type of assay:
- other: chromosome aberration study in mammalian cells
Test material
- Reference substance name:
- 2,2-bis[(allyloxy)methyl]butyl (3-{[({2,2-bis[(allyloxy)methyl]butoxy}carbonyl)amino]methyl}-3,5,5-trimethylcyclohexyl)carbamate
- EC Number:
- 946-937-7
- Molecular formula:
- C36H62N2O8
- IUPAC Name:
- 2,2-bis[(allyloxy)methyl]butyl (3-{[({2,2-bis[(allyloxy)methyl]butoxy}carbonyl)amino]methyl}-3,5,5-trimethylcyclohexyl)carbamate
- Test material form:
- liquid
- Details on test material:
- - Storage: cool and dark
Constituent 1
Method
Species / strain
- Species / strain / cell type:
- Chinese hamster lung fibroblasts (V79)
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9-mix
- Test concentrations with justification for top dose:
- Preliminary study: 9.75, 19.5, 39.0, 78.1, 156.2, 312.5, 625, 1250, 2500 and 5000 µg/mL
Main study: without S9: 80, 160 and 320 µg/mL; with S9: 60, 120 and 240 µg/mL.
The test material dose levels selected for testing in the chromosome aberration assay were as a result of the preliminary toxicity assay. - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: DMSO
Controls
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- cyclophosphamide
- mitomycin C
- Details on test system and experimental conditions:
- ACTIVATION SYSTEM
- The S9 was patch prepared by the supplier and stored at - 70 °C until use in this facility.
- Immediately prior to use, the S9 was thawed and mixed with a cofactor pool to contain as final concentrations in the S9 activated treatment medium with 8 mM MgCl2, 33 mM KCI, 5 mM glucose-6-phosphate, 4 mM nicotinamide-adenine dinucleotide phosphate and 100 µL S9 per millilitre medium.
PRELIMINARY TOXICITY ASSAY
- The concentration range covered 9.75 to 5000 µg/mL in the preliminary toxicity assay.
CHROMOSOME ABERRATION ASSAY
- The medium pH of this concentration was approximately 7.0.
- Cells were treated for 3 and 24 hours without metabolic activation (-S9- mix) and for 3 hours only with metabolic activation (+ S9- mix).
- 200 cells were counted per solvent control group
- 100 cells were counted per positive control group
- 200 cells were counted per test material treatment group
DETERMINATION OF CYTOTOXICITY
- The percentage of cells with structural or numerical aberrations were measured.
- To insure the evaluation of first division metaphase cells, the dividing cells were arrested in metaphase and harvested for microscopic evaluation of chromosome aberrations at approximately 24 hours after initiating treatment. - Evaluation criteria:
- The solvent and positive controls fulfilled the requirements for a valid test.
Results and discussion
Test results
- Key result
- Species / strain:
- Chinese hamster lung fibroblasts (V79)
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Additional information on results:
- PRELIMINARY TOXICITY ASSAY
- Visible precipitate was observed in test medium concentrations of 312.5 to 5000 µg/mL. The results of the preliminary toxicity test can be seen in Tables 1, 2 and 3.
MAIN TEST
- 3 Hour Treatment without Metabolic Activation
When the cells were treated for 3 hours without metabolic activation with the test material, the chromosome aberrations were less than 5%. The percentage of cells with structural or numerical aberrations in the test material treated group was not significantly increased above that of the solvent control at any dose level (p>0.05, x2. Test). The percentage of cells with structural aberrations in the Mitomycin C (positive control) group was statistically significant (p< 0.01, x2 Test).
- 24 Hour Treatment without Metabolic Activation
When the cells were treated for 24 hours without metabolic activation, the test material did not cause the chromosome aberration rate to be more than 5%. The percentage of cells with structural or numerical aberrations in the test material treated group was not significantly increased above that of the solvent control at any dose level (p > 0.05, x2. Test). The percentage of cells with structurally aberrations in the Mitomycin C (positive control) group was statistically significant (p<0.01, x2 Test).
- 3 Hour Treatment with Metabolic Activation
When the cells were treated for 3 hours with metabolic activation, the test material did not cause the chromosome aberration rate to be more than 5%. The percentage of cells with structural or numerical aberrations in the test material treated group was not significantly increased above that of the solvent control at any dose level (p>0.05, x2 Test). The percentage of cells with structurally aberrations in the Cyclophosphamide (positive control) group was statistically significant (p<0.01, x2 Test).
Any other information on results incl. tables
Table 1: Preliminary toxicity assay (in the non-activated 3 hour exposure group)
Concentration (µg/mL) |
5000 |
2500 |
1250 |
625 |
312.5 |
156.2 |
78.1 |
39.0 |
19.5 |
9.75 |
0 (DMSO) |
Cell survival rate (%) |
0 |
9.7 |
36.3 |
74.3 |
86.6 |
94.6 |
95.0 |
95.7 |
100.2 |
97.4 |
100.0 |
Solubility of the test material |
+ |
+ |
+ |
+ |
+ |
- |
- |
- |
- |
- |
- |
Table 2: Preliminary toxicity assay (in the non-activated 24 hour exposure group)
Concentration (µg/mL) |
5000 |
2500 |
1250 |
625 |
312.5 |
156.2 |
78.1 |
39.0 |
19.5 |
9.75 |
0 (DMSO) |
Cell survival rate (%) |
0 |
9.1 |
20.7 |
43.7 |
60.6 |
81.7 |
99.6 |
102.2 |
99.1 |
97.1 |
100.0 |
Solubility of the test material |
+ |
+ |
+ |
+ |
+ |
- |
- |
- |
- |
- |
- |
Table 3: Preliminary toxicity assay (in the S9-activated 3 hour exposure group)
Concentration (µg/mL) |
5000 |
2500 |
1250 |
625 |
312.5 |
156.2 |
78.1 |
39.0 |
19.5 |
9.75 |
0 (DMSO) |
Cell survival rate (%) |
0 |
6.8 |
17.9 |
31.8 |
40.0 |
60.3 |
97.8 |
96.7 |
100.4 |
101.3 |
100.0 |
Solubility of the test material |
+ |
+ |
+ |
+ |
+ |
- |
- |
- |
- |
- |
- |
+ = visible precipitate, - = solution
Table 4: The results of the in vitro chromosome aberration assay of the test material on cultured CHL cells
Treatment |
Dose (µg/mL) |
S9 activation |
Treatment time (h) |
Counting cells |
Number of aberrations |
Rate of aberrations (%) |
||
Numerical |
Structural |
Numerical |
Structural |
|||||
DMSO |
0 |
- |
3 |
200 |
0 |
2 |
0 |
1.0 |
Mitomycin C |
0.25 |
- |
3 |
100 |
0 |
51 |
0 |
51.0** |
Test material |
320 |
- |
3 |
200 |
0 |
3 |
0 |
1.5 |
160 |
- |
3 |
200 |
0 |
0 |
0 |
0.0 |
|
80 |
- |
3 |
200 |
0 |
2 |
0 |
1.0 |
|
DMSO |
0 |
- |
24 |
200 |
0 |
1 |
0 |
0.5 |
Mitomycin C |
0.20 |
- |
24 |
100 |
0 |
46 |
0 |
46.0** |
Test material |
320 |
- |
24 |
200 |
0 |
1 |
0 |
0.5 |
160 |
- |
24 |
200 |
0 |
4 |
0 |
2.0 |
|
80 |
- |
24 |
200 |
0 |
2 |
0 |
1.0 |
|
DMSO |
0 |
+ |
3 |
200 |
0 |
1 |
0 |
0.5 |
Cyclophosphamide |
20 |
+ |
3 |
100 |
0 |
43 |
0 |
43.0** |
Test material |
240 |
+ |
3 |
200 |
0 |
2 |
0 |
1.0 |
120 |
+ |
3 |
200 |
0 |
1 |
0 |
0.5 |
|
60 |
+ |
3 |
200 |
0 |
2 |
0 |
1.0 |
** = P < 0.01, compared with DMSO control
Applicant's summary and conclusion
- Conclusions:
- Under the conditions of the study, the test material was concluded to be negative for the induction of structural or numerical chromosome aberrations in both non-activated and S9 activated test systems in the in vitro mammalian chromosome aberration test using CHL cells. The test material was not considered to be clastogenic.
- Executive summary:
The genetic toxicity of the test material was examined using the chromosome aberration test in accordance with the standardised guidelines OECD 473, EPA OPPTS 870.5375 and "Guidelines for the testing of chemicals Section 4: Health Effects, Ministry of environmental protection of People's Republic of China, 473". The purpose of this study was to evaluate the clastogenic potential of the test material based on its ability to induce chromosome aberration in Chinese hamster lung fibroblasts (CHL) cells. The study consisted of a preliminary toxicity assay and a chromosome aberration assay. The clastogenic potential of the test material was evaluated by measuring the frequency of cells with structural chromosome aberrations in CHL cultures treated with the test material in comparison with frequency in cultures treated with the solvent only. The test material was also assessed for its potential to induce numerical chromosome aberrations. The chromosome aberration assay was conducted using standard procedures by exposing CHL cells to various concentrations of test material in the presence and absence of exogenous metabolic activation supplied by Aroclor-induced rat liver S9. DMSO was used as solvent for the test material and was the solvent control. In the non-activated test system, treatment time was 3 hours or 24 hours; and in the S9 activated system the treatment time was 3 hours. To insure the evaluation of first division metaphase cells, the dividing cells were arrested in metaphase and harvested for microscopic evaluation of chromosome aberrations at approximately 24 hours after initiating treatment. In the non-activated 3 hour and 24 hour exposure groups, CHL cultures were exposed to the test material at concentrations of 320, 160 and 80 µg/mL. In the S9 activated 3 hour exposure group, CHL cultures were exposed to the test material at concentrations of 240, 120 and 60 µg/mL. Solvent control (DMSO) and appropriate positive controls (Mitomycin C in the absence of S9 and Cyclophosphamide in the presence of S9) also were tested for each treatment condition.
For each of the exposure groups, there was no statistically significant increase in the percentage of cells with structural or numerical chromosome aberrations compared with the corresponding solvent control at any of the test material concentrations evaluated microscopically. The solvent and positive controls fulfilled the requirements for a valid test. Under the conditions of the study the test material was concluded to be negative for the induction of structural or numerical chromosome aberrations in both non-activated and S9 activated test systems in the in vitro mammalian chromosome aberration test using CHL cells. The test material was not considered to be clastogenic in this in vitro study.
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