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EC number: 943-242-0 | 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 gene mutation study in mammalian cells
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Study period:
- 27 Aug - 24 Oct 2012
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: According to the ECHA guidance document “Practical guide 6: How to report read-across and categories (March 2010)”, the reliability was changed from RL1 to RL2 to reflect the fact that this study was conducted on a read-across substance.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 012
- Report date:
- 2012
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.17 (Mutagenicity - In Vitro Mammalian Cell Gene Mutation Test)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: ICH Harmonised Tripartite Guideline S2 (R1): 'Guidance on Genotoxicity Testing and Data Interpretation for Pharmaceuticals Intended for Human Use (EMA/CHMP/ICH/126642/2008)'
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- Behörde Soziales, Familie, Gesundheit und Verbraucherschutz, Hamburg, Germany
- Type of assay:
- mammalian cell gene mutation assay
Test material
- Reference substance name:
- 2,2-dimethyl-1,3-propanediyl dioleate
- EC Number:
- 255-713-1
- EC Name:
- 2,2-dimethyl-1,3-propanediyl dioleate
- Cas Number:
- 42222-50-4
- IUPAC Name:
- 2,2-dimethylpropane-1,3-diyl bisoctadec-9-enoate
- Details on test material:
- - Name of test material (as cited in study report): 2,2-dimethyl-1,3-propanediyl dioleate
- Analytical purity: 100%
- Physical state: light yellowish, clear liquid
- Batch No.: OE10124A
- Storage condition of test material: at room temperature, in a tightly closed container; kept away from heat, sparks, flames and direct sunlight
Constituent 1
Method
- Target gene:
- TK locus
Species / strain
- Species / strain / cell type:
- mouse lymphoma L5178Y cells
- Details on mammalian cell type (if applicable):
- - Type and identity of media: growth medium: RPMI 1640 medium supplemented with 0.05% Pluronic® F68, 2 mM L-glutamine, 220 µg/mL sodium pyruvate, 100 µg/mL gentamycin, 2.5 µg/mL fungizone and fetal bovine serum (10% v/v);
treatment medium: growth medium without sodium pyruvate, gentamycin and fungizone;
cleaning medium: growth medium supplemented with approx. 4.0E-05 M thymidine, 1.2E-04 M hypoxanthine, 3.3E-05 M glycine and 7.2E-07 M methotrexate;
recovery medium: growth medium supplemented with approx. 4.0E-05 M thymidine, 1.2E-04 M hypoxanthine and 3.3E-05 M glycine;
selection medium: growth medium containing 3 µg/mL trifluorothymidine (TFT)
- Properly maintained: yes
- Periodically checked for Mycoplasma contamination: yes
- Periodically checked for karyotype stability: yes
- Periodically "cleansed" against high spontaneous background: yes
- Metabolic activation:
- with and without
- Metabolic activation system:
- co-factor supplemented post-mitochondrial fraction (S9 mix), prepared from the livers of rats treated with Aroclor 1254
- Test concentrations with justification for top dose:
- Preliminary experiment: 25, 100, 250, 1000, 2500 and 5000 µg/mL
- 24 h treatment: without metabolic activation
- 4 h treatment: with metabolic activation
Main assay: 312.5, 625, 1250, 2500 and 5000 µg/mL
- Experiment I - 3 h treatment: with and without metabolic activation
- Experiment II – 24 h treatment: without metabolic activation
- Experiment II – 3 h treatment: with metabolic activation - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: acetone
- Justification for choice of solvent/vehicle: the test substance was completely dissolved in acetone, but not soluble in water or DMSO.
Controls
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- acetone
- True negative controls:
- no
- Positive controls:
- yes
- Remarks:
- -S9: methylmethanesulfonate, 10 and 15 g/mL; +S9: 3-methylcholanthrene, 2.5 and 4 µg/mL
- Positive control substance:
- 3-methylcholanthrene
- methylmethanesulfonate
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in medium
DURATION
- Exposure duration: Experiment I: 3 h (± S9); Experiment II: 24 h (-S9) and 3 h (+S9)
- Expression time (cells in growth medium): after the end of treatment, cells were plated for survival and incubated for the expression period in parallel, i.e. an aliquot of the cells was diluted to 8 cells/mL and 0.2 mL of each culture was placed in 2 different 96 well microtiter plates (192 wells, averaging 1.6 cells/well) and incubated for 1 week, whereas the rest of the cells was incubated for 2 days for the expression period (plating efficiency step 1). The cells for the plating of survival were counted after 1 week and the number of viable clones was recorded. The cells incubated for the expression period were maintained below 10E+6 cells per mL and a minimum of 4 concentration levels plus positive and negative control were selected for 5-trifluoro-thymidine (TFT) resistance. At the end of the second expression period the selected cultures were diluted to 1E+4 cells/mL and plated for survival (plating efficiency step 2) and TFT resistance in parallel (plating efficiency step 2). The plating for survival was identical to the above described method (plating efficiency step 1 in 192 wells with average 1.6 cells/well). For the plating for TFT resistance 3 µg/mL TFT (final concentration) was added to the cultures and 0.2 mL of each suspensions placed into four 96-well microtiter plates (384 wells, averaging 2E+3 cells/well). The plates were incubated for 11-14 days.
- Selection time (if incubation with a selection agent): 11-14 days
- Fixation time (start of exposure up to fixation or harvest of cells): 11-15 days
SELECTION AGENT (mutation assays): 3 µg/mL trifluorothymidine (TFT)
NUMBER OF REPLICATIONS: single treated cultures and duplicate solvent control cultures each in two independent experiments
DETERMINATION OF CYTOTOXICITY
- Method: cloning efficiency; relative total growth; other: suspension growth, relative suspension growth, plating efficiency and relative survival
OTHER EXAMINATIONS:
- Other: small and large colonies were differentiated, as small colonies are capable to indicate chromosomal mutations.
OTHER:
- Concentration selection for the main experiment: the lowest separation factor of 2 as recommended by the guidelines was used and 5 concentrations were selected. Since no increase in the mutant frequency was observed in the preliminary experiment, it was considered acceptable not to add any further lower concentrations, as these additional lower concentrations would provide no further information. - Evaluation criteria:
- The minimum criterion considered necessary to demonstrate mutagenesis for any given treatment was a mutant frequency ≥ 2 compared to the concurrent background mutant frequency. The observation of a mutant frequency that met the minimum criterion for a single treated culture within a range of assayed concentrations was not considdered as sufficient to evaluate a test item as a mutagen.
The test results were positive, if the following criteria were met:
- a concentration-related or toxicity-related increase in mutant frequency preferably for at least 3 concentrations (depending on the concentration steps chosen and toxicity at which mutagenic activity appeared).
- the mutant frequency for a single concentration at or near the highest testable toxicity was ≥ 4 times the concurrent background mutant frequency. Smaller increases at a single concentration near the highest testable toxicity needed to be confirmed by a repeat assay.
- either parameter (concentration or toxicity (percent relative growth)) was used to establish whether the increase in mutant frequency was related to an increase in effective treatment.
- treatments inducing less than 10% relative growth were included in the assay, but not used as primary evidence for mutagenicity.
The test item was considered as negative in this assay if neither of the above criteria were met. A test item was evaluated as non-mutagenic in a single assay if the minimum increase in mutant frequency was not observed for a range of applied concentrations that extended toxicity causing 10% to 20% relative growth or a range of applied concentrations extending to at least twice the solubility limit in culture media. - Statistics:
- The significance of increases in mutant frequencies (total wells with clones), by comparison with concurrent controls and the global evaluation factor (GEF), was assessed according to the recommendations of the Mouse Lymphoma Workgroup, Aberdeen, 2003. For microwell assays, the GEF is defined as 126 mutants per 1E+6 viable cells. For valid data, the test item was considered to be mutagenic in this assay if the mutant frequency (MF) of any test concentration exceeded the sum of the mean control mutant frequency plus GEF and the linear trend test was positive. This would indicate a positive, biologically relevant response.
Results and discussion
Test results
- Species / strain:
- mouse lymphoma L5178Y cells
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- Positive controls validity:
- valid
- Additional information on results:
- RANGE-FINDING/SCREENING STUDIES: in a preliminary cytotoxicity test with concentrations ranging from 25 to 5000 µg/mL, no signs of cytotoxicity were noted in the experiment without and with metabolic activation (24-h or 4-h exposure, respectively) at any of the concentrations tested. Hence, the highest concentration of the test substance selected for treatment in the main study was 5000 µg/mL.
COMPARISON WITH HISTORICAL CONTROL DATA: mutant frequencies of the positive and negative controls were within the respective historical ranges. The mutant frequencies in treated colonies were within the range of the negative control values. - Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
Any other information on results incl. tables
Table 1. Experiment I - 3 h exposure - With Metabolic Activation
Concentration [µg/mL] |
Plating efficiency 2 |
Relative survival [%] |
Mutants per 1E+06 surviving cells |
% large colonies of total colonies |
% small colonies of total colonies |
ratio small/large colonies |
|
SC* |
1.1193 |
100 |
57.93 |
45.7 |
54.3 |
1.19 |
|
312.5 |
0.8796 |
79 |
79.30 |
48.0 |
52.0 |
1.08 |
|
625 |
0.7270 |
65 |
81.71 |
51.2 |
48.8 |
0.95 |
|
1250 |
0.9208 |
82 |
62.88 |
42.9 |
57.1 |
1.33 |
|
2500 |
1.0124 |
90 |
57.19 |
50.0 |
50.0 |
1.00 |
|
5000 |
0.9208 |
82 |
69.29 |
52.2 |
47.8 |
0.92 |
|
3-MCA, 2.5 |
0.3096 |
28 |
693.15 |
43.3 |
56.7 |
1.31 |
|
3-MCA, 4.0 |
0.3596 |
32 |
653.50 |
52.1 |
47.9 |
0.92 |
3-MCA = 3-methylcholanthrene; SC = solvent control (acetone)
* mean value of 2 parallel cultures
Table 2. Experiment I - 3 h exposure - Without Metabolic Activation
Concentration [µg/mL] |
Plating efficiency 2 |
Relative survival [%] |
Mutants per 1E+06 surviving cells |
% large colonies of total colonies |
% small colonies of total colonies |
ratio small/large colonies |
|
SC* |
0.8866 |
100 |
72.27 |
54.3 |
45.7 |
0.84 |
|
312.5 |
0.9649 |
109 |
66.12 |
45.7 |
54.3 |
1.19 |
|
625 |
0.9499 |
107 |
71.85 |
46.9 |
53.1 |
1.13 |
|
1250 |
0.9804 |
111 |
65.08 |
45.7 |
54.3 |
1.19 |
|
2500 |
1.2033 |
136 |
59.12 |
58.8 |
41.2 |
0.70 |
|
5000 |
1.1602 |
131 |
60.12 |
52.0 |
48.0 |
0.92 |
|
MMS, 10 |
0.1627 |
18 |
1782.42 |
27.8 |
72.2 |
2.60 |
|
MMS, 15 |
0.2248 |
25 |
1919.48 |
37.8 |
62.2 |
1.64 |
MMS = methylmethanesulfonate; SC = solvent control (acetone)
* mean value of 2 parallel cultures
Table 3. Experiment II - 3 h exposure - With Metabolic Activation
Concentration [µg/mL] |
Plating efficiency 2 |
Relative survival [%] |
Mutants per 1E+06 surviving cells |
% large colonies of total colonies |
% small colonies of total colonies |
ratio small/large colonies |
|
SC* |
0.9070 |
100 |
53.48 |
47.9 |
52.1 |
1.09 |
|
312.5 |
0.8664 |
96 |
50.21 |
43.8 |
56.3 |
1.29 |
|
625 |
0.9208 |
102 |
55.01 |
51.4 |
48.6 |
0.95 |
|
1250 |
0.8164 |
90 |
67.37 |
45.0 |
55.0 |
1.22 |
|
2500 |
0.6769 |
75 |
62.20 |
41.9 |
58.1 |
1.38 |
|
5000 |
0.8286 |
91 |
66.38 |
45.0 |
55.0 |
1.22 |
|
3-MCA, 2.5 |
0.4203 |
46 |
894.72 |
48.3 |
51.7 |
1.07 |
|
3-MCA, 4.0 |
0.4598 |
51 |
776.64 |
52.0 |
48.0 |
0.92 |
3-MCA = 3-methylcholanthrene; SC = solvent control (acetone)
* mean value of 2 parallel cultures
Table 4. Experiment II - 24 h exposure - Without Metabolic Activation
Concentration [µg/mL] |
Plating efficiency 2 |
Relative survival [%] |
Mutants per 1E+06 surviving cells |
% large colonies of total colonies |
% small colonies of total colonies |
ratio small/large colonies |
|
SC* |
0.7274 |
100 |
55.94 |
48.3 |
51.7 |
1.07 |
|
312.5 |
0.6674 |
92 |
54.61 |
51.9 |
48.1 |
0.93 |
|
625 |
0.7166 |
99 |
74.73 |
51.3 |
48.7 |
0.95 |
|
1250 |
0.6866 |
94 |
61.32 |
51.6 |
48.4 |
0.94 |
|
2500 |
0.8045 |
111 |
61.16 |
47.2 |
52.8 |
1.12 |
|
5000 |
0.7065 |
97 |
55.56 |
55.2 |
44.8 |
0.81 |
|
MMS, 10 |
0.3654 |
50 |
1139.30 |
39.2 |
60.8 |
1.55 |
|
MMS, 15 |
0.2537 |
35 |
2005.13 |
37.6 |
62.4 |
1.66 |
MMS = methylmethanesulfonate; SC = solvent control (acetone)
* mean value of 2 parallel cultures
RATIO OF SMALL TO LARGE COLONIES
No change was observed in the ratio of small to large mutant colonies between treated and solvent control cultures.
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information):
negative
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