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EC number: 500-288-2 | CAS number: 103213-20-3
- 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 Apr - 16 Jun 2015
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- GLP - Guideline study, tested with the source substance Fatty acids, C18-unsatd., dimers, hydrogenated, 2-ethylhexyl esters (CAS 68440-06-2). In accordance to the ECHA guidance document “Practical guide 6: How to report read-across and categories (Dec 2012)”, 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:
- 2 015
- Report date:
- 2015
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
- Version / remarks:
- (1997)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.17 (Mutagenicity - In Vitro Mammalian Cell Gene Mutation Test)
- Version / remarks:
- (2008)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.5300 - In vitro Mammalian Cell Gene Mutation Test
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- THE DEPARTMENT OF HEALTH OF THE GOVERNMENT OF THE UNITED KINGDOM
- Type of assay:
- mammalian cell gene mutation assay
Test material
- Reference substance name:
- Fatty acids, C18-unsatd., dimers, hydrogenated, 2-ethylhexyl esters
- EC Number:
- 500-214-9
- EC Name:
- Fatty acids, C18-unsatd., dimers, hydrogenated, 2-ethylhexyl esters
- Cas Number:
- 68440-06-2
- Molecular formula:
- C44H84O4
- IUPAC Name:
- Fatty acids, C18-unsatd., dimers, hydrogenated, 2-ethylhexyl esters
- Test material form:
- not specified
- Details on test material:
- - Name of test material (as cited in study report): only trade name given
- Storage condition of test material: room temperature in the dark
- Expiration date of the lot/batch: 05 May 2016
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:
- Basic medium: RPMI 1640 medium with Glutamax-1 and HEPES buffer (20 mM) supplemented with penicillin/streptomycin (100 U/mL and 100 μg/mL, respectively), sodium pyruvate (1 mM), amphotericin (2.5 µg/mL) and 10% donor horse serum (R10 medium)
- Exposure medium: RPMI 1640 with 20% donor horse serum (R20) and without serum (R0) are used during the study course. - Additional strain / cell type characteristics:
- not applicable
- Metabolic activation:
- with and without
- Metabolic activation system:
- co-factor supplemented post-mitochondrial fraction (S9-mix), prepared from the livers of Sprague Dawley rats treated with a suspension of phenobarbital (80 mg/kg bw) and ß-naphthoflavone (100 mg/kg bw).
- Test concentrations with justification for top dose:
- Preliminary Cytotoxicity Test:
- 9.77, 19.53, 39.06, 78.13, 156.25, 312.5, 625, 1250, 2500 µg/mL (with and without metabolic activation)
Experiment 1:
- 4.88, 9.77, 19.53, 39.06, 78.13, 156.25 µg/mL (with and without metabolic activation)
Experiment 2:
- 9.77, 19.53, 39.06, 78.13, 156.25, 312.5 µg/mL (without metabolic activation)
- 4.88, 9.77, 19.53, 39.06, 78.13, 156.25, µg/mL (with metabolic activation) - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: acetone
- Justification for choice of solvent/vehicle: Following solubility checks performed in-house for previous studies with the same test item, the test item was accurately weighed and formulated in acetone prior to serial dilutions being prepared. The test item was considered to be a complex mixture (UVCB), therefore the maximum proposed dose level in the solubility test was set at 5000 µg/mL. However, acetone is toxic to LY5178Y cells at dose volumes greater than 0.5% of the total culture volume. Therefore, the test item was formulated at 500 mg/mL and dosed at 0.5% to give a maximum achievable dose level of 2500 µg/mL.
Controls
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- cyclophosphamide
- ethylmethanesulphonate
- Remarks:
- -S9-mix: Ethylmethanosulphonate (EMS): 400 µg/mL (experiment I), 150 µg/mL (experiment II); +S9-mix: Cyclophosphamide (CP): 1.5 µg/mL (experiment I and II)
- Details on test system and experimental conditions:
- METHOD OF APPLICATION
- in suspension
DURATION
- Exposure duration: Experiment I: 4 h (with and without metabolic activation); Experiment II: 24 h (without metabolic activation), 4 h (with metabolic activation)
- Expression time (cells in growth medium): On Day 2 of the experiment, the cells were plated for determination of the mutant efficiency in 96-well microtitre plates containing TFT selective medium. The microtitre plates were incubated for 10 or 14 days.
- Selection time: 10 – 14 days
SELECTION AGENT
- 4 μg/mL trifluorothymidine (TFT)
NUMBER OF REPLICATIONS
- each experiment was performed in duplicates (with and without metabolic activation).
DETERMINATION OF CYTOTOXICITY
- Method: relative total growth
OTHER EXAMINATIONS
- Small and large colonies were differentiated, as small colonies are capable to indicate chromosomal mutations. - Evaluation criteria:
- For a test item to demonstrate a mutagenic response it must produce a statistically significant increase in the induced mutant frequency (IMF) over the concurrent vehicle mutant frequency value. Any test item dose level that has a mutation frequency value that is greater than the corresponding vehicle control by the global evaluation factor (GEF) of 126*10-6 and demonstrates a positive linear trend will be considered positive. However, if a test item produces a modest increase in mutant frequencies, which only marginally exceeds the GEF value and is not reproducible or part of a dose-related response, then it may be considered to have no toxicological significance. Conversely, when a test item induces modest reproducible increases in the mutation frequencies that do not exceed the GEF value then scientific judgement will be applied. If the reproducible responses are significantly dose-related and include increases in the absolute numbers of mutant colonies then they may be considered to be toxicologically significant.
- Statistics:
- The global evaluation factor (GEF) has been defined by the IWGT as the mean of the negative/solvent MF distribution plus one standard
deviation. For the micro well version of the assay the GEF is 126.
A test substance is considered positive (mutagenic) in the mutation assay if it induces a MF of more than MF(controls) + 126 in a dosedependent
manner. An observed increase should be biologically relevant and will be compared with the historical control data range.
A test substance is considered equivocal (questionable) in the mutation assay if no clear conclusion for positive or negative result can be made
after an additional confirmation study.
A test substance is considered negative (not mutagenic) in the mutation assay if none of the tested concentrations reaches a mutation frequency
of MF(controls) + 126.
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:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: There was no marked change in pH when the test item was dosed into media.
- Effects of osmolality: Osmolality did not increase by more than 50 mOsm.
- Precipitation: A cloudy precipitate of the test item was observed in both experiments at and above 39.06 µg/mL which turned to a greasy/oily precipitate at 156.25 µg/mL at the end of exposure.
RANGE-FINDING/SCREENING STUDIES
The dose range of the test item used in the preliminary toxicity test was 9.77 to 2500 µg/mL. In all three exposure groups there was no evidence of marked reductions in %RSG values of cells treated with test item. In the 4-hour exposure groups a cloudy precipitate of the test item was observed at and above 39.06 µg/mL which turned to greasy/oily precipitate at and above 156.25 µg/mL at the end of exposure. In the 24-hour exposure group a cloudy precipitate of the test item was observed at and above 39.06 µg/mL which turned to greasy/oily precipitate at and above 312.5 µg/mL. In the subsequent mutagenicity experiments the maximum dose level was limited to 156.25 µg/mL in the 4-hour exposures, and 312.5 µg/mL in the 24-hour exposure due to the incidence of greasy/oily precipitate (with no marked toxicity apparent).
COMPARISON WITH HISTORICAL CONTROL DATA
The results of both mutagenicity experiments were within the historical control data
ADDITIONAL INFORMATION ON CYTOTOXICITY
No evidence of marked toxicity following exposure to the test item in either the absence or presence of metabolic activation was recorded in both experiments, as indicated by the %RSG and RTG 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: Results of Preliminary Cytotoxicity Test
Dose (µg/mL) |
%RSG (-S9) 4-hour exposure |
%RSG (+S9) 4-hour exposure |
%RSG (-S9) 24-hour exposure |
0 |
100 |
100 |
100 |
9.77 |
101 |
98 |
105 |
19.53 |
117 |
102 |
103 |
39.06 |
97 |
103 |
104 |
78.13 |
93 |
111 |
102 |
156.25 |
93 |
97 |
101 |
312.5 |
105 |
98 |
104 |
625 |
92 |
93 |
104 |
1250 |
98 |
98 |
111 |
2500 |
116 |
99 |
117 |
%RSG: Relative suspension growth
Table 2: Results of experiment I
Dose (µg/ml) |
RSG (%) |
RS (day2)(%) |
RTG
|
MF |
||
total |
small |
large |
||||
4-hour exposure –S9-mix |
||||||
0 |
100 |
75.69 |
1.00 |
147.86 |
63.1 |
76.5 |
4.88 |
99 |
80.34 |
1.06 |
149.50 |
73.9 |
66.7 |
9.77 |
95 |
85.11 |
1.06 |
137.25 |
66.3 |
62.9 |
19.53 |
90 |
97.17 |
1.16 |
120.21 |
49.2 |
64.1 |
39.06 |
94 |
83.01 |
1.03 |
113.60 |
50.7 |
57.6 |
78.13 |
93 |
88.81 |
1.09 |
124.16 |
53.8 |
63.6 |
156.25 |
90 |
75.40 |
0.89 |
135.57 |
48.3 |
80.7 |
400 (EMS) |
73 |
58.16 |
0.55 |
802.44 |
253.3 |
372.4 |
4-hour exposure +S9-mix |
||||||
0 |
100 |
90.38 |
1.00 |
118.43 |
68.1 |
44.2 |
4.88 |
105 |
91.99 |
1.06 |
118.11 |
63.0 |
48.8 |
9.77 |
102 |
107.20 |
1.21 |
101.35 |
55.4 |
40.6 |
19.53 |
95 |
98.08 |
1.03 |
102.59 |
59.0 |
38.6 |
39.06 |
96 |
105.02 |
1.11 |
105.00 |
49.6 |
49.6 |
78.13 |
97 |
96.26 |
1.03 |
109.52 |
55.6 |
48.2 |
156.25 |
98 |
94.51 |
1.03 |
114.96 |
49.0 |
59.7 |
1.5 (CP) |
76 |
65.31 |
0.56 |
584.31 |
395.7 |
106.8 |
%RSG: Relative suspension growth
RS: Relative suspension in % (day 2)
RTG: Relative total growth
MF: Mutant frequency (5-TFT resistant mutants/106 viable cells 2 days after treatment
EMS: Ethylmethanosulphonate
CP: Cyclophosphamide
Table 3: Results of experiment II
Dose (µg/ml) |
RSG (%) |
RS (day 2) (%) |
RTG
|
MF |
||
total |
small |
large |
||||
24-hour exposure –S9-mix |
||||||
0 |
100 |
91.58 |
1.00 |
94.45 |
42.1 |
48.3 |
9.77 |
87 |
88.81 |
0.89 |
113.30 |
52.2 |
55.4 |
19.53 |
90 |
83.70 |
0.88 |
108.92 |
46.9 |
57.1 |
39.06 |
79 |
83.01 |
0.81 |
107.94 |
49.0 |
54.1 |
78.13 |
87 |
84.40 |
0.87 |
93.38 |
35.0 |
54.9 |
156.25 |
93 |
79.70 |
0.86 |
96.98 |
45.7 |
47.5 |
312.5 |
90 |
91.18 |
0.94 |
84.77 |
41.5 |
40.0 |
150 (EMS) |
57 |
56.92 |
0.41 |
1304.16 |
398.3 |
461.8 |
4-hour exposure +S9-mix |
||||||
0 |
100 |
82.33 |
1.00 |
150.94 |
69.5 |
72.1 |
4.88 |
100 |
87.30 |
1.06 |
122.61 |
54.7 |
61.3 |
9.77 |
104 |
91.18 |
1.16 |
126.31 |
58.7 |
60.3 |
19.53 |
96 |
91.18 |
1.07 |
131.73 |
61.9 |
61.9 |
39.06 |
86 |
97.17 |
1.02 |
103.56 |
46.2 |
52.1 |
78.13 |
98 |
82.33 |
0.99 |
90.20 |
46.0 |
40.9 |
156.25 |
82 |
92.81 |
0.92 |
111.86 |
45.3 |
60.8 |
1.5 (CP) |
75 |
56.92 |
0.52 |
752.68 |
485.3 |
143.8 |
%RSG: Relative suspension growth
RS: Relative suspension in % (day 2)
RTG: Relative total growth
MF: Mutant frequency (5-TFT resistant mutants/106 viable cells 2 days after treatment
EMS: Ethylmethanosulphonate
CP: Cyclophosphamide
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information):
negative
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