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EC number: 203-757-7 | CAS number: 110-33-8
- 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 based on grouping of substances (category approach)
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Comparable to guideline study with acceptable restrictions (no data on test substance purity, limited documentation)
Data source
Reference
- Reference Type:
- publication
- Title:
- Responses of the L5178Y tk+/tk- Mouse Lymphoma Cell Forward Mutation Assay: III. 72 Coded Chemicals
- Author:
- McGregor, D.B. et al.
- Year:
- 1 988
- Bibliographic source:
- Environmental Molecular Mutagenesis 12: 85-154
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
- Deviations:
- yes
- Remarks:
- (no data on colony sizing, very high concentrations tested, limited documentation; no data on analytical purity of the test substance)
- GLP compliance:
- not specified
- Type of assay:
- mammalian cell gene mutation assay
Test material
- Reference substance name:
- Bis(2-ethylhexyl) adipate
- EC Number:
- 203-090-1
- EC Name:
- Bis(2-ethylhexyl) adipate
- Cas Number:
- 103-23-1
- Molecular formula:
- C22H42O4
- IUPAC Name:
- bis(2-ethylhexyl) adipate
- Details on test material:
- - Name of test material (as cited in study report): Di(2-Ethylhexyl)adipate
- Analytical purity: no data
Constituent 1
Method
- Target gene:
- TK locus
Species / strain
- Species / strain / cell type:
- mouse lymphoma L5178Y cells
- Details on mammalian cell type (if applicable):
- Fischer´s medium (F0) was supplemented with 2 M L-glutamine, sodium pyruvate (110 µg/mL) 0.05% pluronic F68, antibiotics, and 10% heat-inactivated donor horse serum (v/v) (F10P).
- Metabolic activation:
- with and without
- Metabolic activation system:
- cofactor supplemented post-mitochondrial fraction (S9-mix), prepared with the livers of rats treated with Aroclor 1254
- Test concentrations with justification for top dose:
- Experiment 1: 312.5, 625, 1250, 2500, and 5000 µg/mL
Experiment 2: 1800, 2600, 3400, 4200, and 5000 µg/mL
Experiment 3 and 4: 1000, 2000, 3000, 4000, and 5000 µg/mL - Vehicle / solvent:
- acetone
Controls
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: (+S9): 3-Methylcholanthrene (MCA; 2.5 µg/mL); (-S9): mehtyl metahnesulphonate (MMS; 15 µg/mL)
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in medium
If no clear positive response was observed in two experiments in the absence of S9 mix, 2 experiments were performed in the presence of S9-mix. Insignificant responses were investigated by further tests involving RLN (uninduced S9) activation.
DURATION
- Preincubation period: 4 h
- Expression time (cells in growth medium): 48 h
- Selection time (if incubation with a selection agent): 11-14 days at 37 °C
- Fixation time (start of exposure up to fixation or harvest of cells): 14-17 days
SELECTION AGENT (mutation assays): trifluorothymidine (3 µg/mL)
STAIN (for cytogenetic assays): no data
NUMBER OF REPLICATIONS: duplicates per concentration per experiment (negative control: 3)
DETERMINATION OF CYTOTOXICITY
- Method: cloning efficiency, relative total growth - Evaluation criteria:
- Increase in mutant frequency compared to negative control.
Mutant fraction (MF) was calculated as follows: 200 x (mutant clones per plate)/(total clones per plate) = mutants/10E+06 clonable cells
Quality control criteria:
- The cloning efficiency of the solvent control has to be between 50% and 60%.
- Average mutant fraction of the solvent controls has to be > 15 and 110 mutants per 10E+06 surviving cells.
- At least two solvent control cultures have to be accepted.
- A positive control culture is rejected if a chi-square test for consistency of the acceptable mutant fractions shows P<5%.
- A positive control culture is rejected if the relative total growth (RTG) is < 1%. - Statistics:
- The statistical analysis was based upon the mathematical model proposed for this system and consisted of a dose-trend test and a variance anaysis of pair-wise comparisons of each dose against the vehicle control.
Results and discussion
Test results
- Species / strain:
- mouse lymphoma L5178Y cells
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Remarks:
- only in experiment 4, an increase in mutant fraction was observed from 2000 µg/mL
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- from approx. 1000 µg/mL in all experiments
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: yes, at 1000 µg/mL, but testing was continued up to 5000 µg/mL
RANGE-FINDING/SCREENING STUDIES: a screening test was performed to find the highest applicable concentration
The first experiment was a toxicity test in which cell population expansion was measured. Ten-fold differences in test compound concentrations were used in the toxicity test, the highest being 5 mg/mL .
ADDITIONAL INFORMATION ON CYTOTOXICITY: significant toxicity (RTG < 50%) was observed in all experiments (exp 1: from 1250 µg/mL, exp 2: from 1800 µg/mL, exp 3: from 1000 µg/mL, and exp 4: from 2000 µg/mL)
In experiment 4, the LOED (lowest observed effective dose) was 2000 µg/mL. However, the test substance was considered as negative in this chromosome aberration test, because:
- precipitation occurred from 1000 µg/mL
- no clear dose-relationship in mutant frequency increase was observed,
- cytotoxicity occurred from 1000 µg/mL
- the positive result was not reproducible in the other experiments, although the same conditions (with S9, same concentration) were applied and the relative total growth was comparable, no increase in the average mutation factor was observed in experiment 3. - 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 the Mouse Lymphoma Cell Assay
Experiment 1 - without S9 |
Experiment 2 - without S9 |
||||||||||
Conc. (µg/mL) |
CE (%) |
RTG (%) |
MC |
MF |
AVG MF |
Conc. (µg/mL) |
CE (%) |
RTG (%) |
MC |
MF |
AVG MF |
Acetone |
78 |
96 |
60 |
26 |
|
Acetone |
92 |
100 |
75 |
27 |
|
0 |
84 |
85 |
49 |
19 |
24 |
0 |
63 |
97 |
31 |
16 |
22 |
91 |
105 |
65 |
24 |
103 |
104 |
61 |
20 |
||||
85 |
114 |
67 |
26 |
84 |
98 |
63 |
25 |
||||
312.5 |
75 |
74 |
64 |
28 |
26 |
1800 |
88 |
26 |
41 |
16 |
18 |
80 |
80 |
57 |
24 |
74 |
25 |
47 |
21 |
||||
625.0 |
88 |
75 |
35 |
13 |
20 |
2600 |
73 |
24 |
51 |
23 |
18 |
80 |
70 |
64 |
27 |
88 |
23 |
36 |
14 |
||||
1250 |
69 |
25 |
58 |
28 |
23 |
3400 |
97 |
20 |
48 |
17 |
16 |
75 |
38 |
39 |
17 |
93 |
15 |
44 |
16 |
||||
2500 |
79 |
13 |
50 |
21 |
27 |
4200 |
78 |
15 |
35 |
15 |
20 |
70 |
16 |
68 |
32 |
69 |
13 |
50 |
24 |
||||
5000 |
87 |
13 |
48 |
18 |
|
5000 |
74 |
12 |
37 |
17 |
17 |
lethal |
|
|
|
72 |
13 |
36 |
17 |
||||
(MMS) 15 |
32 |
25 |
112 |
119 |
118* |
(MMS) 15 |
44 |
29 |
110 |
83 |
83* |
44 |
24 |
156 |
118 |
39 |
34 |
97 |
84 |
Experiment 3 - with S9 |
Experiment 4 – with S9 |
|||||||||
Conc. (µg/mL) |
CE (%) |
RTG (%) |
MC |
MF |
AVG |
CE (%) |
RTG (%) |
MC |
MF |
AVG MF |
Acetone |
80 |
98 |
72 |
30 |
|
102 |
116 |
82 |
27 |
|
0 |
76 |
109 |
55 |
24 |
33 |
109 |
101 |
114 |
35 |
37 |
70 |
98 |
88 |
42 |
100 |
101 |
111 |
37 |
|||
73 |
94 |
78 |
36 |
68 |
82 |
102 |
50 |
|||
1000 |
65 |
39 |
47 |
24 |
32 |
93 |
70 |
116 |
42 |
40 |
75 |
38 |
90 |
40 |
100 |
67 |
115 |
38 |
|||
2000 |
50 |
27 |
53 |
36 |
33 |
111 |
28 |
294 |
88 |
73* |
48 |
22 |
43 |
30 |
101 |
32 |
176 |
58 |
|||
3000 |
59 |
18 |
55 |
31 |
34 |
93 |
23 |
226 |
81 |
85* |
59 |
19 |
65 |
37 |
91 |
21 |
242 |
89 |
|||
4000 |
56 |
16 |
61 |
37 |
39 |
78 |
20 |
187 |
80 |
80* |
53 |
22 |
66 |
41 |
100 |
26 |
238 |
79 |
|||
5000 |
40 |
16 |
37 |
31 |
34 |
94 |
28 |
240 |
85 |
81* |
48 |
13 |
53 |
37 |
77 |
27 |
177 |
77 |
|||
(MCA) 2.5 |
29 |
16 |
187 |
214 |
222* |
55 |
11 |
603 |
364 |
363* |
32 |
21 |
223 |
231 |
55 |
11 |
592 |
361 |
CE = cloning efficiency (%)
RTG = relative total growth (%)
MC = mutant colony count
MF = mutant fraction (mutant colony per 10E+06 clonable cells)
AVG MF = group average mutant fraction
* Statistically significant different from control (P < 5%)
MMS = methyl metahnesulphonate
MCA = 3-methylcholanthrene
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information):
negative
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