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EC number: 290-754-9 | CAS number: 90218-76-1
- 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
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- Nanomaterial pour density
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- 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
![](https://poisoncentres.echa.europa.eu/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Genetic toxicity: in vitro
Administrative data
- Endpoint:
- in vitro gene mutation study in mammalian cells
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- May 28 to August 5, 2009
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: well documented study performed according to OECD Guideline and GLP
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 009
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
- Deviations:
- no
- GLP compliance:
- yes
- Type of assay:
- mammalian cell gene mutation assay
Test material
- Reference substance name:
- 1,2,4-Benzenetricarboxylic acid, mixed decyl and octyl triesters
- EC Number:
- 290-754-9
- EC Name:
- 1,2,4-Benzenetricarboxylic acid, mixed decyl and octyl triesters
- Cas Number:
- 90218-76-1
- Molecular formula:
- C33H51O6 to C39H66O6
- IUPAC Name:
- tris(mixed decyl and octyl)benzene-1,2,4-tricarboxylate
- Test material form:
- liquid
- Details on test material:
- - Name of test material (as cited in study report): 1,2,4-Benzentricarboxylic acid, decyl octyl ester, Label name LINPLAST 810 TM unstab.
- Substance type: pure active substance
- Physical state: liquid
- Stability under test conditions: no data
- Storage condition of test material: ambient temperature
Constituent 1
Method
- Target gene:
- thymidine kinase locus
Species / strain
- Species / strain / cell type:
- mouse lymphoma L5178Y cells
- Details on mammalian cell type (if applicable):
- - Type and identity of media:
Minimal medium A: RPMI 1640 medium supplemented with penicillin, streptomycin sulphate, sodium pyrovate, L-glutamine, non-essential amino acids and F 68 Pluronic
Minimal medium B: same as Minimal medium A without F68 Pluronic
Complete medium (5%): Minimal medium A supplemented with 5% v/v heat-inactivated horse serum
Complete Medium (10%: Minimal medium A supplemented with 10% v/v heat-inactivated horse serum
Complete medium A (20%): Minimal medium A supplemented with 20% v/v heat-inactivated horse serum
Complete medium B (20%): Minimal medium B supplemented with 20% v/v heat-inactivated horse serum
- Periodically checked for Mycoplasma contamination: yes
- Periodically "cleansed" against high spontaneous background: yes - Additional strain / cell type characteristics:
- other: Generation time and mutation rates (spontaneous and induced) were checked in the testing laboratory
- Metabolic activation:
- with and without
- Metabolic activation system:
- liver S9 mix of Phenobarbital - 5,6-Benzoflavone induced male Sprague Dawley rats
- Test concentrations with justification for top dose:
- With and without metabolic activation:
Toxicity test (range finding): 9.77, 19.5, 39.1, 78.1, 156, 313, 625, 1250 and 2500 µg/mL
1. experiment: 156, 313, 625 and 1250 and 2500 µg/mL with and without metabolic activation
2. experiment: 156, 313, 625, 1250 and 2500 µg/mL without metabolic activation; resp. 875, 1138, 1479, 1923 and 2500 µg/mL with metabolic activation - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: ethanol
- Justification for choice of solvent/vehicle: solvent giving the best solubility/dispersal characteristics
Controls
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: in the absence of metabolic activation (4 h/24h exposure): methyl methanesulphonate (MMS, 5.0/10.0 µg/ml); in the presence of metabolic activation: Benzo(a)pyrene (B(a)P, 2.0 µg/mL)
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in medium
DURATION
- Exposure duration:
Experiment 1: 3 h (with and without metabolic activation)
Experiment 2: 24 h (without metabolic activation) and 3 h (with metabolic activation)
- Expression time (cells in growth medium): 2 days
- Selection time (if incubation with a selection agent): 14 days (mutation selection assay)
SELECTION AGENT (mutation assays): trifluorothymidine (TFT), final concentration: 3.0 µg/mL in Complete medium B (20%)
NUMBER OF REPLICATIONS: 2
NUMBER OF CELLS EVALUATED: mutation selection assay: 2000 per well; cloning efficiency assay: 1.6 cells per well (8 cells/mL)
DETERMINATION OF CYTOTOXICITY
- Method: cloning efficiency (Cell concentrations were adjusted to 8 cells/mL and, for each dose level, 0.2 mL was plated into 96 microtitre wells, incubated for 7 days. Wells containing viable clones were identified by the eye using background illumination and then counted.)
OTHER EXAMINTATIONS
- Colony sizing: small and large type mutants, estimated for solvent and positive controls
- Observations of pH and osmolality: the treatment solutions were measured during performance of one the main experiments - Evaluation criteria:
- Criteria for a positive result:
- the induced mutant frequency is higher than the global evaluation factor suggested for the microwell method (126 x 10E-6) at one or more doses
- there is a significant dose-relationship as indicated by the linear trend analysis
Results which only partially satisfy the above criteria will be dealt with on a case-by-case basis. Similarly, positive responses seen only at high levels of cytotoxicity will require careful interpretation when assessing their biological significance. Any increase in mutant frequency should lie outside the historical control range to have biological relevance. - Statistics:
- Statisitical analysis was performed according to UKEMS guidelines (Robinson W.D., 1990). The following methods were applied:
- Results of individual plates within a replicate treatment were checked for consistency by calculation of Chi-square.
- Heterogeneity factors were calculated for survival, viability and mutation. Values obtained should not exceed 10.8 times the current heterogeneity factor where 10.8 is the one-sided 0.1% level of the F-distribution with 1 and infinitive degrees of freedom.
- Overall consistency was evaluated by calculation of the ratio of the heterogeneity factors of the experiment to the current heterogeneity factor. This ratio should not exceed the one-sided 1% critical values from the F-distribution.
- The estimated heterogeneity factors of the experiment were combined with the current heterogeneity factor to define the updated estimated factors.
- Comparison of each treatment with the control: for each comparison, the ratio Di²/var(Di) was compared to the critical values for the one tailed Dunnett`s test.
- Test for linear trend: The evaluation of a linear trend in mutant frequency with the treatment dose was performed using weighted regression. The slope and its variance var(b) were calculated to form the test statistic b²/var(b), which was compared to tabulated critical values of Chi-square with 1 degree of freedom.
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
- Remarks:
- Precipitation in all tested concentrations
- 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: no
- Effects of osmolality: no
- Water solubility: not soluble
- Precipitation: yes, particles in suspension and opacity were observed by adding solution at 250 mg/mL in ethanol to RPMI complete medium (10%) in a ratio 1:100 in the solubility trial, on the basis of this result a concentration of 2500 µg/mL was selcted as the highest dose level to be used in the test. Opacity, resp. slight opacity was observed at concentrations of 1250, 625 and 313 µg/mL.
- Other confounding effects: no
RANGE-FINDING/SCREENING STUDIES: No relevant toxicity was noted at any dose level tested using the short treatment time. In the absence of S9 metabolic activation, using the long treatment time, slight reduction of relative survival (RS) was noted at several concentrations without any dose relationship.
COMPARISON WITH HISTORICAL CONTROL DATA: The solvent and positive control mean mutant fractions were within the normal ranges experienced in the testing laboratory.
Any other information on results incl. tables
Table 1a: Toxicity test in the absence of S9 mix (3h exposure) | ||||||
Concentration µg/mL) |
Cloning efficiency | Relative Survival (%) | ||||
0 (Solvent control) | 0.98 | 100 | ||||
9.77 | 0.95 | 92 | ||||
19.5 | 1.18 | 100 | ||||
39.1 | 0.98 | 88 | ||||
78.1 | 1.16 | 101 | ||||
156 | 1.18 | 106 | ||||
313 | 1.23 | 104 | ||||
625 | 0.91 | 73 | ||||
1250 | 1.05 | 94 | ||||
2500 | 1.06 | 88 | ||||
Table 1b: Toxicity test in the absence of S9 mix (24h exposure) | ||||||
Concentration (µg/mL) |
Cloning efficiency | Relative Survival (%) | ||||
0 (Solvent control) | 1.14 | 100 | ||||
9.77 | 0.87 | 96 | ||||
19.5 | 0.72 | 81 | ||||
39.1 | 0.75 | 78 | ||||
78.1 | 0.74 | 77 | ||||
156 | 0.84 | 79 | ||||
313 | 0.76 | 60 | ||||
625 | 1.00 | 82 | ||||
1250 | 0.96 | 98 | ||||
2500 | 0.76 | 95 | ||||
Table 1c: Toxicity test in the presence of S9 mix (3h exposure) | ||||||
Concentration (µg/mL) |
Cloning efficiency | Relative Survival (%) | ||||
0 (Solvent control) | 1.18 | 100 | ||||
9.77 | 1.18 | 97 | ||||
19.5 | 1.03 | 99 | ||||
39.1 | 1.18 | 113 | ||||
78.1 | 1.18 | 103 | ||||
156 | 1.00 | 101 | ||||
313 | 1.20 | 85 | ||||
625 | 1.18 | 90 | ||||
1250 | 1.20 | 92 | ||||
2500 | 1.14 | 103 | ||||
Table 2a: Mutation test in the absence of S9 Mix (3h exposure) (Summary of means of data) 1. Experiment | ||||||
Concentration (µg/mL) |
Relative Total Growth (%) | Mutant fraction (x 10-6) |
Induced mutant fraction (x 10-6) | |||
0 (Solvent control) | 100 | 59.5 | N/A | |||
156* | 92 | 62.8 | 3.36 | |||
313* | 89 | 65.8 | 6.29 | |||
625* | 75 | 60.7 | 1.19 | |||
1250* | 83 | 57.5 | - | |||
2500* | 83 | 54.3 | - | |||
MMS 10.0 (Positive Control) | 63 | 351.0 | 291.5** | |||
N/A: not applicable | ||||||
* precipitation ** Induced mutant frequency > global evaluation factor (GEF = 126 x 10E-6) | ||||||
Induced mutant fraction (IMF): Mutant fraction of treatment minus mutant fraction of solvent control | ||||||
- : IMF <= 0 | ||||||
Table 2b: Mutation test in the presence of S9 Mix (3h exposure) (Summary of means of data) 1. Experiment | ||||||
Concentration (µg/mL) |
Relative Total Growth (%) | Mutant fraction (x 10-6) |
Induced mutant fraction (x 10-6) | |||
0 (Solvent control) | 100 | 52.2 | N/A | |||
156* | 123 | 48.0 | - | |||
313* | 94 | 64.5 | 12.30 | |||
625* | 90 | 71.9 | 19.79 | |||
1250* | 96 | 67.1 | 14.89 | |||
2500* | 99 | 63.5 | 11.36 | |||
B(a)P 2.00 (Positive control) | 55 | 580.5 | 528.4** | |||
N/A: not applicable | ||||||
* precipitation ** Induced mutant frequency > global evaluation factor (GEF = 126 x 10 E-6) | ||||||
Induced mutant fraction (IMF): Mutant fraction of treatment minus mutant fraction of vehicle group | ||||||
- : IMF <= 0 | ||||||
Table 2c: Mutation test in the absence of S9 Mix (24h exposure) (Summary of means of data) 2. Experiment | ||||||
Concentration (µg/mL) |
Relative total growth (%) | Mutant fraction (x 10-6) |
Induced mutant fraction (x 10-6) | |||
0 (Solvent control) | 100 | 77.2 | N/A | |||
156* | 86 | 60.1 | - | |||
313* | 82 | 73.8 | - | |||
625* | 87 | 60.1 | - | |||
1250* | 89 | 74.4 | - | |||
2500* | 102 | 78.8 | 1.22 | |||
MMS 5.00 (Positive control) | 85 | 734.8 | 657.6** | |||
N/A: not applicable | ||||||
* precipitation ** Induced mutation frequency > global evaluation factor (GEF = 126 x 10 E-6) | ||||||
Induced mutant fraction (IMF): Mutant fraction of treatment minus mutantt fraction of vehicle group | ||||||
- : IMF <= 0 | ||||||
Table 2b: Mutation test in the presence of S9 Mix (4h exposure) (Summary of means of data) 2. Experiment | ||||||
Concentration (µg/mL) |
Relative total growth (%) | Mutant fraction (x 10-6) |
Induced mutant fraction (x 10-6) | |||
0 (Solvent control) | 100 | 56.3 | N/A | |||
875* | 81 | 62.6 | 6.27 | |||
1138* | 136 | 96.2** | 39.87** | |||
1479* | 90 | 54.9 | - | |||
1923* | 79 | 70.2 | 13.89 | |||
2500* | 81 | 60.8 | 4.56 | |||
B(a)P 2.00 (Positive control) | 33 | 658.6 | 602.4*** | |||
N/A: not applicable | ||||||
* precipitation ** statistically significant at p<0.05 *** Induced mutant frequency > global evaluation factor (GEF = 126 x 10 E-6) | ||||||
Induced mutant fraction (IMF): Mutant fraction of treatment minus mutantt fraction of vehicle group | ||||||
- : IMF <= 0 | ||||||
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information):
negative with metabolic activation
negative without metabolic activation
1,2,4-Benzenetricarboxylic acid, decyl octyl ester is not mutagenic in mouse lymphoma L5178Y cells, in either the absence or the presence of S9 mix, when tested in ethanol, under the reported experimental conditions. - Executive summary:
The test item 1,2,4 -Benzenetricarboxylic acid, decyl octyl ester was examined for mutagenic activity by assaying for the induction of 5 -trifluorothymidine resistant mutants in mouse lymphoma L5178Y cells after in vitro treatment, in the absence and presence of S9 metabolic activation, using a fluctuation method.
The study was designed to comply with the experimental methods indicated in: Test method B.17 "in vitro mammalian cell gene mutation test" described in Council Regulation (EC) No. 440/2008 and OECD Guideline for the testing of chemicals No. 476 (adopted July 1997).
A solubility trial indicated that the maximum practicable concentration of the test item in the final test medium was 2500 µg/mL using ethanol as the solvent. On the basis of this result a preliminary cytotoxicity assay was performed. Both in the absence and presence of S9 metabolic activation, the test item was assayed at a maximum dose level of 2500 µg/mL and at a wide range of lower dose levels: 1250, 625, 313, 78.1, 39.1, 19.5 and 9.77 µg/mL. No relevant toxicity was observed at any dose level at any sampling time, in the absence and presence of S9 metabolism.
Based on the toxicity results obtained in the preliminary assay, two independent assays for mutation to 5 -trifluorothymidine resistance were performed using the following dose levels and treatment times:
Assay No. 1: 156, 313, 626, 1250 and 2500 µg/mL, 3 hours treatment with and without metabolic activation
Assay No. 2: 156, 313, 625, 1250 and 2500 µg/mL, 24 hours treatment without meatbolic activation; resp. 875, 1138, 1479, 1923 and 2500 µg/mL, 3 hours treatment with metabolic activation.
No relevant increases in mutant frequencies were observed following treatment with the test item, in the absence or presence of S9 metabolism.
Negative and positive control treatments were included in each mutation experiment in the absence and presence of S9 metabolism. The mutant frequencies in the solvent control cultures fell within the normal range. Marked increases were obtained with the positive control treatments indicating the correct functioning of the assay system.
It was concluded that 1,2,4 -Benzenetricarboxylic acid, decyl octyl ester does not induce mutation at the TK locus of L5178Y mouse lymphoma cells in vitro in the absence or presence of S9 metabolic activation, under the reported experimental conditions.
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