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EC number: 422-630-9 | CAS number: 22208-25-9
- 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
Endpoint summary
Administrative data
Key value for chemical safety assessment
Genetic toxicity in vitro
Description of key information
Key study: EU Method B.14 (GLP study). The substance was determined to be negative with and without metabolic activation in Salmonella strains.
Key study: EU Method B.10 (GLP study). The substance was determined to be negative with and without metabolic activation in human lymphocytes.
Link to relevant study records
- Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.10 (Mutagenicity - In Vitro Mammalian Chromosome Aberration Test)
- GLP compliance:
- yes
- Type of assay:
- in vitro mammalian chromosome aberration test
- Species / strain / cell type:
- lymphocytes: Human
- Metabolic activation:
- with and without
- Metabolic activation system:
- Aroclor-1254 induced rat liver S9-mix
- Test concentrations with justification for top dose:
- Concentration range in the first main test (with metabolic activation): 1000 - 5000 µg/ml
Concentration range in the second main test (with metabolic activation): 333 - 3330 µg/ml
Concentration range in the first main test (without metabolic activation): 1000 - 2400 µg/ml
Concentration range in the second main test (without metabolic activation): 100 - 1800 µg/ml
Concentration range in the second main test (without metabolic activation): 100 - 560 µg/ml - Vehicle / solvent:
- Dimethylsulfoxide
- Details on test system and experimental conditions:
- Exposure period (with metabolic activation): 3 hours
Exposure period (without metabolic activation): 3 hours
Fixation time:
First test with metabolic activation: 24 h fixation time.
Second test with metabolic activation: 48 h fixation time.
First test without metabolic activation: 24 h fixation time.
Second test without metabolic activation: 24 h fixation up to 560 ug/ml and 48 h fixation up to 1800 ug/ml. - Key result
- Species / strain:
- lymphocytes: Human
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- cytotoxicity 1st experiment (3h exposure, 24h fixation): with and without S9 mix: 1000 µg/mL 2nd experiment (3h exposure, 48h fixation): with S9 mix: 1000 µg/mL; without S9 mix: 333 µg/mL 2nd experiment (3h exposure, 24h fixation): without S9 mix: 1000 µg
- Additional information on results:
- The test substance did not induce a statistically or biologically significant increase in the number of cells with chromosome aberrations in the absence and in the presence of S9-mix, in two independently repeated experiments.
In the absence and presence of S9-mix the 48h fixation time in the second experiment an increase in the number of polypoploid cells was observed.
It is concluded that the test substance is not clastogenic in human lymphocytes under the experimental conditions. - Conclusions:
- The substance was determined to be negative with and without metabolic activation system.
- Executive summary:
A chromosome aberration test was conducted according to B.10 (GLP study). The human lymphocytes cell line were treated with and without metabolic activation. The substance was solubilized in Dimethylsulphoxide and evaluated at a concentration ranging from 100 to 5000 µg/mL according to the test conditions. The substance was determined to be negative with and without metabolic activation.
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study with acceptable restrictions
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
- GLP compliance:
- yes
- Type of assay:
- bacterial reverse mutation assay
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Metabolic activation:
- with and without
- Metabolic activation system:
- Aroclor 1254-induced rat liver S9 mix
- Test concentrations with justification for top dose:
- Concentration range in the main test (with metabolic activation): 100 - 5000 µg/plate
Concentration range in the main test (without metabolic activation): 100 - 5000 µg/plate - Vehicle / solvent:
- Dimethylsulfoxide
- Key result
- Species / strain:
- other: as specified above
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- > 5000 µg/plate
- Additional information on results:
- All bacterial strains showed negative responses over the entire dose range, i.e. no dose-related, two-fold, increase in the number of revertants in two independently repeated experiments. No precipitation of the test substance was observed on the plates during the whole test period in all tester strains. The bacterial background lawn was not reduced at all concentrations tested and no decrease in the number of revertants was observed.
- Conclusions:
- The substance was determined to be negative with and without metabolic activation system.
- Executive summary:
An Ames test was conducted according to EU Method B.14 (GLP study). The Salmonella strains: TA98, TA100, TA1535 and TA1537 were used in the study and were treated with and without metabolic activation. The substance was solubilized in Dimethylsulphoxide and evaluated at a concentration ranging from 100 to 5000 µg/plate. The substance was determined to be negative with and without metabolic activation.
Referenceopen allclose all
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Description of key information
Key study: Read-across, test method similar to OECD 478. Based on read-across approach from experimental data on analogue hexanedioic acid, 1,6-diethyl ester (diethyl adipate), the test item AA-TMP was determined to be negative in a dominant lethal mutation assay.
Link to relevant study records
- Endpoint:
- in vivo mammalian germ cell study: gene mutation
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Justification for type of information:
- REPORTING FORMAT FOR THE ANALOGUE APPROACH
The analogue substance hexanedioic acid, 1,6-diethyl ester (diethyl adipate, DEA) which shares the same functional groups with the substance 1,1,1-Tri((1,3-dioxobutoxy)-methyl)-propane (AA-TMP) also has comparable values for the relevant molecular properties.
See attached the reporting format. - Reason / purpose for cross-reference:
- read-across source
- Key result
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- not specified
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- not applicable
- Remarks on result:
- other: Read across from an analogue substance
- Additional information on results:
- RESULTS OF DEFINITIVE STUDY
Late fetal deaths (i.e., nonviable, fully formed fetuses) were uncommon; their incidence tended to be equal to or less than that for controls. When present, these deaths apparently occurred randomly, without any dose- or time- relationship to treatment.
For rate of pregnancies, analyses indicated there was a significant (p < 0.05) effect from dose in the first 3 weeks, in which the higher doses produced fewer pregnancies than did the controls. However, no significant effect of dose or time (weeks) was revealed for the 4- to 8-week period.
There was no difference in the number of implants in the treated groups versus control animals.
For early fetal deaths, analyses of the data from all treated groups (with controls) indicated a significant effect of dosage. A similar analysis without controls did not reveal a dosage effect. The postmeiotic data showed a significant dose effect with controls. No dose-effect was apparent when the controls were deleted. For the prerneiotic stage, no significant effects were detected.
The treated groups showed a significant effect of time and dose- week interaction for the 8-wk period in the number of live fetuses/pregnant mouse when controls were included; when analyzed without controls, dose—week interaction was no longer significant. While the analyses did not reveal any significant effects during the first 3 wk after test item administration, significant effects (with and without controls) were noted for weeks and dose- week interaction during the premeiotic stage. - Conclusions:
- Based on read-across approach from experimental data on the analogue diethyl adipate, the test item is considered as negative in a dominant lethal mutation assay.
- Executive summary:
A dominant lethal mutation assay was carried out in Harlan/ICR albino Swiss male mice to investigate the germinal effects of diethyl adipate, DEA. The test item was administered intraperitoneally at dose levels of 1/5, 1 /3, l,'2, and 2/3 of the acute LD50 which correspond to 0.44, 0.73, 1.1 and 1.46 mL/kg. Ten males were injected at each dose level. Group of controls were injected ip with distilled water equivalent to the highest dose of test item administered. Immediately after injection, two virgin female mice were caged with each male mouse. During a period of 8 weeks the females were replaced weekly with two virgin females. Thus. each weekly group was composed of 20 female mice. Number of corpora lutea, total number of implantations, preimplantation losses, early and late fetal deaths, and viable fetuses were counted from the uterine horns and ovaries of sacrificed pregnant females. Dominant lethal mutation was determined directly from the increased number of early fetal deaths in individual mice, and indirectly from the reduced number of total implantations (Epstein et al., 1970). For rate of pregnancies, no significant effect of dose or time (weeks) was revealed during the study. There was no difference in the number of implants in the treated groups versus control animals. Late fetal deaths were lower in the treated animals but early fetal deaths were more common in treated groups. The authors claim that dosage had a significant effect on the number of live fetuses and that DEA thus increased the number of dominant lethals. Although there seems to be a dose response relationship for single weeks, no statistical significant difference exists between group and control data neither for any week nor for the overall data. Thus, the result of the test can be considered negative.
Based on these results, the read-across approach was applied and AA-TMP can be considered as negative in a dominant lethal mutation assay.
Reference
Table 1. Percentage of pregnancies in mice following administration of DEA a, b
Week no. | Control (c) | 0.44 | 0.73 | 1.10 | 1.46 |
1 | 70 | 40 | 40 | 20 | 30 |
2 | 60 | 50 | 45 | 40 | 45 |
3 | 60 | 65 | 55 | 55 | 45 |
4 | 70 | 90 | 70 | 50 | 65 |
5 | 65 | 70 | 80 | 50 | 45 |
6 | 85 | 65 | 75 | 80 | 85 |
7 | 85 | 70 | 85 | 95 | 90 |
8 | 75 | 85 | 85 | 80 | 75 |
Overall mean and SE | 71±3.5 | 67± 5.8 | 67± 6.3 | 59±8.7 | 60± 7.7 |
a Males were mated sequentially over a period of 8 wk after a single ip injection of DEA.
b Values are based on 20 females mated weekly to 10 males.
c In this group, animals were injected with distilled water equivalent to the highest dose of the test compound administered.
Table 2. Total number of implants per pregnancy in mice after ip administration of DEA to males (mean ± SE)
Week no. | Control | 0.44 | 0.73 | 1.10 | 1.46 |
1 | 9.6± 0.34 | 10.4± 1.00 | 10.4± 0.50 | 9.5 ± 1.26 | 10.7 ± 0.71 |
2 | 9.8 ± 0.93 | 10.9 ± 0.38 | 8.7±1.32 | 9.5 ± 1.16 | 10.4± 0.80 |
3 | 10.7 ±0.47 | 9.9 ±0.42 | 9.7 ±0.63 | 10.0 ± 0.65 | 8.0 ± 1.22 |
4 | 11.3 ± 0.35 | 10.9 -r 0.25 | 10.7 ±0.50 | 10.6±0.40 | 9.2± 0.54 |
5 | 10.7 ± 0.46 | 10.2 ± 0.70 | 10.8 ± 0.31 | 11.3 ± 0.26 | 10.8 ± 0.98 |
6 | 10.5 ± 0.53 | 11.1± 0.54 | 11.1± 0.28 | 11.5 ± 0.35 | 11.6± 0.33 |
7 | 9.9 ± 0.79 | 10.2 ± 0.37 | 12.4± 0.45 | 11.5 ± 0.35 | 11.8 ± 0.42 |
8 | 11.1± 0.60 | 11.3 ± 0.24 | 11.2 ± 0.60 | 11.4 ± 0.31 | 10.5 ± 0.55 |
Overall mean ± SE | 10.5 ± 0.56 | 10.6 ± 0.49 | 10.6 ± 0.57 | 10.7 ± 0.59 | 10.4 ± 0.69 |
Table 3. Early fetal deaths per pregnancy in mice after ip administration of DEA to males (mean ± SE)
Week no. | Control | 0.44 | 0.73 | 1.10 | 1 .46 |
1 | 0.50 ±0.17 | 0.75 ± 0.49 | 1.25 ± 1.11 | 1.75 ± 1.44 | 2.17 ± 1.19 |
2 | 0.42 ± 0.26 | 0.70 ± 0.21 | 0.89 ± 0.31 | 1.50 ± 0.33 | 1.33 ±0.50 |
3 | 0.33 ± 0.19 | 0.46 -r 0.14 | 0.64± 0.36 | 1.00 ± 0.62 | 1.00 ± 0.50 |
4 | 0.21 ±0.11 | 0.44± 0.17 | 0.50 ± 0.20 | 0.80 0.25 | 1.08 ± 0.43 |
5 | 0.31± 0.17 | 0.50± 0.23 | 0.56 ± 0.20 | 0.80± 0.47 | 0.89 ± 0.39 |
6 | 0.41±0.15 | 0.69 ±0.31 | 0.67 ±0.25 | 0.56 ± 0.18 | 0.12 ± 0.08 |
7 | 0.41± 0.15 | 0.36J 0.17 | 0.71± 0.21 | 0.68 ± 0.32 | 0.44± 0.15 |
8 | 0.33 ± 0.16 | 0.41± 0.12 | 0.53 ± 0.21 | 0.69 ± 0.22 | 0.67 ± 0.32 |
Overall mean ± SE | 0.37 ± 0.17 | 0.54 ± 0.23 | 0.72 ± 0.36 | 0.97 ± 0.49 | 0.96 ± 0.45 |
Table 4. Number of live fetuses per pregnancy in mice after ip administration of DEA to males (mean ± SE)
Week no. | Control | 0.44 | 0.73 | 1.10 | 1.46 |
1 | 8.9 ± 0.38 | 9.6± 1.43 | 9.1± 1.38 | 7.8 ± 2.66 | 8.5 ± 1.77 |
2 | 9.3 ±0.82 | 10.1±0.43 | 7.8 ± 1.54 | 8.0± 1.25 | 9.1±1.20 |
3 | 10.3 ± 0.38 | 9.5 ± 0.37 | 9.1± 0.94 | 9.8 ± 0.63 | 8.1± 1.11 |
4 | 11.1± 0.37 | 10.3 ± 0.36 | 10.2± 0.48 | 9.8 ±0.39 | 7.5 ± 0.74 |
5 | 10.3 ±0.44 | 9.6± 0.68 | 10.3 ±0.31 | 10.0± 0.42 | 10.0± 0.90 |
6 | 9.8 ± 0.56 | 10.2 ± 0.79 | 10.3 ± 0.29 | 10.9 ± 0.40 | 11.0 ± 0.32 |
7 | 9.4 ± 0.77 | 9.9±0.39 | 11.6±0.51 | 10.7±0.57 | 11.2±0.51 |
8 | 10.7 ± 0.61 | 10.9 ± 0.26 | 10.5 ± 0.66 | 10.6± 0.35 | 9.9 ±0.64 |
Overall mean ± SE | 10.0 ± 0.54 | 10.0 ± 0.59 | 9.9 ± 0.76 | 9.7 ± 0.83 | 9.4 ± 0.90 |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Additional information
Justification for classification or non-classification
Based on the available data, the substance does not need to be classified for genetic toxicity according to the CLP Regulation (EC) no. 1272/2008.
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