Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 203-431-4 | CAS number: 106-79-6
- 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 cytogenicity / micronucleus study
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 6 November 2012 to 7 February 2013
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Fully GLP compliant and in accordance with current test guidelines
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 013
- Report date:
- 2013
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- other: OECD guideline 487
- Deviations:
- no
- GLP compliance:
- yes
- Type of assay:
- in vitro mammalian cell micronucleus test
Test material
- Reference substance name:
- Dimethyl sebacate
- EC Number:
- 203-431-4
- EC Name:
- Dimethyl sebacate
- Cas Number:
- 106-79-6
- Molecular formula:
- C12H22O4
- IUPAC Name:
- 1,10-dimethyl decanedioate
- Test material form:
- other: Colourless solid to liquid (melting point 26°C)
- Details on test material:
- Name: Dimethyl Sebacate
CAS number: 106-79-6
Batch number: 120801
Description: colourless solid
Receipt date: 11 October 2012
Storage details: 15-25°C protected from light and with desiccant from 2 November 2012
Purity: 99.08% (assumed 100% for testing)
Expiry date: August 2013
Constituent 1
Method
- Target gene:
- Human lymphocyte cultures
Species / strain
- Species / strain / cell type:
- lymphocytes: Human lymphocyte cultures
- Details on mammalian cell type (if applicable):
- Blood from two healthy, non-smoking male volunteers from a panel of donors at Covance was used for each experiment in this study. No donor was suspected of any virus infection or exposed to high levels of radiation or hazardous chemicals. All donors are non-smokers and are not heavy drinkers of alcohol. Donors were not taking any form of medication. The measured cell cycle time of the donors used at Covance falls within the range 13 +/- 2 hours. For each experiment, an appropriate volume of whole blood was drawn from the peripheral circulation into heparinised tubes within one day of culture initiation. Blood was stored refrigerated and pooled using equal volumes from each donor prior to use.
- Metabolic activation:
- with and without
- Metabolic activation system:
- S-9 from male Sprague Dawley rats induced with Arcolor 1254
- Test concentrations with justification for top dose:
- Positive controls:
Mitomycin C: stock concentration, 0.060 and 0.080 mg/mL and final concentration, 0.60 and 0.80 µg/mL without metabolic activation
Cyclophosphamide: stock concentration, 0.625 and 1.25 mg/mL and final concentration, 6.25 and 12.50 µg/mL with metabolic activation
Vinblastine: stock concentration, 0.008, 0.010 and 0.012 mg/mL and final concentration, 0.08, 0.10 and 0.12 µg/mL without metabolic activation - Vehicle / solvent:
- DMSO
Controls
- Untreated negative controls:
- yes
- Remarks:
- DMSO
- Negative solvent / vehicle controls:
- no
- True negative controls:
- no
- Positive controls:
- yes
- Remarks:
- For concentrations see test concentrations section.
- Positive control substance:
- cyclophosphamide
- mitomycin C
- other: Vinblastine
- Details on test system and experimental conditions:
- No donor was suspected of any virus infection or exposed to high levels of radiation or hazardous chemicals. All donors are non-smokers and are not heavy drinkers of alcohol. Donors were not taking any form of medication. The measured cell cycle time of the donors used at Covance falls within the range 13 +/- 2 hours. For each experiment, an appropriate volume of whole blood was drawn from the peripheral circulation into heparinised tubes within one day of culture initiation. Blood was stored refrigerated and pooled using equal volumes from each donor prior to use.
Whole blood cultures were established in sterile disposable centrifuge tubes by placing 0.4 mL of pooled heparinised blood into 9.0 mL pre-warmed (in an incubator set to 37 ± 1°C) HEPES-buffered RPMI medium containing 10% (v/v) heat inactivated foetal calf serum and 0.52% penicillin / streptomycin, so that the final volume following addition of S-9 mix/KCl and the test article in its chosen vehicle was 10 mL. The mitogen Phytohaemagglutinin (PHA, reagent grade) was included in the culture medium at a concentration of approximately 2% of culture to stimulate the lymphocytes to divide. Blood cultures were incubated at 37 ± 1°C for approximately 48 hours and rocked continuously. - Evaluation criteria:
- For valid data, the test article was considered to induce clastogenic and/or aneugenic events if:
1. A statistically significant increase in the frequency of micronucleated binucleate (MNBN) cells at one or more concentrations was observed.
2. An incidence of MNBN cells at such a concentration that exceeded the normal range in both replicates was observed.
3. A concentration-related increase in the proportion of MNBN cells was observed.
The test article was considered positive in this assay if all of the above criteria were met.
The test article was considered negative in this assay if none of the above criteria were met. - Statistics:
- Results which only partially satisfied the above criteria were dealt with on a case by case basis. Evidence of a concentration-related effect was considered useful but not essential in the evaluation of a positive result (Scott et al., 1990).
Results and discussion
Test results
- Species / strain:
- lymphocytes: Human lymphocyte cultures
- Metabolic activation:
- with
- Genotoxicity:
- positive
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- Treatment of cells with Dimethyl Sebacate for 3+21 hours and for 24+24 hours in the absence of S-9 resulted in frequencies of MNBN cells that were similar to and not significantly higher than those observed in concurrent vehicle controls at any concentration analysed under either treatment condition. The MNBN cell frequencies of all treated cultures fell within the normal ranges.
Treatment of cells for 3+21 hours in the presence of S-9 resulted in frequencies of MNBN cells that were significantly higher (p < 0.05), compared to those observed in concurrent vehicle controls, at all four concentrations analysed (400.0 to 1600 µg/mL, giving 5% to 55% reductions in RI). The MNBN cell frequencies exceeded the normal range in single cultures at 400.0 and 800.0 µg/mL and in both cultures at 1200 and 1600 µg/mL, with evidence of a concentration-related increase in MNBN cell frequency. - Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
Any other information on results incl. tables
Table 1: Data for 3+21 hour treatments -S-9, Range-Finder - male donors
Treatment (µg/mL) |
Replicate |
Mono |
Bi |
Multi |
Total Number of Cells |
RI |
Cytotoxicity (%) |
Vehicle |
A |
47 |
151 |
2 |
200 |
0.78 |
- |
|
B |
44 |
153 |
3 |
200 |
0.80 |
|
8.355 |
A |
NS |
|
|
|
|
- |
13.93 |
A |
NS |
|
|
|
|
- |
23.21 |
A |
NS |
|
|
|
|
- |
38.68 |
A |
NS |
|
|
|
|
- |
64.47 |
A |
38 |
157 |
5 |
200 |
0.84 |
0 |
107.4 |
A |
32 |
162 |
6 |
200 |
0.87 |
0 |
179.1 |
A |
32 |
158 |
10 |
200 |
0.89 |
0 |
298.5 |
A |
62 |
135 |
3 |
200 |
0.71 |
10 |
497.4 |
A |
166 |
34 |
0 |
200 |
0.17 |
78 |
829.1 |
A |
NE |
|
|
|
|
- |
1382 |
A |
NE |
|
|
|
|
- |
2303 |
A |
NE |
|
|
|
|
- |
NE = Not evaluated – no scoreable cells
NS = Not scored
Mono = Mononucleate
Bi = Binucleate
Multi = Multinucleate
RI = Replication index
Table 2: Data for 3+21 hour treatments +S-9, Range-Finder - male donors
Treatment (µg/mL) |
Replicate |
Mono |
Bi |
Multi |
Total Number of Cells |
RI |
Cytotoxicity (%) |
Vehicle |
A |
46 |
150 |
4 |
200 |
0.79 |
- |
|
B |
44 |
150 |
6 |
200 |
0.81 |
|
8.355 |
A |
NS |
|
|
|
|
- |
13.93 |
A |
NS |
|
|
|
|
- |
23.21 |
A |
NS |
|
|
|
|
- |
38.68 |
A |
NS |
|
|
|
|
- |
64.47 |
A |
NS |
|
|
|
|
- |
107.4 |
A |
NS |
|
|
|
|
- |
179.1 |
A |
NS |
|
|
|
|
- |
298.5 |
A |
40 |
153 |
7 |
200 |
0.84 |
0 |
497.4 |
A |
45 |
151 |
4 |
200 |
0.80 |
1 |
829.1 |
A |
57 |
138 |
5 |
200 |
0.74 |
8 |
1382 |
A |
59 |
137 |
4 |
200 |
0.73 |
9 |
2303 |
A |
93 |
107 |
0 |
200 |
0.54 |
33 |
Table 3: Data for 24+24 hour treatments -S-9, Range-Finder – male donors
Treatment (µg/mL) |
Replicate |
Mono |
Bi |
Multi |
Total Number of Cells |
RI |
Cytotoxicity (%) |
Vehicle |
A |
21 |
145 |
34 |
200 |
1.07 |
- |
|
B |
18 |
151 |
31 |
200 |
1.07 |
|
8.355 |
A |
NS |
|
|
|
|
- |
13.93 |
A |
NS |
|
|
|
|
- |
23.21 |
A |
12 |
158 |
30 |
200 |
1.09 |
0 |
38.68 |
A |
18 |
152 |
30 |
200 |
1.06 |
0 |
64.47 |
A |
11 |
157 |
32 |
200 |
1.11 |
0 |
107.4 |
A |
13 |
164 |
23 |
200 |
1.05 |
1 |
179.1 |
A |
19 |
163 |
18 |
200 |
1.00 |
7 |
298.5 |
A |
19 |
171 |
10 |
200 |
0.96 |
10 |
497.4 |
A |
173 |
27 |
0 |
200 |
0.14 |
87 |
829.1 |
A |
NE |
|
|
|
|
- |
1382 |
A |
NE |
|
|
|
|
- |
2303 |
A |
NE |
|
|
|
|
- |
NE = Not evaluated – no scoreable cells
NS = Not scored
Mono = Mononucleate
Bi = Binucleate
Multi = Multinucleate
RI = Replication index
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information):
positive with metabolic activation
It is concluded that Dimethyl Sebacate showed evidence of inducing micronuclei in cultured human peripheral blood lymphocytes when tested for 3+21 hours in the presence of a rat liver metabolic activation system (S-9). In the same test system, Dimethyl Sebacate did not induce micronuclei when tested up to toxic concentrations for 3+21 hours and for 24+24 hours in the absence of S-9. - Executive summary:
Dimethyl Sebacate was tested in an in vitro micronucleus assay using duplicate human lymphocyte cultures prepared from the pooled blood of two male donors in a single experiment. Treatments covering a broad range of concentrations, separated by narrow intervals, were performed both in the absence and presence of metabolic activation (S-9) from Aroclor 1254-induced rats. The test article was formulated in anhydrous analytical grade dimethyl sulphoxide (DMSO). The highest concentrations analysed in the Micronucleus Experiment were limited by toxicity and were determined following a preliminary cytotoxicity Range-Finder Experiment.
Treatments were conducted (as detailed in Table A) 48 hours following mitogen stimulation by phytohaemagglutinin (PHA). The test article concentrations for micronucleus analysis were selected by evaluating the effect of Dimethyl Sebacate on the replication index (RI). Micronuclei were analysed at three or four concentrations and a summary of the data is presented in the table below:
Table A: Micronucleus Experiment – Results summary
Treatment
Concentration (mg/mL)
Cytotoxicity (%)$
Mean MNBN cell frequency (%)
Historical(%)#
Statistical significance
3+21 hour -S-9
Vehiclea
-
0.45
0.10 – 1.00
-
200.0
0
0.30
NS
250.0
6
0.50
NS
300.0
54
0.50
NS
*MMC, 0.80
ND
9.45
p<0.001
3+21 hour +S-9
Vehiclea
-
0.55
0.00 – 1.00
-
400.0
5
1.15
p<0.05
800.0
18
1.35
p<0.01
1200
40
1.55
p<0.001
1600
55
1.75
p<0.001
*CPA, 12.5
ND
2.55
p<0.001
24+24 hour -S-9
Vehiclea
-
0.40
0.10 - 1.10
-
300.0
7
0.45
NS
330.0
23
0.70
NS
360.0
48
0.50
NS
390.0
61
0.65
NS
*VIN, 0.10
ND
8.10
p<0.001
a Vehicle control was DMSO
* Positive control
# 95th percentile of the observed range
$ Based on replication index
NS Not significant
ND Not determined
Appropriate negative (vehicle) control cultures were included in the test system under each treatment condition. The proportion of micronucleated binucleate (MNBN) cells in the vehicle cultures fell within current historical vehicle control (normal) ranges. Mitomycin C (MMC) and Vinblastine (VIN) were employed as clastogenic and an eugenic positive control chemicals respectively in the absence of rat liver S-9. Cyclophosphamide (CPA) was employed as a clastogenic positive control chemical in the presence of rat liver S-9. Cells receiving these were sampled in the Micronucleus Experiment at 24 hours (CPA, MMC) or 48 hours (VIN) after the start of treatment. All positive control compounds induced statistically significant increases in the proportion of cells with micronuclei.
All acceptance criteria were considered met and the study was accepted as valid.
Treatment of cells with Dimethyl Sebacate for 3+21 hours and for 24+24 hours in the absence of S-9 resulted in frequencies of MNBN cells that were similar to and not significantly higher than those observed in concurrent vehicle controls at any concentration analysed under either treatment condition. The MNBN cell frequencies of all treated cultures fell within the normal ranges.
Treatment of cells for 3+21 hours in the presence of S-9 resulted in frequencies of MNBN cells that were significantly higher (p<0.05), compared to those observed in concurrent vehicle controls, at all four concentrations analysed (400.0 to 1600 µg/mL, giving 5% to 55% reductions in RI). The MNBN cell frequencies exceeded the normal range in single cultures at 400.0 and 800.0 µg/mL and in both cultures at 1200 and 1600 µg/mL, with evidence of a concentration-related increase in MNBN cell frequency.
It is concluded that Dimethyl Sebacate showed evidence of inducing micronuclei in cultured human peripheral blood lymphocytes when tested for 3+21 hours in the presence of a rat liver metabolic activation system (S-9). However, Dimethyl Sebacate did not induce micronuclei in the same test system when tested up to toxic concentrations for 3 + 21 hours and for 24 + 24 hours in the absence of S-9.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.