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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 949-569-5 | CAS number: -
- 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
Skin sensitisation
Administrative data
- Endpoint:
- skin sensitisation: in chemico
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 2019-04-16 to 2019-07-05
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 019
- Report date:
- 2019
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 442C (In Chemico Skin Sensitisation: Direct Peptide Reactivity Assay (DPRA))
- Deviations:
- no
- GLP compliance:
- yes
- Type of study:
- direct peptide reactivity assay (DPRA)
Test material
- Reference substance name:
- Reaction mass of 1-(3,3-dimethylcyclohexyl)ethyl acetate and 2,6,6-trimethylcycloheptanol acetate
- EC Number:
- 949-569-5
- Molecular formula:
- C12H22O2
- IUPAC Name:
- Reaction mass of 1-(3,3-dimethylcyclohexyl)ethyl acetate and 2,6,6-trimethylcycloheptanol acetate
- Test material form:
- liquid
Constituent 1
In chemico test system
- Details on the study design:
- Skin sensitisation (In chemico test system) - Details on study design:
Synthetic peptides:
Cysteine- (SPCC) containing peptide: Ac-RFAACAA-COOH (MW=750.9 g/mol)
Lysine- (SPCL) containing peptide: Ac-RFAAKAA-COOH (MW=775.9 g/mol)
Controls:
For Cysteine Reactivity Assay:
Positive control (PC): Cinnamic aldehyde, prepared as 100 mM in ACN, SPCC stock solution and ACN
Co-elution control: Phosphate buffer pH 7.5, ACN and the test substance without peptide.
For Lysine Reactivity Assay:
Positive control (PC): Cinnamic aldehyde, prepared as 100 mM in ACN, and SPCL stock solution
Co-elution control: Ammonium acetate buffer pH 10.2 and the test substance without peptide.
Test substance preparation:
22.52 mg and 31.47 mg of test item were pre-weighed into a clean amber glass vial and dissolved, just before use, in 1136 μL and 1587 μL ACN, respectively, to obtain 100 mM solutions. No correc tion for the purity/composition of the test item was performed.
Vehicle: Acetonitrile, ACN
Reason for the vehicle: A solubility test to assesse the test items solubility in different solvents was performed before the main test. ACN was chosed as the best solvent in which the test item dissolved and did not for precipitation or cloudy solution.
Test Item Samples:
- Test item solution, ACN and SPCC stock solution
- Test item and SPCL stock solution
Preparation of peptide stock solutions:
SPCC - A stock solution of 0.667 mM SPCC (0.501 mg SPCC/mL) was prepared by dissolving 11.0 mg of SPCC in 21.96 mL phosphate buffer pH 7.5. The mixture was stirred for 5 minutes followed by 5 minutes sonication. Three 0.5 mM SPCC reference control (RC) solutions (RCcysA, RCcysB and RCcysC) were prepared in amber vials by mixing 750 μL of the 0.667 mM SPCC stock solution with 250 μL ACN.
SPCL - A stock solution of 0.667 mM SPCL (0.518 mg SPCL/mL) was prepared by dissolving 10.4 mg of SPCL in 20.08 mL of ammonium acetate buffer pH 10.2 followed by stirring for 5 minutes. Three 0.5 mM SPCL reference control (RC) solutions (RClysA, RClysB and RClysC) were prepared in amber vials by mixing 750 μL of the 0.667 mM SPCL stock solution with 250 μL ACN.
Experimental procedure:
After preparation, the samples were placed in the autosampler in the dark and incubated at 25 ± 2.5 °C. The incubation period was 26 hours for RCcysB-samples and 25 hours for the RClysBsamples. All samples were analysed with HPLC analysis. Prior to HPLC analysis the samples were visually inspected for precipitation. The samples that showed precipitation/phase separation were centrifuged (at 400 g) for 5 minutes at room temperature and supernatant was transferred to a new vial.
Results and discussion
In vitro / in chemico
Resultsopen allclose all
- Key result
- Parameter:
- other: mean % SPCC depletion
- Value:
- 1.4 %
- Positive controls validity:
- valid
- Remarks:
- 80 ± 0.1 %
- Key result
- Parameter:
- other: mean % SPCL depletion
- Value:
- 0.1 %
- Positive controls validity:
- valid
- Remarks:
- 58.8 ± 0.7 %
- Key result
- Parameter:
- other: mean % depletion
- Value:
- 0.8 %
- Positive controls validity:
- valid
Any other information on results incl. tables
Upon preparation as well as after incubation of the SPCC test item samples a precipitate was observed. Upon preparation of the SPCL test item samples a phase separation was observed while after incubation of these samples a precipitate was observed.
In the cysteine reactivity assay the test item showed 1.4 % SPCC depletion while in the lysine reactivity assay the test item showed 0.1 % SPCL depletion. The mean of the SPCC and SPCL depletion was 0.8 % and as a result the test item was considered to be negative in the DPRA and classified in the “no or minimal reactivity class” when using the Cysteine 1:10 / Lysine 1:50 prediction model.
Table 1. SPCC and SPCL Depletion, DPRA Prediction and Reactivity Classification for the Test Item
|
SPCC depletion |
SPCL depletion |
Mean of SPCC and SPCL depletion |
DPRA prediction and reactivity classification |
||
Test item |
Mean |
± SD |
Mean |
± SD |
Cysteine 1:10 / Lysine 1:50 prediction model |
|
1.4 % |
± 0.4 % |
0.1 % |
± 0.2 % |
0.8 % |
Negative: No or minimal reactivity |
SD = Standard Deviation
Table 2. SPCC Peak Area, Concentration and Depletion of the Cinnamic Aldehyde Positive Control Samples
Sample code |
Peak area at 220 nm (μAU) |
Concentration (mM) |
SPCC Depletion |
PCcys-1 |
417946 |
0.100 |
79.9 % |
PCcys-2 |
414846 |
0.099 |
80.0 % |
PCcys-3 |
413080 |
0.099 |
80.1 % |
|
|
Mean |
80.0 % |
|
|
SD |
0.1 % |
SD = Standard Deviation
Table 3. SPCC Peak Area, Concentration, Depletion and Area Ratio (A220/A258) of the Test Item Samples
Sample code |
Peak area at 220 nm (μAU) |
Concentration (mM) |
SPCC Depletion |
Peak area at 258 nm (μAU) |
Area ratio (A220/A258) |
210251/A-cys-1 |
2056772 |
0.498 |
1.0 % |
54723 |
37.59 |
210251/A-cys-2 |
2043642 |
0.495 |
1.6 % |
54528 |
37.48 |
210251/A-cys-3 |
2041676 |
0.494 |
1.7 % |
54442 |
37.50 |
|
|
Mean |
1.4 % |
NA |
37.52 |
|
|
SD |
0.4 % |
NA |
0.06 |
SD = Standard Deviation, NA = Not Applicable.
Table 4. SPCL Peak Area, Concentration and Depletion of the Cinnamic Aldehyde Positive Control Samples
Sample code |
Peak area at 220 nm (μAU) |
Concentration (mM) |
SPCC Depletion |
PClys-1 |
666448 |
0.203 |
59.5 % |
PClys-2 |
674337 |
0.206 |
59.0 % |
PClys-3 |
689184 |
0.210 |
58.1 % |
|
|
Mean |
58.8 % |
|
|
SD |
0.7 % |
SD = Standard Deviation
Table 5. SPCL Peak Area, Concentration, Depletion and Area Ratio (A220/A258) of the Test Item Samples
Sample code |
Peak area at 220 nm (μAU) |
Concentration (mM) |
SPCC Depletion |
Peak area at 258 nm (μAU) |
Area ratio (A220/A258) |
210251/A-lys-1 |
1654675 |
0.507 |
0.0 % |
51344 |
32.23 |
210251/A-lys-2 |
1647770 |
0.505 |
0.0 % |
53515 |
30.79 |
210251/A-lys-3 |
1647770 |
0.502 |
0.3 % |
52392 |
31.28 |
|
|
Mean |
0.1 % |
NA |
31.43 |
|
|
SD |
0.2 % |
NA |
0.73 |
SD = Standard Deviation, NA = Not Applicable.
Applicant's summary and conclusion
- Interpretation of results:
- other: negative for dendritic cells activation
- Conclusions:
- In conclusion, the test item was negative in the DPRA and was classified in the “no or minimal reactivity class” when using the Cysteine 1:10 / Lysine 1:50 prediction model. However, since precipitation was observed after the incubation period for both SPCC and
SPCL, one cannot be sure how much test item remained in the solution to react with the peptides. Consequently, this negative result is uncertain and should be interpreted with due care. - Executive summary:
A study according to OECD TG 442C - Direct Peptide Reactivity Assay (DPRA) was conducted under GLP to determine the reactivity of the test item towards model synthetic peptides containing either cysteine (SPCC) or lysine (SPCL). After incubation of the test item with SPCC or SPCL for 26 and 25 hours, respectively, at 25 °C, the relative peptide concentration was determined by HPLC detection at 220 and 258 nm. As reference control cinnamic aldehyde was used. The test item was tested at test concentration of 100 mM and the reference item at 100 mM. As a vehicle acetonitrile (ACN) was used. Synthetic peptide control solutions of SPCC (containing Ac-RFAACAA-COOH) and SPCL (containing Ac-RFAAKAACOOH) were prepared in ACN. Co-eluent samples containing only the test item and the respective buffer were also tested under the same conditions. After the incubation period samples were injected directly into the HPLC system. The concentration of SPCC or SPCL was photometrically determined at 220 and 258 nm. The ratio of the 220 nm peak area and the 258 nm peak was used as an indicator of co-elution. The mean Percent Cysteine Depletion and Percent Lysine Depletion were calculated for the test item. By using the Cysteine 1:10 / Lysine 1:50 prediction model, the threshold of 6.38 % average peptide depletion was used to support the discrimination between a skin sensitizer and a non-sensitizer. Following this model, the mean % SPCC depletion of the test item was 1.4 % and the mean % SPCL depletion was 0.1 %. The average % depletion of the test item was determined to be 0.8 %. The reference control showed mean % SPCC depletion of 80 % and a mean % SPCL depletion of 58.8 %. All validity criteria were met and the test is considered as valid. The test item was negative in the DPRA and was classified in the “no or minimal reactivity class” when using the Cysteine 1:10 / Lysine 1:50 prediction model. However, since precipitation was observed after the incubation period for both SPCC and SPCL, one cannot be sure how much test item remained in the solution to react with the peptides. Consequently, this negative result is uncertain and should be interpreted with due care.
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.