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EC number: 261-674-1 | CAS number: 59231-35-5
- 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:
- key study
- Study period:
- 03 May 2017 - 13 November 2017
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 017
- Report date:
- 2017
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 442C (In Chemico Skin Sensitisation: Direct Peptide Reactivity Assay (DPRA))
- Version / remarks:
- 05 Feb 2015
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of study:
- direct peptide reactivity assay (DPRA)
- Justification for non-LLNA method:
- Regulation 1223/2009, Article 18, restricts the use of in vivo studies on cosmetic raw materials (the sole use of this substance), therefore a recognised in chemico test was conducted on the test material.
Test material
- Reference substance name:
- Isodecyl 3,5,5-trimethylhexanoate
- EC Number:
- 261-674-1
- EC Name:
- Isodecyl 3,5,5-trimethylhexanoate
- Cas Number:
- 59231-35-5
- Molecular formula:
- C19H38O2
- IUPAC Name:
- 8-methylnonyl 3,5,5-trimethylhexanoate
- Test material form:
- liquid
Constituent 1
- Specific details on test material used for the study:
- The test article, a clear colourless liquid, was identified as Isodecyl 3,5,5-trimethylhexanoate and was received at Covance as follows:
- Test Article - Isodecyl 3,5,5-trimethylhexanoate
- Storage - 15 to 25°C, protected from light
- Purity - UVCB 100%
In chemico test system
- Details on the study design:
- - Objectives:
The study was conducted to quantify the reactivity of Isodecyl 3,5,5-trimethylhexanoate towards model synthetic peptides containing either lysine or cysteine. The data is used as part of an integrated approach to testing and assessment (IATA) to support the discrimination between skin sensitisers and non-sensitisers for the purpose of hazard classification and labelling. The DPRA is an in chemico method which quantifies the remaining concentration of cysteine- or lysine-containing peptides following incubation with the test article. Relative peptide concentration was measured by high performance liquid chromatography (HPLC) with UV detection. Cysteine and lysine peptide percent depletion (PPD) values were then calculated and used in a prediction model which allows assigning the test article to one of four reactivity classes used to support the discrimination between sensitisers and non-sensitisers.
- Test Article Incubation:
Each test solution was prepared at ratios of 1:10 and 1:50 with the cysteine and lysine stock solutions, respectively. The preparations were placed in an incubator set at 25°C or 24±2 hours. At the end of the incubation period all test article and co-elution samples contained small particles, therefore all samples were centrifuged at 400 g for 5 minutes.
- Analytical Method:
The following HPLC conditions were applied:
- Column: Agilent Zorbax SB-C18 2.1 mm x 100 mm, 3.5 µm or equivalent
- Wavelength: 220 nm
- Guard column: Phenomenex Security Guard c18 4 mm x 2 mm
- Flow rate: 0.35 mL/min
- Oven temperature: 30°C
- Sample temperature: 25°C
- Injection volume: 7 µL
- Mobile Phase:
Phase A: 0.1% (v/v) of trifluoroacetic acid in MilliQ water
Phase B: 0.085% (v/v) of trifluoroacetic acid in acetonitrile
Gradient: Time (min) Phase A Phase B
0 90 10
10 75 25
11 10 90
13 10 90
13.5 90 10
20 90 10
- Reference and Co-elution Controls:
Reference controls were prepared for each peptide.
Reference Control A and B for each peptide were prepared by adding 750 µL of peptide stock solution to 250 µL of acetonitrile.
Reference Control C for cysteine was prepared by adding 750 µL of peptide stock solution to 200 µL of acetonitrile and 50 µL vehicle.
Reference Control C for lysine was prepared by adding 750 µL of peptide stock solution to 250 µL vehicle.
Reference Control A (in triplicate) was used to verify the HPLC system suitability prior to the analysis. Reference Control B (six replicates) was used to verify the stability of the reference controls over time and Reference Control C (in triplicate) was used to verify that acetonitrile did not impact the percent peptide depletion.
Co-elution controls were prepared to detect possible co-elution of the test article with the peptides. A mixture of 750 µL of 100 mM Phosphate Buffer pH 7.5, 200 µL of acetonitrile and 50 µL of test article solution was used to detect possible co-elution of the test article with cysteine. A mixture of 750 µL of 100 mM ammonium acetate buffer pH 10.2 and 250 µL of test article solution was used to detect possible co-elution of the test article with lysine.
- Calibration Curves for Peptides:
Calibration curves were prepared for each peptide using a range of concentrations from approximately 0.534 mM to 0.0167 mM (Standards 1 to 6).
Standard 1 for cysteine was prepared at approximatively 0.534 mM by dilution of 1600 µL of the peptide stock solution (0.667 mM) with 400 µL of acetonitrile.
Standards 2 to 6 for cysteine were prepared by serial dilution using dilution buffer (20% acetonitrile in 100 mM Phosphate Buffer pH 7.5).
Standard 1 for lysine was prepared at approximatively 0.534 mM by dilution of 800 µL of the peptide stock solution (0.667 mM) with 200 µL of acetonitrile.
Standards 2 to 6 for lysine were prepared by serial dilution using dilution buffer (20% acetonitrile in 100 mM ammonium acetate buffer pH 10.2).
Samples of dilution buffer alone were also prepared.
- Sample Analysis Sequence:
The analysis sequence for each peptide was as follows:
System suitability Standard 1
Dilution buffer
Calibration standards and reference controls Standard 1
Standard 2
Standard 3
Standard 4
Standard 5
Standard 6
Dilution Buffer
Reference Control A, rep 1
Reference Control A, rep 2
Reference Control A, rep 3
Co-elution controls Co-elution control for test article
Reference controls Reference Control B, rep 1
Reference Control B, rep 3
First set of replicates Reference Control C, rep 1
Positive Control, rep 1
Test sample, rep 1
Second set of replicates Reference Control C, rep 2
Positive Control, rep 2
Test sample, rep 2
Third set of replicates Reference Control C, rep3
Positive Control, rep 3
Test sample, rep 3
Reference controls Reference Control B, rep 4
Reference Control B, rep 5
Reference Control B, rep 6
TEST ARTICLE, POSITIVE CONTROL ARTICLE AND PEPTIDES
The test article, a clear colourless liquid, was identified as Isodecyl 3,5,5-trimethylhexanoate (also known as Isodecyl Isononanoate/Wickenol) and was received at Covance as follows:
Test Article Storage Batch Purity
Isodecyl 3,5,5-trimethylhexanoate 15 to 25°C, protected from light UVCB - 100%
Cinnamic aldehyde (CAS No. 104-55-2, batch number MKBT8955V purity 99.1%, expiry 29 February 2020) was used as the positive control.
The peptides, cysteine (lot number P161108-LC180433 purity 95.92%) and lysine (lot number P160825-LC107617, purity 99.26%) were obtained from RS Synthesis, Louisville, Kentucky, USA.
- Test Article Formulation:
The test article was dissolved in acetonitrile. This was the first of the listed vehicles that produced a visually clear solution at a concentration of 100 mM.
A stock solution containing cysteine at approximately 0.667 mM was prepared in 100 mM Phosphate Buffer pH 7.5 and a stock solution containing lysine at approximately 0.667 mM was prepared in 100 mM ammonium acetate buffer pH 10.2.
Formulations were prepared shortly before testing.
Results and discussion
- Positive control results:
- Cinnamic aldehyde (CAS No. 104-55-2, batch number MKBT8955V purity 99.1%, expiry 29 February 2020) was used as the positive control.
The mean percentage peptide depletion (PPD) values for the positive control were:
- 55.93 for lysine
- 70.73 for cysteine
In vitro / in chemico
Resultsopen allclose all
- Run / experiment:
- other: 1-3
- Parameter:
- other: % peptide depletion (PPD) - lysine
- Value:
- -3.42
- Vehicle controls validity:
- valid
- Negative controls validity:
- not specified
- Positive controls validity:
- valid
- Remarks on result:
- other: The Max PPD value across 3 runs was 3.65, with a mean PPD of 1.22 for the 3 runs
- Run / experiment:
- other: 1-3
- Parameter:
- other: % peptide depletion (PPD) - Cysteine
- Value:
- 1.89
- Vehicle controls validity:
- valid
- Negative controls validity:
- not specified
- Positive controls validity:
- valid
- Remarks on result:
- other: he Max PPD value across 3 runs was 7.51, with a mean PPD of 5.16 for the 3 runs
- Other effects / acceptance of results:
- Lysine Depletion
The percentage peptide depletion values are shown in Table 6.1
The r2 value for the standard calibration curve was 0.9998.
The peptide concentrations for the Reference Controls A and C are shown in Table 6.2
The peak area results for Reference Controls B and C are shown in Table 6.3
Cysteine Depletion
The percentage peptide depletion values are shown in Table 6.4
The r2 value for the standard calibration curve was 0.9943.
The peptide concentrations for the Reference Controls A and C are shown in Table 6.5
The peak area results for Reference Controls B and C are shown in Table 6.6
Any other information on results incl. tables
Table 6.1 - PPD (Lysine)
Substance | Replicate Peptide Peak Areas | Reference Control C Mean Peptide Peak Area |
PPD | Mean PPD | SD |
Test Article | 34.356 | 35.658 | 3.65 | 1.22 | 2.1 |
36.782 | -3.15 | ||||
36.879 | -3.42 | ||||
Positive Control | 15.189 | 35.658 | 57.4 | 55.9 | 3.3 |
14.888 | 58.25 | ||||
17.066 | 52.14 |
Table 6.2 - Peptide concentrations for the Reference Controls A & C (Lysine)
Reference Control | Peptide Concentration (mM) | Mean | ||
Replicate 1 | Replicate 2 | Replicate 3 | ||
A | 0.487 | 0.489 | 0.483 | 0.49 |
C | 0.484 | 0.494 | 0.489 | 0.49 |
Table 6.3 - Peak area results for Reference Controls B & C (Lysine)
Reference Control | Replicate | Peptide Peak Area |
B | 1 | 38.123 |
2 | 36.035 | |
3 | 36.385 | |
4 | 35.96 | |
5 | 36.133 | |
6 | 36.032 | |
C | 1 | 35.306 |
2 | 36.018 | |
3 | 35.649 | |
Mean | 36.182 | |
SD | 0.79 | |
CV | 2.18 |
Table 6.4 - PPD (Cysteine)
Substance | Replicate Peptide Peak Areas | Reference Control C Mean Peptide Peak Area |
PPD | Mean PPD | SD |
Test Article | 25.009 | 25.49 | 1.89 | 5.16 | 2.9 |
23.937 | 6.09 | ||||
23.575 | 7.51 | ||||
Positive Control | 7.667 | 25.49 | 69.92 | 70.7 | 0.7 |
7.411 | 70.93 | ||||
7.303 | 71.35 |
Table 6.5 - Peptide concentrations for the Reference Controls A & C (Cysteine)
Reference Control | Peptide Concentration (mM) | Mean | ||
Replicate 1 | Replicate 2 | Replicate 3 | ||
A | 0.546 | 0.545 | 0.548 | 0.55 |
C | 0.523 | 0.526 | 0.496 | 0.51 |
Table 6.6 - Peak area results for Reference Controls B & C (Cysteine)
Reference Control | Replicate | Peptide Peak Area |
B | 1 | 26.879 |
2 | 26.892 | |
3 | 26.6 | |
4 | 24.656 | |
5 | 24.965 | |
6 | 22.758 | |
C | 1 | 25.894 |
2 | 26.058 | |
3 | 24.518 | |
Mean | 25.479 | |
SD | 1.38 | |
CV | 5.42 |
Applicant's summary and conclusion
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- The test article, Isodecyl 3,5,5-trimethylhexanoate, was considered to be negative in the Direct Peptide Reactivity Assay.
- Executive summary:
The study was conducted to quantify the reactivity of Isodecyl 3,5,5- trimethylhexanoate towards model synthetic peptides containing either lysine or cysteine. The data may be used as part of an integrated approach to testing and assessment (IATA) to support the discrimination between skin sensitisers and nonsensitisers for the purpose of hazard classification and labelling.
The test article was dissolved in acetonitrile at a concentration of 100 mM. The test solutions were incubated at 1:10 and 1:50 ratios with the cysteine and lysine peptides, respectively, for 24±2 hours in glass vials, protected from light and set at 25°C.
The remaining concentration of cysteine- or lysine-containing peptides following the 24 hour incubation period was measured by high performance liquid chromatography (HPLC) with gradient elution and UV detection at 220 nm.
The cysteine depletion value was 5.16%, the lysine depletion value was 1.22% and the mean of the cysteine and lysine depletion values was 3.19%.
The test article, Isodecyl 3,5,5-trimethylhexanoate, was considered to be negative in the Direct Peptide Reactivity Assay.
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