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EC number: 951-275-7 | 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
- Remarks:
- Direct Peptide Reactivity Assay (DPRA)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- The study was conducted between 07 Mar 2017 and 08 Apr 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))
- Deviations:
- no
- GLP compliance:
- yes
- Type of study:
- direct peptide reactivity assay (DPRA)
Test material
- Reference substance name:
- Reaction mass of Rel-(3aR,4S,7R,7aS)-1-(methoxymethylene)octahydro-1H-4,7-methanoindene and Rel-(3aR,4S,7R,7aS)-2-(methoxymethylene)octahydro-1H-4,7-methanoindene
- EC Number:
- 951-275-7
- Molecular formula:
- C12H18O
- IUPAC Name:
- Reaction mass of Rel-(3aR,4S,7R,7aS)-1-(methoxymethylene)octahydro-1H-4,7-methanoindene and Rel-(3aR,4S,7R,7aS)-2-(methoxymethylene)octahydro-1H-4,7-methanoindene
Constituent 1
In chemico test system
- Details on the study design:
- Test Article Preparation
The test articles were prepared at a 100 mM concentration in an appropriate solvent. Calculations using the molecular weight and purity of the test article were performed to determine the appropriate amount of test article to weigh out in order to achieve approximately 3 mL of the 100 mM sample.
The test articles were weighed into prelabeled glass vials and stored at room temperature. The test articles were not dissolved in the solvent until immediately before mixing with the peptides.
Test Article Solubility Test
A solubility test was performed for the test articles in order to determine an appropriate solvent that completely dissolved the test article at a 100 mM concentration. All of the test articles were soluble in acetonitrile with one minute of vortexing.
Peptide Preparation
Custom synthetic peptides of cysteine or lysine (containing phenylalanine to aid in detection) were used in this assay. The purity of each peptide was at least 90%. Peptide samples were newly prepared for each sample set, and a single preparation of the peptide was used throughout the sample set. The cysteine peptide was prepared by weighing an appropriate amount of the peptide to achieve a 0.667 mM concentration in pH 7.6 phosphate buffer. The lysine peptide was prepared by weighing an appropriate amount of the peptide to achieve a 0.667 mM concentration in pH 10.1 ammonium acetate buffer. The peptide solutions were gently mixed on the shaker.
Peptide Standards
A set of serially diluted standards were prepared for each peptide. These standards were prepared by diluting the peptide solutions in dilution buffer (20% acetonitrile in either phosphate or ammonium acetate buffer). Six standards were prepared at concentrations of 0.534- 0.0167 mM. A seventh standard was prepared containing only dilution buffer. Approximately 1 mL of each standard was pipetted into the appropriate prelabeled autosampler vials.
Controls
The positive control used in this assay was cinnamic aldehyde prepared at a concentration of 100 mM. The positive control was reacted with the peptides in the same fashion as the test articles. Reference controls were prepared for each solvent used in the assay. There were three sets of reference controls of acetonitrile run at different points throughout the assay (reference controls A-C). Solvent controls were also prepared for the solvent used in the assay. These controls consist of the solvent (acetonitrile) reacted with the peptide in the absence of test article. A coelution control was also prepared for each test article. The coelution controls consisted of the test article without the peptide. The purpose of the coelution controls was to determine if the test article elution from the HPLC column overlapped with the peptide elution.
HPLC Set-up and Operation
The separations module used in this assay was a Waters 2690/5 HPLC system. This system consisted of a solvent management system for the mobile phases and a sample management system for the test articles and controls. The HPLC system was coupled to a photodiode array detector set at 220 nm. The dimensions of the column used were 2.1 mm x 100 mm x 3.5 micron. The column was primed for at least two hours before the start of the assay. To prime the column, equal parts of mobile phase A (0.1% trifluoroacetic acid in HPLC grade water) and mobile phase B (0.08% trifluoroacetic acid in HPLC grade acetonitrile) were passed through the column.
Once the column was equilibrated and the samples were prepared, the autosampler vials were placed into the designated locations of the separations module carousels. The samples were incubated in the dark at room temperature for 24± 2 hours.
A gradient elution was used in this assay. The mobile phase changed from 10-25% acetonitrile over a 10 minute period to allow for optimal separation and gradually elute most of the sample from the column. This was followed by a rapid increase to 90% acetonitrile to remove anything remaining on the column. The column was allowed to equilibrate back to initial specs for 7 minutes between injections.
The Empower PDA software (version 3) was used to convert the absorbance data from the UV detector into chromatograms of intensity versus retention time for each sample and control. At the end of the run, each chromatogram was integrated in order for the software to calculate the area under the peptide peak. Cysteine and lysine elute from the column at known times, so it was possible to determine which peaks in the chromatograms represented the peptides and use the areas under those peaks for the subsequent calculations.
Results and discussion
- Positive control results:
- Cysteine depletion: 74.48%;
Lysine depletion: 61.55%
In vitro / in chemico
Results
- Key result
- Run / experiment:
- other: Cysteine and Lysine
- Parameter:
- other: Mean Depletion (%)
- Value:
- 4.07
- Positive controls validity:
- valid
- Remarks on result:
- no indication of skin sensitisation
- Other effects / acceptance of results:
- Solubility Assessment
The solubility of Lilial-Me Anthranilate in acetonitrile at a nominal concentration of 100 mM was confirmed by visual inspection.
Reactivity Assessment
All analytical acceptance criteria for each analytical run were met.
Only the cysteine result is reported by the application of the cysteine 1:10 reactivity prediction model (co eluting peaks). Based on this model, reactivity is classed as “no to minimal”, hence the DPRA prediction is negative.
Any other information on results incl. tables
The results of the assay for the test articles can be seen in Table 3. All of the test articles were determined to be non-sensitizers. The results of the assay were considered valid because the acceptance criteria were met as shown in data pages in the Appendix B. Finally, there were no overlaps seen between the test article peak of the coelution control and the peptide peak.
Table 3 DPRA Results
IIVS Test Article Number |
Sponsor’s Designation |
% Mean Peptide Depletion |
% Mean Peptide Depletion of Cysteine and Lysine |
Reactivity (Cysteine and Lysine) |
Potential Sensitizer? |
|
Cysteine |
Lysine |
|||||
17AA08 |
FRET 11-0080 |
0.00 |
0.23 |
0.12 |
Minimal |
No |
17AA09 |
FRET 14-0383 |
6.20 |
1.94 |
4.07 |
Minimal |
No |
17AA10 |
FRET 15-0735 |
0.00 |
0.32 |
0.16 |
Minimal |
No |
Positive Control |
Cinnamic Aldehyde |
74.78 |
61.55 |
|
|
Applicant's summary and conclusion
- Interpretation of results:
- other: “minimal reactivity” and thus is predicted to be negative by DPRA for skin sensitization potential.
- Conclusions:
- All of the three test articles including FRET 14-0383 were determined to be non-sensitizers.
- Executive summary:
Three test articles were tested in at least one valid definitive assay to determine the reactivity classification for the test articles based on the percent depletion of the peptide caused by the test articles. The study was performed in compliance with OECD Guideline for the Testing of Chemicals No. 442C: In Chemico Skin Sensitisation: Direct Peptide Reactivity Assay (DPRA).
All of the three test articles including FRET 14 -0383 were determined to be non-sensitizers.
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