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EC number: 228-193-9 | CAS number: 6163-58-2
- 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 vitro
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 02 October 2017 to 13 October 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:
- 2018
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 442D (In Vitro Skin Sensitisation: ARE-Nrf2 Luciferase Test Method)
- GLP compliance:
- yes
- Type of study:
- direct peptide reactivity assay (DPRA)
- Justification for non-LLNA method:
- As per the updated Annex VII 8.3 requirements
Test material
- Reference substance name:
- Tris(2-methylphenyl)phosphine
- EC Number:
- 228-193-9
- EC Name:
- Tris(2-methylphenyl)phosphine
- Cas Number:
- 6163-58-2
- Molecular formula:
- C21H21P
- IUPAC Name:
- tris(2-methylphenyl)phosphane
- Test material form:
- solid: particulate/powder
- Details on test material:
- Lot number: 2000850599
Analysis date: 19 August 2016
Constituent 1
- Specific details on test material used for the study:
- Chemical name: Tris(2-methylphenyl)phosphine
CAS Number 6163-58-2
Molecular formula C21H21P
Structure codes: SMILES: C1=CC(=C(C=C1)C)P(C2=C(C=CC=C2)C)C3=C(C=CC=C3)C
Appearance: Off-white crystalline powder (determined by Charles River Den Bosch)
In vitro test system
- Details on the study design:
- Synthetic peptides containing cysteine (SPCC) (Ac-RFAACAA-COOH) or synthetic peptides containing lysine (SPCL) (Ac-RFAAKAA-COOH). The molecular weight is 750.9 g/mol for SPCC and 775.9 g/mol for SPCL.
Synthetic Peptide Containing Cysteine (SPCC) Stock Solution
A stock solution of 0.667 mM SPCC (0.501 mg SPCC/mL) was prepared by dissolving 10 mg of SPCC in 19.96 mL phosphate buffer pH 7.5. The mixture was stirred for 5 minutes followed by 5 minutes sonication.
SPCC Reference Control Solutions
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. In addition, a RCcysCacetone:ACN sample was included to evaluate the effect of the solvent that was used to dissolve the test item on the Percent Peptide Depletion. The RCcysCacetone:ACN sample was prepared by mixing 750 µL of the 0.667 mM SPCC stock solution with 200 µL ACN and 50 µL acetone:ACN (1:1, v/v)
Synthetic Peptide Containing Lysine (SPCL) Stock Solution
A stock solution of 0.667 mM SPCL (0.518 mg SPCL/mL) was prepared by dissolving 10 mg of SPCL in 19.31 mL of ammonium acetate buffer pH 10.2 followed by stirring for 5 minutes.
SPCL Reference Control Solutions
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. In addition, a RClysCacetone:ACN sample was included to evaluate the effect of the solvent that was used to dissolve the test item on the Percent Peptide Depletion. The RClysCacetone:ACN sample was prepared by mixing 750 µL of the 0.667 mM SPCL stock solution with 250 µL acetone:ACN (1:1, v/v).
Sample Incubations
After preparation, the samples (reference controls, calibration solutions, co-elution control, positive controls and test item samples) were placed in an incubator at 25±2.5°C. After incubation, the samples were transferred to the autosampler. The incubation time between placement of the samples in the incubator and analysis of the first RCcysB- or RClysBsample was 24.5 hours for cysteine and 25.5 hours for lysine. The time between the first
RCcysB- or RClysB-injection and the last injection of a cysteine or lysine sequence, respectively, did not exceed 30 hours.
Prior to HPLC-PDA analysis the samples were visually inspected for precipitation. The samples that showed precipitation were centrifuged (at 400 g) for 5 minutes at room temperature.
Results and discussion
- Positive control results:
- Positive Control Cinnamic Aldehyde
In vitro / in chemico
Resultsopen allclose all
- Parameter:
- other: Cystine Reactivity Assay
- Remarks:
- 16.1% SPCC depletion
- Value:
- 16.1
- Positive controls validity:
- valid
- Remarks on result:
- positive indication of skin sensitisation
- Parameter:
- other: lysine reactivity assay
- Remarks:
- 0.4% SPCL depletion
- Value:
- 0.4
- Positive controls validity:
- valid
- Remarks on result:
- positive indication of skin sensitisation
- Parameter:
- other: mean of the synthetic peptides containing either cysteine (SPCC) or lysine (SPCL) depletion
- Value:
- 8.2
- Positive controls validity:
- valid
Any other information on results incl. tables
In the cysteine reactivity assay the test item showed 0.1 ± 0.2% SPCC depletion while in the lysine reactivity assay the test item showed 0.8 ± 1.2% SPCL depletion. The mean of the synthetic peptides containing either cysteine(SPCC) or lysine (SPCL) depletion was 0.5% 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.
An overview of the individual results of the cysteine and lysine reactivity assays as well as the mean of the SPCC and SPCL depletion. In the cysteine reactivity assay the test item showed 16.1% SPCC depletion while in the lysine reactivity assay the test item showed 0.4% SPCL depletion. The mean of the SPCC and SPCL depletion was 8.2% and as a result the test item was positive in the DPRA and was classified in the “low reactivity class” when using the Cysteine 1:10 / Lysine 1:50 prediction model.
Applicant's summary and conclusion
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- Tri-o-tolylphosphine was positive in the DPRA and was classified in the “low reactivity class” when using the Cysteine 1:10 / Lysine 1:50 prediction model. However, since
precipitation was observed upon addition of the test item to the SPCC and SPCL peptide solutions, one cannot be sure how much test item remained in the solution to react with the peptides. Consequently, the peptide depletion may be underestimated. - Executive summary:
The objective of this study was to determine the reactivity of Tri-o-tolylphosphine towards model synthetic peptides containing either cysteine (SPCC) or lysine (SPCL). After incubation of the test item with either SPCC or SPCL, the relative peptide concentration was determined by High-Performance Liquid Chromatography (HPLC) with gradient elution and photodiode array (PDA) detection at 220 nm and 258 nm. SPCC and SPCL Percent
Depletion Values were calculated and used in a prediction model which allows assigning the test item to one of four reactivity classes used to support the discrimination between sensitizers and non-sensitizers.
The study procedures described in this report were based on the most recent OECD guideline. Acetone:acetonitrile (ACN) (1:1, v/v) was found to be an appropriate solvent to dissolve the test item and was therefore used in this Direct Peptide Reactivity Assay (DPRA) study.
The validation parameters, i.e. calibration curve, mean concentration of Reference Control (RC) samples A, C and Cacetone:ACN, the CV for RC samples B and C, the mean percent peptide depletion values for the positive control with its standard deviation value and the standard deviation value of the peptide depletion for the test item, were all within the acceptability criteria for the DPRA.
An overview of the individual results of the cysteine and lysine reactivity assays as well as the mean of the SPCC and SPCL depletion are presented in the table below. In the cysteine reactivity assay the test item showed 16.1% SPCC depletion while in the lysine reactivity assay the test item showed 0.4% SPCL depletion. The mean of the SPCC and SPCL depletion was 8.2% and as a result the test item was considered to be positive in the DPRA
and classified in the “low reactivity class” when using the Cysteine 1:10 / Lysine 1:50 prediction model.
In conclusion, since all acceptability criteria were met this DPRA is considered to be valid. Tri-o-tolylphosphine was positive in the DPRA and was classified in the “low reactivity class” when using the Cysteine 1:10 / Lysine 1:50 prediction model. However, since precipitation was observed upon addition of the test item to the SPCC and SPCL peptide solutions, one cannot be sure how much test item remained in the solution to react with the
peptides. Consequently, the peptide depletion may be underestimated
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