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Diss Factsheets
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EC number: 255-410-4 | CAS number: 41496-43-9
- 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
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Skin sensitisation
Administrative data
- Endpoint:
- skin sensitisation: in chemico
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- From July 25, 2021 to September 06, 2021
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study with acceptable restrictions
- Remarks:
- Study performed according to OECD test guideline No. 442C , but not GLP.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 021
- Report date:
- 2021
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 442C (In Chemico Skin Sensitisation Assays addressing the Adverse Outcome Pathway key event on covalent binding to proteins)
- GLP compliance:
- no
- Remarks:
- Although the in vitro test was not carried out in a registered GLP laboratory, the Givaudan in vitro Technologies laboratory based at its Dubendorf site in Switzerland performs all in vitro studies within the "spirit" of GLP.
- Type of study:
- direct peptide reactivity assay (DPRA)
- Justification for non-LLNA method:
- Non-animal testing is the default requirement for skin sensitisation.
Test material
- Reference substance name:
- 2-methyl-3-(p-tolyl)propionaldehyde
- EC Number:
- 255-410-4
- EC Name:
- 2-methyl-3-(p-tolyl)propionaldehyde
- Cas Number:
- 41496-43-9
- Molecular formula:
- C11H14O
- IUPAC Name:
- 2-methyl-3-(4-methylphenyl)propanal
- Test material form:
- liquid
Constituent 1
In chemico test system
- Details of test system:
- cysteine peptide, (Ac-RFAACAA-COOH)
- lysine peptide (Ac-RFAAKAACOOH)
- Details on the study design:
- - Test System(s)
The Lys-peptide Ac-RFAAKAA is incubated at a final concentration of 0.5 mM in an ammonium acetate buffer at pH 10.5 in presence of a final level of 25% acetonitrile and in presence of a 50-fold excess of the test substance (25 mM) dissolved in acetonitrile.
The Cys-peptide Ac-RFAACAA is incubated at a final concentration of 0.5 mM in phosphate buffer at pH 7.5 in presence of a final level of 25% acetonitrile and in presence of a 10-fold excess of the test substance (5 mM) dissolved in acetonitrile.
- Endpoint & Endpoint Detection
24 h after start of the incubation the remaining peptide is quantified with HPLC-UV.
- Endpoint Value
The endpoint is expressed as % peptide depletion.
- Positive control
In each test Cinnamic aldehyde is included as positive control.
- Negative control
In each test Acetonitrile is included as negative control.
- Data Processing
Data evaluation is automatically performed by a standardized Excel template which forms part of the SOP.
- Prediction Model
Based on the average peptide depletion values for both the Cysteine and the Lysine peptide, a reactivity class is attributed to the substances. Average depletion below 6.38% indicates minimal reactivity, substances in this class are predicted as non-sensitizers by the DPRA.
In case co-elution occurs with the Lysine peptide only, an alternative prediction model is proposed by the test guideline. In this Cysteine only model, chemicals are rated as sensitizers if they lead to >13.89% depletion of the Cysteine peptide.
The study protocol was validated with the proficiency chemicals prescribed in the OECD test guideline 442C. The results of the testing on the proficiency chemicals at the test facility is described in Test report RCR 153’453, ‘Direct peptide reactivity assay (DPRA) for skin sensitization testing: Proficiency testing at the Givaudan testing facility. - Vehicle / solvent:
- acetonitrile
- Positive control:
- cinnamic aldehyde
Results and discussion
- Positive control results:
- All the acceptance criteria were fulfilled for the positive control cinnamic aldehyde.
In vitro / in chemico
Resultsopen allclose all
- Key result
- Group:
- test chemical
- Run / experiment:
- mean
- Parameter:
- mean cystein depletion
- Value:
- 11.1 %
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Group:
- test chemical
- Run / experiment:
- mean
- Parameter:
- mean lysine depletion
- Value:
- -1.2 %
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Group:
- test chemical
- Run / experiment:
- mean
- Parameter:
- other: Mean peptide depletion rate
- Value:
- 5 %
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Outcome of the prediction model:
- no or minimal reactivity [in chemico]
- Other effects / acceptance of results:
- ACCEPTANCE OF RESULTS:
- Acceptance criteria met for reference controls: Yes
- Acceptance criteria met for positive control: Yes
- Acceptance criteria met for variability between replicate measurements: Yes
- Acceptance criteria met for the calibration curve: Yes
- Range of historical values if different from the ones specified in the test guideline: see Appendix C of the report attached
Applicant's summary and conclusion
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- The result of the DPRA assay should be used as part of an integrated approach for testing and assessment (IATA). A parallel test in the KeratinoSens™ assay may indicate whether congruent results are obtained by both test methods. According to a detailed analysis on large set of chemicals, two congruent results in these two tests give a good prediction of the sensitizer hazard particularly when predicting human data, while an additional test in a dendritic cell line assessing expression of surface markers may be needed in case of discordant results.
2-methyl-3-(p-tolyl)propionaldehyde was non-reactive and classified into the Minimal reactivity class according to the prediction model. It is therefore considered a non-sensitizer according to the prediction model of the DPRA. However, 2-methyl-3-(p-tolyl)propionaldehyde is an aldehyde, and reactive aldehydes do not always react with the Lys-peptide under DPRA conditions, thus this result should be considered in a weight-of-evidence approach. - Executive summary:
Introduction
The Direct peptide reactivity Assay (DPRA) is an in chemico test to determine the reactivity of test a substance towards peptides.
This assay has been validated for a broad range of low-molecular weight chemicals and it was found to detect reactive skin sensitizers from a broad range of so called applicability domains, i.e. chemicals reacting with proteins by different mechanisms. It was validated by ECVAM and proposed to be used as part of an integrated approach for testing and assessment (IATA).
Experimental
The test substance 2-methyl-3-(p-tolyl)propionaldehyde was dissolved in acetonitrile and mixed with a Cysteine- and a Lysine-containing peptide according to the standard operating procedure of the DPRA. One study with three replicates was conducted. After 24 h incubation time, peptide depletion induced by 2-methyl-3-(p-tolyl)propionaldehyde was determined by HPLC-UV.
Results
2-methyl-3-(p-tolyl)propionaldehyde was non-reactive and classified into the minimal reactivity class according to the DPRA prediction model. It is therefore considered a non-sensitizer according to the prediction model of the DPRA.
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