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EC number: 299-890-3 | CAS number: 93918-10-6
- 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:
- 29 January 2019 - 04 April 2019
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Justification for type of information:
- In chemico study in accordance with Testing and assessment strategy for evaluating the skin sensitisation potential of substances of Chapter R.7a: Endpoint specific guidance Version 6.0 – July 2017.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 019
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 (incl. QA statement)
- Type of study:
- direct peptide reactivity assay (DPRA)
Test material
- Reference substance name:
- Potassium 3,5,5-trimethylhexanoate
- EC Number:
- 299-890-3
- EC Name:
- Potassium 3,5,5-trimethylhexanoate
- Cas Number:
- 93918-10-6
- Molecular formula:
- C9H18O2.K
- IUPAC Name:
- potassium 3,5,5-trimethylhexanoate
- Test material form:
- solid: crystalline
- Details on test material:
- Name: Potassium 3,5,5-trimethylhexanoate
CAS No.: 93918-10-6
Batch No.: PURS151015
Purity: 99.4%
Physical State: solid
Colour: white
Molecular Weight: 196.33 g/mol
Storage Conditions: room temperature
Re-certification Date: 14 October 2016
Constituent 1
- Specific details on test material used for the study:
- Name: Potassium 3,5,5-trimethylhexanoate
CAS No.: 93918-10-6
Batch No.: PURS151015
Purity: 99.4%
Physical State: solid
Colour: white
Molecular Weight: 196.33 g/mol
Storage Conditions: room temperature
Re-certification Date: 14 October 2019
In chemico test system
- Details on the study design:
- This in chemico method is designed to predict and classify the skin sensitising potential of a chemical by assessment of its reactivity towards a synthetic cysteine and lysine containing peptide, by measuring the depletion using high performance liquid chromatography (HPLC).
The correlation of protein reactivity with skin sensitisation potential of a chemical is well established and represents the first and initial key event in the skin sensitisation process as defined by the AOP. It is therefore a crucial step for the sensitising potential of a chemical. This test method is able to detect chemicals that cause skin sensitisation and may be used on its own to classify a chemical into UN GHS “Category 1”.
Results and discussion
- Positive control results:
- Reference controls, co-elution controls and a positive control (PC) were set up in parallel to the test item in order to confirm the validity of the test.
Positive Control: Cinnamic aldehyde ((2E)-3-phenylprop-2-enal) was solved in acetonitrile and was used as positive control. A stock concentration of 100 mM was prepared and was included in every assay run for both peptides.
In vitro / in chemico
Resultsopen allclose all
- Key result
- Run / experiment:
- other: Test item / run 1
- Parameter:
- other: Depletion of the Lysine Peptide [%]
- Value:
- 0
- Vehicle controls validity:
- not examined
- Negative controls validity:
- not examined
- Positive controls validity:
- valid
- Remarks on result:
- no indication of skin sensitisation
- Key result
- Run / experiment:
- other: Test item / run 2
- Parameter:
- other: Depletion of the Lysine Peptide [%]
- Value:
- 0
- Vehicle controls validity:
- not examined
- Negative controls validity:
- not examined
- Positive controls validity:
- valid
- Remarks on result:
- no indication of skin sensitisation
- Key result
- Run / experiment:
- other: Test item / run 3
- Parameter:
- other: Depletion of the Lysine Peptide [%]
- Value:
- 0.12
- Vehicle controls validity:
- not examined
- Negative controls validity:
- not examined
- Positive controls validity:
- valid
- Remarks on result:
- no indication of skin sensitisation
- Run / experiment:
- other: Positive control / run 1
- Parameter:
- other: Depletion of the Lysine Peptide [%]
- Value:
- 61.01
- Vehicle controls validity:
- not examined
- Negative controls validity:
- not examined
- Positive controls validity:
- not applicable
- Remarks on result:
- positive indication of skin sensitisation
- Run / experiment:
- other: Positive control / run 2
- Parameter:
- other: Depletion of the Lysine Peptide [%]
- Value:
- 61.28
- Vehicle controls validity:
- not examined
- Negative controls validity:
- not examined
- Positive controls validity:
- not applicable
- Remarks on result:
- positive indication of skin sensitisation
- Run / experiment:
- other: Positive control / run 3
- Parameter:
- other: Depletion of the Lysine Peptide [%]
- Value:
- 57.61
- Vehicle controls validity:
- not examined
- Negative controls validity:
- not examined
- Positive controls validity:
- not applicable
- Remarks on result:
- positive indication of skin sensitisation
- Key result
- Run / experiment:
- other: Test item / run 1
- Parameter:
- other: Depletion of the Cysteine Peptide [%]
- Value:
- 1.16
- Vehicle controls validity:
- not examined
- Negative controls validity:
- not examined
- Positive controls validity:
- valid
- Remarks on result:
- no indication of skin sensitisation
- Key result
- Run / experiment:
- other: Test item / run 2
- Parameter:
- other: Depletion of the Cysteine Peptide [%]
- Value:
- 0
- Vehicle controls validity:
- not examined
- Negative controls validity:
- not examined
- Positive controls validity:
- valid
- Remarks on result:
- no indication of skin sensitisation
- Key result
- Run / experiment:
- other: Test item / run 3
- Parameter:
- other: Depletion of the Cysteine Peptide [%]
- Value:
- 1.06
- Vehicle controls validity:
- not examined
- Negative controls validity:
- not examined
- Positive controls validity:
- valid
- Remarks on result:
- no indication of skin sensitisation
- Run / experiment:
- other: Positive control / run 1
- Parameter:
- other: Depletion of the Cysteine Peptide [%]
- Value:
- 70.09
- Vehicle controls validity:
- not examined
- Negative controls validity:
- not examined
- Positive controls validity:
- not applicable
- Remarks on result:
- positive indication of skin sensitisation
- Run / experiment:
- other: Positive control / run 2
- Parameter:
- other: Depletion of the Cysteine Peptide [%]
- Value:
- 70.27
- Vehicle controls validity:
- not examined
- Negative controls validity:
- not examined
- Positive controls validity:
- not applicable
- Remarks on result:
- positive indication of skin sensitisation
- Run / experiment:
- other: Positive control / run 3
- Parameter:
- other: Depletion of the Cysteine Peptide [%]
- Value:
- 69.45
- Vehicle controls validity:
- not examined
- Negative controls validity:
- not examined
- Positive controls validity:
- not applicable
- Remarks on result:
- positive indication of skin sensitisation
Applicant's summary and conclusion
- Conclusions:
- In this OECD 442 C DPRA study under the given conditions the test item showed minimal reactivity towards both peptides. The test item might be considered as “non-sensitiser”.
- Executive summary:
The in chemico direct peptide reactivity assay (DPRA) enables detection of the sensitising potential of a test item by addressing the molecular initiating event of the adverse outcome pathway (AOP), namely protein reactivity, by quantifying the reactivity of test chemicals towards synthetic peptides containing either lysine or cysteine. The percentage depletion value of the cysteine and lysine peptide is used to categorize a substance in one of four reactivity classes to support discrimination between skin sensitisers and non-sensitisers.
In the present study Potassium 3,5,5-trimethylhexanoate was dissolved in dist. water, based on the results of the pre-experiments. Based on a molecular weight of 196.33 g/mol a 100 mM stock solution was prepared. The test item solutions were tested by incubating the samples with the peptides containing either cysteine or lysine for 24 ± 2 h at 25 ± 2.5 °C. Subsequently samples were analysed by HPLC.
For the 100 mM stock solution of the test item no turbidity or precipitation was observed when diluted with the cysteine peptide solution. After the 24 h ± 2 h incubation period but prior to the HPLC analysis samples were inspected for precipitation, turbidity or phase separation. No precipitation, turbidity or phase separation was observed for any of the samples.
For the 100 mM stock solution of the test item no turbidity or precipitation was observed when diluted with the lysine peptide solution. After the 24 h ± 2 h incubation period but prior to the HPLC analysis samples were inspected for precipitation, turbidity or phase separation. Phase separation (small droplets) was observed for the samples of the positive control including the co-elution control. No precipitation, turbidity or phase separation was observed for the samples of the test item. Samples were not centrifuged prior to the HPLC analysis. Since the acceptance criteria for the depletion range of the positive control were fulfilled, the observed phase separation was regarded as not relevant.
No co-elution of test item with the peptide peaks was observed. Sensitising potential of the test item was predicted from the mean peptide depletion of both analysed peptides (cysteine and lysine) by comparing the peptide concentration of the test item treated samples to the corresponding reference control.
The 100 mM stock solution of the test item showed minimal reactivity towards the synthetic peptides. The mean depletion of both peptides was ≤ 6.38% (0.39%). Based on the prediction model 1 the test item can be considered as non-sensitiser.
The 100 mM stock solution of the positive control (cinnamic aldehyde) showed high reactivity towards the synthetic peptides. The mean depletion of both peptides was 64.95%. The controls confirmed the validity of the study for both, the cysteine and lysine run.
Conclusion:
Based on the OECD GUIDANCE DOCUMENT ON THE REPORTING OF DEFINED APPROACHES AND INDIVIDUAL INFORMATION SOURCES TO BE USED WITHIN INTEGRATED APPROACHES TO TESTING AND ASSESSMENT (IATA) FOR SKIN SENSITISATION Series on Testing & Assessment No. 256 (ENV/JM/MONO(2016)29 and ENV/JM/MONO(2016)29/ANN1) an Adverse Outcome Pathway-based "2 out of 3" integrated testing strategy approach to skin hazard identification (BASF) was chosen. This defined approach describes an integrated testing strategy (ITS) for the identification of the skin sensitisation hazard of a substance primarily for the purposes of classification and labelling without the use of animal testing. The combination of test methods used covers the first three key events (KEs) of the adverse outcome pathway (AOP) leading to skin sensitisation as formally described by the OECD: KE 1: protein binding (e.g. via the direct peptide reactivity assay (DPRA); OECD TG 442C); KE 2: keratinocyte activation (e.g. via the KeratinoSensTM or LuSens assay; OECD TG 442D); and dendritic cell activation [e.g. via the human cell line activation test (h-CLAT); OECD TG 442E. The prediction model entails that two concordant results obtained from methods addressing different steps of first three KEs of the AOP, determine the final classification. Performance and classifications derived from the “2 out of 3 - Sens ITS” of 213 substances were compared to both high quality animal and human data. Depending on the combination of tests used, the “2 out of 3 - Sens ITS” prediction model generally achieved accuracies slightly exceeding those of the murine local lymph node assay (LLNA) when compared to human data. These results compellingly verify the applicability of this easy to understand integrated testing approach (ITS) for a wide range of chemicals.[Ref. CASE STUDY I of ENV/JM/MONO(2016)29/ANN1, Dr. Robert Landsiedel, BASF SE] The test item does neither bind to proteins in the DPRA nor activate the Nrf2 -Keap1 -ARE toxicity pathway (key event 2 of skin sensitization AOP). In line with the "2 out of 3" integrated testing strategy approach to skin hazard identification presented classification of the test item as skin sensitizer is not justified.
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