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EC number: 229-565-3 | CAS number: 6613-64-5
- 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 vitro
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 2017-06-24 - 2017-09-21
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Cross-reference
- Reason / purpose for cross-reference:
- reference to other study
- Remarks:
- WoE
Reference
- Endpoint:
- skin sensitisation, other
- Remarks:
- SAR-Profiling of structural alerts for skin sensitisation (OECD QSAR Toolbox)
- Type of information:
- (Q)SAR
- Adequacy of study:
- weight of evidence
- Study period:
- 2017-12-11
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- results derived from a (Q)SAR model, with limited documentation / justification, but validity of model and reliability of prediction considered adequate based on a generally acknowledged source
- Justification for type of information:
- 1. SOFTWARE
OECD QSAR Toolbox
2. MODEL (incl. version number)
version 4.1
3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
CAS: 6613-64-5
4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
Name of profilers:
1) Protein binding alerts for skin sensitization by OASIS v1.5
2) Protein binding alerts for skin sensitization according to GHS v1.0
3) Protein binding alerts by OASIS v1.5
4) Protein binding alerts by OECD v2.3
5) Protein binding potency Cys (DPRA 13%) v01
6) Protein binding potency v2.4
7) Protein binding potency h-CLAT v1.0
8) Keratinocyte gene expression v2.0
5. APPLICABILITY DOMAIN
The aim of these profilers is to investigate the presence of alerts within the target molecules responsible for interaction or covalent bindings with proteins. For detailed information, please refer to the attached reports about the specific profilers.
6. ADEQUACY OF THE RESULT
These profiling results are used in a weight-of-evidence approach to assess the skin sensitising potential of SPV. The selected profilers detect structural alerts, which are associated with the potential to bind to or interact with proteins. The binding to skin proteins is the first step of the Adverse Outcome Pathway for skin sensitisation. Binding to skin proteins is essential to induce a specific memory T-cell response associated with skin sensitisation. - Reason / purpose for cross-reference:
- reference to other study
- Remarks:
- WoE
- Guideline:
- other: REACH Guidance on QSARs R.6
- Version / remarks:
- Profiling was performed with the QSAR Toolbox Version 4.1
- Key result
- Parameter:
- other:
- Remarks on result:
- positive indication of skin sensitisation
- Remarks:
- SPV and one of its metabolites is profiled to have protein binding potency by several profilers
- Parameter:
- other:
- Remarks on result:
- positive indication of skin sensitisation based on QSAR/QSPR prediction
- Remarks:
- SPV and one of its metabolites is profiled to have protein binding potency by several profilers
- Conclusions:
- SPV and its metabolites have been profiled with the OECD QSAR Toolbox, version 4.1. A positive indication for skin sensitisation of the query substance and one of its skin metabolites is given by seven different profilers on protein binding potency. This provides evidence that SPV is positive in DPRA.
- Executive summary:
A positive indication for skin sensitisation of the query substance and one of its skin metabolites is given by seven different profilers on protein binding potency. This provides evidence that SPV is positive in DPRA.
SPV
Profiler |
result / suspected MoA |
Protein binding alerts for skin sensitization by OASIS v1.5 |
Michael addition |
Protein binding alerts for skin sensitization according to GHS v1.0 |
Skin sensitization Category 1A |
Protein binding alerts by OASIS v1.5 |
Michael addition |
Protein binding alerts by OECD v2.3 |
Michael addition |
Protein binding potency Cys (DPRA 13%) v01 |
DPRA above 21 % |
Protein binding potency v2.4 |
Moderately reactive (GSH) |
The 'keratinocyte gene expression' was not possible to classify with the relevant profiler.
metabolite
The simulated metabolite is attached as a picture file.
Protein binding potency h-CLAT v1.0 |
Structural alert: Epoxide |
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 017
- Report date:
- 2017
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- other: OECD 442E
- Version / remarks:
- OECD Guideline for the Testing of Chemicals, Part 442E: In Vitro Skin Sensitisation: human Cell Line Activation Test (h-CLAT) (adopted 29. July 2016)
- Deviations:
- yes
- Remarks:
- See "Deviations from the Guideline", Overall remarks, but not affecting the validity of the study or results
- Qualifier:
- according to guideline
- Guideline:
- other: OECD. (2012). The Adverse Outcome Pathway for Skin Sensitisation Initiated by Covalent Binding, Part 1: Scientific Evidence. Series on Testing and Assessment No. 168, Paris
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: Bauch, C., Kolle, S. N., & Ramirez, T. (2012). Putting the parts together: combining in vitro methods to test for skin sensitizing potentials. Regulation of Toxicology and Pharmacology, 63, 489–504
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of study:
- activation of dendritic cells
- Justification for non-LLNA method:
- In vitro study should be performed first. An in vivo study shall be conducted only if in vitro/in chemico test methods described under point 8.3.1 of REACH are not applicable.
Test material
- Reference substance name:
- 1-(3-sulphonatopropyl)-2-vinylpyridinium
- EC Number:
- 229-565-3
- EC Name:
- 1-(3-sulphonatopropyl)-2-vinylpyridinium
- Cas Number:
- 6613-64-5
- Molecular formula:
- C10H13NO3S
- IUPAC Name:
- 3-(2-vinylpyridinium-1-yl)propane-1-sulfonate
- Test material form:
- solid: particulate/powder
Constituent 1
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Source and lot/batch No. of test material: sponsor
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: The test item was stored in the test facility at room temperature (20 ± 5°C) protected from light and humidity.
OTHER SPECIFICS:
Molecular weight 227.28 g/mol
Log Kow ≤ - 3.0 at 21.1 °C
In vitro test system
- Details on the study design:
- This in vitro study was performed to assess the sensitising potential of the test item 1-(3-Sulfopropyl)-2-vinyl-pyridinumbetain (SPV) by quantifying changes in the expression level of the two cell surface markers CD86 and CD54, which are associated with the process of activation of monocytes and dendritic cells. For this purpose the human monocytic leukaemia cell line THP-1 was used and treated with the test item for 24 h before evaluation. The measured expression levels were used to distinguish potential skin sensitizers from non-sensitizers.
The h-CLAT addresses the third key event of the skin sensitisation adverse outcome pathway (AOP) that was defined by the OECD in 2012 and is a part of the AOP-based “two out of three” skin sensitisation integrated testing strategy for hazard identification (Bauch et al., 2012).
In order to conclude on the skin sensitisation potential of the test substance, a human Cell Line Activation Test (h-CLAT) comprises a minimum of two independent and valid experiments. A categorization in the subcategories 1 A and 1 B is not possible. However, a positive result with the h-CLAT may be used on its own to classify a chemical into UN GHS category 1. For a confirmation of a negative result another in vitro skin sensitisation test has to be performed.
Results and discussion
- Positive control results:
- positive, see tables below
In vitro / in chemico
Resultsopen allclose all
- Key result
- Run / experiment:
- other: Experiment IV
- Parameter:
- other: EC200 (for CD54)
- Remarks:
- µg/ml
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- not determinable
- Remarks:
- A calculation of the EC200 was not possible since none of the RFI values was above 200 (for CD54) at any of the tested concentrations.
- Key result
- Run / experiment:
- other: Experiment IV
- Parameter:
- other: EC150 (for CD86)
- Remarks:
- µg/ml
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- not determinable
- Remarks:
- A calculation of the EC150 was not possible since none of the RFI values was above 150 (for CD86) at any of the tested concentrations.
- Key result
- Run / experiment:
- other: Experiment V
- Parameter:
- other: EC200 (for CD54)
- Remarks:
- µg/ml
- Value:
- 175
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- not determinable
- Remarks:
- Because the results were not concordant a calculation of the EC200 was not possible.
- Key result
- Run / experiment:
- other: Experiment V
- Parameter:
- other: EC150 (for CD86)
- Remarks:
- µg/ml
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- not determinable
- Remarks:
- A calculation of the EC150 was not possible since none of the RFI values was above 150 (for CD86) at any of the tested concentrations.
- Key result
- Run / experiment:
- other: Experiment VI
- Parameter:
- other: EC200 (for CD54)
- Remarks:
- µg/ml
- Value:
- 4 696.98
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Run / experiment:
- other: Experiment VI
- Parameter:
- other: EC150 (for CD86)
- Remarks:
- µg/ml
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- not determinable
- Remarks:
- A calculation of the EC150 was not possible since none of the RFI values was above 150 (for CD86) at any of the tested concentrations.
- Other effects / acceptance of results:
- DEMONSTRATION OF TECHNICAL PROFICIENCY: yes
ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: yes
- Acceptance criteria met for positive control: yes
- Acceptance criteria met for variability between replicate measurements: yes
- Range of historical values if different from the ones specified in the test guideline: no
Applicant's summary and conclusion
- Interpretation of results:
- other: potential skin sensitizer
- Conclusions:
- The study was performed according to OECD TG 442E under GLP on the registered substance itself. Positive and negative control were valid.
The h-CLAT addresses the third key event of the skin sensitisation adverse outcome pathway (AOP) that was defined by the OECD in 2012 and is a part of the AOP-based “two out of three” skin sensitisation integrated testing strategy for hazard identification (Bauch et al., 2012). The sensitising potential of the test item was assessed by quantifying changes in the expression level of the two cell surface markers CD86 and CD54, which are associated with the process of activation of monocytes and dendritic cells, after incubation with the test item. The measured expression levels were used to distinguish potential skin sensitizers from non-sensitizers.
Experiment IV: The RFI of CD86 was not ≥ 150 % and the RFI of CD54 was not ≥ 200 % in all tested concentrations.
Experiment V: Again, the RFI of CD86 was not ≥ 150 %. However, the RFI of CD54 was > 200 % in 6 test item concentrations.
Experiment VI: The RFI of CD86 was not ≥ 150 % in all test item concentrations. However, the RFI of CD54 was > 200 % at the highest test item concentration. The EC200 was calculated and is 4696.98 µg/mL.
The majority result of the three individual runs is positive. Therefore, in accordance to the classification criteria the result of this study is “positive”. In conclusion, it can be stated that under the experimental conditions of this study, the test item, 1-(3-Sulfopropyl)-2-vinyl-pyridinumbetain (SPV), was positive in the h-CLAT and is therefore considered to have the potential to activate dendritic cells and is a potential skin sensitiser.
A categorization in the subcategories 1 A and 1 B is not possible. However, a positive result with the h-CLAT may be used on its own to classify a chemical into UN GHS category 1.
According to OECD Toolbox profiling, a positive indication for skin sensitisation of the query substance and one of its skin metabolites is given by seven different profilers on protein binding potency. This provides evidence that SPV is positive in DPRA. With the Danish (Q)SAR Database, a classification was not possible.
Taking into account the magnitude of the results, the substance is not considered to be a strong sensitizer. On the contrary, the substance should be maximally regarded as weak sensitizer. The positive control DNBC resulted with 4 µg/ml (historical control data) in mean RFI values of 874 (CD86) resp. 373 (CD54). According to the guideline 442E, Appendix 2, proficiency substances, the reference ranges are EC150 = 0.5 – 10 µg/ml (CD86) and EC200 = 0.5 – 15 µg/ml (CD54), resulting both in positive results, which matches. The reference ranges as cited in the guideline for the weak solid sensitizer Imidazolidinyl urea are EC150 = 20 – 90 µg/ml (CD86) and EC200 = 20 – 75 µg/ml (CD54), resulting in a positive result, both values for the solid non-sensitizer 4-Aminobenzoic acid are >1000 µg/ml and revealed negative results.
In consequence, the obtained RFI values, although meeting the criteria for classification as positive, are way more in the range of the ones of the non-sensitizer than the ones of the weak sensitizer. In combination with the fact that no protein binding potency alert was identified, it cannot be excluded that the test item is not skin sensitizer at all in vivo. However, taking into account the fact that SPV might be as well positive in the DPRA, SPV should be classified precautionarily as skin sens. Cat. 1, considering the AOP-based “two out of three” skin sensitisation integrated testing strategy. - Executive summary:
This in vitro study is performed according to OECD 442E under GLP to assess the sensitising potential of the test item 1-(3-Sulfopropyl)-2-vinyl-pyridinumbetain (SPV) by quantifying changes in the expression level of the two cell surface markers CD86 and CD54, which are associated with the process of activation of monocytes and dendritic cells.
In total two pre-tests and six experiments (experiment I - VI) with a treatment period of 24 hours were performed whereby experiments I, II and III were invalid and had to be repeated. Therefore, in total three valid experiments (experiment IV, V and VI) were performed. The results and data of the invalid experiments are not included in this final report but will be archived with the raw data.
For the experiments, the highest nominal applied concentration (5000 µg/mL) was chosen based on the results obtained in the pre-tests. A geometric series (factor 1.2) of 7 dilutions was prepared.
As solvent control for the test item, RPMI 1640 was used in a final concentration of 1 % in culture medium.
As positive control, 2,4-dinitrochlorobenzene (DNCB, CAS n. 97-00-7, ≥ 99% purity) was used.
For all experiments the viability was above 90 % in all of the test concentrations.
Experiment IV: The RFI of CD86 was not ≥ 150 % and the RFI of CD54 was not ≥ 200 % in all tested concentrations.
Experiment V: Again, the RFI of CD86 was not ≥ 150 %. However, the RFI of CD54 was > 200 % in 6 test item concentrations.
Experiment VI: The RFI of CD86 was not ≥ 150 % in all test item concentrations. However, the RFI of CD54 was > 200 % at the highest test item concentration
Since the majority result of the three individual runs is positive, the test item is considered as “positive”.
Conclusion: Under the experimental conditions of this study, the test item, 1-(3-Sulfopropyl)-2-vinyl-pyridinumbetain (SPV), was positive in the h-CLAT and is therefore considered to have the potential to activate dendritic cells and therefore to be a potential skin sensitizer.
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