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EC number: 244-520-8 | CAS number: 21668-81-5
- 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:
- 2017-07-26 - 2017-08-31
- 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: 21668-81-5
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
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 UPS. 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: QSAR
- Remarks on result:
- positive indication of skin sensitisation
- Remarks:
- UPS and two of its metabolites is profiled to have protein binding potency by three relevant profilers
- Parameter:
- other: QSAR
- Remarks on result:
- positive indication of skin sensitisation based on QSAR/QSPR prediction
- Remarks:
- UPS and two of its metabolites is profiled to have protein binding potency by three relevant profilers
- Conclusions:
- UPS 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 two of its skin metabolites is given by seven three profilers on protein binding potency. This provides evidence that UPS is positive in DPRA. The keratinocyte gene expression was not possible to classify.
- Executive summary:
A positive indication for skin sensitisation of the query substance and two of its skin metabolites is given by three different profilers on protein binding potency. This provides evidence that UPS is positive in DPRA.
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:
- 3-[(aminoiminomethyl)thio]propanesulphonic acid
- EC Number:
- 244-520-8
- EC Name:
- 3-[(aminoiminomethyl)thio]propanesulphonic acid
- Cas Number:
- 21668-81-5
- Molecular formula:
- C4H10N2O3S2
- IUPAC Name:
- 3-(carbamimidoylsulfanyl)propane-1-sulfonic acid
- Test material form:
- solid: particulate/powder
- Details on test material:
- Storage: Room Temperature (20 ± 5°C), keep away from humidity
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 198.3 g/mol
Log Kow -1.15 (EPISuite KOWWIN (V1.67) estimation)
In vitro test system
- Details on the study design:
- This in vitro study was performed to assess the sensitising potential of the test item 3-[(Amino-iminomethyl)-thio]-1-propanesulphonic acid (UPS) 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 be-fore 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 at least two independent and valid experiments. A categorization in the subcategories 1 A and 1 B is not possible. However, a positive re-sult 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 I
- Parameter:
- other: EC150 (for CD86)
- Remarks:
- µg/ml
- Value:
- 653.91
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Run / experiment:
- other: Experiment I
- Parameter:
- other: EC200 (for CD54)
- 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 II
- Parameter:
- other: EC150 (for CD86)
- Remarks:
- µg/ml
- Value:
- 672.97
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Run / experiment:
- other: Experiment II
- 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.
- 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 controls 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.
In both experiments the RFI of CD54 was not ≥ 200 % at any tested concentration with cell viability ≥ 50 %.
In both experiments the RFI of CD86 was > 150 % at the three highest test item concentrations. The EC150 was calculates and is 653.91 µg/mL in experiment I and 672.97 µg/mL in experiment II.
Since the criteria for a positive result are fulfilled in accordance to the OECD 442E, the result of this study is “positive”.
In conclusion, it can be stated that under the experimental conditions of this study, the test item, 3-[(Amino-iminomethyl)-thio]-1-propanesulphonic acid (UPS), was positive in the h-CLAT and is a potential skin sensitizer.
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 two of its skin metabolites is given by seven three profilers on protein binding potency. This provides evidence that UPS is positive in DPRA. The Danish (Q)SAR Database on the other hand indicated that UPS is not sensitizing.
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 859 (CD86) resp. 368 (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. So it cannot be excluded that the test item is not skin sensitizer at all in vivo, especially in combination with the fact that the Danish (Q)SAR Database did not identify UPS as skin sensitizer. However, taking into account the fact that UPS might be as well positive in the DPRA, UPS 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 was performed according to OECD 442E under GLP to assess the sensitising potential of the test item 3-[(Amino-iminomethyl)-thio]-1-propanesulphonic acid (UPS) 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.
Two valid experiments with a treatment period of 24 hours were performed.
In the experiments, the highest nominal applied concentration (1000 µg/mL) was chosen based on the results obtained in the pre-test and the solubility of the test item. A geometric series (factor 1.2) of 7 dilutions thereof 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.
In both experiments the RFI of CD54 was not ≥ 200 % at any tested concentration with cell viability ≥ 50 %.
In both experiments the RFI of CD86 was > 150 % at the three highest test item concentrations. The EC150 was calculated and is 653.91 µg/mL in experiment I and 672.97 µg/mL in experiment II.
Since the criteria for a positive result are fulfilled in accordance to the OECD 442E, the result of this study is “positive”.
Conclusion: Under the experimental conditions of this study, the test item, 3-[(Amino-iminomethyl)-thio]-1-propanesulphonic acid (UPS), 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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