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EC number: 208-536-9 | CAS number: 532-40-1
- 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
Endpoint summary
Administrative data
Description of key information
Skin sensitisation (OECD 442C): positive (RA CAS 10023-48-0)
Skin sensitisation (OECD 442D): positive (RA CAS 10023-48-0)
WoE conclusion from in vitro skin sensitisation battery: skin sensitising
Key value for chemical safety assessment
Skin sensitisation
Link to relevant study records
- Endpoint:
- skin sensitisation: in chemico
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Justification for type of information:
- refer to analogue justification provided in IUCLID section 13
- Reason / purpose for cross-reference:
- read-across source
- Key result
- Run / experiment:
- other: cysteine run
- Parameter:
- other: mean peptide depletion [%]
- Value:
- 52.81
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks:
- 74.90
- Remarks on result:
- positive indication of skin sensitisation
- Remarks:
- Source: CAS 10023-48-0, 7.4.1-1
- Key result
- Run / experiment:
- other: lysine run
- Parameter:
- other: mean peptide depletion [%]
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- not determinable
- Remarks:
- Source: CAS 10023-48-0, 7.4.1-1 / In the lysine run co-elution of the test substance and the lysine peptide due to a shift of the lysine peptide peak was observed.
- Interpretation of results:
- other: skin sensitising potential based on the key event "protein reactivity"
- Conclusions:
- Under the conditions of this study, the test substance showed reactivity towards selected proteins. The result does not allow for the non-classification or classification as skin sensitiser of the test substance and therefore further evaluation and/or data generation is required.
Based on the analogue approach, the same results were expected for the target substance. - Endpoint:
- skin sensitisation: in vitro
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Justification for type of information:
- refer to analogue justification provided in IUCLID section 13
- Reason / purpose for cross-reference:
- read-across source
- Key result
- Run / experiment:
- other: Experiment 1
- Parameter:
- other: luciferase activity
- Value:
- 3.76
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: Source: CAS 10023-48-0, 7.4.1-2
- Key result
- Run / experiment:
- other: Experiment 1
- Parameter:
- other: cell viability [%]
- Value:
- 79.6
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: Source: CAS 10023-48-0, 7.4.1-2
- Key result
- Run / experiment:
- other: Experiment 1
- Parameter:
- other: EC1.5 [µM]
- Value:
- 810.73
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: Source: CAS 10023-48-0, 7.4.1-2
- Key result
- Run / experiment:
- other: Experiment 2
- Parameter:
- other: luciferase activity
- Value:
- 2.75
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: Source: CAS 10023-48-0, 7.4.1-2
- Key result
- Run / experiment:
- other: Experiment 2
- Parameter:
- other: cell viability [%]
- Value:
- 66
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: Source: CAS 10023-48-0, 7.4.1-2
- Key result
- Run / experiment:
- other: Experiment 2
- Parameter:
- other: EC1.5 [µM]
- Value:
- 268.21
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: Source: CAS 10023-48-0, 7.4.1-2
- Interpretation of results:
- other: skin sensitising potential based on the key event “inflammatory response in keratinocytes”
- Conclusions:
- Under the conditions of the test, the test substance has a keratinocyte activating potential. The result does not allow for the non-classification or classification as skin sensitiser of the test substance and therefore further evaluation and/or data generation is required.
Based on the analogue approach, same results were expected for the target substance.
Referenceopen allclose all
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (sensitising)
- Additional information:
Justification for read-across
There are no reliable data available regarding skin sensitisation for 3-[(4-amino-2-methylpyrimidin-5-yl)methyl]-4-methyl-5-[2-(phosphonooxy)ethyl]-1,3-thiazol-3-ium chloride (CAS 532-40-1). Read-across from an appropriate substance 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-4-methyl-5-[2-(phosphonooxy)ethyl]-thiazolium (CAS 10023-48-0) is conducted in accordance with Regulation (EC) No 1907/2006, Annex XI, 1.5. in order to fulfil the standard data requirements defined in Regulation (EC) No 1907/2006, Annex VII, 8.3. Common functional groups, structural similarities and comparable toxicological properties (according to the joint consideration in Annex VI to CLP) of the source and target substance are the basis of read-across. A detailed analogue approach justification is provided in the technical dossier (see IUCLID Section 13).
In chemico/in vitro
CAS 10023-48-0
The skin sensitising potential of the source substance substance (CAS 10023-48-0) was assessed in a Direct Peptide Reactivity Assay performed according to OECD guideline 442C and in compliance with GLP (reference 7.4.1-1). Test item solutions were incubated with the cysteine and lysine peptide solutions in glass vials using defined ratios of peptide to test item (1:10 cysteine peptide, 1:50 lysine peptide). The reaction solutions were left in the dark at 25 ± 2.5 °C for 24 ± 2 h before running the HPLC analysis. Reference controls, co-elution controls as well as the positive control were set up in parallel. The mean depletion of the cysteine peptide was 52.81%. Using the prediction model defined in the guideline, the test substance is allocated to the reactivity class “moderate reactivity”. In the lysine run a co-elution of the test substance with the lysine peptide peak was observed. However, all validity criteria were fulfilled, and this shift was not considered having an influence on the quality or validity of the overall results. The positive control showed high reactivity towards the synthetic peptides as the mean depletion of both peptides was 64.92%.
Under the conditions of the test, the test substance showed reactivity towards the cysteine peptide. The result does not allow for the non-classification or classification as skin sensitiser of the test substance and therefore further evaluation and/or data generation is required.
The activation of keratinocytes of the source substance (CAS 10023-48-0) was investigated in an ARE-Nrf2 Luciferase Test in the transgenic KeratinoSens™ cell line performed according to OECD guideline 442D and in compliance with GLP (reference 7.4.1-2). Cells were incubated with test substance concentrations of 0.98, 1.95, 3.91, 7.81, 15.63, 31.25, 61.5, 125, 250, 500, 1000, 2000 µM for 48 h at 37°C. After exposure cells were lysed and luciferase activity was assessed by luminescence measurement. The study was conducted in two independent experiments. In the first experiment a max luciferase activity (Imax) induction of 3.76 was determined at a test substance concentration of 2000 µM. The corresponding cell viability was 79.6%. In the second experiment a max luciferase activity (Imax) induction of 2.75 was determined at a test substance concentration of 2000 µM. The corresponding cell viability was 66.0%. Therefore in both experiments the luciferase activity induction was >1.5. The lowest tested concentration with a significant luciferase induction >1.5 (1.70) was found to be 500 µM. The corresponding cell viability was >70% (71.9%). The EC1.5 was 810.73 µM and 268.21 µM in Experiment 1 and 2, respectively. Under the conditions of the test, the test substance has a keratinocyte activating potential.
Conclusion
A weight of evidence approach was applied to the available data on skins sensitisation. The positive results of validated in chemico/in vitro tests covering 2 key events in the molecular initiating event leading to skin sensitisation. Therefore the test substance is considered to show a skin sensitising potential.
Respiratory sensitisation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
According to Article 13 of Regulation (EC) No. 1907/2006 "General Requirements for Generation of Information on Intrinsic Properties of substances", information on intrinsic properties of substances may be generated by means other than tests e.g. from information from structurally related substances (grouping or read-across), provided that conditions set out in Annex XI are met. Annex XI, "General rules for adaptation of this standard testing regime set out in Annexes VII to X” states that “substances whose physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity may be considered as a group, or ‘category’ of substances. This avoids the need to test every substance for every endpoint". Since the analogue concept is applied to 3-[(4-amino-2-methylpyrimidin-5-yl)methyl]-4-methyl-5-[2-(phosphonooxy)ethyl]-1,3-thiazol-3-ium chloride (CAS 532-40-1), data will be generated from information on reference source substance(s) to avoid unnecessary animal testing. Additionally, once the analogue read-across concept is applied, substances will be classified and labelled on this basis.
The available data on the relevant read-across substance 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-4-methyl-5-[2-(phosphonooxy)ethyl]-thiazolium (CAS 10023-48-0) meets the criteria for classification for Skin Sensitisation, Category 1 (H317). Therefore, applying the RA-A approach, the target substance 3-[(4-amino-2-methylpyrimidin-5-yl)methyl]-4-methyl-5-[2-(phosphonooxy)ethyl]-1,3-thiazol-3-ium chloride (CAS 532-40-1) is also considered to meet the criteria for classification for Skin Sensitisation, Category 1 (H317) according to Regulation (EC) No 1272/2008 (CLP).
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
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