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EC number: 205-230-7 | CAS number: 136-09-4
- 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
Key value for chemical safety assessment
Genetic toxicity in vitro
Description of key information
Genetic toxicity (mutagenicity) in bacterial cells (OECD 471, GLP): negative in TA 1535, TA 1537, TA 98, TA 100, and WP2 uvrA with and without metabolic activation
Link to relevant study records
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 21 Apr - 10 May 2017
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Version / remarks:
- adopted Jul 1997
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- Hessisches Ministerium für Umwelt, Klimaschutz, Landwirtschaft und Verbraucherschutz, Wiesbaden, Germany
- Type of assay:
- bacterial reverse mutation assay
- Target gene:
- his operon (for S. typhimurium strains)
trp operon (for E. coli strain) - Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Species / strain / cell type:
- E. coli WP2 uvr A
- Metabolic activation:
- with and without
- Metabolic activation system:
- cofactor supplemented post-mitochondrial fraction (S9 mix), prepared from the livers of rats treated with phenobarbital/β-naphthoflavone
- Test concentrations with justification for top dose:
- Pre-Experiment/Experiment I: 3, 10, 33, 100, 333, 1000, 2500 and 5000 μg/plate with and without metabolic activation
Experiment II: 33, 100, 333, 1000, 2500 and 5000 μg/plate with and without metabolic activation - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: deionized water
- Justification for choice of solvent/vehicle: The solvent was chosen because of its solubility properties and its relative nontoxicity to the bacteria. - Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- sodium azide
- methylmethanesulfonate
- other: 4-nitro-o-phenylene-diamine: -S9: 10 and 50 µg/plate for TA98 and TA1537, respectively; 2-aminoanthracene: +S9: 2.5 or 10 µg/plate for all strains
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in agar (plate incorporation; Experiment I); preincubation (Experiment II)
DURATION
- Preincubation period: 60 min
- Exposure duration: 48 h
NUMBER OF REPLICATIONS: Triplicates each in 2 independent experiments
DETERMINATION OF CYTOTOXICITY
- Method: reduction in the number of revertants
- OTHER: Each batch of S9 was routinely tested for its capability to activate the known mutagens benzo[a]pyrene and 2-aminoanthracene in the Ames test. - Evaluation criteria:
- A test item is considered as a mutagen if a biologically relevant increase in the number of revertants exceeding the threshold of twice (strains TA 98, TA 100, and WP2 uvrA) or thrice (strains TA 1535 and TA 1537) the colony count of the corresponding solvent control is observed.
A dose dependent increase is considered biologically relevant if the threshold is exceeded at more than one concentration.
An increase exceeding the threshold at only one concentration is judged as biologically relevant if reproduced in an independent second experiment.
A dose dependent increase in the number of revertant colonies below the threshold is regarded as an indication of a mutagenic potential if reproduced in an independent second experiment. However, whenever the colony counts remain within the historical range of negative and solvent controls such an increase is not considered biologically relevant. - Statistics:
- According to the OECD guideline 471, a statistical analysis of the data is not mandatory.
- Key result
- Species / strain:
- S. typhimurium TA 1535
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 1537
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 98
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- E. coli WP2 uvr A
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: No precipitation of the test item occurred up to and including the highest dose.
RANGE-FINDING/SCREENING STUDIES: The pre-experiment served as Experiment I, as all strains were tested in the pre-experiment and the results were valid.
HISTORICAL CONTROL DATA (with ranges, means and standard deviation and confidence interval (e.g. 95%)
- Positive historical control data: The positive control data fell within the range of the historical control data (please refer to Table 3 under "any other information on results incl. tables").
- Negative (solvent/vehicle) historical control data: The negative control data (solvent and untreated) fell within the range of the historical control data (please refer to Table 3 under "any other information on results incl. tables"). - Conclusions:
- In conclusion, it can be stated that during the described mutagenicity test and under the experimental conditions reported, the source substance did not induce gene mutations by base pair changes or frameshifts in the genome of the strains used.
Reference
Table 1: Summary of Experiment I (plate incorporation)
Metabolic Activation | Test Group | Dose Level per group and per plate | Revertant Colony Counts (Mean of 3 plates ±SD) | ||||
TA 1535 | TA 1537 | TA 98 | TA 100 | WP2uvrA | |||
Without Activation | Deionised water | 12 ± 3 | 8 ± 3 | 30 ± 10 | 195 ± 8 | 40 ± 3 | |
Untreated | 9 ± 2 | 9 ± 4 | 24 ± 7 | 195 ± 7 | 32 ± 8 | ||
Test substance | 3 µg | 10 ± 3 | 10 ± 4 | 23 ± 3 | 191 ± 9 | 33 ± 6 | |
10 µg | 13 ± 6 | 9 ± 2 | 25 ± 8 | 190 ± 22 | 39 ± 4 | ||
33 µg | 10 ± 3 | 11 ± 5 | 27 ± 3 | 188 ± 15 | 44 ± 5 | ||
100 µg | 13 ± 4 | 7 ± 3 | 29 ± 10 | 191 ± 17 | 38 ± 4 | ||
333 µg | 12 ± 4 | 7 ± 2 | 24 ± 5 | 198 ± 23 | 40 ± 3 | ||
1000 µg | 8 ± 3 | 9 ± 3 | 31 ± 6 | 209 ± 16 | 43 ± 5 | ||
2500 µg | 10 ± 3 | 10 ± 5 | 30 ± 5 | 196 ± 14 | 44 ± 4 | ||
5000 µg | 11 ± 3 | 9 ± 2 | 30 ± 6 | 182 ± 16 | 43 ± 7 | ||
NaN3 | 10 µg | 1327 ± 26 | 2265 ± 83 | ||||
4-NOPD | 10 µg | 354 ± 18 | |||||
4-NOPD | 50 µg | 69 ± 11 | |||||
MMS | 2.0 µL | 922 ± 16 | |||||
With Activation | Deionised water | 12 ± 3 | 17 ± 4 | 33 ± 3 | 165 ± 12 | 43 ± 5 | |
Untreated | 12 ± 4 | 13 ± 2 | 46 ± 4 | 163 ± 4 | 52 ± 5 | ||
Test substance | 3 µg | 15 ± 2 | 16 ± 2 | 37 ± 6 | 166 ± 26 | 47 ± 3 | |
10 µg | 14 ± 3 | 18 ± 3 | 43 ± 5 | 171 ± 29 | 50 ± 4 | ||
33 µg | 11 ± 5 | 13 ± 3 | 32 ± 6 | 189 ± 10 | 44 ± 3 | ||
100 µg | 14 ± 5 | 12 ± 3 | 46 ± 4 | 175 ± 4 | 47 ± 10 | ||
333 µg | 12 ± 3 | 13 ± 4 | 42 ± 4 | 154 ± 16 | 39 ± 9 | ||
1000 µg | 11 ± 4 | 11 ± 1 | 37 ± 6 | 163 ± 8 | 45 ± 3 | ||
2500 µg | 8 ± 1 | 9 ± 3 | 29 ± 8 | 168 ± 11 | 50 ± 4 | ||
5000 µg | 11 ± 1 | 10 ± 5 | 33 ± 3 | 175 ± 11 | 50 ± 3 | ||
2-AA | 2.5 µg | 475 ± 27 | 169 ± 28 | 3890 ± 419 | 4361 ± 172 | ||
2-AA | 10.0 µg | 358 ± 35 |
NaN3 = sodium azide
4-NOPD = 4-nitro-o-phenylene-diamine
MMS = methyl methanesulfonate
2-AA = 2-aminoanthracene
Table 2: Summary of Experiment II (pre-incubation)
Metabolic Activation | Test Group | Dose Level per group and per plate | Revertant Colony Counts (Mean of 3 plates ±SD) | ||||
TA 1535 | TA 1537 | TA 98 | TA 100 | WP2uvrA | |||
Without Activation | Deionised water | 11 ± 3 | 10 ± 1 | 25 ± 5 | 173 ± 12 | 34 ± 3 | |
Untreated | 11 ± 2 | 9 ± 3 | 25 ± 4 | 179 ± 8 | 39 ± 7 | ||
Test substance | 33 µg | 10 ± 1 | 10 ± 5 | 27 ± 6 | 190 ± 6 | 37 ± 5 | |
100 µg | 15 ± 4 | 8 ± 2 | 23 ± 8 | 182 ± 28 | 33 ± 3 | ||
333 µg | 14 ± 6 | 7 ± 3 | 26 ± 6 | 196 ± 23 | 46 ± 1 | ||
1000 µg | 14 ± 2 | 12 ± 3 | 25 ± 3 | 172 ± 14 | 35 ± 7 | ||
2500 µg | 13 ± 2 | 7 ± 0 | 33 ± 6 | 162 ± 19 | 35 ± 1 | ||
5000 µg | 8 ± 2 | 9 ± 1 | 28 ± 8 | 184 ± 7 | 47 ± 3 | ||
NaN3 | 10 µg | 1095 ± 33 | 1643 ± 143 | ||||
4-NOPD | 10 µg | 349 ± 5 | |||||
4-NOPD | 50 µg | 89 ± 17 | |||||
MMS | 2.0 µL | 797 ± 128 | |||||
With Activation | Deionised water | 10 ± 1 | 13 ± 3 | 39 ± 12 | 179 ± 13 | 55 ± 12 | |
Untreated | 13 ± 6 | 17 ± 5 | 43 ± 10 | 137 ± 18 | 47 ± 11 | ||
Test substance | 33 µg | 12 ± 2 | 14 ± 5 | 42 ± 13 | 150 ± 13 | 51 ± 5 | |
100 µg | 11 ± 5 | 11 ± 5 | 35 ± 6 | 163 ± 13 | 54 ± 5 | ||
333 µg | 9 ± 1 | 15 ± 3 | 29 ± 4 | 172 ± 6 | 55 ± 12 | ||
1000 µg | 16 ± 8 | 12 ± 4 | 32 ± 6 | 144 ± 13 | 55 ± 7 | ||
2500 µg | 15 ± 4 | 15 ± 1 | 31 ± 6 | 157 ± 18 | 55 ± 6 | ||
5000 µg | 15 ± 6 | 14 ± 5 | 34 ± 4 | 141 ± 11 | 40 ± 10 | ||
2-AA | 2.5 µg | 301 ± 5 | 126 ± 10 | 2920 ± 93 | 1842 ± 65 | ||
2-AA | 10.0 µg | 329 ± 58 |
NaN3 = sodium azide
4-NOPD = 4-nitro-o-phenylene-diamine
MMS = methyl methanesulfonate
2-AA = 2-aminoanthracene
Table 3: Historical Data
Strain | without S9 mix | with S9 mix | |||||||
Mean | SD | Min | Max | Mean | SD | Min | Max | ||
TA 1535 | Solvent control | 12 | 2.5 | 6 | 25 | 12 | 2.5 | 7 | 26 |
Untreated control | 12 | 3.1 | 6 | 28 | 12 | 2.9 | 7 | 26 | |
Positive control | 1130 | 143.1 | 334 | 1816 | 388 | 58.2 | 176 | 668 | |
TA1537 | Solvent control | 10 | 2.2 | 6 | 19 | 13 | 3.5 | 7 | 30 |
Untreated control | 11 | 2.7 | 5 | 21 | 14 | 4.0 | 7 | 31 | |
Positive control | 82 | 12.7 | 43 | 157 | 191 | 60.8 | 83 | 434 | |
TA 98 | Solvent control | 25 | 4.4 | 13 | 43 | 34 | 6.2 | 15 | 58 |
Untreated control | 27 | 4.9 | 12 | 43 | 37 | 6.5 | 11 | 57 | |
Positive control | 378 | 73.7 | 211 | 627 | 3949 | 771.8 | 360 | 6586 | |
TA 100 | Solvent control | 156 | 26.0 | 78 | 209 | 148 | 32.3 | 73 | 208 |
Untreated control | 176 | 23.6 | 79 | 217 | 172 | 25.4 | 85 | 218 | |
Positive control | 1966 | 293.2 | 498 | 2767 | 3798 | 830.4 | 536 | 6076 | |
WP2uvrA | Solvent control | 41 | 5.6 | 27 | 63 | 50 | 6.8 | 28 | 72 |
Untreated control | 42 | 5.8 | 30 | 63 | 52 | 6.8 | 36 | 88 | |
Positive control | 798 | 362.7 | 319 | 4732 | 378 | 112.6 | 167 | 1265 |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Genetic toxicity in bacteria
Mutagenicity of 2-[3-[(4-amino-2-methylpyrimidin-5-yl)methyl]-4-methyl-1,3-thiazoniol-5-yl]ethyl dihydrogen diphosphate tetrahydrate (CAS 68684-55-9) was tested in a bacterial reverse mutation assay performed according to OECD guideline 471 and under GLP conditions (reference 7.6.1-1). The assay was performed with a standard battery of Salmonella typhimurium tester strains including TA 1535, TA 1537, TA 98 and TA 100, and Escherichia coli WP2uvrA, with and without metabolic activation. The highest concentration of 5000 µg/plate was tested in all bacterial strains. 2-[3-[(4-amino-2-methylpyrimidin-5-yl)methyl]-4-methyl-1,3-thiazoniol-5-yl]ethyl dihydrogen diphosphate (CAS 136-09-4) did not exhibit mutagenic properties in the absence or presence of metabolic activation. Toxicity indicated by reduced number of revertants was not observed in any tester strains in the applied concentration range (from 3 to 5000 µg/plate using the plate incorporation method and from 33 to 5000 µg/plate using the pre-incubation method). The Positive control substances induced a distinct increase in the number of revertants in all strains with and without metabolic activation thereby showing the validity of the assay. The solvent control was also shown to be valid.
Based on the results of the conducted study, 2-[3-[(4-amino-2-methylpyrimidin-5-yl)methyl]-4-methyl-1,3-thiazoniol-5-yl]ethyl dihydrogen diphosphate tetrahydrate (CAS 68684-55-9) is not considered to exhibit mutagenic properties in bacterial cells.
Furthermore, data on cytogenicity and mutagenicity in mammalian cells was available for the source substance, 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-4-methyl-5-[2-(phosphonooxy)ethyl]-thiazolium (CAS 10023-48-0), which were not included in the dossier, since according to the data requirements specified in Annex VII of Regulation (EC) No 1907/2006, data on cytogenicity and mutagenicity in mammalian cells is not required for the tonnage band 1 - 10 t/a. The available data with 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-4-methyl-5-[2-(phosphonooxy)ethyl]-thiazolium (CAS 10023-48-0) revealed no mutagenic and clastogenic properties in V79 cells and in cultured peripheral human lymphocytes, respectively (reference 7.6.1-2 and 7.6.1-3, registration dossier 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-4-methyl-5-[2-(phosphonooxy)ethyl]-thiazolium).
Justification for classification or non-classification
Based on the available data on genetic toxicity, there is no indication that 2-[3-[(4-amino-2-methylpyrimidin-5-yl)methyl]-4-methyl-1,3-thiazoniol-5-yl]ethyl dihydrogen diphosphate induces genetic toxicity in bacteria.
Moreover, the available data with Thiazolium, 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-4-methyl-5-[2-(phosphonooxy)ethyl]- (CAS 10023-48-0) revealed no mutagenic and clastogenic properties in V79 cells and in cultured peripheral human lymphocytes, respectively. Based on the analogue approach, the same results were expected for the target substance. The available data do not meet the classification criteria according to Regulation (EC) No. 1272/2008, and are therefore conclusive but not sufficient for classification.
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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