Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 283-029-3 | CAS number: 84522-34-9
- 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
![](https://www.echa.europa.eu/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Genetic toxicity: in vitro
Administrative data
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- From 2017-06-16 to 2017-07-05
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 017
- Report date:
- 2017
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- other: ICH Harmonised Tripartite Guideline S2(R1). Guidance on Genotoxicity Testing and Data Interpretation for Pharmaceuticals Intended for Human use. CHMP/ICH/126642 ICH Consensus Guideline, Step 5 Guideline (Into Operation June 2012).
- Version / remarks:
- 2012
- Deviations:
- no
- GLP compliance:
- yes
- Type of assay:
- bacterial reverse mutation assay
Test material
- Reference substance name:
- Sodium 5-methyl-N-[2-(4-sulphamoylphenyl)ethyl]pyrazinecarboxamidate
- EC Number:
- 283-029-3
- EC Name:
- Sodium 5-methyl-N-[2-(4-sulphamoylphenyl)ethyl]pyrazinecarboxamidate
- Cas Number:
- 84522-34-9
- Molecular formula:
- C14H16N4NaO3S
- IUPAC Name:
- 5-methyl-N-[2-(4-sulfamoylphenyl)ethyl]pyrazine-2-carboxamide;sodium
Constituent 1
- Specific details on test material used for the study:
- Batch:16024R046
Purity: ≥95%
Method
- Target gene:
- histidine locus in several strains of Salmonella typhimurium and tryptophan locus of Escherichia coli (E. coli) strain
Species / strainopen allclose all
- 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:
- Rat liver metabolic activation system (S9 homogenate)
- Test concentrations with justification for top dose:
- -Dose-range Finding Test:
TA100 and the WP2uvrA, both with and without S9-mix: 1.7, 5.4, 17, 52, 164, 512, 1600 and 5000 μg/plate.
-First Experiment:
TA1535, TA1537 and TA98, both with and without S9-mix: 52, 164, 512, 1600 and 5000 μg/plate.
-Second Experiment:
TA1535, TA1537, TA98, TA100 and the WP2uvrA,both with and without S9-mix: 52, 164, 512, 1600 and 5000 μg/plate. - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: Milli-Q water
- Justification for choice of solvent/vehicle: Through solubility test based on visual assessment, the test item was suspended in Milli-Q water. The stock solution was treated with ultrasonic waves to obtain a homogeneous suspension.
Controlsopen allclose all
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- sodium azide
- Remarks:
- For TA1535, without metabolic activation.
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: ICR-191
- Remarks:
- For TA1537, without metabolic activation
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 2-nitrofluorene
- Remarks:
- For TA1537, TA98, without metabolic activation
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- methylmethanesulfonate
- Remarks:
- For TA100, without metabolic activation
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 4-nitroquinoline-N-oxide
- Remarks:
- For WP2uvrA, wthout metabolic activation
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: 2-aminoanthracene
- Remarks:
- For TA1535, TA1537, TA98, TA100 and WP2uvrA, with metabolic activation
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: Dose-Range Finding Test and Experiment 1: in agar (plate incorporation); Experiment 2: preincubation
- Cell density at seeding (if applicable): the optical density of 1.0 ± 0.1 at 700 nm (1E+09 cells/ml)
DURATION
- Preincubation period: 30 minutes for Experiment 2.
- Exposure duration: 48 ± 4 h both for dose range finding test, Experiment 1 and Experiment 2.
DETERMINATION OF CYTOTOXICITY
- Method: To determine the toxicity of the test item, the reduction of the bacterial background lawn, the increase in the size of the microcolonies and the reduction of the revertant colonies were observed - Evaluation criteria:
- A Salmonella typhimurium reverse mutation assay and/or Escherichia coli reverse mutation assay is considered acceptable if it meets the following criteria:
a) The vehicle control and positive control plates from each tester strain (with or without S9-mix) must exhibit a characteristic number of revertant colonies whencompared against relevant historical control data generated at the lab.
b) The selected dose-range should include a clearly toxic concentration or should exhibit limited solubility as demonstrated by the preliminary toxicity range-finding test or should extend to 5 mg/plate.
c) No more than 5% of the plates are lost through contamination or some other unforeseen event. If the results are considered invalid due to contamination, the xperiment will be repeated. - Statistics:
- A test item is considered negative (not mutagenic) in the test if:
a) The total number of revertants in tester strain TA100 or WP2uvrA is not greater than two (2) times the concurrent control, and the total number of revertants intester strains TA1535, TA1537 or TA98 is not greater than three (3) times the concurrent control.
b) The negative response should be reproducible in at least one follow up experiment. A test item is considered positive (mutagenic) in the test if:
a) The total number of revertants in tester strain TA100 or WP2uvrA is greater than two (2) times the concurrent control, or the total number of revertants in tester strains TA1535, TA1537 or TA98 is greater than three (3) times the concurrent control.
b) In case a repeat experiment is performed when a positive response is observed in one of the tester strains, the positive response should be reproducible in at least one follow up experiment.
Results and discussion
Test resultsopen allclose all
- Key result
- Species / strain:
- S. typhimurium TA 1535
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle 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
- Vehicle 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
- Vehicle 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
- Vehicle 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
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
Any other information on results incl. tables
Dose range finding test/first mutation experiment
-Precipitate: Precipitation of the test item on the plates was observed at the start of the incubation period at concentrations of 512μg/plate and upwards. At the end of the incubation period precipitation was observed at 1600 and 5000μg/plate in the tester strains TA100 and WP2uvrA. Whereas in the tester strains TA1535, TA1537 and TA98, precipitation was only observed at 5000μg/plate.
-Toxicity: No reduction of the bacterial background lawn and no biologically significant decrease in the number of revertants were observed.
-Mutagenicity: In the direct plate test, no increase in the number of revertants was observed upon treatment withtest itemunder all conditions tested.
Second Experiment
-Precipitate: Precipitation of the test item on the plates was observed at the start of the incubation period at concentrations of 164μg/plate and upwards and at 5000μg/plate at the end of the incubation period.
-Toxicity: Cytotoxicity, as evidenced by a decrease in the number of revertants, was observed in the tester strains TA1535, TA1537 and TA98 in the absence of S9-mix at the highest tested concentration.
In tester strain TA1537, a fluctuation in the number of revertant colonies below the laboratory historical control data range was observed at the dose level of 1600μg/plate in the presence of S9-mix. Since no dose-relationship was observed, this reduction is not considered to be caused by toxicity of the test item, rather it is more likely this reduction is caused by an incidental fluctuation in the number of revertant colonies.
-Mutagenicity: In the tester strains TA100 and WP2uvrA, a 2.4-fold increase in the number of revertant colonies compared to the solvent control was observed at 164 and 1600μg/plate, respectively, in the absence of S9-mix. The individual plate counts observed at these concentrations were: 536, 128 and 84 (TA100) and 27, 107 and 22 (WP2uvrA). The values of 536 and 107 were very different from the other two values obtained at 164 and 1600μg/plate, respectively. In addition, the values were not in range with all other number of revertant colonies at all tested concentrations. This observation of the outliers, so far beyond the historical control data range and the two other values of the triplicates, is a rare phenomenon and is probably linked to incidental fluctuations in the number of revertant colonies. The absence of any observed dose effect is confirming that the 536 and 107 values are outliers Therefore, the 2.4-fold increases observed are considered to be related to a specific outlier and to be not biologically relevant. In all other tester strains, the test item did not induce a significant dose-related increase in the number of revertant colonies.
Applicant's summary and conclusion
- Conclusions:
- Test item is not mutagenic in the Salmonella typhimurium reverse mutation assay and in the Escherichia coli reverse mutation assay.
- Executive summary:
The test was performed according to the most recent ICH guideline (2012). Strains of Salmonella typhimurium (S. typhimurium; TA98, TA100, TA1535, and TA1537), and Escherichia coli (E. coli) strain WP2uvrA were treated with the test material in the presence or absence of an exogenous mammalian metabolic activation system (S9). The test was performed in two independent experiments, at first a direct plate assay was performed and secondly a pre-incubation assay.
In the dose-range finding study, the test item was initially tested up to concentrations of 5000 μg/plate in the strains TA100 and WP2uvrAin the direct plate assay. The test item precipitated on the plates at dose levels of 1600 and 5000mg/plate. The bacterial background lawn was not reduced at any of the concentrations tested and no biologically relevant decrease in the number of revertants was observed.
In the first mutation experiment, the test item was tested up to concentrations of 5000 μg/plate in the strains TA1535, TA1537 and TA98. The test item precipitated on the plates at dose level of 5000mg/plate. The bacterial background lawn was not reduced at any of the concentrations tested and no biologically relevant decrease in the number of revertants was observed.
In the second mutation experiment, the test item was tested up to concentrations of 5000 μg/plate in the tester strains TA1535, TA1537, TA98, TA100 and WP2uvrAin the pre-incubation assay. The test item precipitated on the plates at dose level of 5000mg/plate. Cytotoxicity, as evidenced by a decrease in the number of revertants, was observed in the tester strains TA1535, TA1537 and TA98 in the absence of S9-mix at the highest tested concentration.
In this study, acceptable responses were obtained for the negative and strain-specific positive control items indicating that the test conditions were adequate and that the metabolic activation system functioned properly.
The test item did not induce a significant dose-related increase in the number of revertant (His+) colonies in each of the four tester strains (TA1535, TA1537, TA98 and TA100) and in the number of revertant (Trp+) colonies in tester strain WP2uvrA both in the absence and presence of S9-metabolic activation. These results were confirmed in a follow-up experiment.
In conclusion, based on the result-s of this study it is concluded that test item is not mutagenic in the Salmonella typhimuriumreverse mutation assay and in the Escherichia colireverse mutation assay.
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.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
![ECHA](/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/echa_logo.png)