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EC number: 433-460-1 | CAS number: 210880-92-5
- 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
Genetic toxicity: in vitro
Administrative data
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 21 May - 16 Jun 1997
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study with acceptable restrictions
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 999
- Report date:
- 1999
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Version / remarks:
- adopted 2020
- Deviations:
- yes
- Remarks:
- 2-AA was used as the sole indicator of the efficacy of the S9 mix
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Version / remarks:
- adopted 1983
- Deviations:
- no
- GLP compliance:
- yes
- Type of assay:
- bacterial reverse mutation assay
Test material
- Reference substance name:
- -
- EC Number:
- 433-460-1
- EC Name:
- -
- Cas Number:
- 210880-92-5
- Molecular formula:
- C6H8ClN5O2S
- IUPAC Name:
- (E)-N'-[(2-chloro-1,3-thiazol-5-yl)methyl]-N-methyl-N''-nitroguanidine
Constituent 1
Method
- Target gene:
- his operon
Species / strain
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102
- Cytokinesis block (if used):
- None
- Metabolic activation:
- with and without
- Metabolic activation system:
- Cofactor supplemented post-mitochondrial fraction (S9 mix), prepared from the livers of Sprague Dawley rats which received a single intraperitoneal injection of 500 mg/kg bw Aroclor 1254 five days before sacrifice.
The protein concentration of the S9 preparation was 28.4 mg/mL.
S9 fraction was thawed and mixed with S9 cofactor solution, to result in a final concentration of approx. 10 % v/v in the S9 mix. 70 mL cofactor solution are composed as follows: 162.6 mg MgCI2 x 6 H2O, 246.0 mg KCI, 179.1 Glucose-6-phosphate disodium salt, 315.0 mg NADP disodium salt in 100 mM phosphate buffer (pH 7.4).
The final concentration of S9 in the culture was 18.5% (S9 mix) and 1.8% (S9 fraction).
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. - Test concentrations with justification for top dose:
- - Preliminary experiment I (plate incorporation): 16, 50, 158, 500, 1581, 5000 µg/plate
No bacteriotoxic or mutagenic effects were found up to the highest concentration. Therefore, the concentrations were used in the second experiment as well. 5000 µg/plate is recommended as the highest test concentration by the guideline.
- Experiment II (preincubation): 16, 50, 158, 500, 1581, 5000 µg/tube (all strains)
- additional test (preincubation): 16, 32, 48, 64, 80, 96, 110 µg/tube (only TA 102 with S9 mix)
The additional test was neccessary because the revertant count for TA 102 with S9 at 50 µg/tube was ca. 100 colonies higher than control colony count. - Vehicle / solvent:
- - Vehicle/solvent used: Dimethyl sulfoxide (DMSO)
- Justification for choice of solvent/vehicle: The solvent was chosen because of its solubility properties and its relative nontoxicity to the bacteria.
- Justification for percentage of solvent in the final culture medium: not reported
Controls
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- sodium azide
- cumene hydroperoxide
- other: Nitrofurantoin (NF), TA 100, 0.2 µg/plate, -S9 4-Nitro-1,2-phenylene diamine (4-NPDA), TA 1537, 10 µg/plate, and TA 98, 0.5 µg/plate, -S9 2-Aminoanthracene (2-AA), all strains, 3 µg/plate, +S9
- Details on test system and experimental conditions:
- NUMBER OF REPLICATIONS:
- Number of cultures per concentration: triplicate
- Number of independent experiments: 2 (+1 additional test)
METHOD OF TREATMENT/ EXPOSURE:
- Test substance added in agar for plate incorporation test (experiment I) and in bacterial suspension for pre-incubation test (experiment II and additional test)
TREATMENT AND HARVEST SCHEDULE:
- Preincubation period: 20 min
- Exposure duration/duration of treatment: 48 h
METHODS FOR MEASUREMENT OF CYTOTOXICITY
- Method: clearing or diminution of the background lawn, reduction in revertant colonies, reduction in titer - Rationale for test conditions:
- according to OECD guideline
- Evaluation criteria:
- The substance was considered mutagenic when a reproducible and dose-related increase in mutant count was observed in any strain with and/or without metabolic activation. For TA 1535, TA 100 and TA 98 this increase should be about twice that of negative controls, whereas for TA 1537, at least a threefold increase should be reached. For TA 102 an increase of about 150 mutants should be reached. If results are questionable, investigation should continue.
- Statistics:
- Mean values and standard deviation were calculated. According to the OECD guideline 471, a statistical analysis of the data is not mandatory.
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
- Untreated negative controls validity:
- not examined
- True negative controls validity:
- not examined
- 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
- Untreated negative controls validity:
- not examined
- True negative controls validity:
- not examined
- 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
- Untreated negative controls validity:
- not examined
- True negative controls validity:
- not examined
- 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
- Untreated negative controls validity:
- not examined
- True negative controls validity:
- not examined
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 102
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- True negative controls validity:
- not examined
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: No precipitation of the test item was reported up to the highest investigated dose in both experiments.
RANGE-FINDING/SCREENING STUDIES:
In the preliminary plate incorporation experiment I, the concentration range of the test item was 16 - 5000 µg/plate. No bacterial mutagenicity could be evidenced for all tested S. typhimurium strains, both with and without S9 mix. No cytotoxicity was noticed at concentrations up to an including 5000 µg/plate
STUDY RESULTS
Bacteriotoxic effects were not observed up to and including 1581 µg/tube, titer reduction was seen occasionally at 5000 µg/tube. Since cytotoxicity was rather slight and only reported for some strains, assessment was not impaired.
No substantial increase in revertant colony numbers for any of the five strains investigated was observed following treatment with the test item at any concentration level, neither in the presence nor absence of metabolic activation. In experiment II, TA 102 at 50 µg/tube with metabolic activation had about 100 revertant colonies more than the controls. This was not dose-dependent and the result could not be confirmed in the additional experiment with concentrations between 16 and 110 µg/tube, so that the finding is considered incidental. There was also no tendency of higher mutation rates with increasing concentrations in the range below the generally acknowledged border of biological relevance. For summarized results of both experiment I and experiment II, please refer to Attachment 1 in the attached background material.
HISTORICAL CONTROL DATA
The number of revertant colonies observed for the solvent and positive controls were within the range of the laboratory's historical control data. For details, please refer to Attachment 2 in the attached background material.
Applicant's summary and conclusion
- Conclusions:
- The study was performed according to OECD guideline 471 and compliant with GLP. Under the conditions of the assay, the test item was not mutagenic in S. typhimurium strains TA 98, TA 100, TA 1535, TA 1537 and in TA 102 with and without metabolic activation.
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