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EC number: 821-117-0 | CAS number: 1082745-49-0
- 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:
- key study
- Study period:
- January 14-22, 2010
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 010
- Report date:
- 2010
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- no
- GLP compliance:
- yes
- Type of assay:
- bacterial reverse mutation assay
Test material
- Reference substance name:
- 5-Amino-1-(tetrahydro-pyran-4-yl)-1H-pyrazole-4-carbonitrile
- EC Number:
- 821-117-0
- Cas Number:
- 1082745-49-0
- Molecular formula:
- C9H12N4O
- IUPAC Name:
- 5-Amino-1-(tetrahydro-pyran-4-yl)-1H-pyrazole-4-carbonitrile
- Test material form:
- solid: particulate/powder
Constituent 1
Method
Species / strain
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102
- Additional strain / cell type characteristics:
- not specified
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9 mix
- Test concentrations with justification for top dose:
- with & without metabolic activation: CD 11404 BS concentrations used are 100, 300, 1000, 3000 & 5000 μg/plate
A maximum concentration of 5000 μg/plate should be investigated according to relevant
guidelines. In a non-GLP solubility pretest no precipitation was observed at the highest
concentration of 5000 μg/plate. Therefore, 5000 μg/plate was investigated as the highest
concentration. - Vehicle / solvent:
- dimethylsulfoxide (DMSO)
Controls
- Negative solvent / vehicle controls:
- yes
- Positive controls:
- yes
- Positive control substance:
- 9-aminoacridine
- 2-nitrofluorene
- sodium azide
- mitomycin C
- other: 2-Aminoanthracene
- Details on test system and experimental conditions:
- 0.1 mL of the vehicle, test substance or positive control solution, 0.1 mL of a bacterial
shaking culture (6 h, exponential phase) and 0.5 mL phosphate buffer or S9 mix were added
to 2 mL soft agar. After vortexing, these mixtures were overlaid immediately onto minimal
medium plates in triplicate (n = 6 for the negative control).
The test was performed in the presence and absence of rat liver microsomal enzymes
(S9 mix).
No repeat experiment using preincubation was performed because the result was clearly
negative.
Revertant his+ colonies were counted using an ARTEK Counter 880 (non-computerized) after
incubation at 37°C for 2 days (TA 102: 3 days) and the values were listed manually in a word
document. For all replicate platings, the mean number of revertants per test concentration was
calculated. The condition of the background bacterial lawn (residual growth on minimum
histidine) was evaluated macroscopically for evidence of bacteriotoxicity induced by the test
substance. If extreme thinning or complete lack of the microcolony lawn compared to the
negative, vehicle control plates was observed, no revertants were counted. Evidence of test
substance precipitates in the agar overlay was recorded. - Rationale for test conditions:
- The assay was considered valid since the following criteria were met:
All tester strains exhibit a characteristic number of spontaneous revertants per plate. The
addition of the metabolic activation system did not alter significantly the number of
spontaneous revertants per plate and therefore the numbers were combined and given as
ranges (see below). These ranges were taken from about 168 experiments (not filed in the raw
data) conducted in our laboratory.
TA 1535: 5 - 22
TA 1537: 3 - 29
TA 98: 16 - 68
TA 100: 57 - 197
TA 102: 252 - 531
In addition, the reference mutagens induced a distinct increase in the number of revertants,
reflecting also the activity of the metabolizing system. - Evaluation criteria:
- A reproducible, concentration-dependent increase in the number of revertants of at least one
tester strain over the vehicle control value and/or outside the historical control range is
indicative of genotoxic activity. - Statistics:
- No recognizable incidents that might have affected the quality or integrity of the
experimental outcome were noted during the study. The experimental findings are
summarized in Tables 8: 1 (summary) and individual values are given in Tables 8: 2 to 8: 6.
SOLUBILITY AND CYTOTOXICITY
CD 11404 BS did not precipitate and no bacteriotoxicity was observed up to the maximum
recommended concentration of 5000 μg/plate.
MUTAGENICITY
The OD600 of the individual overnight bacterial cultures varied between 2.2 and 2.8 (raw
data). These values correspond to a bacterial titer of ca. 100 millions/0.1 mL.
CD 11404 BS did not increase the number of revertant colonies in different tester strains of
S. typhimurium compared to the negative control when tested up to maximum recommended
concentration. Furthermore, metabolic activation by S9 mix did not alter the mutation
frequency of these bacterial strains.
The validity of this study is given since the vehicle control plates showed spontaneous
revertants in different tester strains of S. typhimurium at frequencies similar to those
described in the literature and within the historical control range experienced in our
laboratory.
The mutagens NaN3, 9-AA, 2-NF, MMC and 2-AA showed the expected strain specific
responses with and without metabolic activation.
Results and discussion
Test resultsopen allclose all
- 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
- 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
- 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
- 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
- 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
Applicant's summary and conclusion
- Conclusions:
- CD 11404 BS caused neither base-pair substitutions nor frameshift mutations in different
strains of S. typhimurium in the presence and absence of metabolic activation when tested up
to the maximum recommended concentration of 5000 μg/plate. Based on these results it was
concluded, that CD 11404 BS is "Ames negative".
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