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EC number: 928-729-8 | CAS number: 188416-20-8
- 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
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- From 28 July 1998 to 3 August 1998
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Study run to a method comparable with current guidelines and to GLP.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 998
- Report date:
- 1998
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:
- 3-(6-chloro-5-fluoropyrimidin-4-yl)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol hydrochloride
- EC Number:
- 928-729-8
- Cas Number:
- 188416-20-8
- Molecular formula:
- C16H13ClF3N5O.HCl
- IUPAC Name:
- 3-(6-chloro-5-fluoropyrimidin-4-yl)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol hydrochloride
- Details on test material:
- - Analytical purity: 90%
- Lot/batch No.: 5ABJ002
Constituent 1
Method
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 pKM 101
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9 mix
- Test concentrations with justification for top dose:
- 5, 15, 50, 150, 500, 1500, 5000 μg/plate
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: The solubility of the substance was assessed at 50 mg active ingredient/ml in water and DMSO. At this concentration the test substance was insoluble in water but dissolved in DMSO.
Controlsopen allclose all
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- Positive controls:
- yes
- Positive control substance:
- other: N-ethyl-N'-nitro-N-nitrosoguanidine
- Remarks:
- In the absence of S9 mix for strain TA1535, TA100 and E. coli WP2.
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- Positive controls:
- yes
- Positive control substance:
- 9-aminoacridine
- Remarks:
- In the absence of S9 mix for strain TA1537.
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- Positive controls:
- yes
- Positive control substance:
- 2-nitrofluorene
- Remarks:
- In the absence of S9 mix for TA98.
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- Positive controls:
- yes
- Positive control substance:
- other: 2-Aminoanthracene
- Remarks:
- In the presence of S9 mix for strain TA1535 and E. coli WP2.
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- Positive controls:
- yes
- Positive control substance:
- benzo(a)pyrene
- Remarks:
- In the presence of S9 mix for strain TA1537, TA98 and TA100.
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in agar (plate incorporation)
NUMBER OF REPLICATIONS: 3
Two independent mutation tests were performed in the presence and absence of S9 mix. The first was a standard plate incorporation assay, the second involved a pre-incubation stage.
Dose levels of up to 5000 μg/plate were tested in the mutation tests. Other dose levels were used were series of ca half-log10 concentration. Six dose levels were used in the second test. - Evaluation criteria:
- The mean number of revertant colonies for all treatment groups is compared with those obtained for the solvent control groups. The mutagenic activity of a test substance is applying following criteria:
a) If treatment with a test substance produces an increase in revertant colony numbers of at twice the concurrent solvent controls, with some evidence of a positive dose-relationship, in two separate experiments, with any bacterial strain either in the presence or absence of S9 mix, it is considered to show evidence of mutagenic activity in this test system. No statistical analysisi is performed.
b) If treatment with a test substance does not produce reproducible increases of at least 1.5 times the concurrent solvent controls, in either mutation test, it is considered to show no evidence of mutagenic activity in this test system. No statistical analysis is performed.
c) If the results obtained fail to satisfy the criteria for a clear "positive " or "negative" response given in paragraphs(a) and (b), additional testing may be performed in order to resolve the issue of the test substance's mutagenic activity in this test system. Modifications to the experimental method will usually be considered, such as the use of a narrower dose range and different levels of S9 in the mix. Should an increase in revertant colony numbers then be observed which satisfies paragraph(a) the substance is consider to show evidence of mutagenic activity in this test system.No statistical analysis is performed.
Results and discussion
Test resultsopen allclose all
- Species / strain:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- 5000 μg/plate in the first mutation test. 5000 μg/plate and 1500μg/plate in the second test .
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Species / strain:
- E. coli WP2 uvr A pKM 101
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- 5000 μg/plate in the first mutation test. 5000 μg/plate and 1500μg/plate in the second test .
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- Toxicity:
In the first test, toxicity was observed towards all of the tester strains at 5000 μg/plate
In the second test, toxicity was observed towards all of the tester strains at 5000 and 1500μg/plate.
No substantial increases in revertant colony numbers of any of the tester strains were observed following treat with UK-103,446-01 at any dose level, in the presence or absence of S9 mix, in either mutation test.
The concurrent positive controls demonstrated the sensitivity of the assay and the metabolising activity of the liver preparations.
The mean revertant colony counts for the solvent controls were within the historical range. The mean revertant colony count for TA100 in the absence of S9 mix in the second test was just below the lower end of the current two year range. However, it was within the overall range for this laboratory. - Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information):
negative
It is concluded that, when tested in DMSO, the substance shows no evidence of mutagenic activity in this bacterial system.
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