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EC number: 925-395-5 | CAS number: 314771-88-5
- 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
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- January 14-16, 2003
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 003
- Report date:
- 2003
Materials and methods
Test guideline
- Guideline:
- other: AMES II
- Deviations:
- not specified
- Principles of method if other than guideline:
- The chemical intermediate BIBW 2992/CDBA 0573 BS was investigated in a modified bacterial mutagenicity test as described by Ames et al. (1975). This high throughput microtitre-based version, called Ames II, is based on the same genetic principle (base-pair substitution and frameshift mutations in the his operon of S. typhimurium) combined with the fluctuation method (Gee et al., 1998).
- GLP compliance:
- no
- Type of assay:
- bacterial reverse mutation assay
Test material
- Reference substance name:
- N-(3-chloro-4-fluorophenyl)-6-nitro-7-[(3S)-oxolan-3-yloxy]quinazolin-4-amine
- EC Number:
- 925-395-5
- Cas Number:
- 314771-88-5
- Molecular formula:
- C18 H14 Cl F N4 O4
- IUPAC Name:
- N-(3-chloro-4-fluorophenyl)-6-nitro-7-[(3S)-oxolan-3-yloxy]quinazolin-4-amine
Constituent 1
Method
Species / strainopen allclose all
- Species / strain / cell type:
- other: S. typhimurium TA Mix (TA 7001, TA 7002, TA 7003, TA 7004, TA 7005, TA 7006)
- Additional strain / cell type characteristics:
- not specified
- Species / strain / cell type:
- S. typhimurium TA 98
- Additional strain / cell type characteristics:
- not specified
- Cytokinesis block (if used):
- none
- Metabolic activation:
- with and without
- Metabolic activation system:
- hepatic microsomal enzymes
- Test concentrations with justification for top dose:
- the test article was tested over a concentration range from 1 to
5000 µg/ml medium with and without microsomal rat liver enzymes. - Vehicle / solvent:
- DMSO
Controls
- Negative solvent / vehicle controls:
- yes
- Positive controls:
- yes
- Positive control substance:
- 4-nitroquinoline-N-oxide
- 2-nitrofluorene
- other: 2-aminoanthracene
- Details on test system and experimental conditions:
- The Ames II test was conducted with and without addition of microsomal liver enzymes from
rats (Aroclor 1254-induced). Following base-pair and frameshift-specific tester strains were
used: S. typhimurium TA Mix (TA 7001, TA 7002, TA 7003, TA 7004, TA 7005 and TA
7006) and TA 98, respectively. The Salmonella strains were described by Gee et al. (1998).
The assay was performed according to the instruction manual for the Ames II (Xenometrix,
Boulder/USA). 0.01 ml of the vehicle, test article or positive control were incubated with 0.24
ml bacterial overnight culture (ca 107/ml)/exposure medium in 24-well plates for 90 min at
37°C and 250 rpm. With metabolic activation 0.2 ml strain mixture and 0.04 ml S9-mix
(30%) were used.
After 90 min the exposed cultures were diluted with pH indicator medium lacking histidine
and aliquoted into 48 wells of a 384-well plate (3 replicates) using a 8-channel pipettor. The
plates were incubated for 48 hrs at 37°C.
To confirm the sensitivity of the tester strains and the metabolic capacity of the S9 fractions,
known diagnostic mutagens were used (2-nitrofluorene/2-NF, 4-nitroquinoline-N-oxide/4-
NQO and 2-aminoanthracene/2-AA, respectively). - Rationale for test conditions:
- The experiment is regarded valid, if the vehicle control showed the normal spontaneous revertant
frequency and the diagnostic mutagens caused the expected increase in the mutation rate. - Evaluation criteria:
- The individual test chemicals were classified according to the following criteria:
Negative: ≤8/48 wells Equivocal: 9-12/48 wells Positive: ≥13/48 wells
Historical control range: 0-7/48 wells in ca 170 experiments (1999-2002)
A concentration-dependent increase of revertant wells (mean of triplicate) over the vehicle
control is indicative for a genotoxic activity of the test article. - Statistics:
- The pH indicator bromocresol purple turns the colour of the cultures from blue to yellow as
the pH drops due to the accumulation of catabolites from the metabolic activity of revertant
cells. The number of positive wells (yellow) out of a total of 48 wells is an indication of the
frequency of reversion per replicate per dose and was compared to the number of spontaneous
revertant wells of the solvent control. Each test point contains 48 wells of a 384-well plate. In
each 48-well section, the wells were scored for the number of revertant wells (yellow) and the
mean value of the triplicates was calculated.
Results and discussion
Test resultsopen allclose all
- Species / strain:
- S. typhimurium TA 98
- Metabolic activation:
- without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- 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
- 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:
- other: S. typhimurium TA Mix (TA 7001, TA 7002, TA 7003, TA 7004, TA 7005 and TA 7006)
- Metabolic activation:
- with
- 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:
- other: S. typhimurium TA Mix (TA 7001, TA 7002, TA 7003, TA 7004, TA 7005 and TA 7006)
- Metabolic activation:
- without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- 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:
- Based on the described results it is concluded, that BIBW 2992/CDBA 0573 BS, when
tested up to bacteriotoxic concentrations, caused neither base-pair substitution nor
frameshift mutations in bacteria. No evidence of genotoxic activity was observed in a
series of S. typhimurium tester strains (TA Mix and TA 98) in the absence and presence
of metabolic activation. The test compound is, therefore, classified as "Ames II negative".
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