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EC number: 603-689-1 | CAS number: 132961-05-8
Toxicological information
Genetic toxicity: in vitro
Currently viewing:
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:
- 2003-12-10 to 2004-01-09
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Remarks:
- Only three strains are tested. However, an expert statement is added in attachment and the field "any other remarks" to justify the fact that no further testing is necessary.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 004
- Report date:
- 2004
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- yes
- Remarks:
- only 3 strains of bacteria used, limited methodology
- GLP compliance:
- no
- Type of assay:
- bacterial reverse mutation assay
Test material
- Reference substance name:
- 3-(2-{4-[(Z)-(2,4-DIFLUOROPHENYL)(HYDROXYIMINO)METHYL]PIPERIDIN-1-YL}ETHYL)-2-METHYL-6,7,8,9-TETRAHYDRO-4H-PYRIDO[1,2-A]PYRIMIDIN-4-ONE
- EC Number:
- 603-689-1
- Cas Number:
- 132961-05-8
- Molecular formula:
- C23H28F2N4O2
- IUPAC Name:
- 3-(2-{4-[(Z)-(2,4-DIFLUOROPHENYL)(HYDROXYIMINO)METHYL]PIPERIDIN-1-YL}ETHYL)-2-METHYL-6,7,8,9-TETRAHYDRO-4H-PYRIDO[1,2-A]PYRIMIDIN-4-ONE
- Test material form:
- solid: particulate/powder
Constituent 1
- Specific details on test material used for the study:
- Name of test material: T 1624, ((Z)-3-[2-[4-[(2,4-difluorophenyl)(hydroxyimino)methyl]-1-piperidinyl]ethyl]-6,7,8,9-tetrahydro-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one)
- Physical state: white powder
- Analytical purity: ~100%
- Storage condition of test material: room temperature in the dark
- Other: date received: 2003-12-01
Method
- Target gene:
- histidine locus
Species / strain
- Species / strain / cell type:
- S. typhimurium, other: TA98, TA 100, and TA 102
- Details on mammalian cell type (if applicable):
- not applicable
- Additional strain / cell type characteristics:
- other:
- Metabolic activation:
- with and without
- Metabolic activation system:
- rat liver homogenate metabolising system (10% liver S9 in standard co-factors)
- Test concentrations with justification for top dose:
- 0.5, 1.5, 5, 15, 50, 150, 500, 1500, 5000 µg/plate
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: no data
Controlsopen allclose all
- Untreated negative controls:
- yes
- Remarks:
- untreated
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: N-ethyl-N'-nitro-N-nitrosoguanidine at 3 µg/plate on TA100
- Remarks:
- without S9
- Untreated negative controls:
- yes
- Remarks:
- untreated
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: mitomycin C at 0.5 µg/plate for TA102
- Remarks:
- without S9
- Untreated negative controls:
- yes
- Remarks:
- untreated
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: 4-Nitroquinoline-1-oxide at 0.2 µg/plate on TA98
- Remarks:
- without S9
- Untreated negative controls:
- yes
- Remarks:
- untreated
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: 2-aminoanthracene at 1 µg/plate for TA100
- Remarks:
- with S9
- Untreated negative controls:
- yes
- Remarks:
- untreated
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: 1,8-dihydroxyanthraquinone at 10 µg/plate for TA 102
- Remarks:
- with S9
- Untreated negative controls:
- yes
- Remarks:
- untreated
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: benzo(a)pyrene at 5 µg/plate on TA98
- Remarks:
- with S9
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: plate incorporation method
Measured aliquots (0.1 mL) of one of the bacterial cultures were dispensed into sets of test tubes followed by 2.0 mL of molten, trace histidine supplemented, top agar, 0.1 mL of the test material formulation, vehicle or positive control and either 0.5 mL of S9-mix or phosphate buffer. The contents of each test tube were mixed and equally distributed onto the surface of Vogel-Bonner Minimal agar plates (one tube per plate).
DURATION
- Exposure duration: 3 days
SELECTION AGENT: histidine
NUMBER OF REPLICATIONS: triplicate
DETERMINATION OF CYTOTOXICITY
- Method: growth of the bacterial background lawn
- Evaluation criteria:
- no data
- Statistics:
- no data
Results and discussion
Test results
- Species / strain:
- S. typhimurium, other: TA 98, TA 100, and TA 102
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
Precipitation: No test material precipitate was observed on the plates at any of the doses tested in either the presence or absence of S9-mix.
RANGE-FINDING/SCREENING STUDIES: no data
COMPARISON WITH HISTORICAL CONTROL DATA:
The vehicle control plates gave counts of revertant colonies within the normal range.
All of the positive control chemicals used in the test induced marked increases in the frequency of revertant colonies, both with and without metabolic activation. Thus, the sensitivity of the assay and the efficacy of the S9-mix were validated.
The S9-mix used in both experiments was shown to be sterile. Results for the negative controls (spontaneous mutation rates) were considered to be acceptable. These data are for concurrent untreated control plates performed on the same day as the Mutation Test.
ADDITIONAL INFORMATION ON CYTOTOXICITY:
The test material caused no visible reduction in the growth of the bacterial background lawn at any dose level. - Remarks on result:
- other: all strains/cell types tested
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results:
negative with and without metabolic activation
The test material was considered to be non-mutagenic under the conditions of this test.
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