1-(6-FLUORO-3,4-DIHYDRO-2H-CHROMEN-2-YL)ETHANONE

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:

2005-01-06 to 2005-02-07

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 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:

2005

Report date:

2005

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

: 1) only three tester strains used 2) no data on the purity of the test substance was provided, and 3) limited information on methodology

GLP compliance:

no

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

1-(6-fluoro-3,4-dihydro-2H-1-benzopyran-2-yl)ethan-1-one

Cas Number:

620176-90-1

Molecular formula:

C11H11FO2

IUPAC Name:

1-(6-fluoro-3,4-dihydro-2H-1-benzopyran-2-yl)ethan-1-one

Test material form:

liquid

Details on test material:

- Name of test material (as cited in study reports): JNJ-7928531-AAA (T001481)
- Physical state: liquid
- Appearance: Colourless, light yellow to brown liquid

Specific details on test material used for the study:

Description: Pale brown liquid
Date received: 2004-12-15
Storage conditions: Room temperature in the dark

Method

Target gene:

histidine locus

Species / strain

Species / strain / cell type:

S. typhimurium, other: strains TA100, TA98 and TA102

Details on mammalian cell type (if applicable):

not applicable

Additional strain / cell type characteristics:

not specified

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, 0.5, 1.5, 5, 15, 50, 150, 500, 1500 and 5000 µg/plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: no data

Controls

Controls 1

Untreated negative controls:

yes

Remarks:

untreated

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

no

Positive controls:

yes

Positive control substance:

N-ethyl-N-nitro-N-nitrosoguanidine

Remarks:

without metabolic activation; for TA100 at 3 µg/plate

Controls 2

Untreated negative controls:

yes

Remarks:

untreated

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

no

Positive controls:

yes

Positive control substance:

mitomycin C

Remarks:

without metabolic activation,for TA102 at 0.5 µg/plate

Controls 3

Untreated negative controls:

yes

Remarks:

untreated

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

no

Positive controls:

yes

Positive control substance:

4-nitroquinoline-N-oxide

Remarks:

without metabolic activation; for TA98 at 0.2 µg/plate

Controls 4

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

Remarks:

with metabolic activation, for TA100 at 1 µg/plate

Controls 5

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

Remarks:

with metabolic activation, for TA102 at 10 µg/plate

Controls 6

Untreated negative controls:

yes

Remarks:

untreated

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

no

Positive controls:

yes

Positive control substance:

benzo(a)pyrene

Remarks:

with metabolic activation;for TA98 at 5 µg/plate

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation)

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 of phosphate buffer. The contents of each test tub e were mixed and equally distributed onto the surface of Vogel-Bonner Minimal agar plates (one tube per plate). This procedure was repeated, in triplicate, for each bacterial strain and for each concentration of the test material both with and without S9-mix.

DURATION
- Exposure duration: 3 days
- Selection time: 3 days (simultaneous with exposure)

SELECTION AGENT: histidine

NUMBER OF REPLICATIONS: triplicates

NUMBER OF CELLS EVALUATED:
- not applicable

DETERMINATION OF CYTOTOXICITY
- Method: visible reduction in the growth of the bacterial lawn or a substantial decrease in the frequency of revertant colonies

OTHER:
- Strains were mutants derived from S. typhimurium LT2. Prior to use, the master strains were checked for characteristics, viability and spontaneous reversion rate.

Evaluation criteria:

no data

Statistics:

no data

Results and discussion

Test results

Species / strain:

S. typhimurium, other: strains TA100, TA98 and TA102

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

TEST-SPECIFIC CONFOUNDING FACTORS
- Evaporation from medium: no data
- Water solubility: no data
- Precipitation: No test substance 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 (DMSO) 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 efficacity of the S9-mix were validated. Results for the negative controls (spontaneous revertion rates) were considered to be acceptable.

ADDITIONAL INFORMATION ON CYTOTOXICITY:
The test substance caused either a visible reduction in the growth of the bacterial background lawn or a substantial decrease in the frequency of revertant colonies to all of the Salmonella strains at 5000 µg/plate (except TA98 in the presence of S9).

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 substance was evaluated for mutagenic potential in the Ames test using S. typhimurium strains TA98, TA100 and TA102 in the absence and presence of metabolic activation. The test substance was considered to be non-mutagenic under the conditions of this test.