α-chloro-4-fluoroacetophenone

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions. Only 4 strains tested.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

Only 4 strains tested

GLP compliance:

no

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

α-chloro-4-fluoroacetophenone

EC Number:

207-256-4

EC Name:

α-chloro-4-fluoroacetophenone

Cas Number:

456-04-2

Molecular formula:

C8H6ClFO

IUPAC Name:

2-chloro-1-(4-fluorophenyl)ethan-1-one

Details on test material:

- Name of test material (as cited in study report): omega-chloro-para-fluoracetophenone (Test substance No.: 87/675)
- Physical state: no data
- Analytical purity: 98 %
- Impurities (identity and concentrations): not reported
- Storage condition of test material: 4°C

Method

Target gene:

histidine auxotrophy

Species / strain

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Metabolic activation:

with and without

Metabolic activation system:

Aroclor 1254-treated rat liver S-9 mix

Test concentrations with justification for top dose:

Experiment 1: 20, 100, 500, 2500, 5000 µg/plate (SPT±S9); Experiment 2: 1, 5, 25, 125, 250 µg/plate (SPT+S9); 0.2, 1, 5, 25, 50 µg/plate (SPT-S9); Experiment 3: 1.5, 5, 15, 50, 150 µg/plate (PIT+S9); 0.1, 0.3, 1, 3, 10 µg (PIT-S9)

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: complete solubility of the test substance in DMSO.

Controls

Controls 1

Untreated negative controls:

yes

Remarks:

Sterility control

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

other: 2-aminoanthracene 10 µg

Remarks:

With S-9, strains TA100, TA98, TA1537, TA1535

Controls 2

Untreated negative controls:

yes

Remarks:

Sterility control

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

other: N-methyl-N´-nitro-N-nitrosoguanidine (MNNG) 5 µg

Remarks:

Without S-9, strains TA100 and TA1535

Controls 3

Untreated negative controls:

yes

Remarks:

Sterility control

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

other: 4-nitro-o-phenylendiamine 10 µg

Remarks:

Without S-9, strain TA98

Controls 4

Untreated negative controls:

yes

Remarks:

Sterility control

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

other: 9-aminoacridine chloride monohydrate 100 µg

Remarks:

Without S-9, strain TA1537

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation) and preincubation

DURATION
- Preincubation period: 20 min
- Exposure duration: 48 hours

NUMBER OF REPLICATIONS: 3 plates

DETERMINATION OF CYTOTOXICITY
- Method: relative total growth, other: reduction of his- background growth, decrease in the number of his+ revertants

Evaluation criteria:

A test substance is characterized as positive in the Ames test if the following requirements are fulfilled:
- doubling of the spontaneous mutation rate (control)
- dose-response relationship
- reproducibility of the results

Results and discussion

Test results

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:

Bacteriotoxic effect depending on strain without S-9 from about 10 µg - 20 µg/plate onward and with S-9 from about 100 - 150 µg/plate onward.

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

Experiment 1:

Standard plate test, maximum number of revertants (mean ± SD):

	Control		Test substance
Strain	-S9	+S9	-S9	+S9
TA1535	17 ± 2	24 ± 2	14 ± 1 (20 µg)	18 ± 3 (20 µg)
TA100	112 ± 8	123 ± 8	103 ± 5 (20 µg)	134 ± 4 (20 µg)
TA1537	7 ± 1	9 ± 1	5 ± 2 (20 µg)	7 ± 1 (20 µg)
TA98	21 ± 2	35 ± 3	contamination (20 µg)	32 ± 0 (20 µg)

Experiment 2:

Standard plate test, maximum number of revertants (mean ± SD):

	Control		Test substance
Strain	-S9	+S9	-S9	+S9
TA1535	15 ± 2	19 ± 3	16 ± 3 (5 µg)	17 ± 1 (25 µg)
TA100	108 ± 2	115 ± 9	109 ± 8 (1µg)	113 ± 5 (5 µg)
TA1537	8 ± 1	9 ± 2	7 ± 1 (1 µg)	12 ±1 (25 µg)
TA98	22 ± 1	32 ± 1	23 ± 2 (0.2 µg)	33 ± 1 (5 µg)

Experiment 3:

Preincubation test, maximum number of revertants (mean ± SD):

	Control		Test substance
Strain	-S9	+S9	-S9	+S9
TA1535	18 ± 5	17 ± 3	19 ± 3 (1.0 µg)	17 ± 5 (15 µg)
TA100	116 ± 9	116 ± 3	116 ± 7 (1.0 µg)	113 ± 4 (5.0 µg)
TA1537	10 ± 2	9 ± 2	9 ± 2 (0.3 µg)	11 ± 2 (5.0 µg)
TA98	21 ± 2	31 ± 3	21 ± 2 (0.1 µg)	38 ± 4 (50 µg)