4-chloro-4'-fluorobutyrophenone

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:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well documented study according to international accepted guidelines and GLP compliant.

Cross-reference

Reason / purpose for cross-reference:

other: Related to Richter composition

Reference

Name:

4-chloro-4'-fluorobutyrophenone

Type of composition:

boundary composition of the substance

State / form:

liquid

Reference substance:

4-chloro-4'-fluorobutyrophenone

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2014

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

4-chloro-4'-fluorobutyrophenone

EC Number:

223-395-3

EC Name:

4-chloro-4'-fluorobutyrophenone

Cas Number:

3874-54-2

Molecular formula:

C10H10ClFO

IUPAC Name:

4-chloro-1-(4-fluorophenyl)butan-1-one

Test material form:

other: liquid

Details on test material:

Test item: 4-chloro-4’-fluorobutyrophenoneCAS No.: 3874-54-2Batch No.: 2607Physical state: liquidColour: yellowish greenStorage: cool, dry place in a tightly closed container

Method

Target gene:

S. typhimurium TA98: hisD3052; TA100: hisG46; TA1535: hisG46; TA1537: hisC3076E. coli WP2 uvr A: trpE

Species / strain

Species / strain 1

Species / strain / cell type:

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

Species / strain 2

Species / strain / cell type:

E. coli WP2 uvr A

Metabolic activation:

with and without

Metabolic activation system:

S9 mix

Test concentrations with justification for top dose:

The following concentrations of the test item were prepared and used in the Initial and Confirmatory Mutation Tests:In Salmonella typhimurium strains:-without metabolic activation: -S9 Mix: 1581, 1000, 750, 500, 250, 158 and 50 μg/plate;-with metabolic activation: +S9 Mix: 5000, 1581, 500, 158, 50 and 15.8 μg/plate;In Escherichia coli WP2 uvrA:-with and without metabolic activation: ±S9 Mix: 5000, 1581, 500, 158, 50 and 15.8 μg/plate.

Vehicle / solvent:

Dimethyl sulfoxide (DMSO)Ultrapure water (UPW)

Controls

Controls 1

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Remarks:

DMSO, UPW

Controls 2

Positive controls:

yes

Remarks:

without metabolic activation

Positive control substance:

other: 4-nitro-1,2-phenylene-diamine

Remarks:

Dose: 4 μg/plate; Vehicle: DMSO; Strain: Salmonella TA98

Controls 3

Positive controls:

yes

Remarks:

without metabolic activation

Positive control substance:

sodium azide

Remarks:

Dose: 2 μg/plate; Vehicle: UPW; Strain: Salmonella TA100 and TA1535

Controls 4

Positive controls:

yes

Remarks:

without metabolic activation

Positive control substance:

9-aminoacridine

Remarks:

Dose: 50 μg/plate; Vehicle: DMSO; Strain: Salmonella TA1537

Controls 5

Positive controls:

yes

Remarks:

without metabolic activation

Positive control substance:

methylmethanesulfonate

Remarks:

Dose: 2 μL/plate; Vehicle: UPW; Strain: E. coli WP2uvrA

Controls 6

Positive controls:

yes

Remarks:

with metabolic activation

Positive control substance:

other: 2-aminoanthracene

Remarks:

Dose: 2 μg/plate; Vehicle: DMSO; Strain: all of Salmonella strains

Controls 7

Positive controls:

yes

Remarks:

with metabolic activation

Positive control substance:

other: 2-aminoanthracene

Remarks:

Dose: 50 μg/plate; Vehicle: DMSO; Strain: E. coli strain

Details on test system and experimental conditions:

The study included a Preliminary Solubility Test, a Preliminary Range Finding Test (Informatory Toxicity Test) an Initial Mutation Test (Plate Incorporation Test) and a Confirmatory Mutation Test (Repeated Plate Incorporation Test).In the different experimental phases of the study the plate incorporation method was used.

Evaluation criteria:

The colony numbers on the control, positive control and the test plates were determined (counted manually), the mean values and appropriate standard deviations and mutation rates were calculated.A test item is considered mutagenic if:- a dose–related increase in the number of revertants occurs and/or;- a reproducible biologically relevant positive response for at least one of the dose groups occurs in at least one strain with or without metabolic activation.An increase is considered biologically relevant if:- in strain Salmonella typhimurium TA100 the number of reversions is at least twice as high as the reversion rate of the vehicle control;- in strain TA98, TA1535, TA1537 and Escherichia coli WP2 uvrA the number of reversions is at least three times higher than the reversion rate of the vehicle control.

Results and discussion

Test results

Test results 1

Species / strain:

S. typhimurium TA 98

Metabolic activation:

without

Genotoxicity:

positive

Remarks:

frameshifts and base pair substitutions

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

the lowest cytotoxic concentration: 1581 μg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 2

Species / strain:

S. typhimurium TA 100

Metabolic activation:

without

Genotoxicity:

positive

Remarks:

frameshifts and base pair substitutions

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

the lowest cytotoxic concentration: 1581 μg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 3

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

the lowest cytotoxic concentration: 5000 μg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 4

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

the lowest cytotoxic concentration: 5000 μg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 5

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

the lowest cytotoxic concentration: 1000 μg/plate (-S9 mix), 5000 μg/plate (+S9 mix)

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 6

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

the lowest cytotoxic concentration: 1000 μg/plate (-S9 mix), 5000 μg/plate (+S9 mix)

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 7

Species / strain:

E. coli WP2 uvr A

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

the lowest cytotoxic concentration: 5000 μg/plate (+/-S9 mix)

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'.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):positive S. typhimurium TA98 and TA100 tester strains carrying frameshift and base pair substitution mutation (-S9 Mix).In conclusion, the test item 4-Chloro-4’-fluorobutyrophenone (CAS 3874-54-2) as a directly-acting compound has mutagenic activity on Salmonella typhimurium TA98 and TA100 tester strains carrying frame shift and base pair substitution mutation, without exogenous metabolic activation (-S9 Mix) under the test conditions used in this study.