Bis(4-fluorophenyl) ketone

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:

2005-11-18 to 2005-12-07

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Report date:

2005

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

other: SEPA test guideline 471

Deviations:

no

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

(incomplete documentation)

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

4,4'-Difluorobenzophenone

IUPAC Name:

4,4'-Difluorobenzophenone

Details on test material:

bis(4-fluorophenyl) ketone, purity 99 %

Method

Target gene:

mutated gene loci responsible for histidine auxotrophy

Species / strain

Species / strain / cell type:

other: S. typhimurium TA 1535, TA 1537, TA 98 and TA 100 and Escherichia coli WP2 uvrA

Additional strain / cell type characteristics:

other: histidine auxotroph

Metabolic activation:

with and without

Metabolic activation system:

S-9 mix from male Sprague-Dawley rat induced with Aroclor 1254 (500 mg/kg single i.p. dose) five days prior to sacrifice.

Test concentrations with justification for top dose:

62, 185, 556, 1667, 5000 µg/Plate

Vehicle / solvent:

DMSO

Controls

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: positive + S-9 mix:   TA 98, 100, 1535, 1537: 2 µg 2-aminoanthracene/ plate; WP2 uvrA: 20 µg 2-aminoanthracene/plate; positive - S-9 mix: TA 98: 50 µg Dexon/plate; TA 100, 1535: 1.5 µg sodium azide/plate; TA 1537: 100 µg 2-Mehoxy-6-chloro-9[3-

Remarks:

with and without

Details on test system and experimental conditions:

Ames test
SYSTEM OF TESTING
- Metabolic activation system:    S-9 mix from male Sprague-Dawley rat induced with Aroclor 1254 (500 mg/kg single i.p. dose)
ADMINISTRATION: 
- Dosing:    
main test: 62, 185, 556, 1667, 5000 µg/Plate (+/- metabolic activation)   
- Number of replicates: 3
- Application: solvent water  main test: 50 g/l;  pre-incubation test: 20 g/l
- Positive and negative control groups and treatment:    
positive + S-9 mix:  
TA 98, 100, 1535, 1537: 2 µg 2-aminoanthracene/ plate
WP2 uvrA: 20 µg 2-aminoanthracene/plate
positive - S-9 mix:
TA 98: 50 µg Dexon/plate
TA 100, 1535: 1.5 µg sodium azide/plate
TA 1537: 100 µg 2-Mehoxy-6-chloro-9[3-(2-chloroethyl)-aminopropylamino]acridine/plate
WP2 uvrA: 2 µg 2-(2-Furyl)-3-(nitro-2-furyl) acryamide
negative: Vehicle DMSO
- incubation ca. 48 hours at ca. 37 °C +/- 2 °C

Evaluation criteria:

For triplicate plating, the means of the numbers of revertants per plate were calculated. Details see Data table. If any count from the test article plate higher than two times of the mean from the vehicle plates (negative controls), the results should be treated as positive, and the test was redesigned and the response-dosage relation curve was calculated.

Statistics:

not reported

Results and discussion

Test results

Species / strain:

other: S. typhimurium TA 1535, TA 1537, TA 98 and TA 100 and Escherichia coli WP2 uvrA

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

other: precipitate in 5000 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Additional information on results:

Details see Data table. All the means of the numbers of revertants per plate were twice less than those of negative group. In 5000μg/plate dose some sample was separated out. There was no positive result found in all of the 4 tester strains under the test conditions.
Based on this result and the mutation toxicity grading criteria in the Toxicological Test Methods of Pesticides for Registration of P. R. China, the test article, 4,4-DIFLUORO BENZOPHENONE, is non-mutagenic in this system.

Remarks on result:

other: other: S. typhimurium TA 1535, TA 1537, TA 98 and TA 100 and Escherichia coli WP2 uvrA

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

μg/plate		(colonies/plate)
		TA1535		TA1537		TA98		TA100		WPuvrA
		-S9	+S9	-S9	+S9	-S9	+S9	-S9	+S9	-S9	+S9
5000	1	18#	25#	12#	19#	24#	15#	114#	128#	22#	37#
	2	17#	26#	13#	16#	17#	14#	112#	120#	26#	33#
	3	16#	24#	15#	14#	18#	16#	116#	122#	24#	30#
	Mean	17	25	13	16	20	15	114	123	24	33
	±SD	1.0	1.0	1.5	2.5	3.8	2.0	2.0	4.2	2.0	3.5
1667	1	17	34	16	16	19	20	116	154	21	34
	2	17	37	15	14	21	20	114	150	19	28
	3	16	36	13	16	23	19	116	148	23	32
	Mean	17	36	15	15	21	20	115	151	21	31
	±SD	0.6	1.5	1.5	1.2	2.0	0.6	1.2	3.1	2.0	3.1
	1	18	33	15	15	24	21	124	152	20	34
	2	17	37	14	17	22	23	118	148	19	32
556	3	18	35	16	19	16	19	116	146	22	30
	Mean	18	35	15	17	21	21	119	149	20	32
	±SD	0.6	2.0	1.0	2.0	4.2	2.0	4.2	3.1	1.5	2.0
	1	19	35	15	17	20	24	138	150	23	26
	2	18	34	17	18	26	20	134	154	21	28
185	3	17	36	18	16	18	19	136	152	19	32
	Mean	18	35	17	17	21	21	136	152	21	29
	±SD	1.0	1.0	1.5	1.0	4.2	2.6	2.0	2.0	2.0	3.1
	1	20	39	16	18	22	26	128	142	24	30
	2	17	35	16	18	24	24	130	166	26	35
62	3	18	34	17	20	21	28	136	158	28	31
	Mean	18	36	16	19	22	26	131	155	26	32
	±SD	1.5	2.6	0.6	1.2	1.5	2.0	4.2	12.2	2.0	2.6
	1	16	38	17	19	18	24	142	158	36	34
DMSO	2	17	36	15	20	20	28	146	162	38	36
0.1mL	3	15	39	20	21	24	22	138	154	30	30
/plate	Mean	16	38	17	20	21	25	142	158	35	33
	±SD	1.0	1.5	2.5	1.0	3.1	3.1	4.0	4.0	4.2	3.1
	1	746		224		1208		786		82
Pos	2	832		200		1342		812		90
S-9^-	3	748		196		1188		826		88
	Mean	775		207		1246		808		87
	±SD	49.1		15.1		83.7		20.3		4.2
	1		216		136		682		1512		156
	2		218		142		676		1366		148
Pos	3		236		148		694		1418		182
S-9^+	Mean		223		142		684		1432		162
	±SD		11.0		6.0		9.2		74.0		17.8

#:precipitation

Applicant's summary and conclusion

Conclusions:

Bis(4 -fluorophenyl) ketone is not mutagenic in the Salmonella Assay with the strains TA97, TA98, TA100 and TA102 as well as in WP2 uvrAi n the
presence and absence of Arocolor-induce liver homogenate fraction (S-9 mix).

Executive summary:

4,4'-DIFLUORO BENZOPHENONE was tested in the Salmonella Assay with the strains TA97, TA98, TA100 and TA102 as well as in WP2 uvrAi n the presence and absence of Arocolor-induce liver homogenate fraction (S-9 mix). The concentrations of test substance were 5000,1667, 556, 185 and 62 mg/plate. Positive and negative controls (vehicle) were performed at the same time with the method and in the absence and presents of S-9 mix . All the dose levels and the controls were planted in triplicate. No positive results were found with all the tester strains in the test. In addition, no apprecciable toxicity was observed. The test article was seperated out in the dose of 5000 µg)plate. Based on this result and the mutation toxicity grading criteria in the Toxicological Test Methods of Pesticides for Registration of P. R. China, the test article, 4,4'-DIFLUORO BENZOPHENONE, is non-mutagenic in this system.