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Genetic toxicity: in vitro

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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 guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
other: SEPA test guideline 471
Deviations:
no
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

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.