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Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

The mutagenicity of the registration substance was investigated using Bacteria Reverse Mutation Assay (Ames test) according to the Guideline OECD 471. No mutagenicity was found.

Link to relevant study records
Reference
Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
GLP compliance:
yes (incl. QA statement)
Type of assay:
bacterial reverse mutation assay
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2
Metabolic activation:
with and without
Metabolic activation system:
S9 liver homogenated, induced by phenobarbital and ß-naphtholflavone
Test concentrations with justification for top dose:
up to the highest dose of 5000 µg/plate
Vehicle / solvent:
DMSO was used as vehicle.
Untreated negative controls:
yes
Remarks:
untreated
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
Positive controls:
yes
Positive control substance:
other: Sodium azide for TA 100 and TA 1535 without S9; Methyl methane sulfonate for WP2uvrA without S9; 4-Nitro-o-phenylene-diamine for TA 98 and TA 1535 without S9; 2-Aminoanthracene for all strains with S9.
Details on test system and experimental conditions:
Exp I: plate incorporation method
Exp II: pre-incubation method
Key result
Species / strain:
S. typhimurium TA 1535
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 1537
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 98
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Key result
Species / strain:
E. coli WP2 uvr A
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid

Experiment: 1 (plate incorporation method)

S9-Mix

(-)

Dose Level Per Plate

Number of Revertants, (Mean)

Base-pair Substitution Strains

Frameshift Strains

TA 100

TA 1535

WP2 uvrA

TA 98

TA 1537

Untreated Control

97

97

100

(98)

13

7

27

(16)

53

50

56

(53)

26

14

32

(24)

20

21

23

(21)

Solvent Control

(DMSO)

108

110

108

(109)

10

11

18

(13)

53

39

53

(48)

31

23

19

(24)

18

24

19

(20)

31.6 µg

116

125

108

(116)

8

13

14

(12)

36

46

43

(42)

24

23

24

(24)

19

15

22

(19)

100 µg

115

100

107

(107)

11

6

12

(10)

46

41

29

(39)

22

20

19

(20)

26

24

15

(22)

316 µg

103

121

115

(113)

13

14

9

(12)

52

53

45

(50)

27

16

20

(21)

16

18

19

(18)

1000 µg

109

96

81

(95)

16

13

9

(13)

43

48

41

(44)

20

20

16

(19)

20

18

19

(19)

2500 µg

87 P

100 P

120 P

(102)

9 P

10 P

7 P

(9)

64 P

37 P

45 P

(49)

25 P

19 P

19 P

(21)

17 P

16 P

18 P

(17)

5000 µg

109 P

117 P

126 P

(117)

11 P

8 P

10 P

(10)

53 P

52 P

62 P

(56)

20 P

24 P

24 P

(23)

21 P

16 P

17 P

(18)

S9-Mix (-)

Name

Dose Level

No. of Revertants

NaN3

NaN3

MMS

4-NOPD

4-NOPD

10 µg

10 µg

1.0 µL

10 µg

40 µg

511

508

466

(495)

1227

1194

1034

(1152)

1049

875

872

(932)

240

263

261

(255)

74

72

70

(72)

P: Precipitation

NaN3

MMS

4-NOPD

sodium azide

methyl methane sulfonate

4-nitro-o-phenylene-diamine

Experiment: 1 (plate incorporation method)

S9-Mix (+)

Dose Level Per Plate

Number of Revertants, (Mean)

 

Base-pair Substitution Strains

Frameshift Strains

 

TA 100

TA 1535

WP2 uvrA

TA 98

TA 1537

 

Untreated Control

115

105

96

(105)

8

11

11

(10)

68

74

63

(68)

19

18

33

(23)

12

16

15

(14)

 

Solvent Control

(DMSO)

93

88

87

(89)

13

11

17

(14)

53

62

46

(54)

34

24

27

(28)

18

19

19

(19)

 

31.6 µg

103

118

108

(110)

10

16

10

(12)

48

66

74

(63)

39

24

27

(30)

19

22

23

(21)

 

100 µg

79

62

87

(76)

9

15

12

(12)

66

50

48

(55)

27

23

22

(24)

18

17

15

(17)

 

316 µg

101

81

100

(94)

10

16

10

(12)

63

55

54

(57)

30

23

35

(29)

16

15

17

(16)

 

1000 µg

90

93

78

(87)

12

2

11

(8)

50

54

50

(51)

28

29

27

(28)

19

18

22

(20)

 

2500 µg

98 P

66 P

108 P

(91)

10 P

13 P

10 P

(11)

58 P

53 P

51 P

(54)

28 P

18 P

22 P

(23)

18 P

17 P

16 P

(17)

 

5000 µg

87 P

97 P

97 P

(94)

11 P

12 P

10 P

(11)

48 P

38 P

37 P

(41)

24 P

27 P

35 P

(29)

15 P

17 P

16 P

(16)

 

S9-Mix (+)

Name

Dose Level

No. of Revertants

2-AA

2-AA

2-AA

2-AA

2-AA

 

2.5 µg

2.5 µg

10 µg

2.5 µg

2.5 µg

 

618

816

783

(739)

164

187

216

(189)

208

188

194

(197)

2736

2261

2517

(2505)

261

185

256

(234)

 

P: Precipitation

2 -AA: Aminoanthracene

Experiment: 2 (pre-incubation method)

S9-Mix

(-)

Dose Level Per Plate

Number of Revertants, (Mean)

Base-pair Substitution Strains

Frameshift Strains

TA 100

TA 1535

WP2 uvrA

TA 98

TA 1537

Untreated Control

84

121

122

(109)

25

26

25

(25)

49

44

61

(51)

35

39

34

(36)

20

21

23

(21)

Solvent Control

(DMSO)

116

94

99

(103)

20

22

21

(21)

38

47

37

(41)

36

27

33

(32)

24

26

27

(26)

10.0 µg

90

101

87

(93)

25

22

23

(23)

44

45

61

(50)

31

23

20

(25)

26

24

23

(24)

31.6 µg

83

104

93

(93)

24

20

25

(23)

54

43

53

(50)

27

29

36

(31)

22

28

29

(26)

100 µg

86

113

86

(95)

27

29

22

(26)

52

46

50

(49)

27

36

22

(28)

25

27

24

(25)

316 µg

78

75

95

(83)

23

24

20

(22)

53

41

66

(53)

39

33

38

(37)

24

28

29

(27)

1000 µg

128

84

118

(110)

24

24

30

(26)

40

32

49

(40)

28

28

34

(30)

20

25

27

(24)

2500 µg

120 P

115 P

119 P

(118)

31 P

28 P

23 P

(27)

40 P

42 P

41 P

(41)

28 P

25 P

33 P

(29)

26 P

24 P

23 P

(24)

5000 µg

76 P

119 P

95 P

(97)

25 P

24 P

23 P

(24)

43 P

43 P

53 P

(46)

22 P

34 P

35 P

(30)

24 P

26 P

24 P

(25)

S9-Mix (-)

Name

Dose Level

No. of Revertants

NaN3

NaN3

MMS

4-NOPD

4-NOPD

10 µg

10 µg

1.0 µL

10 µg

40 µg

837

787

731

(785)

1031

1084

1137

(1084)

451

452

434

(446)

159

191

187

(179)

203

244

219

(222)

P: Precipitation

NaN3

MMS

4-NOPD

sodium azide

methyl methane sulfonate

4-nitro-o-phenylene-diamine

Experiment: 2 (pre-incubation method)

Date Plated: 12 December 2017

 

Date Counted: 19 December 2017

S9-Mix

(+)

Dose Level Per Plate

Number of Revertants, (Mean)

Base-pair Substitution Strains

Frameshift Strains

TA 100

TA 1535

WP2 uvrA

TA 98

TA 1537

Untreated Control

115

94

107

(105)

20

21

24

(22)

48

48

43

(46)

28

31

25

(28)

25

26

27

(26)

Solvent Control

(DMSO)

93

93

103

(96)

21

22

23

(22)

44

50

41

(45)

20

25

25

(23)

28

24

26

(26)

10.0 µg

78

100

102

(93)

20

23

21

(21)

49

52

65

(55)

26

20

20

(22)

27

26

25

(26)

31.6 µg

122

108

111

(114)

24

24

26

(25)

52

56

52

(53)

28

20

28

(25)

24

21

26

(24)

100 µg

77

77

99

(84)

27

21

20

(23)

49

48

50

(49)

27

20

31

(26)

28

25

24

(26)

316 µg

73

74

74

(74)

26

27

29

(27)

56

59

59

(58)

25

31

26

(27)

24

29

24

(26)

1000 µg

77

93

94

(88)

30

25

24

(26)

64

43

59

(55)

31

27

31

(30)

24

26

27

(26)

2500 µg

71 P

70 P

70 P

(70)

30 P

20 P

24 P

(25)

50P

59P

44P

(51)

27 P

27 P

23 P

(26)

20 P

22 P

21 P

(21)

5000 µg

101 P

64 P

96 P

(87)

21 P

32 P

28 P

(27)

48P

49P

49P

(49)

37 P

27 P

24 P

(29)

23 P

24 P

24 P

(24)

S9-Mix (+)

Name

Dose Level

No. of Revertants

2-AA

2-AA

2-AA

2-AA

2-AA

2.5 µg

2.5 µg

10 µg

2.5 µg

2.5 µg

2332

2159

2077

(2189)

226

227

233

(229)

118

121

121

(120)

1498

1707

2035

(1747)

259

279

264

(267)

P: Precipitation

2 -AA: Aminoanthracene

Conclusions:
The mutagenicity of the registration substance was investigated using Bacteria Reverse Mutation Assay (Ames test) according to the Guideline OECD 471. No mutagenicity was found.
Executive summary:

The mutagenicity of the registration substance was investigated using Bacteria Reverse Mutation Assay (Ames test) according to the Guideline OECD 471. Up to the highest concentration of 5000 µg/plate, no mutagenicity was found.

Additional information

Justification for classification or non-classification

The mutagenicity of the registration substance was investigated using Bacteria Reverse Mutation Assay (Ames test) according to the Guideline OECD 471. No mutagenicity was found, which supports no classification.

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