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Genetic toxicity: in vitro

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Endpoint:
in vitro gene mutation study in bacteria
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Remarks:
Summary of available data used for the endpoint assessment of the target substance
Adequacy of study:
key study
Justification for type of information:
refer to analogue justification provided in IUCLID section 13
Cross-referenceopen allclose all
Reason / purpose:
read-across source
Reference
Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
no E.coli or S. typhimurium TA 102 tested
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Version / remarks:
1983
Deviations:
no
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay
Target gene:
his operon
Species / strain / cell type:
other: Salmonella typhimurium TA 98, TA100, TA1535, TA1537.
Metabolic activation:
with and without
Metabolic activation system:
a 9000 x g supernatant from male Syrian Hamster liver and from male Sprague-dawley rat liver both preliminarily induced with Aroclor 1254
Test concentrations with justification for top dose:
0.0, 3.3, 10.0, 33.0, 100.0, 333.0 µg/plate in water as solvent
Vehicle / solvent:
water
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
other: 2-aminoanthracene, 4-nitro-o-phenylene diamine, sodium azide, 9-aminoacridine
Details on test system and experimental conditions:
Ames test preincubation methodology according to Ames, Mutat. Res. 31,347 (1975) and Yahagi, Cancer Lett. 1,91 (1975)
Evaluation criteria:
POSITIVE RESPONSE: was indicated by a reproducable, dose-related increase wether it be two-fold over background or not
Statistics:
analysis based on the models presented by Margolin
Key result
Species / strain:
other: TA 98, TA100, TA1535, TA1537.
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
other: to select dose range the chemical was checked for toxicity to S. typh. TA100
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Conclusions:
p-cresol yielded a negative result when tested in the Ames test according to OECD TG 471 using 4 strains of Salmonella typhimurium with and without metabolic activation systems
Reason / purpose:
read-across source
Reference
Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Remarks:
no information on GLP, no E.coli or S. typhimurium TA 102 tested
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Version / remarks:
1997
Deviations:
yes
Remarks:
no E.coli or S. typhimurium TA 102 tested
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay
Target gene:
his operon
Species / strain / cell type:
other: S. typhimurium TA 1535, TA 1537, TA 98, TA1538 and TA 100
Additional strain / cell type characteristics:
not specified
Metabolic activation:
with and without
Metabolic activation system:
Arclor 1254 induced S9
Test concentrations with justification for top dose:
0, 0.5, 5, 50, 500 and 5000 ug/plate
Vehicle / solvent:
- Vehicle: DMSO
- Justification for choice of solvent/vehicle: widely used
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
other: Sodium azide ( -S9 TA1535 & TA100); 2-Nitrofluorene (-S9 TA1538; -S9 TA98); 9-Aminoacridine (-S9 TA1537); 2-Aminoanthracene (+S9 all strains)
Details on test system and experimental conditions:
METHOD OF APPLICATION: Plate incoporation method

Evaluation criteria:
A dose-related significantly increased number of revertants was evaluated as a positive result.
Statistics:
Dose rsponse effects were assessed using the Joncheere test
Key result
Species / strain:
other: TA 1535, TA 1537, TA1538, TA 98 and TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
Observed in all strains
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid

p-cresol

Conc

TA1535

TA1537

TA1538

TA98

TA100

(ug/plate)

-S9

+S9

-S9

+S9

-S9

+S9

-S9

+S9

-S9

+S9

0

12

22

5

11

16

36

21

23

67

76

0.5

22

31

10

11

16

30

20

30

65

90

5

24

31

3

NT

21

34

18

31

68

81

50

21

26

10

10

14

38

20

31

67

87

500

29

26

6

11

15

37

18

29

64

100

5000*

26

0

0

0

7

20

29

9

3

12

 

 Positive controls

 SA

 526 ± 54

-

-

-

-

-

-

-

 502 ± 28

-

 2NF

-

-

-

-

 284 ± 60

-

 275 ± 74

-

 -

-

 9AA

-

-

 810 ± 95

-

-

-

-

-

-

-

 2AA

-

 306 ± 60

-

 269 ± 47

-

 1027 ± 199

-

 1093 ± 227

-

 723 ± 159

 * toxicity - apparent as a thinning of the background lawn

SA - Sodium azide

2NF - 2 -Nitrofluorene

9AA - 9 -Aminoacridine

2AA - 2 -Aminoanthracene

 

Conclusions:
p-cresol was found to be negative in the Ames study when tested up to a concentration of 5000 ug/plate (the maximum recommended concentration in accordance with currenty regulatory guidelines) in S. typhimurium strains (TA1535, TA1537, TA1538, TA98, TA100). Signs of toxicity was evident at the maximum dose tested, manifest by a slight thinning of the background lawn.
Reason / purpose:
read-across source
Reference
Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
no data on GLP
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Version / remarks:
1997
Deviations:
no
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay
Target gene:
his and trp operon
Species / strain / cell type:
E. coli WP2 uvr A
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Metabolic activation system:
Activation system prepared from rat liver induced with phenobarbital and 5,6-benzoflavone
Test concentrations with justification for top dose:
0, 156, 313, 625, 1250, 2500, 5000 µg/plate
Vehicle / solvent:
DMSO
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
other: without S9-mix: 2-(2-Furyl)-3-(5-nitro-2-furyl)acrylamide, Sodium azide, 9-Aminoacridine;
Details on test system and experimental conditions:
Pre-incubation method,
Plates/test 3,
Replicates 2
Evaluation criteria:
The test substance is considered to be positive for mutagenic activity when assay plates with the test substance a show significant increase in revertant colony count as compared with that on negative control plates and when this effect is reasonably reproducible or dose dependent.
Statistics:
yes, but method not mentioned
Key result
Species / strain:
E. coli WP2 uvr A
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
without S9-mix: >2500 µg/plate; with S9-mix: 5000 µg/plate
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Key result
Species / strain:
other: TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
with and without S9-mix: >2500 µg/plate;
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Conclusions:
m-cresol yielded a negative result when tested in the Ames test according to OECD TG 471 using 4 strains of Salmonella typhimurium (Salmonella typhimurium TA 98, TA100, TA1535, TA1537) and E.coli WP2 uvr Awith and without a metabolic activation system. The positive controls were functional.
Reason / purpose:
read-across source
Reference
Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
no data on GLP
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Version / remarks:
1997
Deviations:
yes
Remarks:
no E.coli or S. typhimurium TA 102 tested
GLP compliance:
no
Type of assay:
bacterial reverse mutation assay
Target gene:
his operon
Species / strain / cell type:
other: S. typhimurium TA 1535, TA 1537, TA 98, TA1538 and TA 100
Additional strain / cell type characteristics:
not specified
Metabolic activation:
with and without
Metabolic activation system:
Arclor 1254 induced S9
Test concentrations with justification for top dose:
0, 0.5, 5, 50, 500 and 5000 µg/plate
Vehicle / solvent:
- Vehicle: DMSO
- Justification for choice of solvent/vehicle: widely used
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
other: Sodium azide ( -S9 TA1535 & TA100); 2-Nitrofluorene (-S9 TA1538; -S9 TA98); 9-Aminoacridine (-S9 TA1537); 2-Aminoanthracene (+S9 all strains)
Details on test system and experimental conditions:
METHOD OF APPLICATION: Plate incoporation method
Evaluation criteria:
A dose-related significantly increased number of revertants was evaluated as a positive result.
Statistics:
Dose rsponse effects were assessed using the Joncheere test
Key result
Species / strain:
other: TA 1535, TA 1537, TA1538, TA 98 and TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
Observed in all strains
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid

m-cresol

Conc

TA1535

TA1537

TA1538

TA98

TA100

(ug/plate)

-S9

+S9

-S9

+S9

-S9

+S9

-S9

+S9

-S9

+S9

0

12

9

5

11

8

18

16

14

91

76

0.5

22

11

5

NT

96

22

17

16

NT

91

5

21

4

6

17

11

20

19

14

117

86

50

23

2*

8

13

7

29

18

14

62

85

500

15

9*

8

16

7

20

15

17

53

97

5000*

0

2

0

0

4

4

3

2

0

32

 

 Positive controls

 SA

 526 ± 54

-

-

-

-

-

-

-

 502 ± 28

-

 2NF

-

-

-

-

 284 ± 60

-

 275 ± 74

-

 -

-

 9AA

-

-

 810 ± 95

-

-

-

-

-

-

-

 2AA

-

 306 ± 60

-

 269 ± 47

-

 1027 ± 199

-

 1093 ± 227

-

 723 ± 159

 * toxicity - apparent as a thinning of the background lawn

SA - Sodium azide

2NF - 2 -Nitrofluorene

9AA - 9 -Aminoacridine

2AA - 2 -Aminoanthracene

 

Conclusions:
m-cresol was found to be negative in the Ames study when tested up to a concentration of 5000 ug/plate (the maximum recommended concentration in accordance with currenty regulatory guidelines) in S. typhimurium strains (TA1535, TA1537, TA1538, TA98, TA100). Signs of toxicity were evident at the maximum dose tested, manifest by a slight thinning of the background lawn.
Reason / purpose:
read-across source
Reference
Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
no E.coli or S. typhimurium TA 102 tested
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Version / remarks:
1983
Deviations:
yes
Remarks:
only 4 strains used
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay
Target gene:
his-operon
Species / strain / cell type:
other: salmonella typhimurium TA98, TA100, TA1535, TA1537
Additional strain / cell type characteristics:
not specified
Metabolic activation:
with and without
Metabolic activation system:
A 9000 x g supernatant from male Syrian Hamster liver and from male Sprague-Dawley rat liver, induced with Aroclor 1254
Test concentrations with justification for top dose:
0.0, 1.0, 3.3, 10.0, 33.0, 100.0 µg/plate in water as solvent
Vehicle / solvent:
water
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
other: 2-aminoanthracene, 4-nitro-o-phenylene diamine, sodium azide, 9-aminoacridine
Details on test system and experimental conditions:
Preincubation methodology according to Ames, Mutat. Res. 31,347 (1975) and Yahagi, Cancer Lett. 1,91 (1975);
Rationale for test conditions:
DETERMINATION OF DOSE: to select dose-range the chemical was checked for toxicity to S. typh. TA 100 (details not given)
Evaluation criteria:
positive response was indicated by a reproducible, dose-related increase whether it be twofold over the background or not
Statistics:
based on the models of Margolin, Kaplan and Zeiger (1981): Proc.Natl. Acad.Sci (USA) 78, 3779-3783
Key result
Species / strain:
other: TA 98, TA100, TA1535, TA1537
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
other: from 33.0 µg/plate onwards
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
no data
Conclusions:
o-cresol yielded a negative result when tested in the Ames test according to OECD TG 471 using 4 strains of Salmonella typhimurium (Salmonella typhimurium TA 98, TA100, TA1535, TA1537) with and without a metabolic activation system. The positive controls were functional.
Reason / purpose:
read-across source
Reference
Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
no E.coli or S. typhimurium TA 102 tested
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Version / remarks:
1983
Deviations:
yes
Remarks:
purity of TS is not given
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay
Target gene:
his-operon
Species / strain / cell type:
other: Salmonella typhimurium TA98, TA100, TA1535, TA1537, TA1538
Additional strain / cell type characteristics:
not specified
Metabolic activation:
with and without
Metabolic activation system:
A 9,000 x g supernatant prepared from sprague-Dawley adult male rat liver induced by Aroclor 1254
Test concentrations with justification for top dose:
0.01, 0.1, 1.0, 5.0, 10.0, 25.0, 50.0 µL/plate
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: DMSO
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
other: Sodium azide, 2-Nitrofluorene, 9-Aminoacridine, 2-Anthracene
Details on test system and experimental conditions:
METHOD OF APPLICATION: in agar (plate incorporation);

Evaluation criteria:
dose-related mutant increase
Statistics:
no data
Key result
Species / strain:
other: TA98, TA100, TA1535, TA1537, TA1538
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
other: 10-50 µL/plate
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Conclusions:
o-cresol was tested for genotoxic effects in the Ames test according to OECD TG 471 using Salmonella typhimurium TA98, TA100, TA1535, TA1537, TA1538 with and without a metabolic activation system and revealed a negative result. The positive controls were functional.
Reason / purpose:
read-across source
Reference
Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
no GLP, no E.coli or S. typhimurium TA 102 tested
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Version / remarks:
1997
Deviations:
yes
Remarks:
no E.coli or S. typhimurium TA 102 tested
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay
Target gene:
his operon
Species / strain / cell type:
other: S. typhimurium TA 1535, TA 1537, TA 98, TA1538 and TA 100
Additional strain / cell type characteristics:
not specified
Metabolic activation:
with and without
Metabolic activation system:
Aroclor 1254 induced S9
Test concentrations with justification for top dose:
0, 5, 50, 500 and 5000 µg/plate
Vehicle / solvent:
- Vehicle: DMSO
- Justification for choice of solvent/vehicle: widely used
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
other: Sodium azide ( -S9 TA1535 & TA100); 2-Nitrofluorene (-S9 TA1538; -S9 TA98); 9-Aminoacridine (-S9 TA1537); 2-Aminoanthracene (+S9 all strains)
Details on test system and experimental conditions:
METHOD OF APPLICATION: Plate incoporation method

Evaluation criteria:
A dose-related significantly increased number of revertants was evaluated as a positive result.
Statistics:
Dose rsponse effects were assessed using the Joncheere test
Key result
Species / strain:
other: TA 1535, TA 1537, TA1538, TA 98 and TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
Observed in all strains
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid

o-cresol

Conc

TA1535

TA1537

TA1538

TA98

TA100

(ug/plate)

-S9

+S9

-S9

+S9

-S9

+S9

-S9

+S9

-S9

+S9

0

22

12

10

14

17

30

21

35

89

108

5

14

11

6

7

12

29

26

35

100

84

50

16

11

9

9

13

16

21

33

107

90

500

30

11

7

4

14

20

22

36

100

90

5000*

0

0

0

0

1

11

0

14

98

30

 

 Positive controls

 SA

 526 ± 54

-

-

-

-

-

-

-

 502 ± 28

-

 2NF

-

-

-

-

 284 ± 60

-

 275 ± 74

-

 -

-

 9AA

-

-

 810 ± 95

-

-

-

-

-

-

-

 2AA

-

 306 ± 60

-

 269 ± 47

-

 1027 ± 199

-

 1093 ± 227

-

 723 ± 159

 * toxicity - apparent as a thinning of the background lawn

SA - Sodium azide

2NF - 2 -Nitrofluorene

9AA - 9 -Aminoacridine

2AA - 2 -Aminoanthracene

 

Conclusions:
o-cresol was found to be negative in the Ames study when tested up to a concentration of 5000 ug/plate (the maximum recommended concentration in accordance with currenty regulatory guidelines) in S. typhimurium strains (TA1535, TA1537, TA1538, TA98, TA100). Signs of toxicity were evident at the maximum dose tested, manifest by a slight thinning of the background lawn.
Reason / purpose:
read-across source
Reference
Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
no
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay
Target gene:
his and trp operon
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Additional strain / cell type characteristics:
not specified
Species / strain / cell type:
E. coli WP2 uvr A
Additional strain / cell type characteristics:
not specified
Metabolic activation:
with and without
Metabolic activation system:
S9 derived from Aroclor 1254 induced male Sprague-Dawley rats
Test concentrations with justification for top dose:
6.7, 10, 33, 67, 100, 333, 667, 1000, 3333 and 5000 µg/plate for strains TA98, TA100, TA1535, TA1537 and WP2 uvrA for the preliminary toxicity study (with and without metabolic activation).
75, 200, 600, 1800 and 5000 µg/plate for TA98, TA100, TA1535, TA1537 and WP2 uvrA for the bacterial mutation assay (with and without metabolic activation).
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: dimethyl sulfoxide (DMSO) (and water for sodium azide dilution in the positive control)
- Justification for choice of solvent/vehicle: Not stated, commonly used solvent
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other:
Remarks:
2-aminoanthracene for WP2 uvrA in the presence of metabolic activation. 2-nitroluorene for TA98; sodium azide for TA100 and TA1535; 9-aminoacridine for TA1537; methyl methanesulfonate for WP2 uvrA in the absence of metabolic activation.
Details on test system and experimental conditions:
METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Preincubation period: 12 hours
- Exposure duration: 48 - 72 hours
Evaluation criteria:
All cultures must demonstrate the characteristic mean number of spontaneous revertants in the vehicle controls.The mean of each positive control must exhibit at least a 3.0 fold increase in the number of revertants over the mean value of the respective control. A minimum of three non toxic dose levels is required for evaluation. A dose level is considered to be toxic if there is a > 50% reduction in the mean number of revertants per plate compared to the mean vehicle control value and at least a moderate reduction in the background lawn.
Key result
Species / strain:
other: TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
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:
cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Additional information on results:
COMPARISON WITH HISTORICAL CONTROL DATA: Historical control data were found to support the study outcome.

The results of the genotoxicity study found that mixed xylenols were not genotoxic at any dose level tested. A summary of the results is presented below.

Table 1: Summary of results of the mutagenicity assay

Dose (µg/plate)

Average revertants per plate ± standard deviation

TA98

TA100

TA1535

TA1537

WP2 uvrA

In the absence of metabolic activation

Vehicle control

17 ± 2

153 ± 13

16 ± 2

7 ± 2

24 ± 3

75

14 ± 5

126 ± 3

23 ± 5

7 ± 1

24 ± 2

200

17 ± 2

126 ± 31

19 ± 4

6 ± 2

20 ± 5

600

14 ± 5

133 ± 26

19 ± 2

6 ± 1

15 ± 3

1800

16 ± 3

125 ± 11

21 ± 7

4 ± 1

13 ± 3

5000

3 ± 1

0 ± 0

3 ± 1

0 ± 0

1 ± 2

Positive control

115 ± 12

551 ± 8

272 ± 6

644 ± 121

117 ± 7

In the presence of metabolic activation

Vehicle control

20 ± 2

151 ± 15

17 ± 5

6 ± 2

20 ± 6

75

22 ± 5

163 ± 20

17 ± 2

5 ± 1

19 ± 6

200

18 ± 5

168 ± 6

19 ± 2

6 ± 2

16 ± 2

600

22 ± 3

154 ± 6

21 ± 4

6 ± 3

16 ± 3

1800

22 ± 2

144 ± 11

23 ± 2

6 ± 2

9 ± 3

5000

4 ± 2

0 ± 0

6 ± 2

0 ± 0

0 ± 0

Positive control

1000 ± 147

74 ± 74

108 ± 9

128 ± 17

794 ± 95

 

Conclusions:
All criteria for a valid study were met. The results indicate that mixed xylenols did not cause a positive response either in the presence or absence of metabolic activation by Aroclor-induced rat liver S9. Mixed xylenols were therefore concluded to be negative for genotoxicity.

Data source

Materials and methods

Test material

Reference
Name:
Unnamed
Type:
Constituent

Results and discussion

Test resultsopen allclose all
Key result
Species / strain:
other: TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
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:
cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Additional information on results:
In the result table above the most critical and relevant value of the weight of evidence approach is given. In the following, the results are shown for the other source substances of this weight of evidence approach:
Source CAS 95-48-7: o-cresol: negative with and without metabolic activation in S. typhimurium TA 98, TA 100, TA 1535, TA 1537, TA 1538; Pepper, 1981
Source CAS 95-48-7: o-cresol: negative with and without metabolic activation in S. typhimurium TA 98, TA 100, TA 1535, TA 1537; Haworth, 1993
Source CAS 95-48-7: o-cresol: negative with and without metabolic activation in S. typhimurium TA 98, TA 100, TA 1535, TA 1537, TA 1538; Pool & Lin, 1982
Source CAS 106-44-5: p-cresol: negative with and without metabolic activation in S. typhimurium TA 98, TA 100, TA 1535, TA 1537; Haworth, 1993
Source CAS 106-44-5: p-cresol: negative with and without metabolic activation in S. typhimurium TA 98, TA 100, TA 1535, TA 1537, TA 1538; Pool & Lin, 1982
Source CAS 108-39-4: m-cresol: negative with and without metabolic activation in S. typhimurium TA 98, TA 100, TA 1535, TA 1537, E. coli WP2 uvr A; MHLW, 2001
Source CAS 108-39-4: m-cresol: negative with and without metabolic activation in S. typhimurium TA 98, TA 100, TA 1535, TA 1537, TA 1538; Pool & Lin, 1982
Remarks on result:
other: Source: mixed xylenols, Merisol, 2004

Applicant's summary and conclusion

Conclusions:
Based on all available information (weight-of-evidence), following an analogue read-across approach, Tar acids, Xylenol fraction (CAS 84989-06-0) is not considered to induce gene mutation in bacteria.
Executive summary:

Available experimental data on source substances (three creosol isomers and mixed xylenols) all give negative results for bacterial gene mutation as shown in several studies according to OECD 471. All study results were negative with and without metabolic activation. As there are no experimental data available regarding bacterial gene mutation for Tar acids, Xylenol fraction (CAS 84989-06-0) a weight-of-evidence approach was conducted taking into account all available data on the source substances which are surrogate substances for the target substance. Therefore, Tar acids, Xylenol fraction (CAS 84989-06-0) was considered to be not mutagenic in bacteria.