Tar acids, xylenol fraction

Genetic toxicity: in vitro

Administrative data

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-reference

Cross-reference 1

Reason / purpose for cross-reference:

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

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:

S. typhimurium, 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

Cross-reference 2

Reason / purpose for cross-reference:

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

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:

S. typhimurium, 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.

Cross-reference 3

Reason / purpose for cross-reference:

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

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:

S. typhimurium, 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.

Cross-reference 4

Reason / purpose for cross-reference:

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

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:

S. typhimurium, 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.

Cross-reference 5

Reason / purpose for cross-reference:

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

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:

S. typhimurium, 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.

Cross-reference 6

Reason / purpose for cross-reference:

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

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:

S. typhimurium, 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.

Cross-reference 7

Reason / purpose for cross-reference:

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

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:

S. typhimurium, 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.

Cross-reference 8

Reason / purpose for cross-reference:

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

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:

S. typhimurium, 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.

Materials and methods

Test material

Test material information

Constituent 1

Reference substance name:

Tar acids, xylenol fraction

EC Number:

284-895-5

EC Name:

Tar acids, xylenol fraction

Cas Number:

84989-06-0

Molecular formula:

not applicable

IUPAC Name:

2,3-dimethylphenol; 2,4-dimethylphenol; 2,5-dimethylphenol; 2,6-dimethylphenol; 3,4-dimethylphenol; 3,5-dimethylphenol

Results and discussion

Test results

Test results 1

Key result

Species / strain:

S. typhimurium, 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

Test results 2

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.