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Toxicological information

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2004
Report Date:
2004

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
no
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): mixed xylenols
- Substance type: alcohol
- Physical state: liquid
- Analytical purity: not stated
- Impurities (identity and concentrations):
- Composition of test material, percentage of components: 2,6-xylenol: 15.24%, 2,4-xylenol: 23.15%, 2,5-xylenol: 16.44%, 2,3-xylenol: 18.82%, 3,5-xylenol: 10.71%, 3,4-xylenol: 15.38% and other compounds
- Isomers composition: not applicable
- Purity test date: not stated
- Lot/batch No.: 20NOV2003
- Expiration date of the lot/batch: not stated
- Stability under test conditions: not stated
- Storage condition of test material: room temperature in the dark

Method

Species / strainopen allclose all
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
Controls
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
- Expression time (cells in growth medium): not stated
- Fixation time (start of exposure up to fixation or harvest of cells): not stated
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.

Results and discussion

Test resultsopen allclose all
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Species / strain:
E. coli WP2 uvr A
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
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.
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

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

 

Applicant's summary and conclusion

Conclusions:
Mixed xylenols were found to be negative for genotoxicity.
Executive summary:

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.