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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:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Additional strain characteristics:
not specified
Metabolic activation:
with and without
Metabolic activation system:
S9 derived from Aroclor 1254 induced male Sprague-Dawley rats
Species / strain:
E. coli WP2 uvr A
Additional strain 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:
- 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
Negative controls:
no
Solvent 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 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:
not specified
Vehicle controls valid:
yes
Negative controls valid:
not applicable
Positive controls valid:
yes
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.
Species / strain:
E. coli WP2 uvr A
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity:
not specified
Vehicle controls valid:
yes
Negative controls valid:
not applicable
Positive controls valid:
yes
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.
Additional information on results:
COMPARISON WITH HISTORICAL CONTROL DATA: Historical control data were found to support the study outcome.

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.