Xylenol

Genetic toxicity: in vitro

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

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

no

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Mixed xylenols

IUPAC Name:

Mixed xylenols

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 / strain

Species / strain 1

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Additional strain / cell type characteristics:

not specified

Species / strain 2

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 results

Test results 1

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

Test results 2

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.