4-(4-isopropoxyphenylsulfonyl)phenol

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1986-09-10 to 1987-01-27

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1987

Report date:

1987

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:

4-(4-isopropoxyphenylsulfonyl)phenol

EC Number:

405-520-5

EC Name:

4-(4-isopropoxyphenylsulfonyl)phenol

Cas Number:

95235-30-6

Molecular formula:

C15H16SO4

IUPAC Name:

4-[4-(propan-2-yloxy)benzenesulfonyl]phenol

Details on test material:

- Name of test material (as cited in study report): D - 8
- Molecular formula: C15 H16 O4 S;
- Molecular weight: 292.4;
- Physical state: white powder;
- Analytical purity: > 99.5 %;
- Purity test date: not stated;
- Lot/batch No.: Not stated;
- Expiration date of the lot/batch: not stated;
- Stability under test conditions: stable at ambient temperature and conditions;
- Storage condition of test material: store in a cool dry place, protected from direct sunlight;

Method

Target gene:

The Salmonella typhimurium histidine (his) reversion system measures his- => his+ reversions. The Salmonella typhimurium strains are constructed to differentiate between base pair (TA 1535, TA 100) and frameshift (TA 1537, TA 98, TA 1538) mutations.

Species / strain

Species / strain 1

Species / strain / cell type:

S. typhimurium TA 1538

Additional strain / cell type characteristics:

not specified

Species / strain 2

Species / strain / cell type:

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

Additional strain / cell type characteristics:

not specified

Metabolic activation:

with and without

Metabolic activation system:

Type and composition of metabolic activation system:
- source of S9 : rat liver homogenate, Aroclor 1254 induced
- concentration or volume of S9 mix and S9 in the final culture medium: S-9 fraction (10% v/v), MgCl2 (8mM), KCl (33 mM), sodium phosphate buffer pH 7.4 (100 mM), glucose-6-phosphate (5 mm), NADH (4 mM)

Test concentrations with justification for top dose:

Test 1: 1500; 500; 150, 50; 15 µg/plate;
Test 2: 5000; 1500; 500, 150; 50; 15; 5 µg/plate;

Vehicle / solvent:

Dimethylsulphoxide

Controls

Controls 1

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2-Aminoanthracene, AA

Remarks:

TA 1535, TA 1537; 2 µg/plate; with S-9 mix

Controls 2

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2-Aminoanthracene, AA

Remarks:

TA 1538, TA 98, TA 100; 0.5 µg/plate; with S-9 mix

Controls 3

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

2-nitrofluorene

Remarks:

TA 1538; 2 µg/plate; without S-9 mix

Controls 4

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

2-nitrofluorene

Remarks:

TA 98; 1 µg/plate; without S-9 mix

Controls 5

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

9-aminoacridine

Remarks:

TA 1537; 80 µg/plate; without S-9 mix

Controls 6

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

N-ethyl-N-nitro-N-nitrosoguanidine

Remarks:

TA 1535; 5 µg/plate; without S-9 mix

Controls 7

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

N-ethyl-N-nitro-N-nitrosoguanidine

Remarks:

TA 100; 3 µg/plate; without S-9 mix

Details on test system and experimental conditions:

Preliminary study:
A preliminary study is performed on all tester strains,with and without metabolic activation, in order to evaluate the toxicity of the test article to bacteria.
Increasing concentrations of the test article are used; examples for which are as follows: 5 - 50 - 500 - 5000 mg/plate. The highest dose is 5000 µg/plate if the formulation type allows this dose level to be reached. A minimum of 5 dose levels are used.
Each concentration is tested in duplicate. At the end of the incubation period, the plates are observed for signs of toxicity. The colonies which appears in the presence of the test article are counted and the intensity of the bacterial lawn examined. These observations are compared with those performed in the presence of the vehicle. The signs of toxicity (reduction in bacterial lawn or reduction of the number of colonies) are noted.
Main study:
Two studies are conducted, the second study being performed to confirm or to complement the results of the first one for example by using a closer range near to the top limit dose.
For each study, each concentration of the test article is tested in triplicate with and without metabolic activation on each bacterial strain.
Concentration of the test substance resulting in precipitation: 1500 µg/plate

Evaluation criteria:

The test article will be considered to be clearly mutagenic if:
- The assay is valid
- The number of revertants in presence of the test article is greater than or equal to twice the number of revertants in the negative control at one dose level (the upper dose before toxicity) or more with a dose correlation
- The positive trends/effects are reproducible.

Results and discussion

Test results

Test results 1

Key result

Species / strain:

S. typhimurium TA 1538

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Test results 2

Key result

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Test results 3

Key result

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Test results 4

Key result

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Test results 5

Key result

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Any other information on results incl. tables

The test article D-8 was tested on 5 strains of Salmonella typhimurium (TA98, TA100, TA1535, TA1537, TA1538) with and without metabolic activation. A range of sub-toxic concentrations was determined in a preliminary study on all tester strains with and without metabolic activation.

Five concentrations (1500, 500, 150, 50 and 15 µg/plate) were tested in triplicate on the strains mentioned above with and without metabolic activation. The results were confirmed in a second independent study, using a closer range near the top of limit dose (5000, 1500, 500, 150, 50, 15, 5 µg/plate). A negative control (vehicle) and a positive control (specific standard mutagen) were included in each study.

Conclusion: Under the experimental conditions employed, it can be concluded that the test article D-8 did not cause an increase in the number of revertants per plate of any of the tester strains used, either in presence or absence of a metabolic activation system in both of the two independent studies performed.

Applicant's summary and conclusion

Conclusions:

D-8 was tested for mutagenic activity in the Ames-test with the bacterial strains S. typhimurium TA98, TA100,TA1535, TA1537, TA1538 with and without metabolic activation in two independent studies. No increase of the number of revertants per plate was observed.

Executive summary:

D-8 was tested on 5 strains of Salmonella typhimurium (TA98, TA100, TA1535, TA1537, TA1538) with and without metabolic activation.

Five concentrations (1500, 500, 150, 50 and 15 µg/plate) were tested in triplicate on the strains mentioned above with and without metabolic activation. The results were confirmed in a second independent study, using a closer range near the top of limit dose (5000, 1500, 500, 150, 50, 15 and 5 µg/plate).

A negative control (vehicle) and a positive control (specific standard mutagen) were included in each study.

D-8 did not cause an increase in the number of revertants per plate of any of the tester strains used, either in presence or absence of a metabolic activation system in both of the two independent studies performed