Reaction mass of dipotassium 3,3'-sulphonylbis(benzenesulphonate) and potassium 3-(phenylsulphonyl)benzenesulphonate

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:

26 July 1990 - 17 September 1990

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

Includes most, but not all, currently recommended bacterial strains

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)

Deviations:

yes

Remarks:

Includes most, but not all, currently recommended bacterial strains

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

Includes most, but not all, currently recommended bacterial strains

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.5100 - Bacterial Reverse Mutation Test (August 1998)

Deviations:

yes

Remarks:

Includes most, but not all, currently recommended bacterial strains

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Reaction mass of dipotassium 3,3'-sulphonylbis(benzenesulphonate) and potassium 3-(phenylsulphonyl)benzenesulphonate

EC Number:

915-932-1

Molecular formula:

Reaction mass of C12H8O8S3.2K and C12H9O5S2.K

IUPAC Name:

Reaction mass of dipotassium 3,3'-sulphonylbis(benzenesulphonate) and potassium 3-(phenylsulphonyl)benzenesulphonate

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

Test Substance Name: DPS
Product Number: 016513
Appearance: White powder
Storage: Room temp
Chemical name: Diphenylsulfone-3-sulfonic acid, Potassium-salt
Content:
- 86.5% DPS
- 5.4% By-product I
- 1.6% By-product III
- 0.8% Diphenylsulfone
- 4.2% H2O

Note: The substance described above is believed to be the same or similar to the reaction mass being registered but was not described as such in 1991.

Method

Target gene:

Salmonella typhimurium

Species / strain

Species / strain / cell type:

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

Metabolic activation:

with and without

Metabolic activation system:

S9 Mix

Test concentrations with justification for top dose:

Test concentrations used were 8, 40, 200, 1000 and 5000 ug/Plate

Vehicle / solvent:

The solvent employed was deionized water and, for the positive controls, DMSO

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: See Remarks

Remarks:

Positive Controls (without S9): sodium azide (TA1535); nitrofurantoin (TA100); 4-nitro-1,2-phenylene diamine (TA1537, TA98); Postive Controls (with S9) 2-aminoantrachene

Details on test system and experimental conditions:

For the mutant count, four plates were used, both with and without 59 mix, for each strain and dose. The same number of plates, filled with thee solvent minus the test substance, comprised the negative control. Each positive control also contained four plate per strain. The doses for the first trial were routinely determined on the basis of a standard protocol: 5000 ug or 5 ul per plate were used as the highest dose, if not limited by solubility. At least four additional doses were routinely used. If less than three doses were used for assessment, at least two repeats were performed. The results of the first experiment were then considered as a pre-test for toxicity. In case of a positive response, however, or if at least three doses could be evaluated for assessment, the first trial was included in the assessment. If the second test confirmed the results of the first, no additional repeat was performed. Doses of repeats were chosen on the basis of the results obtained in the first <0 experiment.

Evaluation criteria:

The following criteria determined the acceptance of an assay:
a) The negative controls had to be within the expected range, as defined by published data (i.e. Maron and Ames, 1983) and the laboratories' own historical data.
b) The positive controls had to show sufficient effects, as defined by the laboratories' experience.
c) Titer determinations had to demonstrate sufficient bacterial density in the suspension.

An assay which did not comply with at least on of the above criteria was not used for assessment. Furthermore, the data generated in this assay needed to be confirmed by two additional independent experiments. Even if the criteria for points (a), (b) and (c) were not met, an assay was accepted if it showed mutagenic activity of the test compound.

Results and discussion

Test results

Test results 1

Key result

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 2

Key result

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 3

Key result

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 4

Key result

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Any other information on results incl. tables

The Salmonella/microsome test, employing doses up to 5000 ug per plate, showed the substance not to produce bacteriotoxic or mutagenic effects. Evaluation of individual dose groups, with respect to relevant assessment parameters (dose effect, reproducibility) revealed no biologically relevant variations from the respective negative controls. No inhibition of growth was noted even at the limit dose. Positive controls, at comparatively low doses, resulted in the expected increases of the mutant counts to well over double those of the negative controls, and thus demonstrated the system's high sensitivity. Despite this sensitivity, no indications of mutagenic effects could be found at assessable doses up to 5000 ug per plate in any of the Salmonella typhimurium strains used.

Applicant's summary and conclusion

Conclusions:

The test item is not matagenic in the bacterial reverse mutation assay.

Executive summary:

In a GLP guideline bacterial reverse mutation assay using the plate incorporation method conducted according to OPPTS 870.5100, OECD 471, and EC method B.13/14, the substance showed no indications of mutagenic effects at doses up to 5000 uq per plate in any of the Salmonella typhimurium strains used.