Reaction mass of 3-[(diphenoxyphosphoryl)oxy]phenyl triphenyl 1,3-phenylene bis(phosphate) and tetraphenyl 1,3-phenylene bis(phosphate)

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

Study period:

September 12, 1988 – October 7, 1988

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Test was conducted according to OECD Test Guideline No. 471, 1983, under GLP Standards, and QA. Chemical identity and purity of the test substance are not reported. One strain not tested.

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Version / remarks:

1983

Deviations:

yes

Remarks:

Only four Salmonella test strains

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

EU Method B.14 (Other effects-Mutagenicity: Salomonella typhimurium - Reverse Mutation Assay, 1984)

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes

Remarks:

Statement of Compliance

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

3-[(diphenoxyphosphoryl)oxy]phenyl diphenyl phosphate

EC Number:

701-337-2

Cas Number:

not available

Molecular formula:

C30H24O8P2

IUPAC Name:

3-[(diphenoxyphosphoryl)oxy]phenyl diphenyl phosphate

Details on test material:

- Name of test material (as cited in study report): CR 733-S
- Physical state: no data
- Lot/batch No.: confidential
- Storage condition of test material: At room temperature in the dark

Method

Target gene:

His-gene: Amino acid histidine

Species / strain

Species / strain / cell type:

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

Details on mammalian cell type (if applicable):

Not applicable

Additional strain / cell type characteristics:

other: S. typhimurium TA98 and TA100: pKM101. All strains: rfa, gal, chl, bio, uvrB

Metabolic activation:

with and without

Metabolic activation system:

Rat liver S9 induced by Aroclor 1254

Test concentrations with justification for top dose:

100, 333, 1000, 3330, and 5000 μg/plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: DMSO

Controls

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: -S9-mix: TA1535: sodium azide; TA1537: 9-aminoacridine; TA98: daunomycine; TA100: methylmethanesulfonate. +S9-mix: all strains: 2-aminoanthracene.

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Selection time (if incubation with a selection agent): 48 hours

SELECTION AGENT (mutation assays): agar containing Histidine

NUMBER OF REPLICATIONS: 3 plates per concentration

NUMBER OF CELLS EVALUATED: 1 x 10*9 viable cells

DETERMINATION OF CYTOTOXICITY
- Method: Viability determination in non-selective agar: the percentage survival of the TA100 culture is determined by comparing the number of colonies on the solvent control plate with those on the plates containing the test substance, both in the absence and presence of S9-mix.

OTHER EXAMINATIONS:
Preliminary toxicity at 1.0, 3.3, 10, 33.3, 100, 333, 1000, 3330, and 5000 ug/plate.
Plate incorporation: independently repeated experiment.

Evaluation criteria:

A test substance is considered negative (not mutagenic) in the Ames test if:
a) The total number of revertants in any test strain at any concentration is not greater than two times the solvent control value, with or without metabolic activation.
b) The negative response should be reproducible in at least one independently repeated experiment.
A test substance is considered positive (mutagenic) in the Ames test if:
a) It induces at least a 2-fold, dose-related increase in the number of revertants with respect to the number induced by the solvent control in any of the test strains, either with or without metabolic activation. However, any mean plate count of less than 20 is considered to be not significant. If the test substance shows in the first test only a positive response at one or two concentrations, the assay is repeated with doses just below and exceeding those showing positive effects in the first test.
b) The positive response should be reproducible in at least one independently repeated experiment.

Statistics:

Mean and Standard Deviation

Results and discussion

Test results

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:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Additional information on results:

RANGE-FINDING/SCREENING STUDIES: The test substance was not toxic towards the test strain TA100 in the preliminary toxicity test, both in the absence and presence of S9-mix. Therefore 5000 ug/plate was chosen as the top dose level in the mutation tests.

COMPARISON WITH HISTORICAL CONTROL DATA: The negative and strain-specific positive control values fell within the laboratory background historical ranges.

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

Not relevant

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative with metabolic activation
negative without metabolic activation

All bacterial strains showed negative responses over the entire dose range of the test substance. Based on the results of this study it is concluded that the test substance can be considered as not mutagenic in the Ames Salmonella/microsome assay.

Executive summary:

CR 733-S was tested in the Salmonella/microsome plate test at 100, 333, 1000, 3330, and 5000 ug/plate in the absence and presence of S9-mix. The test substance did not induce a dose-related increase in the number of revertant (His+) colonies in each of the four test strains (S. typhimurium TA1535, TA1537, TA98, and TA100). These results were confirmed in an independently repeated experiment. The test substance can, therefore, be considered as not mutagenic in this test system.