Diphenyl ether

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:

1978

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study was conducted according to a standard method but was non-GLP.

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:

1978

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

This study used methods and materials described by Ames et al . in Mutation Research (1975) Vol. 31, pp. 347-364.

GLP compliance:

no

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Diphenyl ether

EC Number:

202-981-2

EC Name:

Diphenyl ether

Cas Number:

101-84-8

Molecular formula:

C12H10O

IUPAC Name:

phenoxybenzene

Details on test material:

Technical material
Melting Point: 27C
Specific Gravity: 1.074
Appearance Clear

Method

Target gene:

TA98- hisD3052, TA100-hisG46, TA1535-hisG46, TA1537-hisC3076

Species / strain

Species / strain / cell type:

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

Details on mammalian cell type (if applicable):

No data

Additional strain / cell type characteristics:

not specified

Metabolic activation:

with and without

Metabolic activation system:

The compound was tested in the presence and absence of a mammalian activation system in both plate incorporation and spot tests.

Test concentrations with justification for top dose:

The sample was tested in plate incorporation assays at concentrations of: 0.05, 0.1, 0.13, 0.4, 1, 2, 10, 17, 33, 43, 100, and 500 ug/plate

Vehicle / solvent:

DMSO

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

yes

Positive controls:

yes

Positive control substance:

other: TA98: w/o S-9 4-nitroquinoline-N-oxide, w S-9 2-acetamidofluorene, TA100: w/o S-9 4-nitroquinollne -N-oxide, w S-9 benzo (a) pyrene; TA1535: w/o S-9 NaNO2, w S-9 tris ( 2, 3-dibromopropyl)phosphate, TA1537: w/o S-9 9-aminoacridine, w S-9 2 aminoanthracene

Details on test system and experimental conditions:

No additional data

Evaluation criteria:

A positive response is indicated if three treatments show a response which is significantly different from the solvent controls at the p less than 0.01 level and if there is a dose response.

Statistics:

Statistical analysis for significance of difference between treatments and controls is performed for each treatment using a t-test. Values of revertants / plate are transformed using log to the base 10. Variance is calculated as within-levels pooled variance for the treatment and solvent control revertants / plate. Values of p are calculated for a one-sided t-test.

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:

cytotoxicity

Remarks:

observed at the 33 ug and 100 ug levels with TA1535 and TA1537.

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

MUTAGENICITY TEST RESULTS:
1. Spot Test: The subject compound Diphenyl Oxide was assayed at a maximum concentration of 10 mg per plate using the four test strains TA98, TA100, TA1535, and TA1537. The compound was tested with and without mouse and rat microsomal preparations. No mutagenic activity was observed.
2. Plate Incorporation Test: No significant mutagenic activity was detected towards TA98, TA100, TA1535 or TA1537 in the Salmonella plate incorporation test of Diphenyl Oxide with or without rat S-9 microsomal activation. Maximum concentrations tested were 500 ug per plate in the absence of activation and 500 ug per plate in the presence of microsomal enzymes.

TOXICITY:
The subject compound gave no indication of toxic effects with strains TA98 and TA100 at the 100 ug per plate level. However, toxic damage was observed at the 33 ug and 100 ug levels with TA1535 and TA1537.

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

None

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative

Diphenyl Oxide was not mutagenic towards any of the Salmonella strains assayed under these test conditions.

Executive summary:

The objective of the study was to determine whether any significant mutagenic activity of' the test material could be detected towards Salmonella strains TA98, TA100, TA1535, and TA1537 either in the presence or absence of a mammalian metabolic activation system in both plate incorporation and spot tests. This study used rnethods and materials described by Ames et al. in Mutation Research (1975) Vol. 31, pp. 347-364, and as described in the standard protocol for Salmonella mutagenicity tests on file in the Monsanto Co. Environrnental Health Laboratory: Standard Protocol for Ames/Salmonella Test (2-10-78). The sample was tested in plate incorporation assays at concentrations of: 0.05, 0.1, 0.13, 0.4, 1, 2, 10, 17, 33, 43, 100, and 500 ug/plate.

Diphenyl Oxide was not mutagenic towards any of the Salmonella strains assayed under these test conditions.