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Toxicological information

Genetic toxicity: in vitro

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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-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
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

Reference
Name:
Unnamed
Type:
Constituent
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.