Diphenyl ether

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

In vitro: Several studies were conducted to access genetic toxicity according to standard methods and most were in accordance with GLPs. These studies consisted of: Ames test (gene mutation), CHO/HGPRT (gene mutation), CHO (chromosome aberration) and UDS (DNA damage and or repair).

Link to relevant study records

Reference

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.

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

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

Target gene:

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

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

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.

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'.

None

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

Additional information from genetic toxicity in vitro:

In vitro: In the standard method 1978 key study (ks) Ames study (Klimisch=2), Diphenyl oxide (DPO) was assessed for mutagenic activity using 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. Results indicated that DPO was not mutagenic towards any of the Salmonella strains assayed under these test conditions.

In the standard method 1987 ks CHO/HGPRT mammalian cell forward gene mutation assay (Klimisch=2), there were no statistically significant increases in the mutation frequencies of DPO-treated cultures when compared to the negative controls.

In the standard method 1987 ks chromosome aberration study in Chinese Hamster Ovary (CHO) cells (Klimisch=2), treatment with DPO produced no statistically significant increase in the number of aberrations per cell and the proportion of aberrant metaphases at any dose level evaluated with and without S9 metabolic mix.

In the standard method 1987 ks unscheduled DNA synthesis in primary rat hepatocyte cultures (Klimisch=2), results indicate that DPO is not a genotoxic agent in the in vitro rat hepatocyte DNA repair assay.

Justification for classification or non-classification

Not classified - DPO was negative (non-genotoxic) in all of the in vitro genetic toxicity tests performed.