Oxydiethylene dinitrate

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:

19.8. - 30.8.1985

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Acceptable, well documented study report which meets basic scientific principles. GLP study.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1985

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

other: Maron, D.M., Ames, B.N., Revised methods for the Salmonella Mutagenicity Test. Mutation. Res. 1983; 113:173-215.

Deviations:

yes

Remarks:

See Overall remarks

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: Ames Salmonella/Mammalian Microsome Mutagenesis Test. LAIR Standard Operating Procedure OP-STX-1, Letterman Army Institute of Research, Presidio of San Francisco, CA. 15 November 1983

Deviations:

yes

Remarks:

See Overall remarks

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Oxydiethylene dinitrate

EC Number:

211-745-8

EC Name:

Oxydiethylene dinitrate

Cas Number:

693-21-0

Molecular formula:

C4H8N2O7

IUPAC Name:

2-[2-(nitrooxy)ethoxy]ethyl nitrate

Details on test material:

- Name of test material (as cited in study report): Diethyleneglycol dinitrate
- Physical state: pale yellow liquid
- Analytical purity: 96.6%
- Impurities (identity and concentrations): not identified
- Stability under test conditions: stable
- Storage condition of test material: at room temperature (21°C)

Method

Target gene:

gene for synthesis of histidine

Species / strain

Species / strain 1

Species / strain / cell type:

S. typhimurium TA 97

Species / strain 2

Species / strain / cell type:

S. typhimurium TA 98

Species / strain 3

Species / strain / cell type:

S. typhimurium TA 100

Species / strain 4

Species / strain / cell type:

S. typhimurium TA 102

Metabolic activation:

with and without

Metabolic activation system:

S-9 microsome fraction

Test concentrations with justification for top dose:

0.0016, 0.008, 0.04, 0.2, 1 and 5 µl/plate

Vehicle / solvent:

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

Controls

Controls 1

Untreated negative controls:

yes

Positive controls:

yes

Positive control substance:

benzo(a)pyrene

Controls 2

Untreated negative controls:

yes

Positive controls:

yes

Positive control substance:

other: 2-aminofluorene

Controls 3

Untreated negative controls:

yes

Positive controls:

yes

Positive control substance:

other: 2-aminoanthracene

Controls 4

Untreated negative controls:

yes

Positive controls:

yes

Positive control substance:

4-nitroquinoline-N-oxide

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation)

NUMBER OF REPLICATIONS: Plates were prepared in triplicate.

DETERMINATION OF CYTOTOXICITY
- Method: relative total growth

Evaluation criteria:

Criteria for a positive response are a correlated dose-response relationship and a twofold increase in revertant colony counts relative to the respective negative control counts.

Results and discussion

Test results

Test results 1

Species / strain:

S. typhimurium TA 97

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not determined

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 2

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not determined

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 3

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 4

Species / strain:

S. typhimurium TA 102

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not determined

Untreated negative controls validity:

valid

Positive controls validity:

valid

Applicant's summary and conclusion

Conclusions:

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

Diethyleneglycol dinitrate was evaluated for mutagenic potential in the Ames Test, both in the presence and absence of metabolic activation, and did not induce a positive mutagenic response under conditions of this study.

Executive summary:

The mutagenic potential of diethyleneglycol dinitrate (DEGDN) was assessed by using the Ames Salmonella/Mammalian Microsome Mutagenicity Test. Tester strains TA97, TA98, TAl00, and TA102 were exposed to doses ranging from 5 µl/plate to 0.0016 µl/plate. The test compound was not mutagenic under conditions of this test.