[(octyloxy)methyl]oxirane

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1980-1981

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1981

Report date:

1981

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

Study was performed according Ames et al. (1975).

Principles of method if other than guideline:

- Recommended strains for AT base pair are not included (E.coli WP2 strains or S. typhimurium TA102)
- No historical data presented
- Signs of toxicity not reported for main assay
- Raw data on TA1538, TA98, TA1537 not reported.
- No data on solvent/negative controls

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

[(octyloxy)methyl]oxirane

EC Number:

222-199-5

EC Name:

[(octyloxy)methyl]oxirane

Cas Number:

3385-66-8

Molecular formula:

C11H22O2

IUPAC Name:

2-[(octyloxy)methyl]oxirane

Test material form:

liquid

Details on test material:

Composition (identity and concentrations):
- Octyl glycidyl ether : 99.2% ( Determined by G.C. analysis)
- Octanol: 0.4% ( Determined by G.C. analysis)
- Water: 0.2%
- Free epi-chlorohydrin: < 1ppm
-Other
Oxirane oxygen: 8.7%/8.6% (measured/calculated)

Method

Target gene:

HisG gene

Species / strain

Species / strain 1

Species / strain / cell type:

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

Species / strain 2

Species / strain / cell type:

S. typhimurium TA 1538

Metabolic activation:

with and without

Metabolic activation system:

Aroclor-1254-induced rat liver microsome activation system (S9)

Test concentrations with justification for top dose:

Top dose: 500 µg/plate
Justification for top dose: Top concentration was selected at which the test item reduced 50-75% of the bacterial background lawn compared to the solvent control.
Tester strains (TA1535, TA100, TA1537, TA1538, and TA98)
With and without S9: 500, 166.7, 55.5, 18.5, 6.2, 2.1 µg/plate

Vehicle / solvent:

dimethylsufloxide (DMSO)

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

9-aminoacridine

2-nitrofluorene

N-ethyl-N-nitro-N-nitrosoguanidine

other: 2-Aminoanthracene

Details on test system and experimental conditions:

DOSE RANGE ASSAY:
According to Ames et al. (1975).

5 serial 10-fold dilutions beginning at 100 mg/ml were prepared in dimethylsufloxide (DMSO). A single plate was prepared from each dilution with strain TA100 After 48 h of incubation at 37°C, the number of revertant colonies was determined and the background lawn was examined through a dissecting microscope. The concentration of chemical which reduced the background lawn by 50-75% compared to the solvent control was selected as the highest testable dose. A 50-75% reduction of the background lawn was usually accompanied by a slight reduction in the number of spontaneous revertant colonies for non-mutagenic compounds.

MAIN ASSAY:
According to Ames et al. (1975).

NUMBER OF REPLICATIONS:
- Number of cultures per concentration: In triplicate

METHOD OF TREATMENT/ EXPOSURE:
- plate incorporation

POSITIVE CONTROLS:
Positive controls were run in parallel with each assay.
In the absence of the S9 metabolic activation system:
-N-methyl-N'-nitro-N-nitrosoguanidine (5/µg/plate) for TA1535 and TA100,
-2-nitrofluorene (50/µg/plate) for TA1538 and TA98,
-9-aminoacridine (125/µg/plate) for TA1537.

2-Aminoanthracene (5/µg/plate) was used as a positive control for all 5 strains in the presence of the S9 metabolic activation system.

NEGATIVE CONTROL: water

VEHICLE CONTROL: 0.1 ml DMSO

Evaluation criteria:

Mutation index: (the average number of revertant colonies on the test plates/ the average number of revertant colonies on the solvent control)

A mutation index number of 1 or less indicated as not mutagenic.
Numbers equal or greater than 2.0, when associated with a dose response over at least 3 concentrations, represent a mutagenic response.

Results and discussion

Test results

Test results 1

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

not examined

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Test results 2

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

not examined

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Test results 3

Species / strain:

S. typhimurium TA 1538

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

not examined

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Test results 4

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

not examined

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Test results 5

Species / strain:

S. typhimurium TA 100

Metabolic activation:

without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

not examined

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Test results 6

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with

Genotoxicity:

positive

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

not examined

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Test results 7

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with

Genotoxicity:

positive

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

not examined

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Additional information on results:

RESULTS:
Octyl glycidyl ether induced a weak dose response in the average number of revertant colonies in tester strain TA1535 and TA100 in the presence of metabolic activation: see illustration for detailed results
Maximum mutagenic index was 5.1 and 5.3 for TA1535 and TA100, respectively

Positive controls:
In all cases the positive controls exhibited at least a 10-fold increase in the number of revertant colonies (mutation index > 10):

Applicant's summary and conclusion

Conclusions:

An Ames test was performed according to Ames et al. (1975) with octyl glycidyl ether. Octyl glycidyl ether showed a positive mutagenic response in Salmonella typhimurium tester strains TA100 and TA1535 in the presence of metabolic activation.

Executive summary:

An Ames test was performed according to Ames et al. (1975). Octyl glycidyl ether was tested in triplicate in tester strains TA1535, TA100,TA1538, TA98 and TA1537 up to and including a top dose of 500 µg/plate (limit of cytotoxicity). After 48 hours plates were evaluated for the number of spontaneous revertant colonies compared to the number of revertant colonies in the solvent control. Octyl glycidyl ether showed a dose-dependent increase in revertant colonies in Salmonella typhimurium strains that detect base-pair substitution (TA100 and TA1535) only in the presence of metabolic activation. No mutagenic response was observed in TA1538, TA98 and TA1537 with and without metabolic activation. Based on the mutagenic response observed in this assay Octyl glycidyl ether is considered positive for bacterial mutagenicity.