6-glycidyloxynapht-1-yl oxymethyloxirane

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:

12.02.1986 to 03.03.1986

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline Study performed under GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1986

Report date:

1986

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

JAPAN: Guidelines for Screening Mutagenicity Testing Of Chemicals

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

429-960-2

EC Name:

-

Cas Number:

27610-48-6

Molecular formula:

C16H16O4

IUPAC Name:

2-[({6-[(oxiran-2-yl)methoxy]naphthalen-1-yl}oxy)methyl]oxirane

Test material form:

other: viscous liquid

Details on test material:

-Storage Temperature: Stored at room temperature

Method

Species / strain

Species / strain 1

Species / strain / cell type:

E. coli WP2 uvr A

Species / strain 2

Species / strain / cell type:

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

Species / strain 3

Species / strain / cell type:

S. typhimurium, other: strain TA 1538

Metabolic activation:

with and without

Metabolic activation system:

S-9 mix

Test concentrations with justification for top dose:

Test concentration (microgramme/plate):
0.1, 0.5, 1, 5, 10, 50, 100 and 500 microgramme/plate.

Vehicle / solvent:

Solvent: Dimethylsulphoxide.

Controls

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

9-aminoacridine

2-nitrofluorene

N-ethyl-N-nitro-N-nitrosoguanidine

other: 2-aminoanthracene

Evaluation criteria:

A compound is deemed to provide mutagenic potential if:
- a statistically significant dose related increase in the number of revertant colonies is obtained in two separate experiments and the increase of revertant coloniesis at least twice the concurrent solvent control value.

Statistics:

not mentioned

Results and discussion

Test results

Test results 1

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with

Genotoxicity:

positive

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Positive controls validity:

valid

Test results 2

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with

Genotoxicity:

positive

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Positive controls validity:

valid

Test results 3

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Positive controls validity:

valid

Test results 4

Species / strain:

S. typhimurium TA 100

Metabolic activation:

without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Positive controls validity:

valid

Test results 5

Species / strain:

E. coli WP2 uvr A

Metabolic activation:

with and without

Genotoxicity:

positive

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Positive controls validity:

valid

Test results 6

Species / strain:

S. typhimurium, other: TA98, TA1537 and TA1538

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Positive controls validity:

valid

Applicant's summary and conclusion

Conclusions:

It is concluded that the substance shows evidence of mutagenic activity, possibly as a result of base-pair substitution, when tested in this bacterial system.

Executive summary:

In the dose range finding test the substance was toxic towards the tester strains, especially in the absence of metabolic ctivation, at the higher dose levels. Therefore the top dose levels chosen for the subsequent mutation test were 500 microgr/plate, in the presence of metabolic activation, and 50 microgr/plate, in the absence of metabolic activation.

However, the toxic effect of the substance was less marked with strainWP2 uvrA than the other 5 strains, thus a top dose level of 1000 microgr/plate was chosen for WP2 uvrA in the presence of metabolic activation.

In both mutation tests, increases in revertant colony numbers were observed with tester starins TA 135 and TA 100, in the presence of metabolic activation, and with WP2 uvrA, in the presence and absence of etabolic activation, following treatment with EPICLON EXA-4032.

It is concluded that EPICLON EXA-4032 shows evidence of mutagenic activity, possibly as a result of base-pair substitution, when tested in this bacterial system.