2,3-epoxypropyl o-tolyl ether

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was conducted according to the standard U.S. National Toxicology Program study protocol with GLP compliance.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1986

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

No E. coli tester strains included.

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

2,3-epoxypropyl o-tolyl ether

EC Number:

218-645-3

EC Name:

2,3-epoxypropyl o-tolyl ether

Cas Number:

2210-79-9

Molecular formula:

C10H12O2

IUPAC Name:

oxirane

Constituent 2

Reference substance name:

Oxirane, 2-[(2-methylphenoxy)methyl]-

IUPAC Name:

Oxirane, 2-[(2-methylphenoxy)methyl]-

Details on test material:

As per IUCLID Sections 1.1. 1.2. and 4.1.

Method

Target gene:

Histidine synthesis gene.

Species / strain

Species / strain 1

Species / strain / cell type:

S. typhimurium TA 97

Species / strain 2

Species / strain / cell type:

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

Metabolic activation:

with and without

Metabolic activation system:

Aroclor 1254-induced male, Sprague-Dawley rats and Syrian hamsters liver S9 fraction.

Test concentrations with justification for top dose:

0, 3.3, 10, 33, 100 and 333 ug/plate

Vehicle / solvent:

DMSO

Controls

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: See testing Haworth et al., 1983, Environ. Mutagen., 5. Suppl. 1, 3—142.

Details on test system and experimental conditions:

The test substance was tested in Salmonella strains TA98, TA100, TA1535, and TA1537 and/or TA97 without metabolic activation and with liver S9 preparations from Aroclor 1254-induced male, Sprague-Dawley rats and Syrian hamsters, in a liquid preincubation protocol. Tester strains grown up over night in nutrient broth cultures were to 5 doses, using triplicate plates. Tests were repeated at least once; a chemical was not designated positive or negative unless the results were reproducible. Following the preincubation treatment at approximately 37 C minimal soft agar was added to the treatment test tubes and the contents of the tubes poured over minimal agar plates. The plates were incubated 48-72 hr at 37 C before scoring for histdine positive revertants. For additional methodological details see Haworth et al., 1983, Environ. Mutagen., 5. Suppl. 1, 3—142.

Evaluation criteria:

The test substance was not designated positive or negative unless the results were reproducible. A positive response was defined as a reproducible, dose-related increase in his + revertants over the solvent control level. The tester strains must have demonstrated their relevant genetic characterstics and responded to the positive controls.

Statistics:

None.

Results and discussion

Test results

Test results 1

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

without

Genotoxicity:

positive

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 2

Species / strain:

S. typhimurium TA 100

Metabolic activation:

without

Genotoxicity:

positive

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Additional information on results:

Treatment with the test substance, 2,3-epoxypropyl o-tolyl ether, induced a reproducible, dose-related increase in the frequency of histidine positive revertants in both tester strains TA1535 and TA100 without metabolic activation preparation. The increase in revertant frequency reached 6.2-fold the concurent spontaneous background frequency in tester strain TA100 at the high dose level of 100 ug/plate. A 14.4-fold increase of the His+ revertant frequency was observed in tester strain TA 1535 at the high dose level 333 ug/plate.

Remarks on result:

other: strain/cell type: TA1535

Remarks:

Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
positive only without S9 metabolic activation preparation.

The test substance induced a reproducible, dose-related increase in the His+ revertant frequency in Salmonella tester strains TA1535 and TA100 without rodent liver S9 metabolic activation. Therefore, the test substance is a direct-acting gene-mutagen in Salmonella under the conditions of the study.

Executive summary:

The test substance, 2,3-epoxypropyl o-tolyl ether was evaluated for its potential to induce gene-mutation in bacteria by the U.S. National Toxicology using the preincubation O.E.C.D. test guideline no. 471 method. The test substance induced a reproducible, dose-related increase in the His+ revertant frequency in Salmonella tester strains TA1535 and TA100 without rodent liver S9 metabolic activation. Therefore, the test substance is a direct-acting gene-mutagen in Salmonella under the conditions of the study.