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Toxicological information

Genetic toxicity: in vitro

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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

Constituent 1
Chemical structure
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:
2-[(2-methylphenoxy)methyl]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 / strainopen allclose all
Species / strain / cell type:
S. typhimurium TA 97
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 resultsopen allclose all
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
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.