p-tert-butylphenyl 1-(2,3-epoxy)propyl 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 O.E.C.D. test guideline 471 by the U.S. National toxicology Program with GLP compliance.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1986

Report date:

1986

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

Conducted with both rat and hamster liver derived S9 metabolic activation preperations.

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

p-tert-butylphenyl 1-(2,3-epoxy)propyl ether

EC Number:

221-453-2

EC Name:

p-tert-butylphenyl 1-(2,3-epoxy)propyl ether

Cas Number:

3101-60-8

Molecular formula:

C13H18O2

IUPAC Name:

2-[(4-tert-butylphenoxy)methyl]oxirane

Constituent 2

Reference substance name:

p-tert-butylphenyl-1-(2,3)-epoxypropyl ether

IUPAC Name:

p-tert-butylphenyl-1-(2,3)-epoxypropyl ether

Constituent 3

Reference substance name:

Oxirane, 2-((4-(1,1-dimethylethyl)phenoxy)methyl)-

IUPAC Name:

Oxirane, 2-((4-(1,1-dimethylethyl)phenoxy)methyl)-

Test material form:

other: Liquid at room temperature.

Details on test material:

As per IUCLID5 Sections 1.1. 1.2. and 4.1.

Method

Target gene:

histidine synthesis

Species / strain

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, rat and Syrian hamster liver S9 metabolic activation.

Test concentrations with justification for top dose:

0, 1.0, 3.3, 10, 33 and 67 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:

not specified

Remarks:

As listed: Haworth, S., T. Lawlor, K. Mortelmans, W. Speck and E. Zeiger (1983) Salmonella mutagenicity test results for 250 chemicals, 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, rats and Syrian hamsters, in a liquid incubation protocol. The Salmonella tester straind were grown up over night in nutrient broth to late log phase. The study was performed at 5 doses, using triplicate plates. Tests were repeated at least once. S9 metabolic activation mix or buffer and vehicle, positive control substance or test substance dilution were added culture tubes. The appropriate tester strain was then added to the cultures tubes. The cultures were then incubated for approximately 30 minutes with shaking at approximately 37 C. Following this liquid preincubation treatment, approximately 2 mL of molten minimal soft agar were added to each tube followed by vortexing. The contents of the culture tubes were poured over minimal medium agar plates. The plates were allowed to harden and then incubated at approximately 37 C for 48-72 hr.

Evaluation criteria:

A positive response was defined as a reproducible, dose-related increase in his+ revertants over the solvent control level.

Statistics:

No

Results and discussion

Test results

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:

The test substance did not induce an increase of the gene-mutation frequency in Salmonella strains, TA1535, TA1537 and TA98 with and without liver derived S9 metabolic activation preparation. In the presence of liver S9 metabolic activation an increase ot his+ revertants was not observed in strain TA100 when tested upto 200 ug/plate.

Remarks on result:

other: strain/cell type: TA100

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

Strain TA100 Without S9 Metabolic Activation

_________________________________________

Dose ug/plate Mean his+ Revertants

0 98

1.0 87

3.3 99

10 140

33 225

67 191

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
positive In tester strain TA100 without S9 metabolic avtivation.

The test substance induced a reproducible, dose-related increase of the his+ revertant frequency in Salmonella strain TA100 without liver S9 metabolic activation preparation. The data suggest that the test substance is mutagenic without liver S9 metabilic activation under the conditions of the study.

Executive summary:

The test substance, p-tert-butylphenyl-1 -(2,3 -epoxy)propyl ether was accessed for the potential to induce gene-mutation in an O.E.C.D. test guideline 471 study conducted for the U.S. National Toxicology Program with a liquid preincubation protocol. The test substance induced a reproducible, dose-related increase of the his+ revertant frequency in Salmonella strain TA100 without liver S9 metabolic activation preparation. The increase in his+ mutant frequency reached approximately 2.3 -fold the concurrent vehicle control value at 33 ug/plate. The data suggest that the test substance is mutagenic without liver S9 metabolic activation under the conditions of the study.