Isopentyl salicylate

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1999

Report date:

1999

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Isopentyl salicylate

EC Number:

201-730-4

EC Name:

Isopentyl salicylate

Cas Number:

87-20-7

Molecular formula:

C12H16O3

IUPAC Name:

isopentyl salicylate

Method

Target gene:

Histidine

Species / strain

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102

Metabolic activation:

with and without

Metabolic activation system:

liver homogenate (S9) from Aroclor 1254

Test concentrations with justification for top dose:

5 to 5000 µg per plate.

Vehicle / solvent:

- Vehicle: DMSO

Controls

Controls 1

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Remarks:

water

Positive controls:

yes

Positive control substance:

sodium azide

Controls 2

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

Positive controls:

yes

Positive control substance:

2-nitrofluorene

Controls 3

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

Positive controls:

yes

Positive control substance:

other: 2-Aminoanthracene

Controls 4

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Remarks:

water

Positive controls:

yes

Positive control substance:

mitomycin C

Controls 5

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Remarks:

water

Positive controls:

yes

Positive control substance:

9-aminoacridine

Details on test system and experimental conditions:

METHOD OF APPLICATION: standard plate-incorporation assay with and without liver homogenate activation.

DURATION
- Exposure duration: 48 to 72 h at 37°C in the dark

NUMBER OF REPLICATIONS: 3

EVALUATION
- Counting of the number of revertant colonies (his+ revertants)
- Examination normal background lawn
- Examination precipitates
- Microscopically: microcolony growth

OTHER
When there is any question about the nature of colonies scored as revertants and when positive mutagenic results are obtained, the genotype of revertant colonies are spot-checked by picking and streaking on histidine free plates.
To confirm the reversion properties and specificity of the bacterial strains as well as the activity of the liver homogenates used, positive mutagenesis controls were run simultaneously.
The genotypes of the tester strains (histidine requirement, spontaneous reversion frequency, sensitivity to UV-light, crystal violet and ampicillin) were checked in each experiment. The Vogel-Bonner minimal plates, the test compound, and the S9-mix viere checked for sterility.

Results and discussion

Test results

Species / strain:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

500 µg/plate (TA100, TA102, TA1535 and TA1537); 5000 µg/plate (TA98)

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: all strains/cell types tested

Applicant's summary and conclusion

Conclusions:

Interpretation of results: negative

The test item was not mutagenic to Salmonella typhimurium strains TA98, TA100, TA102, TA1535, and TA1537 in the presence and absence of a metabolizing system.

Executive summary:

The mutagenicity of the test item was studied with five mutant strains of Salmonella typhimurium (TA1535, TA1537, TA98, TA100, and TA102). The study has been performed according to OECD 471 and GLP.

The investigations were carried out using the standard plate incorporation assay with and without liver homogenate (S9) pretreated male rats as metabolic activation system.

The test item did not induce a significant increase in the mutation frequency of any of the tester strains in the absence and presence of a metabolic activation system. Therefore, the test item is under the experimental conditions described, not mutagenic.