2-heptylcyclopentanone

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Study period:

18 July, 2000 - 25 August, 2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Version / remarks:

1997

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

1

Reference substance name:

2-heptylcyclopentanone

EC Number:

205-273-1

EC Name:

2-heptylcyclopentanone

Cas Number:

137-03-1

Molecular formula:

C12H22O

IUPAC Name:

2-heptylcyclopentan-1-one

Test material form:

liquid

Method

Target gene:

S. typhimurium: Histidine gene

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:

Rat liver S9-mix induced by Aroclor 1254

Test concentrations with justification for top dose:

- Experiment 1 and 2:
Due to cytotoxicity in an initial toxicity test, the following dose levels were used:
All 5 strains, without S9: 1.5, 5, 15, 50, 150 and 1500 μg/plate
All 5 strains, with S9: 5, 15, 50, 150, 500 and 1500 μg/plate

Vehicle / solvent:

- Solvent used: DMSO

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Remarks:

50 μL/plate DMSO

Positive controls:

yes

Positive control substance:

9-aminoacridine

2-nitrofluorene

sodium azide

mitomycin C

other: With S9 2-aminoanthracene: 0.7 μg/plate for TA 100, 1 μg/plate for TA 1535, 1.5 μg/plate for TA 98, TA 102 and TA 1537

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Exposure duration: 48 hours

NUMBER OF REPLICATIONS:
- Doses of the test substance were tested in triplicate in each strain.

DETERMINATION OF CYTOTOXICITY
- Method: the plates were examined for a decline in the number of spontaneous revertants, the existence of a normal background lawn and microscopically for microcolony growth.

Evaluation criteria:

No data.

Statistics:

X2-test (Mohn and Ellenberger, 1977)

Results and discussion

Test results

Test results 1

Key result

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

at concentrations of 150 µg/plate and upwards in the absence of S9-mix and at concentrations of 500 µg/plate and upwards in the presence of S9-mix.

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 2

Key result

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

at concentrations of 150 µg/plate and upwards in the absence of S9-mix and at concentrations of 500 µg/plate and upwards in the presence of S9-mix.

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 3

Key result

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

at concentrations of 150 µg/plate and upwards in the absence of S9-mix and at concentrations of 500 µg/plate and upwards in the presence of S9-mix.

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 4

Key result

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

at concentrations of 150 µg/plate and upwards in the absence of S9-mix and at concentrations of 500 µg/plate and upwards in the presence of S9-mix.

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 5

Key result

Species / strain:

S. typhimurium TA 102

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

at concentrations of 150 µg/plate and upwards in the absence of S9-mix and at concentrations of 500 µg/plate and upwards in the presence of S9-mix.

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: No precipitation was observed up to and including the top dose of 1500 μg/plate.

COMPARISON WITH HISTORICAL CONTROL DATA:
The number of spontaneous revertants observed using each of the five strains was close to those previously established in the laboratory and was within the range obtained by Ames et al. (1975) as well as reported by De Serres and Shelby (1979).
Similarly, the results with the positive control substances confirmed the known reversion properties and specificity of the tester strains as well as the full activity of the metabolizing system.

Applicant's summary and conclusion

Conclusions:

The substance is not mutagenic in the Salmonella typhimurium reverse mutation assay performed according to OECD 471 guideline and GLP principles.

Executive summary:

The mutagenic activity of the substance was evaluated in accordance with OECD 471 guideline and according to GLP principles. The test was performed in two independent direct plate experiments, both in the absence and presence of S9-mix up to and including 500 and 1500 μg/plate, respectively. Adequate negative and positive controls were included. Toxicity was observed in all Salmonella strains at concentrations of 150 µg/plate and upwards in the absence of S9-mix and at concentrations of 500 µg/plate and upwards in the presence of S9-mix. The substance did not induce a significant dose-related increase in the number of revertant (His+) colonies in each of the five S. typhimurium tester strains (TA1535, TA1537, TA98, TA100 and TA102), both in the absence and presence of S9-metabolic activation. These results were confirmed in independently repeated experiments. Based on the results of this study it is concluded that the substance is not mutagenic in the Salmonella typhimurium reverse mutation assay.