Cyclopentadecanone

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:

22 August 1997 - 9 September 1997

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)

Version / remarks:

26 May 1983

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 472 (Genetic Toxicology: Escherichia coli, Reverse Mutation Assay)

Version / remarks:

26 May 1973

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

OJ No. L383A, 29-12-1992

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: US EPA Method HG-Gene Muta - S. typhimurium: The Salmonella typhimurium reverse mutation assay

Version / remarks:

1984

Deviations:

no

Test guideline 5

Qualifier:

according to guideline

Guideline:

other: US EPA HG-Gene Muta - E. coli: The Escherichia coli reverse mutation assay

Version / remarks:

1984

Deviations:

no

Test guideline 6

Qualifier:

according to guideline

Guideline:

JAPAN: Guidelines for Screening Mutagenicity Testing Of Chemicals

Version / remarks:

28 January 1985

Deviations:

no

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Cyclopentadecanone

EC Number:

207-951-2

EC Name:

Cyclopentadecanone

Cas Number:

502-72-7

Molecular formula:

C15H28O

IUPAC Name:

cyclopentadecanone

Test material form:

solid: crystalline

Specific details on test material used for the study:

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature in the dark
- Stability under test conditions: stable
- Solubility and stability of the test substance in the solvent/vehicle: soluble at 50 mg/mL in DMSO

Method

Target gene:

S. typhimurium: his
E.coli: try

Species / strain

Species / strain 1

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2

Additional strain / cell type characteristics:

not applicable

Species / strain 2

Species / strain / cell type:

S. typhimurium TA 1538

Additional strain / cell type characteristics:

not applicable

Metabolic activation:

with and without

Metabolic activation system:

Rat S9

Test concentrations with justification for top dose:

312.5, 625, 1250, 2500 and 5000 µg/plate (based on maximal solubility of the test article in DMSO)

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: based on the solubility of the test substance

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

9-aminoacridine

2-nitrofluorene

N-ethyl-N-nitro-N-nitrosoguanidine

other: 2-aminoanthracene

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation);

DURATION
- Exposure duration: 3 days

NUMBER OF REPLICATIONS: triplicate

DETERMINATION OF CYTOTOXICITY
relative total growth
- Any supplementary information relevant to cytotoxicity:
Preliminary toxicity study was performed using 6 tester strains. The maximal tested concentration was 5000 µg/plate . Three ten-fold serial dilutions were also tested. A single plate per dose was used.

Evaluation criteria:

If treatment with a substance produces increase in revertant colony numbers of at least twice of the concurrent negative control, with some evidence of dose-response relationship, in two separate experiments, with any bacterial strain either in the presence or the absence of S9, it is considered to show evidence of mutagenic activity in this test system.
If treatment with a test substance does not produce a reproducible increase of at least 1.5 fold of the concurrent solvent control, at any dose level in any strain, it is considered to show no evidence of mutagenic activity in this test system.

Statistics:

No statistical analysis was performed.

Results and discussion

Test results

Test results 1

Key result

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 2

Key result

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 3

Key result

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 4

Key result

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 5

Key result

Species / strain:

S. typhimurium TA 1538

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 6

Key result

Species / strain:

E. coli WP2 uvr A

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

RANGE-FINDING/SCREENING STUDIES:
The test substance was not toxic to tester strains at the highest concentration of 5000 µg/plate

Applicant's summary and conclusion

Conclusions:

In the reliable study, performed according to OECD Guidelines 471 and 472, the test substance cyclopentadecanone was not mutagenic in the strains S. typhimurium TA98, TA100, TA1535, TA 1537 and TA1538 and E. coli WP2 uvrA, both with and without metabolic activation, up to the highest tested concentration of 5000 µg/plate.

Executive summary:

In the reliable study performed according to OECD Guidelines 471 and 472, cyclopentadecanone did not increase the number of revertant colonies in the tester strains S. typhimurium TA98, TA100, TA1535, TA1537 and TA1538, and E. coli WP2 uvrA, both in the presence and absence of metabolic activation (rat S9), up to the limit concentration of 5000 µg/plate. No cytotoxicity was observed. DMSO was used as a solvent. The testing was performed in triplicate. Positive controls produced satisfactory mutagenic response. Based on the results of the study, cyclopentadecanone was not mutagenic in bacterial cells.