1-benzyl-4-piperidone

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

Study period:

2003-07-31 to 2003-09-07

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

Comparable to OECD guideline 471 study with acceptable restrictions; only 3 strains were tested, only one experiment was performed without justification provided, only brief information on methods. However, study was performed in the presence and absence of metabolic activation with positive and vehicle controls. Expert statement is added in the field "overall remarks" to justify the fact that no further testing is necessary.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

Only 3 strains were tested, brief information on methods.

GLP compliance:

no

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

1-benzyl-4-piperidone

EC Number:

222-782-4

EC Name:

1-benzyl-4-piperidone

Cas Number:

3612-20-2

Molecular formula:

C12H15NO

IUPAC Name:

1-benzylpiperidin-4-one

Details on test material:

- Name of test material: T15
- Substance type: no data
- Physical state: pale yellow liquid
- Analytical purity: 100 %
- Impurities: not applicable
- Composition of test material, percentage of components: no data
- Isomers composition: no data
- Purity test date: no data
- Lot/batch No.: no data
- Expiration date of the lot/batch: no data
- Stability under test conditions: no data
- Storage condition of test material: room temperature in the dark
- Other: received on 2003-04-24

Specific details on test material used for the study:

Description: Pale yellow liquid
Purity: 100%
Date received: 2003-04-24
Storage conditions: Room temperature in the dark

Method

Target gene:

histidine locus

Species / strain

Species / strain / cell type:

S. typhimurium, other: TA100, TA98 and TA102

Details on mammalian cell type (if applicable):

not applicable

Additional strain / cell type characteristics:

not specified

Metabolic activation:

with and without

Metabolic activation system:

10 % rat liver S9 in standard co-factors

Test concentrations with justification for top dose:

0, 0.5, 1.5, 5, 15, 50, 150, 500, 1500 and 5000 µg/plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: no data

Controls

Controls 1

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

N-ethyl-N-nitro-N-nitrosoguanidine

Remarks:

Without S9; at 3 µg/plate for TA100

Controls 2

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

mitomycin C

Remarks:

Without S9; at 0.5 µg/plate for TA102

Controls 3

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

4-nitroquinoline-N-oxide

Remarks:

without S9: at 0.2 µg/plate for TA98

Controls 4

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2-aminoanthracene

Remarks:

with S9; at 1 µg/plate for TA100

Controls 5

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 1,8-dihydroxyanthraquinone

Remarks:

with S9; at 10 µg/plate for TA102

Controls 6

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

benzo(a)pyrene

Remarks:

with S9; at 5 µg/plate for TA98

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Exposure duration: 3 days
- Selection time (if incubation with a selection agent): 3 days - simultaneous with exposure

SELECTION AGENT: histidine

NUMBER OF REPLICATIONS: triplicates

DETERMINATION OF CYTOTOXICITY:
- Method: reduction in the growth of the bacterial background lawn

Evaluation criteria:

no data

Statistics:

no data

Results and discussion

Test results

Species / strain:

S. typhimurium, other: TA98, TA100 and TA102

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

TEST-SPECIFIC CONFOUNDING FACTORS:
- Evaporation from medium: no data
- Water solubility: no data
- Precipitation: none

RANGE-FINDING/SCREENING STUDIES: no data

COMPARISON WITH HISTORICAL CONTROL DATA:
The vehicle control plates gave counts of revertant colonies within normal range. All of the positive controls induced marked increases in the frequency of revertant colonies, both with and without metabolic activation. Thus, the sensitivity of the assay and the efficacy of the S9 mix were validated.

ADDITIONAL INFORMATION ON CYTOTOXICITY:
The test substance caused no visible reduction in the growth of the bacterial background lawn at any dose level.

Remarks on result:

other: all strains/cell types tested

Applicant's summary and conclusion

Conclusions:

Interpretation of the results:
negative with and without metabolic activation

The test substance was evaluated for mutagenic potential using the "Ames Test" in S. typhimurium strains TA100, TA98 and TA102 in the absence and presence of metabolic activation. Based on the results, the test substance was considered to be non-mutagenic under the conditions of the study.