1H-Indole-6-carboxylic acid, 3-cyclopentyl-1-methyl-, 1-methylethyl ester

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:

2007

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2007

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

propan-2-yl 3-cyclopentyl-1-methyl-1H-indole-6-carboxylate

EC Number:

935-121-6

Cas Number:

1253789-90-0

Molecular formula:

C18 H23 N O2

IUPAC Name:

propan-2-yl 3-cyclopentyl-1-methyl-1H-indole-6-carboxylate

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): CD00006066XX
- Physical state: tan powder
- Storage condition of test material: room temperature in the dark with desiccant
- Lot/batch No.: 7330-038-2
- Purity : 98.0 %

Method

Species / strain

Species / strain / cell type:

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

Metabolic activation:

with and without

Test concentrations with justification for top dose:

1.5, 5.0, 15.0, 50.0, 150.0, 500.0 , 1500.0, 5000.0 µg/plate ( initial toxicity-mutation assay )
50.0, 150.0, 500.0 , 1500.0, 5000.0 µg/plate ( confirmatory mutagenicity assay )

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: acetone;

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

9-aminoacridine

2-nitrofluorene

sodium azide

methylmethanesulfonate

other: 2-aminoanthracene

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation)

Evaluation criteria:

For the test article to be evaluated positive, it must cause a dose-related increase in the mean revertants per plate of at least one tester strain over a minimum of two increasing concentrations of the test article.
Data set for tester strains TA 1535/TA 1537 were judged positive if the increase in mean revertants at the peak of the dose response is equal to or
greater than 3.0-times the mean vehicle control.
Data set for tester strains TA 98/TA 100 and WP2 uvr A were judged positive if the increase in mean revertants at the peak of the dose response is
equal to or greater than 2.0-times the mean vehicle control.
An equviocal response is a biologically relevant increase in a revertant count that partially meets the criteria for evaluation as positive. This could be a dose- responsive increase that does not achieve the respective threshold cited above or a non-dose responsive increase that is equal or greater than the respective threshold cited. A response will be evaluate as negative, if it is neither positive nor equivocal.

Results and discussion

Test results

Species / strain:

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

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

No background lawn toxicity was observed but decreases in revertant counts were observed at 5000 µg/plate with tester strain TA 98 in the absence of S9 activation and testers strain TA 1537 in the presence of S9 activation.
Toxicity was observed beginning at 1500 or 5000 µg/plate with the tester strain TA 98 in the absence of S9 activation and tester strain WP2 uvr A in the presence and absence of S9 activation.

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative

All criteria for a valid study were met as described in the protocol. The results of the CD00006066XX-Bacterial Reverse Mutation Assay indicate that, under the test conditions of this study, CD00006066XX did not cause a positive response in either the presence or absence of Aroclor-induced rat
liver S9.

Executive summary:

The test article, CD00006066XX, was tested in the Bacterial Reverse Mutation Assay using Salmonella typhimurium and Escherichia coli tester strains in the presence and absence of Aroclor-induced rat liver S9. The assay was performed in two phases, using the plate incorporating method. The first phase, the initial toxicity-mutation assay, was used to establish the dose-range for the confirmatory mutagenicity assay and to provide a perliminary mutagenicity evaluation. The second phase, the confirmatory mutagenicity assay, was used to evaluate and confirm the mutagenic potential of the test article.

In the initial toxicity-mutation assay, the maximum dose tested was 5000 µg/plate. The dose levels tested were 1.5, 5, 5.0, 15, 50, 150, 500, 1500 and 5000 µg/plate. In the initial toxicity-mutation assay, no positive mutagenic response was observed. No background lawn toxicity was observed but decreases in revertant counts were observed at 5000 µg/plate with tester strain TA 98 in the absence of S9 activation and testers strain TA 1537 in the presence of S9 activation.Based on the findings of the initial toxicity-mutation assay, the maximum dose plated in the confirmatory mutagenicity assay, was 5000 µg/plate.

In the confiramtory mutagenicity assay, no positive mutagenic response was observed. The dose level tested were 50, 150, 500, 1500 and 5000 µg/plate .Toxicity was observed beginning at 1500 or 5000 µg/plate with the tester strain TA 98 in the absence of S9 activation and tester strain WP2 uvr A in the presence and absence of S9 activation.

Under the test conditions of this study, CD00006066XX, was concluded to be negative in the Bacterial Reverse Mutation Assay.