1H-Indole-6-carboxylic acid, 3-cyclopentyl-

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

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2005

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:

3-cyclopentyl-1H-indole-6-carboxylic acid

Cas Number:

494799-36-9

Molecular formula:

C14 H15 N O2

IUPAC Name:

3-cyclopentyl-1H-indole-6-carboxylic acid

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): CD 6002 SE
- Analytical purity: 99.7 %
- Storage : room temperature and ambient humidity
- Lot/batch No.: TSA-05-003

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:

TA 98, TA 100 with and without metabolic activation : 10, 20, 39, 78, 156, 313, 625, 1250, 2500, 5000 µg/plate
TA 1535, TA 1537 WP2 uvrA with and without metabolic activation: 31, 63, 125, 250, 500, 1000 µg/plate

Vehicle / solvent:

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

Controls

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:

S.typhimurium strains TA 1535, TA 1537, TA 98 : An increase in mean revertant numbers to greater or equal to 3x the concurrent vehicle control
mean revertant number or 20, whichever is greater.
S. typhimurium strain TA 100 and E.coli WP2 uvrA :An increase in mean revertant numbers to greater or equal to 2x the concurrent vehicle control
revertant number.
A positive response typically includes a reproducible dose-related significant increase in mean revertant numbers that my be reduced at high dose
levels due to cytotoxicity.
These criteria are guidelines for evaluation and may be modulated by other biological factors that are discussed within the context of the report.

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:

not specified

Positive controls validity:

valid

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

CD 6002 was non-mutagenic when tested in Salmonella typhimurium strains, TA 1535, TA 1537, TA 98, TA 100 and Escherichia coli WP2 uvrA (pKM101) in the absence and presence of an activation system over a range of doses that included toxic levels.
It is concluded that CD 6002 SE was non-mutagenic under the conditions in this assay.

Executive summary:

The mutagenic potential of CD 6002 SE was investigated in a study with Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and Escherichia coli WP2 uvrA.

The test were conducted between October 11,2005 and October 13,2005 using the plate incorporation method in presence and absence of an Aroclor 1254 -induced rat liver preparation and co-factors (S9 mix ) required for mixed function oxidase activity. Each dose level and control was plated triplicate.

The bacteria, Salmonella typhimurium strains TA 100 and TA 98 were treated initially with dose levels of 10, 20, 39, 78, 156, 313, 625, 1250, 2500 and 5000 µg/plate of CD 6002 SE in presence and absence of an activation system.

The test article precipitated at the two highest dose levels, 2500 and 5000 µg/plate, upon addition to the aqueous solution. In TA 98 there was a reduction in colony numbers and/or a thin lawn at dose levels greater or equal to 12500 µg/plate in presence and absence of an activation system. In TA 100 there was a reduction in colony numbers and/or a thin lawn at dose levels greater than or equal to 625 µg/plate in the absence of an activation system and at dose level greater than or equal to 313 µg/plate in the presence of an activation system. These observations are indicative of toxicity.

CD 6002 SE was then tested at dose levels of 31, 63, 125, 250, 500 and 1000 µg/plate in Salmonella typhimurium TA 1535 and

TA 1537 and Escherichia coli WP2 uvrA (pKM101) with and without S9 mix.

There was evidence of a reduction in colonies in TA 1535, TA 1537 of the highest dose level, 1000 µg/plate in both absence and presence of an activation system. There was no evidence of a significant increase in the number of colonies in any of the trains, when tested in either presence or absence of an S9 mixture.

CD 6002 was non-mutagenic when tested in Salmonella typhimurium strains, TA 1535, TA 1537, TA 98, TA 100 and Escherichia coli WP2 uvrA (pKm101) in the presence or absence of an activation system over a range of doses that included toxic levels.