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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:
2005
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

Constituent 1
Chemical structure
Reference substance name:
methyl 3-cyclopentyl-1-methyl-1H-indole-6-carboxylate
Cas Number:
494799-38-1
Molecular formula:
C16 H19 N O2
IUPAC Name:
methyl 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): CD 6003 XX
- Physical state: powder:
- Analytical purity: 99.7 %
- Lot/batch No.: T1031
- Storage condition of test material: room temperature, ambient humidity and protected from light

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:
7.8, 15.6. 31.3, 62.5, 125.0, 250.0 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);

NUMBER OF REPLICATIONS: 3


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 6003 XX did not induce a significant increase in colony numbers in Salmonella typhimurium strains TA 153, TA 1537, TA 98, TA 100 and
Escherichia coli WP2 uvrA ( pKM101 ) in the presence and absence of a post-mitochondrial fraction (S9 mix) from Aroclor induced rat liver , when
tested up to 250 µg/plate , which was toxic and exceeded the limits of solubility. It is concluded that CD 6003 XX was non-mutagenic under the
conditions of this study.
Executive summary:

The mutagenic potential of CD 6003 XX was investigated in a study with Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and Escherichia coli WP2 uvrA ( pKM101 ).

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 were treated with 7.8, 15.6. 31.3, 62.5, 125.0 and 250.0 µg/plate of CD 6003 XX in the presence and absence of an activation system.

At the highest dose level, 250 µg/plate, the test article precipitated upon addition to the aqueous agar/bacteria mixture. There was a reduction of colonies, indicative of toxicity, in TA 100 at dose level greater or equal to 62.g µg/plate in the absence of an activation system.There was no evidence of toxicity in the other strains. There was no evidence of a significant increase in the number of colonies in any of the strains, when tested in either the presence and absence of S9 mixture.

CD 6003 XX 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 and absence of an activation system at dose levels up to 250 µg/plate , which was toxic and exceeded the limits of solubility.

It is concluded that CD 6003 XX was non-mutagenic under the conditions of this study.

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