1H-Indole, 1-[[4-[2-(hexahydro-1H-azepin-1-yl)ethoxy]phenyl]methyl]-3-methyl-5-(phenylmethoxy)-2-[4-(phenylmethoxy)phenyl]-

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Report date:

2002

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

1-[4-(2-Azepan-1-yl-ethoxy)-benzyl]-5-(benzyloxy)-2(benzyloxyphenyl)-3-methyl-1H-indole

Cas Number:

198480-21-6

Molecular formula:

C44 H46 N2 O3

IUPAC Name:

1-[4-(2-Azepan-1-yl-ethoxy)-benzyl]-5-(benzyloxy)-2(benzyloxyphenyl)-3-methyl-1H-indole

Test material form:

solid: particulate/powder

Method

Species / strain

Species / strain 1

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Species / strain 2

Species / strain / cell type:

E. coli WP2 uvr A

Metabolic activation:

with and without

Metabolic activation system:

S9 mix

Test concentrations with justification for top dose:

33, 100, 333, 1000, 2500, 5000 ug/plate
Each concentration was tested in triplicate.

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

sodium azide

methylmethanesulfonate

other: 2-aminoanthracene; 4-nitro-o-phenylene-diamine

Results and discussion

Test results

Species / strain:

bacteria, other: all strain tested

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Additional information on results:

The plates incubated with the test item showed normal background growth up to 5000 ug/plate with and without metabolic activation in both independent experiments.
Minor toxic effects, evident as a reduction in the number of revertants, were observed without metabolic activation in strain TA 1535 at 5000 ug/plate and in strain TA 1537 at 2500 and 5000 ug/plate.
No substantial increase in revertant colony numbers of any of the five tester strains was observed following treatment with TSE 8 at any dose level, neither in the presence nor absence of metabolic activation (S9 mix). There was also no tendency of higher mutation rates with increasing concentrations in the range below the generally acknowledged border of biological relevance.

Appropriate reference mutagens were used as positive controls. They showed a distinct increase of induced revertant colonies.
The historical range of positive controls was exceeded in strains TA 1535 without metabolic activation and in strain TA 98 with metabolic activation. This effect indicates the sensitivity of the strains rather than compromising the assay.

Any other information on results incl. tables

Toxic effects were observed at the following concentrations:

Strain	without S9 mix (ug/plate)	with S9 mix (ug/plate)
TA1535	5000	-
TA1537	2500, 5000	-
TA98	5000	5000
TA100	2500, 5000	5000
WP2 uvrA	2500, 5000	2500, 5000

Applicant's summary and conclusion

Conclusions:

It can be stated that during the mutagenicity test the test item did not induce gene mutations by base pair changes or frameshifts in the genome of the strains used.
TSE 8 is considered to be non -mutagenic in this Salmonella typhi. and Escherichia coli reverse mutation assay.