tert-Butyl rel-(3R,5S,6E)-7-[3-(4-fluorophenyl)-1-(propan-2-yl)-1H-indol-2-yl]-3,5-dihydroxyhept-6-enoate

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro cytogenicity / chromosome aberration study in mammalian cells

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

key study

Study period:

24 October 2001- 04 March 2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Report date:

2002

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: EEC Directive 2000/32/EC, Part B: Methods for the Determination of Toxicity; B.10 "Mutagenicity: In Vitro mammalian Chromosome Aberration Test.

GLP compliance:

yes

Type of assay:

in vitro mammalian chromosome aberration test

Test material

Test material information

Constituent 1

Reference substance name:

00945

IUPAC Name:

00945

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Method

Target gene:

Cultured peripheral human lymphocytes

Species / strain

Species / strain / cell type:

lymphocytes:

Additional strain / cell type characteristics:

not specified

Metabolic activation:

with

Metabolic activation system:

Aroclor-1254 induced rat liver S9-mix

Vehicle / solvent:

Dimethyl sulfoxide

Controls

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

cyclophosphamide

mitomycin C

Results and discussion

Test results

Test results 1

Species / strain:

lymphocytes:

Metabolic activation:

without

Genotoxicity:

not determined

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 2

Species / strain:

lymphocytes:

Metabolic activation:

with

Genotoxicity:

not determined

Cytotoxicity / choice of top concentrations:

no cytotoxicity, but tested up to precipitating concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

The possible clastogenicity of the test substance was tested in two independent experiments. The positive control chemicals for both cytogenetic assays (MMC-C and CP) both produced statistically significant increases in the frequency of aberrant cells. It was therefore concluded that the test conditions were adequate and that the metabolic activation system (S9 -mix) functioned properly.

Applicant's summary and conclusion

Conclusions:

It is concluded that the test is valid and that the test substance is not clastogenic in human lymphocytes under the experimental conditions described in the report. Negative result

Executive summary:

The possible clastogenicity of the test substance was tested in two independant experiments. In the first cytogenetic assay, in the absence of S9 -mix (the metabolic activation system), the test substance induced a statistically significant increase in the number of cells with chromosome aberrations at the intermediate concentration of 75ug/ml when gaps were induced only. Since the type of aberrations observed were only breaks and gaps, the increase was not dose dependant and well within our historical background control data it was considered to be not biologically relevant. In the presence of S9 -mix, the test substance did not induce a statiscally significant or biologically relevant increase in the number of cells with chromosome aberrations.

In the second cytogenetic assay, Diolat did not induce a statiscally significant or biologically relevant increase in the number of cells with chromosome aberrations.