1,3-Dioxane-4-acetic acid, 6-[2-[2-(4-fluorophenyl)-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrol-1-yl]ethyl]-2,2-dimethyl-, 1,1-dimethylethyl ester, (4R,6R)-

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

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Report date:

2007

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EU Method B.10 (Mutagenicity - In Vitro Mammalian Chromosome Aberration Test)

Deviations:

no

GLP compliance:

yes

Type of assay:

in vitro mammalian chromosome aberration test

Test material

Test material information

Constituent 1

Reference substance name:

tert-butyl 2-[(4R,6R)-6-{2-[2-(4-fluorophenyl)-3-phenyl-4-(phenylcarbamoyl)-5-(propan-2-yl)-1H-pyrrol-1-yl]ethyl}-2,2-dimethyl-1,3-dioxan-4-yl]acetate

EC Number:

700-258-0

Cas Number:

125971-95-1

Molecular formula:

C40H47FN2O5

IUPAC Name:

tert-butyl 2-[(4R,6R)-6-{2-[2-(4-fluorophenyl)-3-phenyl-4-(phenylcarbamoyl)-5-(propan-2-yl)-1H-pyrrol-1-yl]ethyl}-2,2-dimethyl-1,3-dioxan-4-yl]acetate

Method

Species / strain

Species / strain / cell type:

lymphocytes:

Metabolic activation:

with and without

Metabolic activation system:

S9 + micture of cofactors

Test concentrations with justification for top dose:

30μg/ml; 3μg/ml; 300ng/ml

Vehicle / solvent:

Methanol

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

other: cyclophosphamide; thiotepa

Evaluation criteria:

Genotoxic effect of the test substance was evaluated as a percentage of aberrant metaphases; i.e. cells in metaphase positive against the total number of evaluated metaphases.
Genotoxic effect of the test substance is manifested in case of a number of aberrant metaphases being higher than 5 %. Percentage of aberrant metaphases in controls must not exceed 3 %.

Results and discussion

Test results

Species / strain:

lymphocytes:

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity, but tested up to precipitating concentrations

Remarks:

Negative(medium, solvent) and positive controls (etoposide)

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: strain/cell type: human lymphocytes acquired from peripheral blood of healthy volunteers

Remarks:

Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
other: negative without metabolic activation; negative with metabolic activation;

The test substance, Acetonide Atorvastatine, did not show any genotoxic effect with or without metabolic activation in the above-mentioned chromosome aberration test under given experimental condition.
Negative effect in vitro chromosome aberration test indicates that the test substance did not induce chromosome aberrations in culture human somatic cells.