(2S-cis)-2,3-dihydro-3-hydroxy-2-(4-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one

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

Study period:

November 12 – 20, 1998

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1998

Report date:

1998

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:

(2S-cis)-2,3-dihydro-3-hydroxy-2-(4-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one

EC Number:

255-799-0

EC Name:

(2S-cis)-2,3-dihydro-3-hydroxy-2-(4-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one

Cas Number:

42399-49-5

Molecular formula:

C16H15NO3S

IUPAC Name:

(2S-cis)-2,3-dihydro-3-hydroxy-2-(4-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one

Details on test material:

Appearance: whitish powder
Storage conditions: at room temperature

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:

S. typhimurium TA 102

Metabolic activation:

with and without

Metabolic activation system:

S9 mix

Test concentrations with justification for top dose:

Test article dosage levels
The test article dosage leves,espresse as quantities of substance per plate, were the following:
- 50, 150, 500, 1500 and 5000 µg/plate
- 15, 50, 150, 500 and 1500 µg/plate

Preparation of the test article solutions
In each experiment, an exact amount of the test article DTZ 62 was dissolved in dimethyl sulfoxide and further diluted in the same solvent to give the following concentrations:
- 50,15, 5, 1.5 and 0.5 mg/ml
- 15, 5, 1.5, 0.5 and 0.15 mg/ml

Vehicle / solvent:

Dimethyl sulfoxide

Controls

Untreated negative controls:

yes

Remarks:

Dimethyl sulfoxide

Negative solvent / vehicle controls:

yes

Remarks:

Dimethyl sulfoxide

Positive controls:

yes

Remarks:

Hydrazine sulphate, 9-aminoacridine HCl monohydrate, Mitomycin C, Doxorubicine HCl, 2-Aminofluorene

Details on test system and experimental conditions:

Tester strain storage and control
The S. typhimurium strain were stored in growth medium plus 25 µg/ml ampicillin and 8% dimethyl sulphoxide, at -80°C.
Fresh bacterial cultures were subcultivated on complete medium and stored in a refrigerator for up to 1 month, except TA102 S. typhimurium strain which was stored for up to 2 weeks.
Both permanent cultures and Master plates were checked to confirm the tester strain genotype.
The liquid culture used to prepare Master plates or the first overnight cultures from fresh Master plates was submitted to the following controls.

Results and discussion

Test results

Test results 1

Species / strain:

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

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Test results 2

Species / strain:

S. typhimurium TA 102

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

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

In the concentration range investigated, the test substance did not show any mutagenic activity with or without the addition of S9 liver homogenate fractions.