2,4(1H,3H)-Pyrimidinedione, 1-[2-deoxy-3,5-bis-O-(4-methylbenzoyl)-.beta.-L-erythro-pentofuranosyl]-5-methyl-

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:

26.01.2004 - 23.02.2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)

Deviations:

no

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

[(2S,3R,5S)-3-[(4-methylbenzoyl)oxy]-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-2-yl]methyl 4-methylbenzoate

EC Number:

608-497-1

Cas Number:

3056-13-1

Molecular formula:

C26 H26 N2 O7

IUPAC Name:

[(2S,3R,5S)-3-[(4-methylbenzoyl)oxy]-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-2-yl]methyl 4-methylbenzoate

Method

Target gene:

his

Species / strain

Species / strain / cell type:

other: S. typhimurium TA97a, TA98, TA100, TA102 and TA1535

Metabolic activation:

with and without

Metabolic activation system:

S9-mix

Test concentrations with justification for top dose:

7.4, 22, 67, 200 and 600 μg/plate

Vehicle / solvent:

- Vehicle/solvent used: dimethylsulfoxide (DMSO)

Controls

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: -S9: 4-Nitro-o-phenylene-diamine (TA97a), t-Butyl-hydroperoxide (TA102), 2-Nitrofluorene (TA98), Sodium azide (TA100, TA1535); +S9: 2-Aminoanthracene (TA98, TA100, TA1535), 1,8-Dihydroxy-anthraquinone (TA102), 7,12-Dimethylbenz[a]anthracene (TA97a)

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Exposure duration: 48 h

NUMBER OF REPLICATIONS: three replications each in two independent experiments

DETERMINATION OF CYTOTOXICITY
- Method: growth of bacterial background lawn

Evaluation criteria:

A reproducible increase in the number of revertants to more than 2,5-fold (TA98, TA 1535) and 1,67-fold (TA97a, TA100, TA102), respectively, of the amount of spontaneous revertants in at least one of the concentrations.

Results and discussion

Test results

Species / strain:

other: S. typhimurium TA97a, TA98, TA100, TA102 and TA1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Additional information on results:

RANGE-FINDING/SCREENING STUDIES:
In a preliminary test, toxicity was tested in TA100. No toxicity was observed up to 556 µg/plate. At higher concentrations, the evaluation of the plates was not possible because of the precipitation of the test substance.

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

In none of the concentrations tested and with none of the strains used an increase of the mutation frequency to more than the threshold values (250% of the controls for strains TA98 and TA1535, 167% of the controls for strains TA97A, TA100 and TA102) was obtained. Metabolic activation did not change these results.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative