3-(4-amino-2-methylpyrimidin-5-ylmethyl)-5-(2-hydroxyethyl)-4-methylthiazole-2(3H)-thione

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:

18.04. - 26.07.2001

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The accordance of the study with its protocol, the OECD Guideline and the Principles of Good Laboratory Practice (GLP) is guaranteed.

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2001

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

3-(4-amino-2-methylpyrimidin-5-ylmethyl)-5-(2-hydroxyethyl)-4-methylthiazole-2(3H)-thione

EC Number:

206-077-9

EC Name:

3-(4-amino-2-methylpyrimidin-5-ylmethyl)-5-(2-hydroxyethyl)-4-methylthiazole-2(3H)-thione

Cas Number:

299-35-4

Molecular formula:

C12H16N4OS2

IUPAC Name:

3-[(4-amino-2-methylpyrimidin-5-yl)methyl]-5-(2-hydroxyethyl)-4-methyl-2,3-dihydro-1,3-thiazole-2-thione

Method

Target gene:

TA97a: hisD6610, TA 98: hisD3052; TA 100 and TA 1535 hisG46, TA102: hisG428

Species / strain

Species / strain / cell type:

other: TA 1535, TA 97a, TA 98, TA 100 und TA 102

Details on mammalian cell type (if applicable):

not applicable

Additional strain / cell type characteristics:

other: TA97a, TA98 and TA100: uvrB; TA100 & 102: pKM 101

Metabolic activation:

with and without

Metabolic activation system:

S9

Test concentrations with justification for top dose:

5 mg/ dish

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

yes

Positive controls:

yes

Positive control substance:

benzo(a)pyrene

Remarks:

Migrated to IUCLID6: additional: Sodiumazide, 4-Nitro-2-phenylendiamin

Results and discussion

Test results

Species / strain:

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

Metabolic activation:

with and without

Genotoxicity:

negative

Remarks:

-

Cytotoxicity / choice of top concentrations:

not determined

Remarks:

-

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'. Remarks: -

Any other information on results incl. tables

no additional remarks

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative

Thiotiamin can be considered as not mutagenic in the Ames test under the described experimental conditions.

Executive summary:

Thiotiamin was evaluated for mutagenic activity in the Ames test. A standard plate incorporation and a preincubation modification assay in absence and in presence of an exogenous metabolic activation system (S9) were performed. Five Salmonella typhimurium

tester strains (TA1535, TA97, TA98, TA100, and TA102) were employed. The activity of the S9 -mix and the responsiveness of the tester strains were verified by including appropriate controls into each experiment. The substance was dissolved in dimethylsulfoxide (DMSO). As concentration 5 mg/plate was chosen for the main experiment.

No significant increase in the number of revertant colonies was apparent in all five tester strains (TA1535, TA97, TA98, TA100, and TA102) using both methods, after treatment with Thiotiamin.

Based on these data Thiotiamin can be considered as not mutagenic in the Ames test under the described experimental conditions.