1H-Purine-2,6-dione, 8-bromo-7-(2-butyn-1-yl)-3,7-dihydro-3-methyl-1-[(4-methyl-2-quinazolinyl)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:

2004

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The chemical intermediate CD 616 BS was investigated in a modified bacterial reversemutation test as described by Ames et al. (1975). The traditional Salmonella microsomemutation assay (Ames test) is used extensively as a routine test for mutagenicity for morethan 25 years. The high throughput microtitre-based version, called Ames II, is based onthe same genetic principle (base-pair substitution and frameshift mutations in the hisoperon of S. typhimurium) as the traditional Ames test but combined with the fluctuationmethod (Gee et al., 1998). Because of its high concordance (80%) compared with thestandard assay, the Ames II procedure seems an effective screen for identifying bacterialmutagens (Flueckiger et al., 2004).

GLP compliance:

no

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

8-bromo-7-(but-2-yn-1-yl)-3-methyl-1-[(4-methylquinazolin-2-yl)methyl]-2,3,6,7-tetrahydro-1H-purine-2,6-dione

EC Number:

922-028-0

Cas Number:

853029-57-9

Molecular formula:

C20 H17 Br N6 O2

IUPAC Name:

8-bromo-7-(but-2-yn-1-yl)-3-methyl-1-[(4-methylquinazolin-2-yl)methyl]-2,3,6,7-tetrahydro-1H-purine-2,6-dione

Method

Species / strain

Species / strain / cell type:

other: TA 7001, TA 7002, TA 7003, TA 7004, TA 7005, TA 7006 and TA 98

Test concentrations with justification for top dose:

1 to 2500 μg/mL

Vehicle / solvent:

DMSO

Controls

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

yes

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

4-nitroquinoline-N-oxide

2-nitrofluorene

other: 2-aminoanthracene

Results and discussion

Test results

Species / strain:

other: TA 7001, TA 7002, TA 7003, TA 7004, TA 7005, TA 7006 and TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Remarks:

No bacteriotoxicity was seen up to 2500 μg/mL

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Additional information on results:

CD 616 BS precipitated at concentrations ≥500 μg/mL in the medium

Applicant's summary and conclusion

Conclusions:

Based on the described results it is concluded, that CD 616 BS, when tested up to insoluble concentrations, caused neither base-pair substitutions nor frameshift mutations in bacteria. No evidence of genotoxic activity was observed in a series of S. typhimurium tester strains (TA Mix and TA 98) in the absence and presence of metabolic activation. The test article is, therefore, classified as "Ames II negative".