Propanedioic acid, 2-[2-(2-amino-6-chloro-9H-purin-9-yl)ethyl]-, 1,3-dimethyl ester

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:

20.08.2007 - 17.10.2007

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2007

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:

1,3-dimethyl 2-[2-(2-amino-6-chloro-9H-purin-9-yl)ethyl]propanedioate

Cas Number:

172529-93-0

Molecular formula:

C12 H14 Cl N5 O4

IUPAC Name:

1,3-dimethyl 2-[2-(2-amino-6-chloro-9H-purin-9-yl)ethyl]propanedioate

Constituent 2

Reference substance name:

2-Amino-6-chloro-9-(methyl-2-carbomethoxybutanoate-4- yl)purine

IUPAC Name:

2-Amino-6-chloro-9-(methyl-2-carbomethoxybutanoate-4- yl)purine

Details on test material:

Formula: C12H14ClN5O4.
Appearance: White to pale yellow solid.
expiry date: 31 December 2007.

Method

Species / strain

Species / strain / cell type:

other: TA97a, TA98, TA100, TA102 and TA1535

Metabolic activation:

with and without

Metabolic activation system:

S9 mix

Test concentrations with justification for top dose:

62, 185, 556, 1667 and 5000 μg per plate without external metabolisation, and 62, 185, 556, 1667 and 5000 μg per plate with S9-mix from Aroclor 1254 induced microsomes of rat liver as an external metabolising system.

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

yes

Positive controls:

yes

Positive control substance:

other: Sodium Azide, 4-Nitro-o-phenylene-diamine, t-Butyl-hydroperoxide, 2- Aminoanthracene, 1,8-Dihydroxy-anthraquinone, 7,12-Dimethylbenz[a]anthracene, 2-Nitrofluorene

Results and discussion

Test results

Species / strain:

other: TA97a, TA98, TA100, TA102 and TA1535

Metabolic activation:

with and without

Genotoxicity:

negative

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'.

Any other information on results incl. tables

All positive control groups showed significantly increased mutation frequencies which demonstrate the sensitivity of the test system.

No toxicity of the test substance to the bacteria was observed up to 5000 μg per plate.

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

According to the results obtained in this study, "Fam-stage-1" is non-mutagenic in the Ames test with the strains TA97a, TA98, TA100, TA102 and TA1535 with and without an external metabolising system up to 5000 μg/plate, which is the limit concentration for this kind of test.