Pyrimidine-2,4,6-triyltriamine

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Study period:

End 1990

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Version / remarks:

1983

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OTS 798.5265 (The Salmonella typhimurium Bacterial Reverse Mutation Test)

Version / remarks:

1985, amended 1987

Deviations:

no

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Pyrimidine-2,4,6-triyltriamine

EC Number:

213-720-7

EC Name:

Pyrimidine-2,4,6-triyltriamine

Cas Number:

1004-38-2

Molecular formula:

C4H7N5

IUPAC Name:

2,4,6-Triaminopyrimidine

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source: Lonza AG
- Batch: 37
- Purity: 99.8%

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature and protected from light
- No determinations of stability, homogeneity or achieved concentration were undertaken on solutions

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Final dilution of a dissolved solid: see concentrations
- Limit of solubility in water: 36.5 mg/ml

FORM AS APPLIED IN THE TEST: solution

Method

Target gene:

his

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 1538

Metabolic activation:

with and without

Metabolic activation system:

Type and composition of metabolic activation system:
- source of S9 : rat liver
- method of preparation of S9 mix: Young male CD rats were administered a single intraperitoneal injection of Aroclor 1254 to induce microsomal enzyme activity.

Vehicle / solvent:

- Solvent used: distilled water

Controls

Untreated negative controls:

yes

Remarks:

S9 and test material

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

9-aminoacridine

2-nitrofluorene

sodium azide

benzo(a)pyrene

other: 2-Aminoanthracene (2 µg/plate)

Details on test system and experimental conditions:

NUMBER OF REPLICATIONS:
- Number of cultures per concentration: triplicate
- Number of independent experiments : 2

METHOD OF TREATMENT/ EXPOSURE:
- Test substance added in medium

TREATMENT AND HARVEST SCHEDULE:
- Exposure duration/duration of treatment: 2 days

Results and discussion

Test results

Test results 1

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not determined

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

True negative controls validity:

not applicable

Positive controls validity:

valid

Test results 2

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not determined

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

True negative controls validity:

not applicable

Positive controls validity:

valid

Test results 3

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not determined

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

True negative controls validity:

not applicable

Positive controls validity:

valid

Test results 4

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not determined

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

True negative controls validity:

not applicable

Positive controls validity:

valid

Test results 5

Species / strain:

S. typhimurium TA 1538

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not determined

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

True negative controls validity:

not applicable

Positive controls validity:

valid

Applicant's summary and conclusion

Conclusions:

The test material was devoid of mutagenic activity in the Ames test.

Executive summary:

The test substance was examined for mutagenic activity in five histidine-dependent auxotrophs of Salmonella typhimurium, strains TA 98, TA 1538, TA 100, TA 1535 and TA 1537, using pour-plate assays. Each test, in each strain, was conducted on two seperate occasions. The studies, which were conducted in the absence and presence of an activating system derived from rat liver (S-9 mix), employed a range of levels of the test substance from 50 to 5000 µg/plate, selected following a preliminary toxicity test in strain TA 98. All tests included solvent (distilled water) controls with and without S9 mix. No increases in reversion to prototrophy were obtained with any of the five bacterial strains at the test substances' levels tested, either in the presence or absence of S9 mix. Marked increases in the number of revertant colonies were induced by the known mutagens benzo[a]pyrene, 2 -nitroflourene, 2 -aminoanthracene, 9 -aminoacridine and sodium azidine when examined under similar conditions. It was concluded that the test substance was devoid of mutagenicity activity under the conditions of the test.