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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro DNA damage and/or repair study
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Justification for type of information:
Data is from publication.

Data source

Reference
Reference Type:
publication
Title:
Poly(adenosinediphosphoribose) Polymerase Inhibitors Stimulate Unscheduled Deoxyribonucleic Acid Synthesis in Normal Human Lymphocytes.
Author:
James L. Sims, Georgina W. Sikorski, Donna M. Catino, Sosamma J. Berger, and Nathan A. Berger
Year:
1982
Bibliographic source:
Biochemistry Vol. 21; Pg. no. 1813-1821, 1982.

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: As mention below
Principles of method if other than guideline:
To evaluate the mutagenic potential of 2- Pyrazinecarboxylic acid in Normal human lymphocytes by DNA Repair Synthesis.
GLP compliance:
not specified
Type of assay:
other: DNA Repair Synthesis.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Specific details on test material used for the study:
- Name of test material (as cited in study report): Pyrazine-2-carboxylic acid
- Molecular formula (if other than submission substance): C5H4N2O2
- Molecular weight (if other than submission substance): 124.098 g/mol
- Substance type: Organic
- Physical state: Solid

Method

Target gene:
Thymidine
Species / strain
Species / strain / cell type:
lymphocytes: Normal human
Details on mammalian cell type (if applicable):
Not applicable
Additional strain / cell type characteristics:
not specified
Cytokinesis block (if used):
Not specified
Test concentrations with justification for top dose:
2mM
Vehicle / solvent:
Not specified
Controls
Untreated negative controls:
not specified
Negative solvent / vehicle controls:
not specified
True negative controls:
not specified
Positive controls:
not specified
Details on test system and experimental conditions:
Human lymphocyte cells not treated with DNA damaging agents are used as a control.
Rationale for test conditions:
Not specified
Evaluation criteria:
The amount of [3H]dTMP incorporated by DNA-damaged cells incubated in the presence of hydroxyurea was taken as the 100% level for unscheduled DNA synthesis.
Stimulation of unscheduled DNA synthesis in the presence of test substance was expressed relative to the 100% level.
Statistics:
Results are presented as the means of assays performed in triplicate.

Results and discussion

Test results
Key result
Species / strain:
lymphocytes: Human
Metabolic activation:
not specified
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
not specified
Untreated negative controls validity:
not specified
Positive controls validity:
not specified
Additional information on results:
-Other- Pyrazine-2-carboxylic acid showed 0% inhibition of the enzyme, i.e; the compound did not inhibited the enzyme poly(ADP-ribose) polymerase and were unable to stimulate unscheduled DNA synthesis.

Applicant's summary and conclusion

Conclusions:
The test substance 2-Pyrazinecarboxylic acid was unable to stimulate the unscheduled DNA synthesis in UV or MNNG treated human lymphocytes. Thus, the test result was found to be negative.
Executive summary:

DNA repair test was conducted for 2-Pyrazinecarboxylic acid (98 -97 - 5) by using human lymphocytes . It was damaged by treating DNA damaging agents such as UV irradiation or N-methyl-N’-nitro-N-nitrosoguanidine (MNNG). The lymphocytecells were exposed to the test substance pyrazine-2-carboxylic acid for 6 hr incubation with [3H]thymidine in the

presence of 10 mM hydroxyurea.at 37ᵒC.Lymphocyte cells not treated with DNA damaging agents are used as a control. For the DNA repair assay, lymphocyte is prepared in the following manner- Normal human lymphocytes were isolated from peripheral blood and were suspended at 2 × 106cells/mL in complete medium composed of α- modified Eagles medium buffered with 25 mM Hepes, pH 7.2, and supplemented with 10% fetal calf serum, 50 units/mL penicillin, and 50 µg/mL streptomycin.The amount of [3H]dTMP incorporated by DNA-damaged cells incubated in the presence of hydroxyurea was taken as the 100% level for unscheduled DNA synthesis. Stimulation of unscheduled DNA synthesis in the presence of test substance was expressed relative to the 100% level. Results are presented as the means of assays performed in triplicates.96% of DNA synthesis was occurred by the test substance as compared to the control which shows 100% unscheduled DNA synthesis in DNA damaged lymphocytes. The test substance showed 0% inhibition of the enzyme and also were unable to stimulate unscheduled DNA synthesis. Thus, the test was considered to be negative. Therefore 2-Pyrazinecarboxylic acid (98 -97 -5) was not likely to be classified as gene mutant in vitro.