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EC number: 202-718-1 | CAS number: 98-97-5
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
Administrative data
Key value for chemical safety assessment
Genetic toxicity in vitro
Description of key information
Experimental study on genetic toxicity in vitro was conducted by James L. Simset al.( Biochemistry, 1982) to determine the mutagenic nature of target substance pyrazine-2-carboxylic acid (98-97-5). 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 was 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
Link to relevant study records
- 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.
- Qualifier:
- according to guideline
- 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.
- 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 - Target gene:
- Thymidine
- 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
- 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.
- 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.
- 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.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Genotoxicity In-vitro
Various publications were reviewed to determine the mutagenic nature of pyrazine-2-carboxylic acid (98-97-5). The studies are as mentioned below:
Experimental study on genetic toxicity in vitro was conducted by James L. Simset al.( Biochemistry, 1982) to determine the mutagenic nature of target substance pyrazine-2-carboxylic acid (98-97-5). 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 was 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.
Supporting gene mutation toxicity was predicted for Pyrazine-2-carboxylic acid (98-97-5) using the battery approach from Danish QSAR database (2017). The study assumed the use of Salmonella typhimurium bacteria in the Ames test. The end point for gene mutation has been modeled in the Danish QSAR using the three software systems Leadscope, CASE Ultra and SciQSAR. Based on predictions from these three systems, a fourth and overall battery prediction is made. The battery prediction is made using the so called Battery algorithm. With the battery approach it is in many cases possible to reduce “noise” from the individual model estimates and thereby improve accuracy and/or broaden the applicability domain.
In a Gene mutation toxicity study was performed by Errol Zeiger et al.( Environmental Mutagenesis,1987) to determine the mutagenic nature of Pyrazinamide (RA CAS no98-96-4; IUPAC name: pyrazine-2-carboxamide . The read across substances share high similarity in structure and log kow .Therefore, it is acceptable to derive information on mutation from the analogue substance. Mutagenicity effect of Pyrazinamide was evaluated in Salmonella typhimurium. Salmonella typhimurium strains TA100, TA1535, TA1537, TA98 were used in the study. Mutagenic assay was performed by preincubation method. The assay performed in presence and absence pf metabolic activator i.e. Aroclor 1254-induced rat liver S-9 and Aroclor 1254-induced hamster liver S-9.DMSO was used as solvent for test substance.The test chemical, Salmonella culture and S-9 mix or buffer incubated at 37 °C for 20 min without shaking. Agar was added on plate, content of tubes were mixed poured on surface of petri dish that contain Vogel Bonner medium. The mutant colonies on plates were counted after 2 days post incubation. Doses of test substance 0, 100, 333, 1000, 3333, 10000 ug/plate were tested in triplicate. Experiments were repeated 1 week following of initial trial. Sodium azide was used as positive control substance in absence of metabolic activation for strains TA100, TA1535. 9-aminocaridine and 4-nitro-o-phenylenediamine were positive control in absence of metabolic activation for strains TA1537 and TA98 respectively. The positive control with metabolic activation for all strains was 2-aminoanthracene. In results of study, there was no increase in dose related mean number of revertant colonies compared to solvent control across all strains.Therefore, Pyrazinamide was not mutagenic in bacteria Salmonella typhimurium. Hence Pyrazinamide not likely to be classified as gene mutation in vitro.
In a Gene mutation toxicity study was performed by T.B. Adams et al (Food and Chemical Toxicology, 2002) to determine the mutagenic nature of Pyrazinamide (98-96-4); IUPAC name: pyrazine-2-carboxamide. The read across substances share high similarity in structure and log kow .Therefore, it is acceptable to derive information on mutation from the analogue substance. Mutagenicity effect of Pyrazinamide was evaluated in Salmonella typhimurium. Salmonella typhimurium strains TA100, TA1535, TA1537, TA98 were used in the study. Mutagenic assay was performed by preincubationmethod. The assay performed in presence and absence pf metabolic activator i.e. Aroclor 1254-induced rat liver S-9 and Aroclor 1254-induced hamster liver S-9.DMSO was used as solvent for test substance.The test chemical, Salmonella culture and S-9 mix or buffer incubated at 37 °C for 20 min without shaking. Agar was added on plate, content of tubes were mixed poured on surface of petri dish that contain Vogel Bonner medium. The mutant colonies on plates were counted after 2 days post incubation. Doses of test substance 0, 100, 333, 1000, 3333, 10000 ug/plate were tested in triplicate. Experiments were repeated 1 week following of initial trial. Sodium azide was used as positive control substance in absence of metabolic activation for strains TA100, TA1535. 9-aminocaridine and 4-nitro-o-phenylenediamine were positive control in absence of metabolic activation for strains TA1537 and TA98 respectively. The positive control with metabolic activation for all strains was 2-aminoanthracene. In results of study, there was no increase in dose related mean number of revertant colonies compared to solvent control across all strains.Therefore, Pyrazinamide was not mutagenic in bacteria Salmonella typhimurium. Hence Pyrazinamide not likely to be classified as gene mutation in vitro.
Based on the data available for the target chemical and its read across substance, it is concluded that pyrazine-2-carboxylic acid (98-97-5) does not exhibit gene mutation in vitro. Hence the test chemical is not likely to classify as a gene mutant in vitro.
Justification for classification or non-classification
Thus based on the data available and CLP criteria for the target chemical , it is concluded that pyrazine-2-carboxylic acid (98-97-5) does not exhibit gene mutation in vitro. Hence the test chemical is not likely to classify as a gene mutant in vitro.
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