Pyrazine-2-carboxylic acid

Toxicity to microorganisms

Link to relevant study record(s)

Reference

Endpoint:

toxicity to microorganisms, other

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Justification for type of information:

Data is from peer reviewed journal

Qualifier:

according to guideline

Guideline:

other: refer below principle

Principles of method if other than guideline:

Toxicity to micro-organisms study was conducted on Mycobacterium tuberculosis.

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material: Pyrazine-2-carboxylic acid
- Molecular formula: C5H4N2O2
- Molecular weight: 124.099 g/mol
- Substance type: organic
- Physical state: solid
- Smiles: c1ncc(C(=O)O)nc1
- InChI: 1S/C5H4N2O2/c8-5(9)4-3-6-1-2-7-4/h1-3H,(H,8,9)
- Radiolabelling: Yes

Analytical monitoring:

not specified

Details on sampling:

- Concentrations: 300 µg/ml (300 mg/l) and 100 µg/ml (100 mg/l).

Vehicle:

not specified

Test organisms (species):

Mycobacter sp.

Details on inoculum:

- Preparation of inoculum for exposure: M. tuberculosis culture was prepared in Middlebrook 7H9 medium supplemented with 10% (vol/vol) OADC enrichment (Difco), 0.2% (vol/vol) glycerol, and 0.05% (vol/vol) Tween 80.

Test type:

not specified

Water media type:

not specified

Limit test:

no

Total exposure duration:

72 h

pH:

6 or 6.8

Details on test conditions:

TEST SYSTEM
- Test vessel: Test tube
- No. of organisms per vessel: 105 CFU/ml

OTHER TEST CONDITIONS
- Adjustment of pH: pH of the medium was adjusted to 6 or 6.8 with an aqueous solution of 4.25% phosphoric acid or 5% dibasic potassium phosphate.
- Test concentrations: 300 mg/l and 100 mg/l.

Key result

Duration:

72 h

Dose descriptor:

other: MIC

Effect conc.:

300 mg/L

Nominal / measured:

not specified

Conc. based on:

test mat.

Basis for effect:

growth inhibition

Remarks on result:

other: at pH 6.8

Duration:

72 h

Dose descriptor:

other: MIC

Effect conc.:

100 mg/L

Nominal / measured:

not specified

Conc. based on:

test mat.

Basis for effect:

growth inhibition

Remarks on result:

other: at pH 6

Validity criteria fulfilled:

not specified

Conclusions:

From experimental result the minimum inhibition concentration (MIC) value was observed to be 300 mg/l at pH 6.8 and 100 mg/l at pH 6 at 72 hrs exposure period.

Executive summary:

Toxicity study of micro-organism to the test substance was conducted using Mycobacterium tuberculosis. When test bacteria was exposed to the test substance pyrazinoic acid, decreased in growth of the bacteria was observed. From experimental result the minimum inhibition concentration (MIC) value was observed to be 300 mg/l at pH 6.8 and 100 mg/l at pH 6 at 72 hrs exposure period.

Description of key information

Toxicity study of micro-organism to the test substance was conducted usingMycobacterium tuberculosis.When test bacteria was exposed to the test substance pyrazinoic acid, decreased in growth of the bacteria was observed.From experimental result the minimum inhibition concentration (MIC) value was observed to be 300 mg/l at pH 6.8 and 100 mg/l at pH 6 at 72 hrs exposure period.

Additional information

Five experimental studies from peer reviewed journal for toxicity to micro organisms endpoint of test chemical Pyrazine-2-carboxylic acid (Cas no. 98-97-5) were summarised as follows:

 

First data from journal Antimicrobial Agents and Chemotherapy, Vol. 51, No. 2, Pg. no. 752–754, Feb. 2007 suggests toxicity study of micro-organism to the test substance was conducted using Mycobacterium tuberculosis.When test bacteria was exposed to the test substance pyrazinoic acid, decreased in growth of the bacteria was observed. From experimental result the minimum inhibition concentration (MIC) value was observed to be 300 mg/l at pH 6.8 and 100 mg/l at pH 6 at 72 hrs exposure period.

Whereas Antimicrobial Agents and Chemotherapy, Vol. 33, No. 8, p. 1252-1254, Aug. 1989 journal indicate the minimum inhibition concentration (MIC) values for different M. tuberculosis strains are observed to be-For M. tuberculosis strains M6733 and W478: 240 µg/ ml (240 mg/l) and For M. tuberculosis strains H37Rv, H6927, H5009, W7804, M6669, T6790, T7505 and 1620: 480 µg/ ml (480 mg/l)

And Journal of Antimicrobial Chemotherapy Vol.53, Pg. no. 192–196, 2004 indicate toxicity study of micro-organism to the test substance was conducted using Mycobacterium tuberculosis BCG strain.When test bacteria was exposed to the test substance pyrazinoic acid with exposure duration of 3 weeks, decreased in cfu counts was observed. From experimental condition the minimum inhibition concentration (MIC) value was observed to be 25 mg/l i.e 4% growth inhibition was occur.

One another journal for target mention the MIC value for different strains of M. tuberculosis of test chemical Pyrazinoic acid (Cas no.98-97-5) are observed as:

For M. tuberculosis strain CDC89 - 1 µg/ml (1 mg/l)

For M. tuberculosis strain CDC72 -≤1 µg/ml (≤1 mg/l)

For M. tuberculosis strain H6777 - 4 µg/ml (4 mg/l)

For M. tuberculosis strain M142, T2614, CA516 and W11053 - 8 µg/ml (8 mg/l)

For M. tuberculosis strain T2603, ATCC 25618, M4812, DHMH 5207 and DHMH 4319 – 16 µg/ml (16 mg/l)

For M. tuberculosis strain DOL, ATCC 27294, M4597, ATCC 35801, F7091, H6128, W6126, DHMH 444, W4693, T5721, ATCC 35828, M4809, VA 205, DHMH 6577, BDDIS 20 and CDC-BP-98 – 32 µg/ml (32 mg/l)

For M. tuberculosis strain H3652 -≤8 µg/ml (≤8 mg/l)

For M. tuberculosis strain T494 – 128 µg/ml (128 mg/l)

And lastly Saudi Pharmaceutical Journal Vol. 22, Pg. no. 376–380, 2014 indicate briefly as toxicity study of micro-organism to the test substance was conducted using Mycobacterium tuberculosis H37Rv (ATCC 27294).When test bacteria was exposed to the test substance pyrazinoic acid with exposure duration of 6 days, decreased in growth of the bacteria was found. The MIC value was found to be 15620000 mg/l.

Thus all minimum inhibition concentration (MIC) values from all studies give the conclusion that test substance Pyrazine-2-carboxylic acid (Cas no. 98-97-5) may have no concern for toxicity to micro organism.