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Ecotoxicological information

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Description of key information

Short-term toxicity to fish

Using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the six closest read across substances, the short term toxicity on fish was predicted for Pyrazine-2-carboxylic acid (Cas no. 98-97-5). Lethal concentration i.e LC50 value was estimated to be 116.63 mg/l for Danio rerio for 96 hrs duration. Based on the effect value, Pyrazine-2-carboxylic acid (Cas no. 98-97-5) was non toxic to fish, hence it can be considered to be not classified as per the CLP classification criteria for aquatic environment.

Short-term toxicity to aquatic invertebrates

Using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the six closest read across substances, the short term toxicity on aquatic invertebrate was predicted for Pyrazine-2-carboxylic acid (Cas no. 98-97-5). Effect concentration i.e EC50 value was estimated to be 303.54 mg/l for Daphnia magna for 48 hrs duration. Based on the effect value, Pyrazine-2-carboxylic acid (Cas no. 98-97-5) was non toxic to aquatic invertebrates, hence it can be considered to be not classified  as per the CLP classification criteria for aquatic environment.

Toxicity to aquatic algae and cyanobacteria

Using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances, the short term toxicity on aquatic algae and cyanobacteria was predicted for target substance Pyrazine-2-carboxylic acid. EC50 value was estimated to be 145.27 mg/l for Pseudokirchneriella subcapitata for 72 h duration. This effect value indicating that the substance Pyrazine-2-carboxylic acid (CAS no. 98-97-5) does not pose a significant hazard to algae and thus consider to be not classifies as per the CLP classification criteria.

Toxicity to microorganisms

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.( Antimicrobial Agents and Chemotherapy, Vol. 51, No. 2, Pg. no. 752–754, Feb. 2007.)

Additional information

Short-term toxicity to fish

Two studies from prediction reports and experimental study from authorative database for short term fish toxicity endpoint for test chemical Pyrazine-2-carboxylic acid (Cas no. 98-97-5) with relevant read across which is close to target using Log Kow as descriptor were reviewed as follows:

 

Using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances, the short term toxicity to fish was predicted for Pyrazine-2-carboxylic acid (Cas no. 98-97-5) . LC50 value was estimated to be 116.63 mg/L on Danio rerio (previous name: Brachydanio rerio) for 96 hrs duration. Based on this value it can be concluded that the Pyrazine-2-carboxylic acid can be considered as non toxic to fish at environmentally relevant concentrations.

Above prediction assist by experimental study for read across chemical Pyridine (Cas no. 110-86-1) from authorative database Japan chemicals collborative knowledge database (J-check); 2017 In acute toxicity test of Pyridine to Oryzias latipes according to OECD Guideline 203 (Fish, Acute Toxicity Test) in freshwater condition for 96 hrs.During experiment the lethal concentration (LC50) was determined to be >100 mg/l.

Both studies for target and read across substance indicate that the chemical is likely to be non toxic to fish with lethal concentration range >100-116.63 mg/l. Thus, based on the available information, the test substance Pyrazine-2-carboxylic acid (Cas no. 98-97-5) can be considered as non toxic to aquatic environment and thus not classified in aquatic environment as per the CLP criteria.

Short-term toxicity to aquatic invertebrates

Short term toxicity to aquatic invertebrates for Pyrazine-2-carboxylic acid (Cas no. 98-97-5) was summaries with couple of estimated data for target and two experimental studies with two read across substances are summaries as follows:

 

Using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances, the short term toxicity on aquatic invertebrates was predicted for Pyrazine-2-carboxylic acid (Cas no. 98-97-5).EC50 value was estimated to be 303.54 mg/l for Daphnia magna for 48 hrs duration. Based on the value, the Pyrazine-2-carboxylic acid was likely to be non-toxic to aquatic invertebrates and can be considered as not classified as per the CLP regulations.

Likewise prediction by three different model i.e, Battery, Leadscope and SciQSAR used within Danish QSAR database indicate the short term toxicity on Daphnia Magna was predicted for test substance  Pyrazine-2-carboxylic acid (CAS: 98-97-5). The average EC50 value was given by the third model i.e, Battery model. On the basis of effects observed in a static freshwater system, the effect concentration EC50 value for the substance Pyrazine-2-carboxylic acid is estimated to be 304.94 mg/l for Daphnia Magna during 48 hr exposure duration.

Both predictions for target assist by experimental study of read across (2E)-but-2-enedioic acid (Cas no.110-17-8) (J. Water Pollut. Control Fed.52 (8): 2117-2130, 1980) which indicate the objective of the study to determine the ability of wet oxidation to achieve maximum destruction of the material. The acute static toxicity test was performed in Daphnia magna for 48 hrs according to the “Methods for Acute Toxicity Tests with Fish, macro invertebrates and Amphibians.” The test was performed in 154.5 mg/l CaCO3hardness condition, 7.7 pH and at 22 degree C temperature. After the experiment, the EC 50 value in 48 hrs for aquatic invertebrates for  (2E)-but-2-enedioic acid (Cas no.110-17-8) was determined to be 212 mg/l.

From same peer reviewed journal for another read across (2Z)-but-2-enedioic acid (Cas no.110-16-7) study was performed same as above. After the experiment, the EC 50 value in 48 hrs for aquatic invertebrates for (2Z)-but-2-enedioic acid (Cas no.110-16-7) was determined to be 316.2 mg/l.

Based on the predictions of target and experimental studies of read across chemical, it was considered that Pyrazine-2-carboxylic acid (Cas no. 98-97-5) was not hazardous to aquatic invertebrates and can be considered to be not classified as per the CLP regulation.

Toxicity to aquatic algae and cyanobacteria

Four studies including predicted data from validated tool and experimental data from secondary data source for toxicity to aquatic algae endpoint of test chemical Pyrazine-2-carboxylic acid (Cas no. 98-97-5) with relevant read across which is close to target using log Kow as primary descriptor were summarised as follows:

 

Using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the six closest read across substances, which indicate the short term toxicity on aquatic algae and cyanobacteria was predicted for target substance chemical Pyrazine-2-carboxylic acid (Cas no. 98-97-5). The EC50 value was estimated to be 145.27mg/l for Pseudokirchneriella subcapitata for 72 h duration. 

 

Similarly, prediction by three different model i.e, Battery, Leadscope and SciQSAR used within Danish QSAR database indicate the short term toxicity on green algae was predicted for test substance  Pyrazine-2-carboxylic acid (CAS: 98-97-5). The average EC50 value was given by the third model i.e, Battery model. On the basis of effects observed in a static freshwater system, the effect concentration EC50 value for the substance Pyrazine-2-carboxylic acid is estimated to be 158.69 mg/l for Pseudokirchneriella subcapitata during 72 hr exposure duration.

 

For the read across substance, Sodium 2-ethylhexanoate (Cas no. 19766-89-3), toxicity test to green algae study was carried out according to OECD Guideline 201 (Alga, Growth Inhibition Test). The study was based on the growth rate effects of the test compound sodium 2-ethylhexanoate (Cas no.19766-89-3)on green algae. And the effect concentration (EC50) was observed to be 500 mg/l and no observed effect concentration (NOEC) was observed to be 130 mg/l at 72 hrs exposure period. (Japan chemicals collaborative knowledge database (J-check), 2017)

For another read across chemical Succinic acid (Cas no. 110-15-6) from robust summary posted to the HPV Challenge Program Dec. 22, 2006, in a static test method, the effect concentration (EC50) of substance Succinic acid in test species Spirulina labyrinthiformis (blue-green algae) was observed to be 120 mg/l for 72 hrs exposure period.  

Thus based on the effects from all studies give the conclusion that test substance Pyrazine-2-carboxylic acid (Cas no. 98-97-5) with effect concentrations in the range 120 to 500 mg/l was likely to be non toxic to aquatic algae at environmentally relevant concentrations and can be considered to be not classified as per the CLP classification criteria.

Toxicity to microorganisms

Five studies including experimental data 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.