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Ecotoxicological information

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Description of key information

Short term toxicity to aquatic invertebrates:

Based on the prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the closest seven read across substances, toxicity on daphnia magna was predicted for 2,4-Pyridinedicarboxylic acid (499 -80 -9). Based on the immobility of test organism the EC50 value was estimated to be 230.749 mg/l when 2,4-Pyridinedicarboxylic acid exposed to daphnia magna for 48 hrs. Based on this value it can be concluded that the substance 2,4-Pyridinedicarboxylic acid is considered to be not toxic to aquatic environment and not classified as per the criteria mentioned in CLP regulation.    

Toxicity to aquatic algae and cyanobacteria:

Based on the prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the closest five read across substances, toxicity on Pseudokirchneriella subcapitata (previous names: Raphidocelis subcapitata, Selenastrum capricornutum) was predicted for 2,4-Pyridinedicarboxylic acid (499 -80 -9). Based on the growth rate inhibition of test organism, the EC50 value was estimated to be 246.9925 mg/l when 2,4-Pyridinedicarboxylic acid exposed to Pseudokirchneriella subcapitata for 72 hrs. Based on this value it can be concluded that the substance 2,4-Pyridinedicarboxylic acid is considered to be not toxic to aquatic green algae Pseudokirchneriella subcapitata (previous names: Raphidocelis subcapitata, Selenastrum capricornutum) and not classified as per the criteria mentioned in CLP regulation.    

 

Additional information

Summarized result of toxicity of 2,4-Pyridinedicarboxylic acid (Pyridine-2,4-dicarboxylic acid) (499-80-9) on the growth and other activity of aquatic invertebrates, algae and cyanobacteria by considering the data for target as well as RA chemical which was selected on the basis of structural similarity and log Kow as the primary descriptor are as follows:  

Short term toxicity to aquatic invertebrates:

The aim of the study was to determine the behavior of chemical when it comes in contact with the aquatic invertebrates directly or indirectly. For the determination purpose predicted study for the target chemical and experimental study for the read across was used which was selected on the basis of structural and functional similarity were reviewed are summarized as below:

 

In a prediction done by SSS (2017), based on the prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the closest seven read across substances, toxicity on daphnia magna was predicted for 2,4-Pyridinedicarboxylic acid (499 -80 -9). Based on the immobility of test organism the EC50 value was estimated to be 230.749 mg/l when 2,4-Pyridinedicarboxylic acid exposed to daphnia magna for 48 hrs. Based on this value it can be concluded that the substance 2,4-Pyridinedicarboxylic acid is considered to be not toxic to aquatic environment and not classified as per the criteria mentioned in CLP regulation.    

The first study was supported by the second predicted weight of evidence study using ACD labs predicted median Lethal Concentration (LC50) of daphnia magna using v5.0.0.184. The value is supported by estimated Reliability Index (RI). Based on this, the LC 50 value for test item 2,4-Pyridinedicarboxylic acid (499 -80 -9) was predicted to be 7100 mg/l for Daphnia magna.On the basis of predicted value it can be concluded that the substance 2,4-Pyridinedicarboxylic acid is considered to be not toxic to aquatic environment as per the criteria mentioned in CLP regulation.

 

Similarly the third predicted study was used from Danish QSAR database, 2017. Based on the average value of both models (Leadscope Enterprise model and SciMatics SciQSAR model), the result were predicted in Battery model. Based on the Danish (Q)SAR Database, the 48 hours EC50 was estimated to be 103.6029 mg/l on Daphnia Magna for substance 2,4-Pyridinedicarboxylic acid with immobilization effects. Thus based on this value it can be concluded that the substance 2,4-Pyridinedicarboxylic acid cannot be classified as toxic as per the criteria of CLP regulation.

 

The fourth weight of evidence study for the target chemical 2,4-Pyridinedicarboxylic acid (499-80-9) done based on the prediction done by EPI suite, ECOSAR version 1.1, on the basis of similarity of structure to chemicals for which the aquatic toxicity has been previously measured by structure-activity relationships (SARs) program, the LC 50 value for short term toxicity to aquatic invertebrates was predicted. On the basis of this program, the LC 50 value for short term toxicity to aquatic invertebrates was predicted to be 1321.51 mg/l for 2,4-Pyridinedicarboxylic acid in 48 hrs. Based on this value it can be concluded that the substance is considered to be not toxic to aquatic environment and cannot be classified as per the criteria mentioned in CLP regulation.

Similarly the above predicted study was supported by the experimental studies for the read across chemicals which was structurally and functionally similar to the target chemical. First Terephthalic acid (100-21-0) from j-check, 2017, An acute immobilization test was used to test how a range of concentrations of Terephthalic acid exerts different degrees of toxic effects on the swimming capability of Daphnia magna under otherwise identical test conditions. A short term study in a semi-static test design was performed according to guidelines OECD Guideline 202 (Daphnia sp., Acute Immobilisation Test and Reproduction Test). Analytical method conducted by using HPLC method. 100 microL/L vehicle were used. 100 mL per vessel test solution volume added. Test conducted on 20 daphnia per concentration, where test performed in 4 replicates. Dechlorinated tap water collected from Tsukuba City, Ibaraki Prefecture were used. Based on the immobility of daphnia magna due to the chemical Terephthalic acid, the EC50 was ≥ 20 mg/l. Thus based on the effect concentration and readily biodegradability of chemical Terephthalic acid, it can be concluded that the chemical was nontoxic and can be consider to be not classified as toxic as per the CLP classification criteria.

 

In the sixth weight of evidence study from HSDB and OECD SIDS report, for the read across chemical (121-91-5) study was conducted to determine the toxic effect of chemical 1,3 Benzene dicarboxylic acid (Isophthalic acid) on the mobility of daphnia magna for 48hrs. Standards methods as per the OECD guideline were used in the test. 5 daphnids per concentration added in the test solution. Test performed in the 4 replicates, were observation of pH, effect on growth and other effects were measured. Based on the immobility of daphnia magna for 48hrs of exposure duration with the chemical, the EC0 was 876 mg/l. Based on the effect of chemical 1,3 Benzene dicarboxylic acid (Isophthalic acid) on the growth of daphnia magna, it can be concluded that the chemical was nontoxic and can be consider to be not classified as per the CLP classification criteria.

 

Similarly another read across chemical (59-67-6) from Fisheries Science 1994 also supports the nontoxic nature and classification of target chemical, Inhibitory effect was measured for B. Amphitrite by nicotinic acid. The test sample in the Petri dish was dissolved or dispersed in 5 m/ of filtered sea water. Ten cyprid larvae of B. amphitrite were transferred to each Petri dish and incubated in a darkroom at 23°C for 24h, The number of B. amphitrite settled and metamorphosed on the bottom of each Petri dish was counted to evaluate the effect of the test sample. TBTO and CuSO4 which are known to be antifouling chemicals were also applied as the positive controls in the assay. The highly active fractions were lyophilized, chromatographed and purified by HPLC. After that the minimum inhibitory concentration (MIC) or LOEC for nicotinic acid (59-67-6) was determined to be 20 mg/l. Based on the value, the nicotinic acid was considered to be toxic to aquatic invertebrates but as it was readily biodegradable it can considered to be not classified as per the CLP regulations.

 

Thus on the basis of all studies including predicted for the target chemical 2,4-Pyridinedicarboxylic acid (Pyridine-2,4-dicarboxylic acid) (499-80-9) (from QSAR toolbox version 3.4, ACD lab, Danish QSAR, EPIsuite) and experimental for the read across chemicals from (j-check, HSDB, OECD SIDS report and Fisheries Science 1994), it can be concluded that the target chemical was nontoxic and can be consider to be not classified as toxic to aquatic invertebrates as per the CLP classification criteria.  

Toxicity to aquatic algae and cyanobacteria:

The aim of the study was to determine the behavior of chemical (Pyridine-2,4-dicarboxylic acid) (499-80-9) when it comes in contact with the aquatic invertebrates directly or indirectly. For the determination purpose predicted study for the target chemical and experimental study for the read across was used which was selected on the basis of structural and functional similarity were reviewed are summarized as below:

 

In a prediction done by SSS (2017), Based on the prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the closest five read across substances, toxicity on Pseudokirchneriella subcapitata (previous names: Raphidocelis subcapitata, Selenastrum capricornutum) was predicted for 2,4-Pyridinedicarboxylic acid (499 -80 -9). Based on the growth rate inhibition of test organism, the EC50 value was estimated to be 246.9925 mg/l when 2,4-Pyridinedicarboxylic acid exposed to Pseudokirchneriella subcapitata for 72 hrs. Based on this value it can be concluded that the substance 2,4-Pyridinedicarboxylic acid is considered to be not toxic to aquatic green algae Pseudokirchneriella subcapitata (previous names: Raphidocelis subcapitata, Selenastrum capricornutum) and not classified as per the criteria mentioned in CLP regulation.    

 

Similarly the second predicted study was used from Danish QSAR database, 2017, Based on the prediction done using the three different models i.e, Battery, Leadscope and SciQSAR used within Danish QSAR database, the short term toxicity on green algae was predicted for test substance  2,4-Pyridinedicarboxylic acid (CAS:499 -80 -9). 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  2,4-Pyridinedicarboxylic acid is estimated to be 225.8131 mg/l for Pseudokirchneriella subcapitata during 72 hr exposure duration. Thus, on the basis of EC50 value,it can be concluded that the 2,4-Pyridinedicarboxylic acid can be considered as non-toxic to green algae at environmentally relevant concentrations and can be considered not-classified as per the CLP classification criteria.

 

The third weight of evidence study for the target chemical 2,4-Pyridinedicarboxylic acid (499-80-9) done based on the prediction done using theEPI Suite ECOSAR version 1.10, the short term toxicity on green algae was predicted for test substance 2,4-Pyridinedicarboxylic acid (499 -80 -9). On the basis of effects observed in a static freshwater system, the effect concentration EC50 value for the substance is estimated to be 569.703 mg/l for green algae for 96 hrs duration. Based on this value, it can be concluded that the test chemical 2,4-Pyridinedicarboxylic acid can be considered as non-toxic to green algae at environmentally relevant concentrations and can be considered not-classified as per the CLP classification criteria.

 

Predicted study was supported by the experimental studies for the read across chemicals which was structurally and functionally similar to the target chemical. First Terephthalic acid (100-21-0) from j-check, 2017. This study was performed in order to evaluate the toxic potential of Terephthalic acid towards freshwater green algae. Test conducted in the static system for the total exposure duration of 72hrs. After the 72 hrs no effect were observed on the growth of algae at 18 and 19 mg/l and the 50% growth inhibited was greater than NOEC value 18 and 19 mg/l. Based on the growth rate inhibition, biomass and area under the growth curve, the EC50 was > 18 and > 19 mg/l. Based on the growth rate NOEC was 18 mg/l and on the basis of biomass and area under the growth curve NOEC was 19 mg/l. Thus the effect concentration and readily biodegradability of chemical Terephthalic acid, it can be concluded that the chemical was nontoxic and can be consider to be not classified as toxic as per the CLP classification criteria.

 

Similarly in the fifth weight of evidence study from HSDB and OECD SIDS report, for the read across chemical 1,3 Benzene dicarboxylic acid (Isophthalic acid) (121-91-5) toxicity was carried out on the Scenedesmus subspicatus. Study was performed to evaluate the nature and effect of chemical 1,3 Benzene dicarboxylic acid (Isophthalic acid) when it comes in contact with the aquatic algae Scenedesmus subspicatus. Test conducted according to the OECD guideline 201. Based on the growth rate inhibition of Scenedesmus subspicatus (green algae) due to the chemical 1,3 Benzene dicarboxylic acid (Isophthalic acid) the NOEC was 969 mg/l. As at 969 mg/ no effect were observed on the growth of algae so it can be consider that the concentration at which 50% growth inhibited was > 969 mg/l. hence on the basis of this phenomenon it can be concluded that the chemical was nontoxic and can be consider to be not classified as per the CLP classification criteria.

 

Study on read across chemical Nicotinic acid (59-67-6) from HSDB and OECD SIDS report also supports the nontoxic nature and classification of target chemical. Short term toxicity to Scenedesmus subspicatus (green algae) study was carried out for 72 hrs. The study was performed according to OECD Guideline 201 (Alga, Growth Inhibition Test) and other method DIN 38412L9, respectively. The study was based on the effects of the test compound Nicotinic acid (CAS no. 59 -67 -6) on green algae in a static fresh water system. Test chemical concentration used for the study was in the range of 90 -100 mg/l. The growth inhibition was concentration and pH dependent. Based on effect on growth rate of the test organism green algae, the 72 hr EC0, EC10 and EbC50 value was determined to be 25, 30 and 90 mg/l, respectively. Thus, based on the EC50 value, it can be concluded that the substance Nicotinic acid can be considered as toxic to aquatic organisms. Since the chemical is readily biodegradable in nature, chemical Nicotinic acid can be considered as non-toxic to aquatic organisms and thus can considered to be not classified as per the CLP classification criteria.

 

Thus on the basis of all studies including predicted for the target chemical 2,4-Pyridinedicarboxylic acid (Pyridine-2,4-dicarboxylic acid) (499-80-9) (from QSAR toolbox version 3.4, Danish QSAR, EPIsuite) and experimental for the read across chemicals from (j-check, HSDB, OECD SIDS report), it can be concluded that the target chemical was nontoxic and can be consider to be not classified as toxic to aquatic algae and cyanobacteria as per the CLP classification criteria.  

Based on the overall studies on the invertebrates and algae, including predicted and experimental, it can be concluded that the chemical was nontoxic and can be consider to be not classified as toxic as per the CLP classification criteria.