Pyridine-2,4-dicarboxylic acid

Toxicity to aquatic algae and cyanobacteria

Link to relevant study record(s)

Reference

Endpoint:

toxicity to aquatic algae and cyanobacteria

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification

Justification for type of information:

QMRF report has been attached

Qualifier:

according to guideline

Guideline:

OECD Guideline 201 (Alga, Growth Inhibition Test)

Principles of method if other than guideline:

Prediction was done using the OECD QSAR toolbox version 3.4.

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material : pyridine-2,4-dicarboxylic acid
-IUPAC name: 2,4-Pyridinedicarboxylic acid
- Molecular formula : C7H5NO4
- Molecular weight : 167.12 g/mol
- Smiles notation : c1(cc(ncc1)C(O)=O)C(O)=O
- InChl : 1S/C7H5NO4/c9-6(10)4-1-2-8-5(3-4)7(11)12/h1-3H,(H,9,10)(H,11,12)
- Substance type: Organic
- Physical state: Solid

Analytical monitoring:

not specified

Vehicle:

not specified

Test organisms (species):

Pseudokirchneriella subcapitata (previous names: Raphidocelis subcapitata, Selenastrum capricornutum)

Test type:

static

Water media type:

freshwater

Total exposure duration:

72 h

Hardness:

0.24 mmol (24 mg CaCO3/L)

Test temperature:

21.1- 22.9

pH:

7.0-7.7

Nominal and measured concentrations:

Estimated data

Reference substance (positive control):

not specified

Duration:

72 h

Dose descriptor:

EC50

Effect conc.:

246.993 mg/L

Nominal / measured:

estimated

Conc. based on:

test mat.

Basis for effect:

growth rate

Remarks on result:

other: Other details not known

Details on results:

The EC50 was 246.9925 mg/l based on the inhibition ofgrowth rate.

The prediction was based on dataset comprised from the following descriptors: EC50
Estimation method: Takes average value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

(((((((((((("a" or "b" or "c" or "d" )  and ("e" and ( not "f") )  )  and ("g" and ( not "h") )  )  and "i" )  and ("j" and ( not "k") )  )  and ("l" and ( not "m") )  )  and ("n" and ( not "o") )  )  and ("p" and ( not "q") )  )  and ("r" and ( not "s") )  )  and "t" )  and ("u" and ( not "v") )  )  and ("w" and "x" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Aromatic compound OR Carbonic acid derivative by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Acid, aromatic attach [-COOH] OR Alcohol, olefinic attach [-OH] OR Aromatic Carbon [C] OR Aromatic Nitrogen OR Carbonyl, olefinic attach [-C(=O)-] OR Carbonyl, one aromatic attach [-C(=O)-] OR Miscellaneous sulfide (=S) or oxide (=O) OR Olefinic carbon [=CH- or =C<] OR Pyridine, non fused rings  by Organic functional groups (US EPA) ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Aryl OR Carboxylic acid OR Overlapping groups OR Pyridine/ Pyridinium ion by Organic Functional groups (nested) ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Aryl OR Carboxylic acid OR Pyridine/ Pyridinium ion by Organic Functional groups ONLY

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.4

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> Polycyclic Aromatic Hydrocarbon and Naphthalenediimide Derivatives OR SN1 OR SN1 >> Alkylation after metabolically formed carbenium ion species OR SN1 >> Alkylation after metabolically formed carbenium ion species >> Polycyclic Aromatic Hydrocarbon and Naphthalenediimide Derivatives OR SN2 OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation >> Polycyclic Aromatic Hydrocarbon and Naphthalenediimide Derivatives by DNA binding by OASIS v.1.4

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules by DPRA Cysteine peptide depletion

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as High reactive OR High reactive >> alpha,beta-carbonyl compounds with polarized multiple bonds OR High reactive >> Di-methacrylic acid esters OR High reactive >> Vinyl pyridines OR Moderate reactive OR Moderate reactive >> Mono-methacrylic acid esters by DPRA Cysteine peptide depletion

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Class 5 (Not possible to classify according to these rules) by Acute aquatic toxicity classification by Verhaar (Modified) ONLY

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Acid moiety AND Pyridine-alpha by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Alkoxy Silanes by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Acid moiety AND Pyridine-alpha by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Anilines (amino-meta) by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Acid moiety AND Pyridine-alpha by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Esters by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Acid moiety AND Pyridine-alpha by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Inorganic Compound by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Acid moiety AND Pyridine-alpha by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as SHOULD NOT BE PROFILED by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Very fast by Bioaccumulation - metabolism half-lives ONLY

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as Non-Metals by Groups of elements

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as Alkali Earth by Groups of elements

Domain logical expression index: "w"

Parametric boundary:The target chemical should have a value of log Kow which is >= -0.752

Domain logical expression index: "x"

Parametric boundary:The target chemical should have a value of log Kow which is <= 1.11

Validity criteria fulfilled:

not specified

Conclusions:

The EC50 was 246.9925 mg/l based on the inhibition of growth rate of Pseudokirchneriella subcapitata (previous names: Raphidocelis subcapitata, Selenastrum capricornutum) due to the exposure of chemical 2,4-Pyridinedicarboxylic acid for 72hrs.

Executive summary:

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.    

Description of key information

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.    

 

Key value for chemical safety assessment

EC50 for freshwater algae:

246.993 mg/L

Additional information

The aim of the study was to determine the behavior of chemical 2,4-Pyridinedicarboxylic acid (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.