Pyridine-2,4-dicarboxylic acid

Endpoint summary

Description of key information

Skin irritation

The dermal irritation potential of target chemical 2,4-Pyridinedicarboxylic acid (CAS No: 499-80-9) was assessedin various experimental studies which were conducted on rabbits for target chemical2,4-Pyridinedicarboxylic acid (CAS No: 499-80-9) and its structurally similar read across substancesIsophthtalic acid [CAS: 121-91-5] and terephthalic acid [CAS: 100-21-0]. The predicted data usingQSAR toolboxhas also been compared with the experimental data.Based on the available data for the target and read across substances and applying the weight of evidence approach, it can be concluded that chemical 2,4-Pyridinedicarboxylic acid (CAS No: 499-80-9) is unable to cause skin irritation and thus considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

 

Eye irritation

An ocular irritation potential of target chemical 2,4-Pyridinedicarboxylic acid (CAS No: 499-80-9) was assessedin various experimental studies which were conducted on rabbits for target chemical2,4-Pyridinedicarboxylic acid (CAS No: 499-80-9) and its structurally similar read across substancesIsophthtalic acid [CAS: 121-91-5] and terephthalic acid [CAS: 100-21-0]. The predicted data usingQSAR toolboxhas also been compared with the experimental data.Based on the available data for the target and read across substances and applying the weight of evidence approach, it can be concluded that chemical 2,4-Pyridinedicarboxylic acid (CAS No: 499-80-9) is unable to cause eye damage and thus can be considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

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:

Data is from OECD QSAR toolbox version 3.4 and QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: estimated data

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.4

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material (IUPAC name): 2,4-Pyridinedicarboxylic acid
- Common name: Pyridine-2,4-dicarboxylic 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

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

No data available

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

No data available

Duration of treatment / exposure:

4 hours

Observation period:

24 hours

Number of animals:

3

Details on study design:

No data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

24 h

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No skin irritation was observed in treated rabbits.

Estimation method: Takes mode value from the 7 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 ( not "j") )  )  and "k" )  and "l" )  and "m" )  and "n" )  and "o" )  and "p" )  and ("q" and "r" )  )

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 AN2 OR AN2 >>  Michael-type addition, quinoid structures OR AN2 >>  Michael-type addition, quinoid structures >> Quinone methides OR AN2 >> Michael-type conjugate addition to activated alkene derivatives OR AN2 >> Michael-type conjugate addition to activated alkene derivatives >> Alpha-Beta Conjugated Alkene Derivatives with Geminal Electron-Withdrawing Groups OR AN2 >> Nucleophilic addition to alpha, beta-unsaturated carbonyl compounds OR AN2 >> Nucleophilic addition to alpha, beta-unsaturated carbonyl compounds >> Alpha, Beta-Unsaturated Aldehydes OR AN2 >> Schiff base formation OR AN2 >> Schiff base formation >> Alpha, Beta-Unsaturated Aldehydes OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> Polycyclic Aromatic Hydrocarbon and Naphthalenediimide Derivatives OR Radical OR Radical >> ROS formation after GSH depletion OR Radical >> ROS formation after GSH depletion >> Quinone methides 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 OR SN2 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Quinoline Derivatives OR SN2 >> SN2 at an activated carbon atom OR SN2 >> SN2 at an activated carbon atom >> Quinoline Derivatives by DNA binding by OASIS v.1.4

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Non binder, without OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Non binder, impaired OH or NH2 group OR Non binder, MW>500 OR Non binder, non cyclic structure by Estrogen Receptor Binding

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as No alert found by Protein binding by OASIS v1.4

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Acylation involving an activated (glucuronidated) carboxamide group OR Acylation >> Acylation involving an activated (glucuronidated) carboxamide group >> Carboxylic Acid Amides OR Acylation >> Acylation involving an activated (glucuronidated) sulfonamide group OR Acylation >> Acylation involving an activated (glucuronidated) sulfonamide group >> Arenesulfonamides OR Acylation >> Direct acylation involving a leaving group OR Acylation >> Direct acylation involving a leaving group >> (Thio)Acyl and (thio)carbamoyl halides and cyanides  OR Acylation >> Direct acylation involving a leaving group >> Carboxylic Acid Amides OR AN2 OR AN2 >> Michael addition to activated double bonds OR AN2 >> Michael addition to activated double bonds >> alpha,beta-Unsaturated Carbonyls and Related Compounds OR AN2 >> Michael addition to alpha, beta-unsaturated acids and esters OR AN2 >> Michael addition to alpha, beta-unsaturated acids and esters >> alpha,beta-Unsaturated Carboxylic Acids and Esters OR AN2 >> Michael-type addition to activated double bonds in vinyl pyridines OR AN2 >> Michael-type addition to activated double bonds in vinyl pyridines >> Ethenyl Pyridines OR AN2 >> Michael-type addition to quinoid structures  OR AN2 >> Michael-type addition to quinoid structures  >> Carboxylic Acid Amides OR AN2 >> Nucleophilic addition at polarized N-functional double bond OR AN2 >> Nucleophilic addition at polarized N-functional double bond >> Arenesulfonamides OR AN2 >> Nucleophilic addition to pyridonimine tautomer of aminopyridoindoles or aminopyridoimidazoles (hypothesized) OR AN2 >> Nucleophilic addition to pyridonimine tautomer of aminopyridoindoles or aminopyridoimidazoles (hypothesized) >> Heterocyclic Aromatic Amines OR Michael addition OR Michael addition >> Michael addition on conjugated systems with electron withdrawing group OR Michael addition >> Michael addition on conjugated systems with electron withdrawing group >> alpha,beta-Carbonyl compounds with polarized double bonds  OR Michael addition >> Michael addition on conjugated systems with electron withdrawing group >> Cyanoalkenes OR Michael addition >> Michael addition on polarised Alkenes OR Michael addition >> Michael addition on polarised Alkenes >> Polarised Alkene - alkenyl pyridines, pyrazines, pyrimidines or triazines  OR Nucleophilic addition OR Nucleophilic addition >> Addition to carbon-hetero double bonds OR Nucleophilic addition >> Addition to carbon-hetero double bonds >> Ketones OR Radical reactions OR Radical reactions >> ROS generation and direct attack of hydroxyl radical to the C8 position of nucleoside base OR Radical reactions >> ROS generation and direct attack of hydroxyl radical to the C8 position of nucleoside base >> Heterocyclic Aromatic Amines OR Schiff base formation OR Schiff base formation >> Schiff base formation with carbonyl compounds OR Schiff base formation >> Schiff base formation with carbonyl compounds >> Aldehydes OR SE reaction (CYP450-activated heterocyclic amines) OR SE reaction (CYP450-activated heterocyclic amines) >> Direct attack of arylnitrenium cation to the C8 position of nucleoside base  OR SE reaction (CYP450-activated heterocyclic amines) >> Direct attack of arylnitrenium cation to the C8 position of nucleoside base  >> Heterocyclic Aromatic Amines OR SN2 OR SN2 >> SN2 Reaction at a sp3 carbon atom OR SN2 >> SN2 Reaction at a sp3 carbon atom >> Activated alkyl esters and thioesters  OR SR reaction (peroxidase-activated heterocyclic amines) OR SR reaction (peroxidase-activated heterocyclic amines) >> Direct attack of arylnitrenium radical to the C8 position of nucleoside base OR SR reaction (peroxidase-activated heterocyclic amines) >> Direct attack of arylnitrenium radical to the C8 position of nucleoside base >> Heterocyclic Aromatic Amines by Protein binding by OASIS v1.4

Domain logical expression index: "k"

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: "l"

Referential boundary: The target chemical should be classified as Reactive unspecified by Acute aquatic toxicity MOA by OASIS ONLY

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "n"

Similarity boundary:Target: OC(=O)c1ccnc(C(O)=O)c1
Threshold=50%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "o"

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

Domain logical expression index: "p"

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

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of log Kow which is >= -0.092

Domain logical expression index: "r"

Parametric boundary:The target chemical should have a value of log Kow which is <= 1.87

Interpretation of results:

other: not irritating

Conclusions:

The chemical 2,4-Pyridinedicarboxylic acid (CAS No: 499-80-9) was estimated to be not irritating to the skin of New Zealand White rabbits. Based on the estimated result 2,4-Pyridinedicarboxylic acid (CAS No: 499-80-9) can be considered to be not irritating to skin

Executive summary:

The dermal irritation potential of 2,4-Pyridinedicarboxylic acid (CAS No: 499-80-9) was estimated using OECD QSAR toolbox version 3.4 with logPow as the primary descriptor. The chemical 2,4-Pyridinedicarboxylic acid (CAS No: 499-80-9) was estimated to be not irritating to the skin of New Zealand White rabbits. Based on the estimated result 2,4-Pyridinedicarboxylic acid (CAS No: 499-80-9) can be considered to be not irritating to skin and can be classified under the category ˋ Not Classified’ as per CLP regulation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

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:

Data is from OECD QSAR toolbox version 3.4 and QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: estimated data

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.4

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

No data available

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

No data available

Duration of treatment / exposure:

single application

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

3

Details on study design:

No data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

72 h

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No eye irritation was observed n treated rabbits.

Estimation method: Takes mode value from the 7 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 ( not "j") )  )  and "k" )  and "l" )  and ("m" and ( not "n") )  )  and "o" )  and "p" )  and ("q" and "r" )  )

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 AN2 OR AN2 >>  Michael-type addition, quinoid structures OR AN2 >>  Michael-type addition, quinoid structures >> Quinone methides OR AN2 >> Michael-type conjugate addition to activated alkene derivatives OR AN2 >> Michael-type conjugate addition to activated alkene derivatives >> Alpha-Beta Conjugated Alkene Derivatives with Geminal Electron-Withdrawing Groups OR AN2 >> Nucleophilic addition to alpha, beta-unsaturated carbonyl compounds OR AN2 >> Nucleophilic addition to alpha, beta-unsaturated carbonyl compounds >> Alpha, Beta-Unsaturated Aldehydes OR AN2 >> Schiff base formation OR AN2 >> Schiff base formation >> Alpha, Beta-Unsaturated Aldehydes OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> Polycyclic Aromatic Hydrocarbon and Naphthalenediimide Derivatives OR Radical OR Radical >> ROS formation after GSH depletion OR Radical >> ROS formation after GSH depletion >> Quinone methides 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 OR SN2 >> Alkylation, direct acting epoxides and related >> Epoxides and Aziridines 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 OR SN2 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Quinoline Derivatives OR SN2 >> SN2 at an activated carbon atom OR SN2 >> SN2 at an activated carbon atom >> Quinoline Derivatives by DNA binding by OASIS v.1.4

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Non binder, without OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Non binder, impaired OH or NH2 group OR Non binder, MW>500 OR Non binder, non cyclic structure by Estrogen Receptor Binding

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as No alert found by Protein binding by OASIS v1.4

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Acylation involving an activated (glucuronidated) carboxamide group OR Acylation >> Acylation involving an activated (glucuronidated) carboxamide group >> Carboxylic Acid Amides OR Acylation >> Direct acylation involving a leaving group OR Acylation >> Direct acylation involving a leaving group >> (Thio)Acyl and (thio)carbamoyl halides and cyanides  OR Acylation >> Direct acylation involving a leaving group >> Carboxylic Acid Amides OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides OR AN2 OR AN2 >> Michael addition to activated double bonds OR AN2 >> Michael addition to activated double bonds >> alpha,beta-Unsaturated Carbonyls and Related Compounds OR AN2 >> Michael addition to alpha, beta-unsaturated acids and esters OR AN2 >> Michael addition to alpha, beta-unsaturated acids and esters >> alpha,beta-Unsaturated Carboxylic Acids and Esters OR AN2 >> Michael-type addition to activated double bonds in vinyl pyridines OR AN2 >> Michael-type addition to activated double bonds in vinyl pyridines >> Ethenyl Pyridines OR AN2 >> Michael-type addition to quinoid structures  OR AN2 >> Michael-type addition to quinoid structures  >> Carboxylic Acid Amides OR AN2 >> Nucleophilic addition to pyridonimine tautomer of aminopyridoindoles or aminopyridoimidazoles (hypothesized) OR AN2 >> Nucleophilic addition to pyridonimine tautomer of aminopyridoindoles or aminopyridoimidazoles (hypothesized) >> Heterocyclic Aromatic Amines OR Michael addition OR Michael addition >> Michael addition on conjugated systems with electron withdrawing group OR Michael addition >> Michael addition on conjugated systems with electron withdrawing group >> alpha,beta-Carbonyl compounds with polarized double bonds  OR Michael addition >> Michael addition on conjugated systems with electron withdrawing group >> Cyanoalkenes OR Michael addition >> Michael addition on polarised Alkenes OR Michael addition >> Michael addition on polarised Alkenes >> Polarised Alkene - alkenyl pyridines, pyrazines, pyrimidines or triazines  OR Nucleophilic addition OR Nucleophilic addition >> Addition to carbon-hetero double bonds OR Nucleophilic addition >> Addition to carbon-hetero double bonds >> Ketones OR Radical reactions OR Radical reactions >> ROS generation and direct attack of hydroxyl radical to the C8 position of nucleoside base OR Radical reactions >> ROS generation and direct attack of hydroxyl radical to the C8 position of nucleoside base >> Heterocyclic Aromatic Amines OR Schiff base formation OR Schiff base formation >> Schiff base formation with carbonyl compounds OR Schiff base formation >> Schiff base formation with carbonyl compounds >> Aldehydes OR SE reaction (CYP450-activated heterocyclic amines) OR SE reaction (CYP450-activated heterocyclic amines) >> Direct attack of arylnitrenium cation to the C8 position of nucleoside base  OR SE reaction (CYP450-activated heterocyclic amines) >> Direct attack of arylnitrenium cation to the C8 position of nucleoside base  >> Heterocyclic Aromatic Amines OR SN2 OR SN2 >> SN2 Reaction at a sp3 carbon atom OR SN2 >> SN2 Reaction at a sp3 carbon atom >> Activated alkyl esters and thioesters  OR SR reaction (peroxidase-activated heterocyclic amines) OR SR reaction (peroxidase-activated heterocyclic amines) >> Direct attack of arylnitrenium radical to the C8 position of nucleoside base OR SR reaction (peroxidase-activated heterocyclic amines) >> Direct attack of arylnitrenium radical to the C8 position of nucleoside base >> Heterocyclic Aromatic Amines by Protein binding by OASIS v1.4

Domain logical expression index: "k"

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: "l"

Referential boundary: The target chemical should be classified as Reactive unspecified by Acute aquatic toxicity MOA by OASIS ONLY

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND (!Undefined)Group CN Lipid Solubility < 0.4 g/kg AND Group All Melting Point > 200 C by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Group All Aqueous Solubility < 0.000005 g/L OR Group All Aqueous Solubility < 0.00002 g/L OR Group All log Kow > 9 OR Group C Aqueous Solubility < 0.0001 g/L OR Group C Aqueous Solubility < 0.0005 g/L OR Group C Melting Point > 55 C OR Group CN Aqueous Solubility < 0.1 g/L OR Group CN log Kow > 4.5 OR Group CNS log Kow > 1.5 OR Group CNS Melting Point > 50 C by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "p"

Similarity boundary:Target: OC(=O)c1ccnc(C(O)=O)c1
Threshold=60%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of log Kow which is >= -0.0941

Domain logical expression index: "r"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.02

Interpretation of results:

other: not irritating

Conclusions:

 The chemical 2,4-Pyridinedicarboxylic acid (CAS No: 499-80-9)was estimated to be not sensitizing to the skin of Dunkin-Hartley guinea pigs. Based on the estimated result 2,4-Pyridinedicarboxylic acid (CAS No: 499-80-9) failed to induce skin sanitization effects and hence is considered to be not sensitizing to Dunkin-Hartley guinea pigs

Executive summary:

The skin sensitization potential of 2,4-Pyridinedicarboxylic acid (CAS No: 499-80-9) was estimated using OECD QSAR toolbox version 3.4 with log Pow as the primary descriptor. The chemical 2,4-Pyridinedicarboxylic acid (CAS No: 499-80-9)was estimated to be not sensitizing to the skin of Dunkin-Hartley guinea pigs. Based on the estimated result 2,4-Pyridinedicarboxylic acid (CAS No: 499-80-9) failed to induce skin sanitization effects and hence is considered to be not sensitizing to Dunkin-Hartley guinea pigs and can be classified under the category ˋ Not Classified’ as per CLP regulation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

Various studieshas been investigated for the test chemical2,4-Pyridinedicarboxylic acid (CAS No: 499-80-9) to observe the potential for dermal irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits and humans for target chemical and its structurally similar read across substances Isophthtalic acid [CAS: 121-91-5] and terephthalic acid [CAS: 100-21-0].The predicted data using the OECD QSAR toolbox has also been compared with the experimental data and summarized as below;

 

 In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the skin irritation potential was estimated for test chemical2,4-Pyridinedicarboxylic acid (CAS No: 499-80-9).The chemical 2,4-Pyridinedicarboxylic acid (CAS No: 499-80-9) is estimated to be not irritating to skin of New Zealand White rabbits.

 

 The above result was further supported by the experimental studies summarized in Hazardous Substance Databank (HSDB) {U S National Library of Medicine, last updated 2012} for two read across substances Isophthtalic acid [CAS: 121-91-5] and terephthalic acid [CAS: 100-21-0] as follows;

 

In the skin irritation study of terephthalic acid [CAS: 100-21-0], 10 mL oily paste containing 80% terephthalic acid was applied to the equal sites on the hands of human volunteers (number not specified).The volunteers were observed for signs of irritation (duration not specified). No skin irritation was observed when Terephthalic acid applied as an oily paste and hence it was considered as not irritating to human skin.

 

In case of Isophthtalic acid [CAS: 121-91-5], 500 mg undiluted isophthalic acidwas applied for 24 hours to abraded or unabraded skin of 6 albino rabbits that was previously clipped. The treated site was occluded. The rabbits were observed for signs of irritation and reactions were scored at 24 hours and 72 hours according to Draize method. With intact skin, mild erythema was noted in 1/6 animals at 24 hr (score=0.2/8), and 0/6 animals at 72 hr (score=0/8). With abraded skin, mild erythema was noted in 3/6 animals at 24 hr (score=0.5/8) and 0/6 animals at 72 hr (score=0/8). No edema was observed. Based on these observations and scores, isophthalic acid was considered to be not irritating to albino rabbit skin.

 

 Thus based on the available data for the target and read across substances and applying the weight of evidence approach, it can be concluded that chemical 2,4-Pyridinedicarboxylic acid (CAS No: 499-80-9) is unable to cause skin irritation and considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

 

Eye irritation:

In different studies,the test chemical2,4-Pyridinedicarboxylic acid (CAS No: 499-80-9) has been investigated for potential for ocular irritationto a greater or lesser extent. The studies are based on in vivo experiments in rabbits for target chemical2,4-Pyridinedicarboxylic acid (CAS No: 499-80-9) andits structurally similar read across substancessubstanceIsophthtalic acid [CAS: 121-91-5] and terephthalic acid [CAS: 100-21-0].The predicted data using the OECD QSAR toolbox has also been compared with the experimental data and summarized as below;

 

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the eye irritation potential was estimated for test chemical2,4-Pyridinedicarboxylic acid (CAS No: 499-80-9).The chemical 2,4-Pyridinedicarboxylic acid (CAS No: 499-80-9) is estimated to be not irritating to eye of New Zealand White rabbits.

 

The IFA GESTIS {GESTIS SUBSTANCE Database (information system in hazardous substance of the Berufsgenossenscheftn)} andEUROPEAN COMMISSION – European Chemicals Bureau {IUCLID Dataset;EUROPEAN COMMISSION – European Chemicals Bureau;18–FEB–2000} reportedan eye irritation study of read across chemicalisophthalic acid (CAS No:121-91-5)on six rabbits that supported the above mentioned result for the target chemical. In this test,Isophthalic acid was administered undiluted at a dose of 0.1 gram into one eye of each of six rabbits, with the other eye serving as an untreated control. The treated eye of each rabbit was scored for irritation at 1, 2, 3, 4, 7, and 14 days following test article administration. The control eye was used for comparison.The maximum irritation score of 5.3/110.0 was obtained 1 day after administration of the test article. Ocular Irritation was seen in all rabbits during the study, but only three rabbits exhibited positive reactions. Complete recovery from all signs of ocular irritation was evident in two rabbits by the 2nd day, in five rabbits by the 4th day, and in all rabbits by the final scoring interval. Since all the ocular lesions had cleared upto 14 days, the chemical isophthalic acid (CAS No:121-91-5) was considered to be not irritating to the rabbits’ eye.

 

The above results were further supported by the experimental study reported by MAK Collection for Occupational Health and Safety {Phthalic acid and its isomers (isophthalic acid and terephthalic acid) [MAK Value Documentation, 2009]. The MAK Collection for Occupational Health and Safety. 194–221.2012}on six albino rabbits for read across chemicalTerephthalic acid (CAS no: 100-21-0). When chemical was applied at a concentration of 100 mg (undiluted) to one eye of each of six albino rabbits, slight irritation of the iris and conjunctiva was observed , which was 9.0 of a total score of 110 after one hour and 4.5 after 24 hours. All symptoms had disappeared 48 hours after application. Thus on the basis of observed results, the chemical Terephthalic acid (CAS no: 100-21-0) was considered to be not irritating to the eyes of albino rabbits.

 

Thus on the basis of available data for thetarget chemical2,4-Pyridinedicarboxylic acid (CAS No: 499-80-9)and its structurally similar read across substancesIsophthtalic acid [CAS: 121-91-5] and terephthalic acid [CAS: 100-21-0], it can be concluded that the chemical 2,4-Pyridinedicarboxylic acid (CAS No: 499-80-9) is unable to cause eye irritation and considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

 

 

Justification for classification or non-classification

The skin and eye irritation potential of test chemical 2,4-Pyridinedicarboxylic acid (CAS No: 499-80-9) and its structurally similar read across substanceswere observed in various studies. The results obtained from these studies indicate that the chemical 2,4-Pyridinedicarboxylic acid is unlikely to cause skin and eye irritation. Hence 2,4-Pyridinedicarboxylic acid (CAS No: 499-80-9)can be classified under the category “Not Classified” for skin and eye as per CLP.