3,5-diaminobenzoic acid

Endpoint summary

Description of key information

Skin Irritation:

The dermal irritation potential of 3,5-Diaminobenzoic acid was estimated using OECD QSAR toolbox v3.4 with logPow as the primary descriptor.

3,5-Diaminobenzoic acid was estimated to be not irritating to the skin of CBA mice

Based on the estimated results, 3,5-Diaminobenzoic acid can be considered to be not irritating to skin and can be classified under the category “Not Classified” as per CLP regulation.

Eye Irritation:

The ocular irritation potential of 3,5-Diaminobenzoic acid was estimated using OECD QSAR toolbox v3.4 with logPow as the primary descriptor.

3,5-Diaminobenzoic acid was estimated to be not irritating to the eyes of New Zealand White rabbits.

Based on the estimated results, 3,5-Diaminobenzoic acid can be considered to be not irritating to eyes and can be classified under the category “Not Classified” as per CLP regulation.

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 v3.4 and the QMRF report has been attached

Qualifier:

equivalent or similar to guideline

Guideline:

other: predicted data

Principles of method if other than guideline:

Prediction was done using OECD QSAR toolbox v3.4

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material (as cited in study report): 3,5-Diaminobenzoic acid
- Molecular formula: C7H8N2O2
- Molecular weight: 152.1522 g/mol
- Substance type: Organic
- Physical state: Solid

Species:

mouse

Strain:

CBA

Details on test animals or test system and environmental conditions:

no data available

Type of coverage:

not specified

Preparation of test site:

not specified

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

no data available

Duration of treatment / exposure:

no data available

Observation period:

no data available

Number of animals:

no data available

Details on study design:

no data available

Other effects / acceptance of results:

no data available

Irritation parameter:

overall irritation score

Basis:

mean

Score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No irritation observed

Estimation method: Takes mode value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

((((((((("a" or "b" or "c" or "d" or "e" or "f") and("g" and(not "h")) ) and("i" and(not "j")) ) and "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") )

Domain logical expression index: "a"

Referential boundary:The target chemical should be classified as Anilines (Acute toxicity) by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary:The target chemical should be classified as Aminoaniline, meta AND Aniline AND Aryl AND Carboxylic acid by Organic Functional groups

Domain logical expression index: "c"

Referential boundary:The target chemical should be classified as Aminoaniline, meta AND Carboxylic acid AND Overlapping groups by Organic Functional groups (nested)

Domain logical expression index: "d"

Referential boundary:The target chemical should be classified as Acid, aromatic attach [-COOH] AND Alcohol, olefinic attach [-OH] AND Aliphatic Nitrogen, one aromatic attach [-N] AND Aromatic Carbon [C] 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<] by Organic functional groups (US EPA)

Domain logical expression index: "e"

Referential boundary:The target chemical should be classified as Amine AND Aromatic compound AND Carbonic acid derivative AND Carboxylic acid AND Carboxylic acid derivative AND Primary amine AND Primary aromatic amine by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "f"

Referential boundary:The target chemical should be classified as Aromatic amines by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "g"

Referential boundary:The target chemical should be classified as Radical AND Radical >> Radical mechanism via ROS formation (indirect) AND Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines AND SN1 AND SN1 >> Nucleophilic attack after nitrenium ion formation AND SN1 >> Nucleophilic attack after nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines by DNA binding by OASIS v.1.4

Domain logical expression index: "h"

Referential boundary:The target chemical should be classified as AN2 OR AN2 >>  Michael-type addition, quinoid structures OR AN2 >>  Michael-type addition, quinoid structures >> Quinones and Trihydroxybenzenes OR AN2 >> Schiff base formation OR AN2 >> Schiff base formation >> Polarized Haloalkene Derivatives OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation >> Geminal Polyhaloalkane Derivatives OR AN2 >> Shiff base formation after aldehyde release OR AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters OR AN2 >> Thioacylation via nucleophilic addition after cysteine-mediated thioketene formation OR AN2 >> Thioacylation via nucleophilic addition after cysteine-mediated thioketene formation >> Haloalkenes with Electron-Withdrawing Groups OR AN2 >> Thioacylation via nucleophilic addition after cysteine-mediated thioketene formation >> Polarized Haloalkene Derivatives OR No alert found OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> Amino Anthraquinones OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide and Aminoalkylamine Side Chain OR Non-covalent interaction >> DNA intercalation >> Fused-Ring Primary Aromatic Amines OR Non-covalent interaction >> DNA intercalation >> Quinones and Trihydroxybenzenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Amino Anthraquinones OR Radical >> Radical mechanism via ROS formation (indirect) >> Diazenes and Azoxyalkanes OR Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Geminal Polyhaloalkane Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroaniline Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroarenes with Other Active Groups OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR Radical >> Radical mechanism via ROS formation (indirect) >> p-Aminobiphenyl Analogs OR Radical >> Radical mechanism via ROS formation (indirect) >> Quinones and Trihydroxybenzenes OR SN1 >> Carbenium ion formation OR SN1 >> Carbenium ion formation >> Alpha-Haloethers OR SN1 >> Direct nucleophilic attack on diazonium cation (DNA alkylation) OR SN1 >> Direct nucleophilic attack on diazonium cation (DNA alkylation) >> Diazenes and Azoxyalkanes OR SN1 >> Nucleophilic attack after carbenium ion formation OR SN1 >> Nucleophilic attack after carbenium ion formation >> Specific Acetate Esters OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Amino Anthraquinones OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Fused-Ring Primary Aromatic Amines OR SN1 >> Nucleophilic attack after nitrenium ion formation >> p-Aminobiphenyl Analogs OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitroaniline Derivatives OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> Specific Acetate Esters OR SN2 >> Acylation involving a leaving group after metabolic activation OR SN2 >> Acylation involving a leaving group after metabolic activation >> Geminal Polyhaloalkane Derivatives 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 >> Haloalkenes with Electron-Withdrawing Groups OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation >> Polarized Haloalkene Derivatives OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate Esters OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation >> Geminal Polyhaloalkane Derivatives OR SN2 >> SN2 at sp3 and activated sp2 carbon atom OR SN2 >> SN2 at sp3 and activated sp2 carbon atom >> Polarized Haloalkene Derivatives OR SN2 >> SN2 at sp3-carbon atom OR SN2 >> SN2 at sp3-carbon atom >> Alpha-Haloethers OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 >> Nitroarenes with Other Active Groups by DNA binding by OASIS v.1.4

Domain logical expression index: "i"

Referential boundary:The target chemical should be classified as AN2 AND AN2 >> Michael-type addition to quinoid structures  AND AN2 >> Michael-type addition to quinoid structures  >> Substituted Anilines 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) ester group OR Acylation >> Acylation involving an activated (glucuronidated) ester group >> Arenecarboxylic Acid Esters OR Acylation >> Acylation involving an activated (glucuronidated) sulfonamide group OR Acylation >> Acylation involving an activated (glucuronidated) sulfonamide group >> Arenesulfonamides OR AN2 >> Nucleophilic addition at polarized N-functional double bond OR AN2 >> Nucleophilic addition at polarized N-functional double bond >> Arenesulfonamides 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  by Protein binding by OASIS v1.4

Domain logical expression index: "k"

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

Domain logical expression index: "l"

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

Domain logical expression index: "m"

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

Domain logical expression index: "n"

Referential boundary:The target chemical should be classified as No alert found by rtER Expert System ver.1 - USEPA

Domain logical expression index: "o"

Referential boundary:The target chemical should be classified as 4-Alkoxyanilines OR 4-Alkylanilines by rtER Expert System ver.1 - USEPA

Domain logical expression index: "p"

Referential boundary:The target chemical should be classified as No alert found by Respiratory sensitisation

Domain logical expression index: "q"

Referential boundary:The target chemical should be classified as Pro-Michael Addition OR Pro-Michael Addition >> Pro-quinone and related OR Pro-Michael Addition >> Pro-quinone and related >> Aminophenols OR Pro-Michael Addition >> Pro-quinone and related >> Phenylenediamines by Respiratory sensitisation

Domain logical expression index: "r"

Referential boundary:The target chemical should be classified as Aromatic Amine Type Compounds by Oncologic Primary Classification

Domain logical expression index: "s"

Referential boundary:The target chemical should be classified as Phenol Type Compounds by Oncologic Primary Classification

Domain logical expression index: "t"

Parametric boundary:The target chemical should have a value of log Kow which is >= -2.08

Domain logical expression index: "u"

Parametric boundary:The target chemical should have a value of log Kow which is <= 0.773

Interpretation of results:

other: not irritating

Conclusions:

3,5-Diaminobenzoic acid was estimated to be not irritating to the skin of CBA mice

Executive summary:

The dermal irritation potential of 3,5-Diaminobenzoic acid was estimated using OECD QSAR toolbox v3.4 with logPow as the primary descriptor.

3,5-Diaminobenzoic acid was estimated to be not irritating to the skin of CBA mice

Based on the estimated results, 3,5-Diaminobenzoic acid can be considered to be not irritating to skin and can be classified under the category “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 v3.4 and the QMRF report has been attached

Qualifier:

equivalent or similar to guideline

Guideline:

other: predicted data

Principles of method if other than guideline:

Prediction was done using OECD QSAR toolbox v3.4

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material (as cited in study report): 3,5-Diaminobenzoic acid
- Molecular formula: C7H8N2O2
- Molecular weight: 152.1522 g/mol
- Substance type: Organic
- Physical state: Solid

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

no data available

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

100 µL

Duration of treatment / exposure:

8 days

Observation period (in vivo):

8 days

Duration of post- treatment incubation (in vitro):

no data available

Number of animals or in vitro replicates:

6

Details on study design:

no data available

Other effects / acceptance of results:

no data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 8 days

Score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No irritation observed

Estimation method: Takes mode value from the 6 nearest neighbours
Domain  logical expression:Result: In Domain

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

Domain logical expression index: "a"

Referential boundary:The target chemical should be classified as Anilines (Acute toxicity) by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary:The target chemical should be classified as Aminoaniline, meta AND Aniline AND Aryl AND Carboxylic acid by Organic Functional groups

Domain logical expression index: "c"

Referential boundary:The target chemical should be classified as Aminoaniline, meta AND Carboxylic acid AND Overlapping groups by Organic Functional groups (nested)

Domain logical expression index: "d"

Referential boundary:The target chemical should be classified as Acid, aromatic attach [-COOH] AND Alcohol, olefinic attach [-OH] AND Aliphatic Nitrogen, one aromatic attach [-N] AND Aromatic Carbon [C] 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<] by Organic functional groups (US EPA)

Domain logical expression index: "e"

Referential boundary:The target chemical should be classified as Amine AND Aromatic compound AND Carbonic acid derivative AND Carboxylic acid AND Carboxylic acid derivative AND Primary amine AND Primary aromatic amine by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "f"

Referential boundary:The target chemical should be classified as Aromatic amines by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "g"

Referential boundary:The target chemical should be classified as Radical AND Radical >> Radical mechanism via ROS formation (indirect) AND Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines AND SN1 AND SN1 >> Nucleophilic attack after nitrenium ion formation AND SN1 >> Nucleophilic attack after nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines by DNA binding by OASIS v.1.4

Domain logical expression index: "h"

Referential boundary:The target chemical should be classified as AN2 OR AN2 >>  Michael-type addition, quinoid structures OR AN2 >>  Michael-type addition, quinoid structures >> Quinones and Trihydroxybenzenes OR AN2 >> Schiff base formation OR AN2 >> Schiff base formation >> Polarized Haloalkene Derivatives OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation >> Geminal Polyhaloalkane Derivatives OR AN2 >> Shiff base formation after aldehyde release OR AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters OR AN2 >> Thioacylation via nucleophilic addition after cysteine-mediated thioketene formation OR AN2 >> Thioacylation via nucleophilic addition after cysteine-mediated thioketene formation >> Haloalkenes with Electron-Withdrawing Groups OR AN2 >> Thioacylation via nucleophilic addition after cysteine-mediated thioketene formation >> Polarized Haloalkene Derivatives OR No alert found OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> Amino Anthraquinones OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide and Aminoalkylamine Side Chain OR Non-covalent interaction >> DNA intercalation >> Fused-Ring Primary Aromatic Amines OR Non-covalent interaction >> DNA intercalation >> Quinones and Trihydroxybenzenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Amino Anthraquinones OR Radical >> Radical mechanism via ROS formation (indirect) >> Diazenes and Azoxyalkanes OR Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Geminal Polyhaloalkane Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroaniline Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroarenes with Other Active Groups OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR Radical >> Radical mechanism via ROS formation (indirect) >> Polynitroarenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Quinones and Trihydroxybenzenes OR SN1 >> Carbenium ion formation OR SN1 >> Carbenium ion formation >> Alpha-Haloethers OR SN1 >> Direct nucleophilic attack on diazonium cation (DNA alkylation) OR SN1 >> Direct nucleophilic attack on diazonium cation (DNA alkylation) >> Diazenes and Azoxyalkanes OR SN1 >> Nucleophilic attack after carbenium ion formation OR SN1 >> Nucleophilic attack after carbenium ion formation >> Specific Acetate Esters OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Amino Anthraquinones OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Fused-Ring Primary Aromatic Amines OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitroaniline Derivatives OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Polynitroarenes OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> Specific Acetate Esters OR SN2 >> Acylation involving a leaving group after metabolic activation OR SN2 >> Acylation involving a leaving group after metabolic activation >> Geminal Polyhaloalkane Derivatives 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 >> Haloalkenes with Electron-Withdrawing Groups OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation >> Polarized Haloalkene Derivatives OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate Esters OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation >> Geminal Polyhaloalkane Derivatives OR SN2 >> SN2 at sp3 and activated sp2 carbon atom OR SN2 >> SN2 at sp3 and activated sp2 carbon atom >> Polarized Haloalkene Derivatives OR SN2 >> SN2 at sp3-carbon atom OR SN2 >> SN2 at sp3-carbon atom >> Alpha-Haloethers OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 >> Nitroarenes with Other Active Groups by DNA binding by OASIS v.1.4

Domain logical expression index: "i"

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: "j"

Referential boundary:The target chemical should be classified as High reactive OR High reactive >> Activated haloarenes OR Low reactive OR Low reactive >> Sulfanilic acid derivatives by DPRA Cysteine peptide depletion

Domain logical expression index: "k"

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

Domain logical expression index: "l"

Similarity boundary:Target: Nc1cc(N)cc(C(O)=O)c1
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "m"

Similarity boundary:Target: Nc1cc(N)cc(C(O)=O)c1
Threshold=40%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "n"

Referential boundary:The target chemical should be classified as No alert found by Respiratory sensitisation

Domain logical expression index: "o"

Referential boundary:The target chemical should be classified as Pro-Michael Addition OR Pro-Michael Addition >> Pro-quinone and related OR Pro-Michael Addition >> Pro-quinone and related >> Aminophenols OR Pro-Michael Addition >> Pro-quinone and related >> Phenylenediamines by Respiratory sensitisation

Domain logical expression index: "p"

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

Domain logical expression index: "q"

Referential boundary:The target chemical should be classified as SN2 OR SN2 >> SN2 Reaction at a sp3 carbon atom OR SN2 >> SN2 Reaction at a sp3 carbon atom >> Activated alkyl esters and thioesters  by Protein binding alerts for skin sensitization by OASIS v1.4

Domain logical expression index: "r"

Referential boundary:The target chemical should be classified as Aromatic Amine Type Compounds by Oncologic Primary Classification

Domain logical expression index: "s"

Referential boundary:The target chemical should be classified as Halogenated Aromatic Hydrocarbon Type Compounds by Oncologic Primary Classification

Domain logical expression index: "t"

Referential boundary:The target chemical should be classified as No alert found by DNA alerts for CA and MNT by OASIS v.1.1

Domain logical expression index: "u"

Referential boundary:The target chemical should be classified as Radical OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR SN1 OR SN1 >> Nucleophilic attack after nitrenium ion formation OR SN1 >> Nucleophilic attack after nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines by DNA alerts for CA and MNT by OASIS v.1.1

Domain logical expression index: "v"

Parametric boundary:The target chemical should have a value of log Kow which is >= -2.08

Domain logical expression index: "w"

Parametric boundary:The target chemical should have a value of log Kow which is <= 1.36

Interpretation of results:

other: not irritating

Conclusions:

3,5-Diaminobenzoic acid was estimated to be not irritating to the eyes of New Zealand White rabbits.

Executive summary:

The ocular irritation potential of 3,5-Diaminobenzoic acid was estimated using OECD QSAR toolbox v3.4 with logPow as the primary descriptor.

3,5-Diaminobenzoic acid was estimated to be not irritating to the eyes of New Zealand White rabbits.

Based on the estimated results, 3,5-Diaminobenzoic acid can be considered to be not irritating to eyes and can be classified under the category “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:

In different studies,3,5-Diaminobenzoic acidhas been investigated for potential for dermal irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits along with predicted data for target chemicaland its functionally similar read across substances 6 –amino-m-Toluenesulfonic acid [CAS: 88-44-8] and Toluene-2,4 diamine [CAS: 95-80-7].The predicted data using the OECD QSAR toolbox has also been compared with the experimental data.

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 for3,5 -Diaminobenzoic acid.3,5 -Diaminobenzoic acid was estimated to be not irritating to the skin of CBA mice.

Skin irritation effects were also estimated by four different models i.e, Battery, Leadscope, SciQSAR and CASE Ultra used within Danish QSAR database for 3,5 -Diaminobenzoic acid. Based on estimation, No severe skin irritation effects were known when 3,5-Diaminobenzoic acid was exposed to rabbit skin.

Both the estimated data suggests the possibility of3,5-Diaminobenzoic acidbeing not irritating to skin.

These results are further supported by the experimental study summarized in SIDS Initial Assessment Report For SIAM 16 -4-AMINOTOLUENE-3-SULFONIC ACID, OECD SIDS, 27-30 May 2003, for thefunctionally similar read across substances 6 –amino-m-Toluenesulfonic acid [CAS: 88-44-8].Patch test was performed on humans in accordance with IMDG code (2002). 50 mg/patch was applied under occlusive conditions to the inner arm of 5 male volunteers for 4 hours. The test site was observed for erythema and edema till 14 days post dosing. 6 –amino-m-Toluenesulfonic acid was not irritating to the skin of humans in 6hr patch test. Hence, 6 –amino-m-Toluenesulfonic acid can be considered not irritating to skin.

The above results are also supported bythe experimental study summarized in The MAK Collection for Occupational Health and Safety. 1–352, 2012, for the functionally similar read across substance Toluene-2,4 diamine [CAS: 95-80-7]. 2.5% aqueous solution of toluene-2,4-diamine was applied to the clipped skin of rabbits under occlusive conditions for 24 hours. The rabbits were observed for effects till 72 hours. No irritation was observed in rabbits till 72 hours. Hence, toluene-2,4-diamine can be considered as not irritating to skin.

Based on the available data for the target as well as read across substances and applying the weight of evidence approach,3,5-Diaminobenzoic acidwas not irritating to skin.Comparing the above annotations with the criteria of CLP regulation, test chemical can be classified under the category “Not Classified”.

                                       

Eye Irritation:

In different studies,3,5-Diaminobenzoic acidhas been investigated for potential for ocular irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits along with predicted data for target chemicaland its structurally similar read across substances 3,5 Dimethylaniline [CAS:108-69-0] and m–phenylenediamine [CAS: 108-45-2].The predicted data using the OECD QSAR toolbox has also been compared with the experimental data.

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the ocular irritation potential was estimated for3,5 -Diaminobenzoic acid.3,5 -Diaminobenzoic acid was estimated to be not irritating to the eyes of New Zealand White rabbits.

This result is supported by the experimental study summarized in GESTIS for CAS: 108-69-0; Institut für Arbeitsschutz der Deutschen Gesetzlichen Unfallversicherung (IFA) GESTIS-database on hazardous substance, 2016, for thestructurally similar read across substance, 3,5 Dimethylaniline [CAS:108-69-0].In a standardized rabbit eye test (OECD 405), the undiluted 3,5-xylidine caused only slight eye irritation, which can be considered as not irritating.

The above results are further supported by the experimental study summarized in IUCLID dataset for the CAS: 108-45-2; EUROPEAN COMMISSION – European Chemicals Bureau; 2000,for thestructurally similar read across substance, m–phenylenediamine [CAS: 108-45-2].2.5% aqueous solution of m-phenylenediamine having pH= 7 was instilled into the eyes of 3 rabbits for 10 minutes. The rabbits were observed for effects till 7 days. No irritation was observed in rabbits.

Hence, m-phenylendiamine can be considered as not irritating to eyes.

Based on the available data for the target as well as read across substances and applying the weight of evidence approach,3,5-Diaminobenzoic acidwas not irritating to eyes.Comparing the above annotations with the criteria of CLP regulation, test chemical can be classified under the category “Not Classified”.

Justification for classification or non-classification

Available data for 3,5-Diaminobenzoic acid suggests that it is not likely to cause any irritation to eyes and skin.

3,5-Diaminobenzoic acid can be classified under the category “Not Classified” as per CLP regulation.