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Administrative data

Description of key information

Skin Irritation:

The dermal irritation potential of 4-[(3-aminobenzoyl)amino]-5-hydroxynaphthalene-1,7-disulphonic acid was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor.

4-[(3-aminobenzoyl)amino]-5-hydroxynaphthalene-1,7-disulphonic acid was estimated to be not irritating to the skin of New Zealand White rabbits.

Based on the estimated result; 4-[(3-aminobenzoyl)amino]-5-hydroxynaphthalene-1,7-disulphonic acid can be considered not irritating to skin and can be classified under the category “Not Classified” as per CLP regulation.

Eye Irritation:

The ocular irritation potential of 4-[(3-aminobenzoyl)amino]-5-hydroxynaphthalene-1,7-disulphonic acid was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor.

4-[(3-aminobenzoyl)amino]-5-hydroxynaphthalene-1,7-disulphonic acid was estimated to be not irritating to the eyes of New Zealand White rabbits.

Based on the estimated result; 4-[(3-aminobenzoyl)amino]-5-hydroxynaphthalene-1,7-disulphonic acid can be considered not irritating to the 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 v3.3 and the QMRF report has been attached
Reference:
Composition 0
Qualifier:
according to
Guideline:
other: Estimated data
Principles of method if other than guideline:
Prediction was done using OECD QSAR toolbox v3.3
GLP compliance:
not specified
Test material information:
Composition 1
Specific details on test material used for the study:
- Name of test material: 4-[(3-aminobenzoyl)amino]-5-hydroxynaphthalene-1,7-disulphonic acid
- IUPAC name: 4-[(3-aminobenzoyl)amino]-5-hydroxynaphthalene-1,7-disulphonic acid
- Molecular formula: C17H14N2O8S2
- Molecular weight: 438.4356 g/mole
- Smiles : c1cc(cc(c1)N)C(=O)Nc2ccc(c3c2c(cc(c3)S(=O)(=O)O)O)S(=O)(=O)O
- Inchl: 1S/C17H14N2O8S2/c18-10-3-1-2-9(6-10)17(21)19-13-4-5-15(29(25,26)27)12-7-11(28(22,23)24)8-14(20)16(12)13/h1-8,20H,18H2,(H,19,21)(H,22,23,24)(H,25,26,27)
- Substance type: Organic
- Physical state: Solid
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
no data available
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
not specified
Controls:
not specified
Amount / concentration applied:
0.5g
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
3
Details on study design:
no data available
Other effects / acceptance of results:
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 signs of irritation observed

Estimation method: Takes mode value from the 7 nearest neighbours
Domain  logical expression:Result: In Domain

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

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Naphthalene sulfonic acids, condensates by OECD HPV Chemical Categories

Domain logical expression index: "b"

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

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Non-covalent interaction AND Non-covalent interaction >> DNA intercalation AND Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide Side Chain by DNA binding by OASIS v.1.3

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Primary aromatic amine by DNA binding by OECD

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Strong binder, NH2 group AND Strong binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Ester aminolysis AND Acylation >> Ester aminolysis >> Amides by Protein binding by OASIS v1.3

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Direct Acylation Involving a Leaving group AND Acylation >> Direct Acylation Involving a Leaving group >> Acetates by Protein binding by OECD

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Acid moiety AND Amides AND Anilines (Unhindered) AND Phenol Amines AND Phenols by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Non-covalent interaction AND Non-covalent interaction >> DNA intercalation AND Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide Side Chain by DNA binding by OASIS v.1.3

Domain logical expression index: "j"

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 OR AN2 >> Carbamoylation after isocyanate formation OR AN2 >> Carbamoylation after isocyanate formation >> N-Hydroxylamines OR AN2 >> Michael-type addition on alpha, beta-unsaturated carbonyl compounds OR AN2 >> Michael-type addition on alpha, beta-unsaturated carbonyl compounds >> Four- and Five-Membered Lactones OR AN2 >> Schiff base formation OR AN2 >> Schiff base formation >> Dicarbonyl compounds 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 >> Shiff base formation for aldehydes OR AN2 >> Shiff base formation for aldehydes >> Geminal Polyhaloalkane Derivatives OR No alert found OR Non-covalent interaction >> DNA intercalation >> Amino Anthraquinones OR Non-covalent interaction >> DNA intercalation >> Coumarins OR Non-covalent interaction >> DNA intercalation >> Fused-Ring Primary Aromatic Amines OR Non-covalent interaction >> DNA intercalation >> Quinones OR Non-specific OR Non-specific >> Incorporation into DNA/RNA, due to structural analogy with  nucleoside bases    OR Non-specific >> Incorporation into DNA/RNA, due to structural analogy with  nucleoside bases    >> Specific Imine and Thione Derivatives OR Radical OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Amino Anthraquinones OR Radical >> Radical mechanism via ROS formation (indirect) >> Coumarins OR Radical >> Radical mechanism via ROS formation (indirect) >> Diazenes 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) >> N-Hydroxylamines OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitro Azoarenes 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) >> p-Substituted Mononitrobenzenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Quinones OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Specific Imine and Thione Derivatives OR SN1 OR SN1 >> Alkylation after metabolically formed carbenium ion species OR SN1 >> Alkylation after metabolically formed carbenium ion species >> Polycyclic Aromatic Hydrocarbon Derivatives OR SN1 >> Carbenium ion formation OR SN1 >> Carbenium ion formation >> Alpha-Haloethers 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 metabolic nitrenium ion formation >> N-Hydroxylamines OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> p-Aminobiphenyl Analogs OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitro Azoarenes 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 >> p-Substituted Mononitrobenzenes OR SN1 >> Nucleophilic substitution on diazonium ions OR SN1 >> Nucleophilic substitution on diazonium ions >> Specific Imine and Thione Derivatives OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> Specific Acetate Esters OR SN2 >> Acylation involving a leaving group  OR SN2 >> Acylation involving a leaving group  >> Geminal Polyhaloalkane Derivatives 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 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 Derivatives OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Sulfonates and Sulfates OR SN2 >> Alkylation, ring opening SN2 reaction OR SN2 >> Alkylation, ring opening SN2 reaction >> Four- and Five-Membered Lactones OR SN2 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Coumarins OR SN2 >> Direct acting epoxides formed after metabolic activation >> Quinoline Derivatives OR SN2 >> Direct acylation involving a leaving group OR SN2 >> Direct acylation involving a leaving group >> Acyl Halides OR SN2 >> DNA alkylation OR SN2 >> DNA alkylation >> Alkylphosphates, Alkylthiophosphates and Alkylphosphonates OR SN2 >> DNA alkylation >> Vicinal Dihaloalkanes OR SN2 >> Internal SN2 reaction with aziridinium and/or cyclic sulfonium ion formation (enzymatic) OR SN2 >> Internal SN2 reaction with aziridinium and/or cyclic sulfonium ion formation (enzymatic) >> Vicinal Dihaloalkanes 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 an activated carbon atom OR SN2 >> SN2 at an activated carbon atom >> Quinoline 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.1.3

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Primary aromatic amine by DNA binding by OECD

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Michael addition OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Hydroquinones OR No alert found OR Schiff base formers OR Schiff base formers >> Direct Acting Schiff Base Formers OR Schiff base formers >> Direct Acting Schiff Base Formers >> Mono aldehydes OR SN1 >> Nitrenium Ion formation >> Aromatic azo OR SN1 >> Nitrenium Ion formation >> Aromatic nitro by DNA binding by OECD

Domain logical expression index: "m"

Parametric boundary:The target chemical should have a value of log Kow which is >= -4.49

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.71

Interpretation of results:
other: not irritating
Conclusions:
4-[(3-aminobenzoyl)amino]-5-hydroxynaphthalene-1,7-disulphonic acid was estimated to be not irritating to the skin of New Zealand White rabbits.
Executive summary:

The dermal irritation potential of 4-[(3-aminobenzoyl)amino]-5-hydroxynaphthalene-1,7-disulphonic acid was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor.

4-[(3-aminobenzoyl)amino]-5-hydroxynaphthalene-1,7-disulphonic acid was estimated to be not irritating to the skin of New Zealand White rabbits.

Based on the estimated result; 4-[(3-aminobenzoyl)amino]-5-hydroxynaphthalene-1,7-disulphonic acid can be considered 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 v 3.3 and the QMRF report has been attached
Reference:
Composition 0
Qualifier:
according to
Guideline:
other: Estimated data
Principles of method if other than guideline:
Prediction was done using OECD QSAR toolbox v3.3
GLP compliance:
not specified
Test material information:
Composition 1
Specific details on test material used for the study:
- Name of test material: 4-[(3-aminobenzoyl)amino]-5-hydroxynaphthalene-1,7-disulphonic acid
- IUPAC name: 4-[(3-aminobenzoyl)amino]-5-hydroxynaphthalene-1,7-disulphonic acid
- Molecular formula: C17H14N2O8S2
- Molecular weight: 438.4356 g/mole
- Smiles : c1cc(cc(c1)N)C(=O)Nc2ccc(c3c2c(cc(c3)S(=O)(=O)O)O)S(=O)(=O)O
- Inchl: 1S/C17H14N2O8S2/c18-10-3-1-2-9(6-10)17(21)19-13-4-5-15(29(25,26)27)12-7-11(28(22,23)24)8-14(20)16(12)13/h1-8,20H,18H2,(H,19,21)(H,22,23,24)(H,25,26,27)
- 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:
not specified
Controls:
not specified
Amount / concentration applied:
100 mg
Duration of treatment / exposure:
24 hours
Observation period (in vivo):
7 days
Duration of post- treatment incubation (in vitro):
no data available
Number of animals or in vitro replicates:
3
Details on study design:
no data available
Other effects / acceptance of results:
no data available
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
7 d
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
no signs of irritation observed

Estimation method: Takes mode value from the 8 nearest neighbours
Domain  logical expression:Result: In Domain

(((((((("a" or "b" or "c" or "d" or "e" or "f" or "g" or "h" )  and ("i" and ( not "j") )  )  and ("k" and ( not "l") )  )  and ("m" and ( not "n") )  )  and "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 Naphthalene sulfonic acids, condensates by OECD HPV Chemical Categories

Domain logical expression index: "b"

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

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Non-covalent interaction AND Non-covalent interaction >> DNA intercalation AND Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide Side Chain by DNA binding by OASIS v.1.3

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Primary aromatic amine by DNA binding by OECD

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Strong binder, NH2 group AND Strong binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Ester aminolysis AND Acylation >> Ester aminolysis >> Amides by Protein binding by OASIS v1.3

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Direct Acylation Involving a Leaving group AND Acylation >> Direct Acylation Involving a Leaving group >> Acetates by Protein binding by OECD

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Acid moiety AND Amides AND Anilines (Unhindered) AND Phenol Amines AND Phenols by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Non-covalent interaction AND Non-covalent interaction >> DNA intercalation AND Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide Side Chain by DNA binding by OASIS v.1.3

Domain logical expression index: "j"

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 OR AN2 >> Carbamoylation after isocyanate formation OR AN2 >> Carbamoylation after isocyanate formation >> N-Hydroxylamines OR AN2 >> Michael-type addition on alpha, beta-unsaturated carbonyl compounds OR AN2 >> Michael-type addition on alpha, beta-unsaturated carbonyl compounds >> Four- and Five-Membered Lactones 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 >> Shiff base formation for aldehydes OR AN2 >> Shiff base formation for aldehydes >> Geminal Polyhaloalkane Derivatives OR No alert found OR Non-covalent interaction >> DNA intercalation >> Amino Anthraquinones OR Non-covalent interaction >> DNA intercalation >> Coumarins OR Non-covalent interaction >> DNA intercalation >> Fused-Ring Primary Aromatic Amines OR Non-covalent interaction >> DNA intercalation >> Quinones OR Non-specific OR Non-specific >> Incorporation into DNA/RNA, due to structural analogy with  nucleoside bases    OR Non-specific >> Incorporation into DNA/RNA, due to structural analogy with  nucleoside bases    >> Specific Imine and Thione Derivatives OR Radical OR Radical >> Radical mechanism by ROS formation OR Radical >> Radical mechanism by ROS formation >> Polynitroarenes OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Amino Anthraquinones OR Radical >> Radical mechanism via ROS formation (indirect) >> Coumarins OR Radical >> Radical mechanism via ROS formation (indirect) >> Diazenes 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) >> N-Hydroxylamines OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitro Azoarenes 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-Substituted Mononitrobenzenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Quinones OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Specific Imine and Thione Derivatives OR SN1 OR SN1 >> Alkylation after metabolically formed carbenium ion species OR SN1 >> Alkylation after metabolically formed carbenium ion species >> Polycyclic Aromatic Hydrocarbon Derivatives OR SN1 >> Carbenium ion formation OR SN1 >> Carbenium ion formation >> Alpha-Haloethers 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 metabolic nitrenium ion formation >> N-Hydroxylamines OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitro Azoarenes 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 SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> p-Substituted Mononitrobenzenes OR SN1 >> Nucleophilic substitution on diazonium ions OR SN1 >> Nucleophilic substitution on diazonium ions >> Specific Imine and Thione Derivatives OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> Specific Acetate Esters OR SN2 >> Acylation involving a leaving group  OR SN2 >> Acylation involving a leaving group  >> Geminal Polyhaloalkane Derivatives 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 >> Polycyclic Aromatic Hydrocarbon Derivatives OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Sulfonates and Sulfates OR SN2 >> Alkylation, ring opening SN2 reaction OR SN2 >> Alkylation, ring opening SN2 reaction >> Four- and Five-Membered Lactones OR SN2 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Coumarins OR SN2 >> Direct acting epoxides formed after metabolic activation >> Quinoline Derivatives OR SN2 >> Direct acylation involving a leaving group OR SN2 >> Direct acylation involving a leaving group >> Acyl Halides OR SN2 >> DNA alkylation OR SN2 >> DNA alkylation >> Alkylphosphates, Alkylthiophosphates and Alkylphosphonates OR SN2 >> DNA alkylation >> Vicinal Dihaloalkanes OR SN2 >> Internal SN2 reaction with aziridinium and/or cyclic sulfonium ion formation (enzymatic) OR SN2 >> Internal SN2 reaction with aziridinium and/or cyclic sulfonium ion formation (enzymatic) >> Vicinal Dihaloalkanes 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 an activated carbon atom OR SN2 >> SN2 at an activated carbon atom >> Quinoline 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.1.3

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Ester aminolysis AND Acylation >> Ester aminolysis >> Amides by Protein binding by OASIS v1.3

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as No alert found OR Nucleophilic addition OR Nucleophilic addition >> Addition to carbon-hetero double bonds OR Nucleophilic addition >> Addition to carbon-hetero double bonds >> Ketones OR SN2 OR SN2 >> Interchange reaction with sulphur containing compounds OR SN2 >> Interchange reaction with sulphur containing compounds >> Thiols and disulfide compounds  OR SNAr OR SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds OR SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds >> Activated aryl and heteroaryl compounds by Protein binding by OASIS v1.3

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Direct Acylation Involving a Leaving group AND Acylation >> Direct Acylation Involving a Leaving group >> Acetates by Protein binding by OECD

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as No alert found OR SN2 OR SN2 >> SN2 reaction at sp3 carbon atom OR SN2 >> SN2 reaction at sp3 carbon atom >> Alkyl diazo by Protein binding by OECD

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"

Referential boundary: The target chemical should be classified as Not categorized by Repeated dose (HESS)

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as 3-Methylcholantrene (Hepatotoxicity) Alert by Repeated dose (HESS)

Domain logical expression index: "r"

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

Domain logical expression index: "s"

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

Domain logical expression index: "t"

Parametric boundary:The target chemical should have a value of log Kow which is >= -2.62

Domain logical expression index: "u"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.59

Interpretation of results:
other: not irritating
Conclusions:
4-[(3-aminobenzoyl)amino]-5-hydroxynaphthalene-1,7-disulphonic acid was estimated to be not irritating to the eyes of New Zealand White rabbits.
Executive summary:

The ocular irritation potential of 4-[(3-aminobenzoyl)amino]-5-hydroxynaphthalene-1,7-disulphonic acid was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor.

4-[(3-aminobenzoyl)amino]-5-hydroxynaphthalene-1,7-disulphonic acid was estimated to be not irritating to the eyes of New Zealand White rabbits.

Based on the estimated result; 4-[(3-aminobenzoyl)amino]-5-hydroxynaphthalene-1,7-disulphonic acid can be considered not irritating to the 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:

Several studies were performed to ascertain the degree of dermal irritation caused by 4-[(3-aminobenzoyl)amino]-5-hydroxynaphthalene-1,7-disulphonic acidin living organisms. These studies include in vivo studies in rabbits as well as predicted data for the target chemical as well its structurally similar read across substances, Disodium 5-acetamido-4-hydroxy-3 -(phenyldiazenyl)naphthalene-2,7-disulfonate[CAS: 3734-67-6], D&C Red 33[CAS: 3567-66-6] and functionally similar read across substance, Disodium 4-hydroxy-3-[(4 -sulphonatonaphthyl)azo]naphthalene sulphonate[CAS: 3567-69-9]. Thepredicted 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 v3.3 with log kow as the primary descriptor, the skin irritation potential was estimated for4-[(3-aminobenzoyl)amino]-5 -hydroxynaphthalene-1,7-disulphonic acid. 4-[(3-aminobenzoyl)amino]-5-hydroxynaphthalene-1,7-disulphonic acidwas not irritating to New Zealand White rabbit skin.

 

A study was designed and conducted(Sustainability Support Services (Europe) AB, Sweden,2016) to determine the dermal reaction profile of thestructurally similar read across substance, Disodium 5-acetamido-4-hydroxy-3-(phenyldiazenyl)naphthalene-2,7-disulfonate in Sprague Dawley rats. The study was performed as per OECD Guidelines 402 and complying to the GLP procedures.

The test item was applied to shorn skin of 5 male and 5 female animals at 2000 mg/kg body weight. Administration of the test item at 2000 mg/kg did not result in any skin reaction at the site of application during the study period of 14 days. Administration of the test item did not result in any signs of toxicity and mortality during the study period of 14 days.   Animals exhibited normal body weight gain through the study period of 14 days. Gross pathological examination did not reveal any abnormalities attributable to the treatment.

The overall irritation score of the substance was determined to be 0 and no erythema and edema (skin irritation) were observed at the end of 14 days after patch removal. Hence, it was concluded that disodium 5-acetamido-4-hydroxy-3-(phenyldiazenyl)naphthalene-2,7-disulfonate was not-Irritating to the skin of rats under the experimental conditions tested .Thus it can be concluded that the substance, disodium 5-acetamido-4-hydroxy-3-(phenyldiazenyl)naphthalene-2,7-disulfonate can be classified under the category "Not Classified" as per CLP regulation.

 

In a similar study conducted (Sustainability Support Services (Europe) AB, Sweden, 2016) for thefunctionally similar read across substance, Disodium 4-hydroxy-3-[(4 -sulphonatonaphthyl)azo]naphthalene sulphonate[CAS: 3567-69-9].The test substance, ‘Disodium 4-hydroxy-3-[(4-sulphonatonaphthyl)azo] naphthalenesulphonate’ is nonirritant to the skin of Sprague Dawley rats when applied to the shorn skin of 5 male and 5 female animals at the tested dose level of 2000 mg/kg body weight. Also the erythema and edema score of rats was calculated as 0. Thus it can be concluded that the substance Disodium 4-hydroxy-3-[(4-sulphonatonaphthyl)azo] naphthalenesulphonate can be classified under "Not Classified" category.

The above results are supported by the experimental study performed by JAMES E. FULTON, JR(J. Soc. Cosmet. Chem., 40, 321-333 (November/December 1989)) to indicate the Comedogenicity and irritancy of thestructurally similar read across substance,D&C Red 33[CAS: 3567-66-6]. D&C Red 33 was mixed in propylene glycol at a 9 to 1 dilution for testing unless otherwise indicated (10% concentration). Colonies of New Zealand albino rabbits that have genetically good ears and free from mites were used. Three rabbits, weighing two to three kilograms, were used for each assay. Animals were housed singly in suspended cages and fed Purina Rabbit Chow and water ad libitum. Animals were maintained on a 12-hour light and 12-hour dark cycle. A dose of 1 ml of the test material was applied and spread once daily to the entire inner surface of once for five days per week for two weeks. The opposite untreated ear of each animal served as an untreated control.

The irritancy produced by repeated application of the chemical on the surface epidermis in the rabbit ear is evaluated on a scale of 0 to 5. The grades are summarized as follows:

 0 = No irritation; 1 = few scales, no Erythema; 2 = diffuse scaling, no Erythema; 3 = Generalized scaling with Erythema; 4 = Scaling, Erythema and Edema; 5 = Epidermal necrosis and slough.

D&C Red 33 falls under Grade 2 (Diffuse scaling, but no erythema observed).Hence it can be concluded that D & C Red No 33 was not irritating to rabbit ears.

Based on the available data for the target chemical, structurally and functionally similar read across substances, 4-[(3-aminobenzoyl)amino]-5-hydroxynaphthalene-1,7-disulphonic acid is not likely to cause any irritation to skin. Hence, by applying the weight of evidence approach, 4-[(3-aminobenzoyl)amino]-5-hydroxynaphthalene-1,7-disulphonic acid can be considered not irritating to skin and classified under the category “Not Classified” as per CLP criteria.

Eye Irritation:

Several studies were performed to ascertain the degree of ocular irritation caused by 4-[(3-aminobenzoyl)amino]-5-hydroxynaphthalene-1,7-disulphonic acidin living organisms. These studies include in vivo studies in rabbits as well as predicted data for the target chemical as well its structurally similar read across substance, D&C Red 33[CAS: 3567-66-6] and functionally similar read across substance, Ponceau SX [CAS: 4548-53-2]. Thepredicted 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 v3.3 with log kow as the primary descriptor, the eye irritation potential was estimated for4-[(3-aminobenzoyl)amino]-5 -hydroxynaphthalene-1,7-disulphonic acid. 4-[(3-aminobenzoyl)amino]-5-hydroxynaphthalene-1,7-disulphonic acidwas not irritating to New Zealand White rabbit eye.

 

This result is supported by the experimental study summarized in Scientific Committee on Cosmetology (seventh series), 1988; for thefunctionally similar read across substance, Ponceau SX [CAS: 4548-53-2]. Ponceau SX 5% in formulation was instilled into the eyes of rabbits and observed for signs of irritation (duration not mentioned).

Ponceau SX 5% in formulation did not cause any irritation to rabbit eyes.

Hence, Ponceau SX can be considered not irritating to rabbit eyes.

The above results are further supported by the experimental study summarized in Scientific Committee on Consumer Safety (SCCS)-SCCP/1102/07; for thestructurally similar read across substance, D&C Red 33[CAS: 3567-66-6]. 0.2 ml of a 10% aqueous solution (20 mg) or suspension of the test material was applied twice daily, five times weekly, for four weeks to the conjunctival sac of one eye of each of a group of six or more albino rabbits (40 applications). One hour after each application, the eyes were examined for evidence of staining and the irritation was scored according to Draize.

The overall irritation score after 20 days of observation was 0.0. Hence, disodium 5-amino-4-hydroxy-3-(phenylazo)naphthalene-2,7-disulphonate was considered to be not irritating to rabbit eyes.

Based on the available data for the target chemical, structurally and functionally similar read across substances, 4-[(3-aminobenzoyl)amino]-5-hydroxynaphthalene-1,7-disulphonic acid is not likely to cause any irritation to eyes. Hence, by applying the weight of evidence approach, 4-[(3-aminobenzoyl)amino]-5-hydroxynaphthalene-1,7-disulphonic acid can be considered not irritating to eyes and classified under the category “Not Classified” as per CLP criteria.

Justification for classification or non-classification

Available data for 4-[(3-aminobenzoyl)amino]-5-hydroxynaphthalene-1,7-disulphonic acid indicates that it is not likely to cause severe irritation or corrosion to skin and eyes.

Hence, 4-[(3-aminobenzoyl)amino]-5-hydroxynaphthalene-1,7-disulphonic acid can be classified under the category “Not Classified” for skin and eyes as per CLP regulation.