Registration Dossier

Skin irritation:

The dermal irritation potential of 7-benzamido-4-hydroxynaphthalene-2-sulphonic acid was estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor.

7-benzamido-4-hydroxynaphthalene-2-sulphonic acid was estimated to be not irritating to the skin of New Zealand White rabbits.

Based on the estimated results, 7-benzamido-4-hydroxynaphthalene-2-sulphonic 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 7-benzamido-4-hydroxynaphthalene-2-sulphonic acid was estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor.

7-benzamido-4-hydroxynaphthalene-2-sulphonic acid was estimated to be not irritating to the eyes of New Zealand White rabbits.

Based on the estimated results, 7-benzamido-4-hydroxynaphthalene-2-sulphonic acid can be considered not irritating to eyes and can be classified under the category “Not Classified” as per CLP regulation

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

Qualifier:

according to guideline

Guideline:

other: estimated data

Principles of method if other than guideline:

Prediction was done using OECD QSAR toolbox v3.3

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material: 7-(benzoylamino)-4-hydroxynaphthalene-2-sulfonic acid
- Molecular formula: C17H13NO5S
- Molecular weight: 343.3577 g/mol
- Smiles notation: c1ccc(cc1)C(=O)Nc2ccc3c(c2)cc(cc3O)S(=O)(=O)O
- InChl: 1S/C17H13NO5S/c19-16-10-14(24(21,22)23)9-12-8-13(6-7-15(12)16)18-17(20)11-4-2-1-3-5-11/h1-10,19H,(H,18,20)(H,21,22,23)
- 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:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

0.5 g

Duration of treatment / exposure:

4 hours

Observation period:

72 hours

Number of animals:

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 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 ( not "l") ) ) and "m" ) and "n" ) and ("o" and ( not "p") ) ) and ("q" and ( not "r") ) ) and "s" ) and ("t" and "u" ) )

Domain logical expression index: "a"

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: "b"

Referential boundary: The target chemical should be classified as Low reactive AND Low reactive >> N-substituted aromatic amides by DPRA Cysteine peptide depletion

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Low reactive AND Low reactive >> N-substituted aromatic amides by DPRA Lysine peptide depletion

Domain logical expression index: "d"

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

Domain logical expression index: "e"

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: "f"

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: "g"

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: "h"

Referential boundary: The target chemical should be classified as AN2 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 >> Coumarins 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) >> Coumarins 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) >> 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 >> 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 >> 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 >> 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 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: "i"

Referential boundary: The target chemical should be classified as Low reactive AND Low reactive >> N-substituted aromatic amides by DPRA Lysine peptide depletion

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Low reactive >> Activated haloarenes OR Low reactive >> Organic disulfides by DPRA Lysine peptide depletion

Domain logical expression index: "k"

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: "l"

Referential boundary: The target chemical should be classified as 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-carbonyls 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: "m"

Referential boundary: The target chemical should be classified as No superfragment by Superfragments ONLY

Domain logical expression index: "n"

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

Domain logical expression index: "o"

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

Domain logical expression index: "p"

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 >> Phenylenediamines by Respiratory sensitisation

Domain logical expression index: "q"

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

Domain logical expression index: "r"

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 by Protein binding alerts for skin sensitization by OASIS v1.3

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Not calculated by Hydrolysis half-life (Kb, pH 7)(Hydrowin) ONLY

Domain logical expression index: "t"

Parametric boundary:The target chemical should have a value of log Kow which is >= -1.88

Domain logical expression index: "u"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.58

Interpretation of results:

other: not irritating

Conclusions:

7-benzamido-4-hydroxynaphthalene-2-sulphonic acid was estimated to be not irritating to the skin of New Zealand White rabbits.

Executive summary:

The dermal irritation potential of 7-benzamido-4-hydroxynaphthalene-2-sulphonic acid was estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor.

7-benzamido-4-hydroxynaphthalene-2-sulphonic acid was estimated to be not irritating to the skin of New Zealand White rabbits.

Based on the estimated results, 7-benzamido-4-hydroxynaphthalene-2-sulphonic acid can be considered not irritating to skin and can be classified under the category “Not Classified” as per CLP regulation.

Endpoint conclusion:

no adverse effect observed (not irritating)

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 v3.3 and the QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: estimated data

Principles of method if other than guideline:

Prediction was done using OECD QSAR toolbox v3.3

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material: 7-(benzoylamino)-4-hydroxynaphthalene-2-sulfonic acid
- Molecular formula: C17H13NO5S
- Molecular weight: 343.3577 g/mol
- Smiles notation: c1ccc(cc1)C(=O)Nc2ccc3c(c2)cc(cc3O)S(=O)(=O)O
- InChl: 1S/C17H13NO5S/c19-16-10-14(24(21,22)23)9-12-8-13(6-7-15(12)16)18-17(20)11-4-2-1-3-5-11/h1-10,19H,(H,18,20)(H,21,22,23)
- 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:

0.1 gm

Duration of treatment / exposure:

72 hours

Observation period (in vivo):

21 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:

21 d

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 "j" ) and "k" ) and ("l" and "m" ) )

Domain logical expression index: "a"

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: "b"

Referential boundary: The target chemical should be classified as Low reactive AND Low reactive >> N-substituted aromatic amides by DPRA Cysteine peptide depletion

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Low reactive AND Low reactive >> N-substituted aromatic amides by DPRA Lysine peptide depletion

Domain logical expression index: "d"

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

Domain logical expression index: "e"

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: "f"

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: "g"

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: "h"

Referential boundary: The target chemical should be classified as AN2 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 >> Coumarins 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) >> Coumarins 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) >> 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 >> 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 >> 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 >> 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 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: "i"

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

Domain logical expression index: "j"

Similarity boundary:Target: Oc1cc(S(O)(=O)=O)cc2cc(NC(=O)c3ccccc3)ccc12
Threshold=10%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as No superfragment by Superfragments ONLY

Domain logical expression index: "l"

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

Domain logical expression index: "m"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.6

Interpretation of results:

other: not irritating

Conclusions:

7-benzamido-4-hydroxynaphthalene-2-sulphonic acid was estimated to be not irritating to the eyes of New Zealand White rabbits.

Executive summary:

The ocular irritation potential of 7-benzamido-4-hydroxynaphthalene-2-sulphonic acid was estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor.

7-benzamido-4-hydroxynaphthalene-2-sulphonic acid was estimated to be not irritating to the eyes of New Zealand White rabbits.

Based on the estimated results, 7-benzamido-4-hydroxynaphthalene-2-sulphonic acid can be considered not irritating to eyes and can be classified under the category “Not Classified” as per CLP regulation

Endpoint conclusion:

no adverse effect observed (not irritating)

Endpoint conclusion:

no study available

Skin Irritation

In different studies, 7-benzamido-4-hydroxynaphthalene-2-sulphonic acid has 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 chemical and its functionally similar read across substances, 3-acetamido-5-amino-4-hydroxybenzenesulphonic acid [CAS: 40306-45-0] and 3-Amino-4- methoxybenzanilide [CAS: 120-35-4].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 dermal irritation potential was estimated for 7-benzamido-4 -hydroxynaphthalene-2-sulphonic acid. 7-benzamido-4-hydroxynaphthalene-2-sulphonic acid was estimated to be not irritating to the skin of New Zealand White rabbits.

This result is further supported by the experimental study performed according to OECD 404 (Sustainability Support Services (Europe) AB has letter of access) on the functionally similar read across substance, 3-acetamido-5-amino-4-hydroxybenzenesulphonic acid [CAS: 40306-45-0]. 3 female New Zealand White rabbits were used for the study.The animals were prepared 24 hrs prior to application of test product. The furs from the dorsal area of trunk of animals were removed with electric clippers exposing an area measuring approximately 6 cm2 of body surface area of animal. The care was taken such that abrasion penetrated the Stratum corneum only and not dermis. 0.5 gm of test compound was applied on a small area (approximately 6 cm2) of intact skin site. The rabbits were observed for signs of irritation till 14 days. The result obtained from present study reveals that the test compound 3-acetamido-5-amino-4-hydroxybenzenesulphonic acid was non irritant to skin of the New Zealand white rabbits when applied to the shaven back intact skin.

These results are further supported by the experimental study summarized in BG Chemie InfoCenter, TOXIKOLOGISCHE BEWERTUNGEN; TOXICOLOGICAL EVALUATION, last updated: 02/2005; functionally similar read across substance, 3-Amino-4- methoxybenzanilide [CAS: 120-35-4]. The study was performed according to OECD 404 Guidelines.3 New Zealand white rabbits (weighing 1.9 to 2.5 kg) were used for the study. About 25 cm² of skin on the dorsal trunk had been shaved with electric clippers 24 hours before exposure. 500 mg of the chemical (mixed into a paste with 0.3 ml polyethylene glycol 400) was applied semi-occlusively to 25 cm² of skin on the dorsal trunk and exposed for 4 hours. After 4 hours, the excess chemical was washed from the test site with lukewarm tap water. The rabbits were assessed for signs of irritation after 30 to 60 minutes and after 24, 48 and 72 hours of exposure period.

The mean irritation indices were 0.1 for erythema and eschar formation and 0.0 for oedema formation. From 48 hours after patch removal onwards, all animals were free of signs of irritation.

Based on the observations and scores, 3-Amino-4- methoxybenzanilide was considered to be practically not irritating to New Zealand White rabbit skin.

Based on the available data for the target as well as read across chemicals and applying the weight of evidence approach, 7-benzamido-4-hydroxynaphthalene-2-sulphonic acid can be considered 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, 7-benzamido-4-hydroxynaphthalene-2-sulphonic acid has 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 chemical and its functionally similar read across substances, 3-acetamido-5-amino-4-hydroxybenzenesulphonic acid [CAS: 40306-45-0] and 3-Amino-4- methoxybenzanilide [CAS: 120-35-4].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 for 7-benzamido-4 -hydroxynaphthalene-2-sulphonic acid. 7-benzamido-4-hydroxynaphthalene-2-sulphonic acid was estimated to be not irritating to the skin of New Zealand White eyes.

This result is further supported by the experimental study performed according to OECD 405 (Sustainability Support Services (Europe) AB has letter of access) on the functionally similar read across substance, 3-acetamido-5-amino-4-hydroxybenzenesulphonic acid [CAS: 40306-45-0]. 3-acetamido-5-amino-4-hydroxybenzenesulphonic acid was moistened with distilled water and then placed in the conjunctival sac of one eye of 3 female New Zealand Whtie rabbits after gentle pulling the lower eye lid away from the eye ball. The eye lids were then gently held together for about one second to prevent the loss of the material. The other eyes remained untreated, served as control. The eyes of the test animal were not washed for at least 24 hours following instillation of the test compound. The eyes were examined at 1, 24, 48 and 72 hours after test substance application. 3-acetamido-5-amino-4-hydroxybenzenesulphonic acid produced some blood vessels of conjunctiva were observed hyperemic at 1 hour after the application of test substance. 3-acetamido-5-amino-4-hydroxybenzenesulphonic acid can be considered not irritating to the eyes of New Zealand white rabbit under test conditions.

These results are further supported by the experimental study summarized in BG Chemie InfoCenter, TOXIKOLOGISCHE BEWERTUNGEN; TOXICOLOGICAL EVALUATION, last updated: 02/2005; functionally similar read across substance, 3-Amino-4- methoxybenzanilide [CAS: 120-35-4]. The study was performed according to OECD 405 Guidelines.100 mg of 3-Amino-4- methoxybenzanilide was instilled into the conjunctival sac of 3 New Zealand white rabbits (weighing 2.0 to 2.5 kg) and observed for signs of irritation. The reactions were observed and scored 1, 24, 48 and 72 hours post-instillation of the test chemical.

The mean irritation indices for reddening of the conjunctiva, conjunctival swelling, iritis and clouding of the cornea were 0.3, 0.0, 0.0 and 0.0, respectively. Based on the scores, 3-Amino-4- methoxybenzanilide was considered to be practically not irritating to New Zealand White rabbit eyes.

Based on the available data for the target as well as read across chemicals and applying the weight of evidence approach, 7-benzamido-4-hydroxynaphthalene-2-sulphonic acid can be considered not irritating to eyes.Comparing the above annotations with the criteria of CLP regulation, test chemical can be classified under the category “Not Classified”.

Available data for 7-benzamido-4-hydroxynaphthalene-2-sulphonic acid suggests that it is not likely to cause any irritation to eyes and skin.

7-benzamido-4-hydroxynaphthalene-2-sulphonic acid can be classified under the category “Not Classified” as per CLP regulation