Registration Dossier

Skin Irritation:

The dermal irritation potential of sodium 2-[(4-aminophenyl)amino]-5-nitrobenzene-1-sulfonate was estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor.

Sodium 2-[(4-aminophenyl)amino]-5-nitrobenzene-1-sulfonate was estimated to be not irritating to the skin of New Zealand White rabbits.

Based on the estimated results, sodium 2-[(4-aminophenyl)amino]-5-nitrobenzene-1-sulfonate 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 sodium 2-[(4-aminophenyl)amino]-5-nitrobenzene-1-sulfonate was estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor.

Sodium 2-[(4-aminophenyl)amino]-5-nitrobenzene-1-sulfonate was estimated to be not irritating to the eyes of New Zealand White rabbits.

Based on the estimated results, sodium 2-[(4-aminophenyl)amino]-5-nitrobenzene-1-sulfonate can be considered to be 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 the test chemical: sodium 2-[(4-aminophenyl)amino]-5-nitrobenzene-1-sulfonate
Molecular Formula: C12H10N3NaO5S
Molecular Weight: 331.283 g/mol
Smiles Notation: c1cc(ccc1N)Nc2ccc(cc2S(=O)(=O)[O-])[N+](=O)[O-].[Na+]
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:

occlusive

Preparation of test site:

abraded

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

0.5 ml

Duration of treatment / exposure:

single application

Observation period:

24 and 72 hours

Number of animals:

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:

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 6 nearest neighbours
Domain logical expression:Result: In Domain

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

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 Amine OR Anion OR Aromatic compound OR Cation OR Nitro compound OR Primary amine OR Primary aromatic amine OR Secondary amine OR Secondary aromatic amine OR Sulfonic acid derivative by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Aliphatic Nitrogen, one aromatic attach [-N] OR Aliphatic Nitrogen, two aromatic attach [-N-] OR Aromatic Carbon [C] OR Miscellaneous sulfide (=S) or oxide (=O) OR Nitro, aromatic attach [-NO2] OR Nitrogen, two or tree olefinic attach [>N-] OR Olefinic carbon [=CH- or =C<] OR Suflur {v+4} or {v+6} OR Sulfonate, aromatic attach [-SO2-O] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Aryl OR Nitrobenzene OR Overlapping groups OR Precursors quinoid compounds OR Sulfonic acid by Organic Functional groups (nested) ONLY

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Aniline OR Aryl OR Nitrobenzene OR Precursors quinoid compounds OR Sulfonic acid by Organic Functional groups ONLY

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.3

Domain logical expression index: "g"

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 >> Nucleophilic addition to alpha, beta-unsaturated carbonyl compounds OR AN2 >> Nucleophilic addition to alpha, beta-unsaturated carbonyl compounds >> alpha, beta-Unsaturated Aldehydes OR AN2 >> Schiff base formation OR AN2 >> Schiff base formation >> alpha, beta-Unsaturated Aldehydes OR AN2 >> Shiff base formation after aldehyde release OR AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters OR Michael addition OR Michael addition >> Quinone type compounds OR Michael addition >> Quinone type compounds >> Quinone methides 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 Side Chain OR Non-covalent interaction >> DNA intercalation >> Fused-Ring Primary Aromatic Amines OR Non-covalent interaction >> DNA intercalation >> Quinones 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) >> Fused-Ring Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroalkanes 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 >> ROS formation after GSH depletion OR Radical >> ROS formation after GSH depletion >> Quinone methides OR SN1 OR SN1 >> Alkylation after metabolically formed carbenium ion species OR SN1 >> Alkylation after metabolically formed carbenium ion species >> Polycyclic Aromatic Hydrocarbon 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 >> 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 >> 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 >> Nitrobiphenyls and Bridged Nitrobiphenyls 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 SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> Specific Acetate Esters 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 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Quinoline Derivatives OR SN2 >> Nucleophilic substitution after nitrite formation OR SN2 >> Nucleophilic substitution after nitrite formation >> Nitroalkanes OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate Esters 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: "h"

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

Domain logical expression index: "i"

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

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Alkaline Earth OR Halogens OR Metalloids OR Metals OR Rare Earth OR Transition Metals by Groups of elements

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Group 1 - Alkali Earth Li,Na,K,Rb,Cs,Fr AND Group 14 - Carbon C AND Group 15 - Nitrogen N AND Group 16 - Oxygen O AND Group 16 - Sulfur S by Chemical elements

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Group 15 - Phosphorus P by Chemical elements

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Amine AND Anion AND Aromatic compound AND Cation AND Nitro compound AND Primary amine AND Primary aromatic amine AND Secondary amine AND Secondary aromatic amine AND Sulfonic acid derivative by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "n"

Similarity boundary:Target: Nc1ccc(Nc2ccc(N(=O)=O)cc2S(=O)(=O)O{-}.[Na]{+})cc1
Threshold=10%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "o"

Similarity boundary:Target: Nc1ccc(Nc2ccc(N(=O)=O)cc2S(=O)(=O)O{-}.[Na]{+})cc1
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Benzene/ Naphthalene sulfonic acids (Less susceptible) Rank C by Repeated dose (HESS)

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as 3-Methylcholantrene (Hepatotoxicity) Alert OR Not categorized by Repeated dose (HESS)

Domain logical expression index: "r"

Parametric boundary:The target chemical should have a value of log Kow which is >= -3.99

Domain logical expression index: "s"

Parametric boundary:The target chemical should have a value of log Kow which is <= -1.5

Interpretation of results:

other: not irritating

Conclusions:

Sodium 2-[(4-aminophenyl)amino]-5-nitrobenzene-1-sulfonate was estimated to be not irritating to the skin of New Zealand White rabbits

Executive summary:

The dermal irritation potential of sodium 2-[(4-aminophenyl)amino]-5-nitrobenzene-1-sulfonate was estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor.

Sodium 2-[(4-aminophenyl)amino]-5-nitrobenzene-1-sulfonate was estimated to be not irritating to the skin of New Zealand White rabbits.

Based on the estimated results, sodium 2-[(4-aminophenyl)amino]-5-nitrobenzene-1-sulfonate can be considered to be 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 the test chemical: sodium 2-[(4-aminophenyl)amino]-5-nitrobenzene-1-sulfonate
Molecular Formula: C12H10N3NaO5S
Molecular Weight: 331.283 g/mol
Smiles Notation: c1cc(ccc1N)Nc2ccc(cc2S(=O)(=O)[O-])[N+](=O)[O-].[Na+]
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:

0.1 ml

Duration of treatment / exposure:

single exposure

Observation period (in vivo):

72 hours

Duration of post- treatment incubation (in vitro):

no data available

Number of animals or in vitro replicates:

8

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 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" ) and ("f" and ( not "g") ) ) and ("h" and ( not "i") ) ) and "j" ) and ("k" and ( not "l") ) ) and "m" ) and "n" ) and ("o" and ( not "p") ) ) and ("q" and "r" ) )

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 Amine OR Anion OR Aromatic compound OR Cation OR Nitro compound OR Primary amine OR Primary aromatic amine OR Secondary amine OR Secondary aromatic amine OR Sulfonic acid derivative by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Aliphatic Nitrogen, one aromatic attach [-N] OR Aliphatic Nitrogen, two aromatic attach [-N-] OR Aromatic Carbon [C] OR Miscellaneous sulfide (=S) or oxide (=O) OR Nitro, aromatic attach [-NO2] OR Nitrogen, two or tree olefinic attach [>N-] OR Olefinic carbon [=CH- or =C<] OR Suflur {v+4} or {v+6} OR Sulfonate, aromatic attach [-SO2-O] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Aryl OR Nitrobenzene OR Overlapping groups OR Precursors quinoid compounds OR Sulfonic acid by Organic Functional groups (nested) ONLY

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Aniline OR Aryl OR Nitrobenzene OR Precursors quinoid compounds OR Sulfonic acid by Organic Functional groups ONLY

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.3

Domain logical expression index: "g"

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 >> Nucleophilic addition to alpha, beta-unsaturated carbonyl compounds OR AN2 >> Nucleophilic addition to alpha, beta-unsaturated carbonyl compounds >> alpha, beta-Unsaturated Aldehydes OR AN2 >> Schiff base formation OR AN2 >> Schiff base formation >> alpha, beta-Unsaturated Aldehydes OR AN2 >> Shiff base formation after aldehyde release OR AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters OR Michael addition OR Michael addition >> Quinone type compounds OR Michael addition >> Quinone type compounds >> Quinone methides 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 Side Chain OR Non-covalent interaction >> DNA intercalation >> Fused-Ring Primary Aromatic Amines OR Non-covalent interaction >> DNA intercalation >> Quinones 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) >> Fused-Ring Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroalkanes 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 >> ROS formation after GSH depletion OR Radical >> ROS formation after GSH depletion >> Quinone methides OR SN1 OR SN1 >> Alkylation after metabolically formed carbenium ion species OR SN1 >> Alkylation after metabolically formed carbenium ion species >> Polycyclic Aromatic Hydrocarbon 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 >> 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 >> 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 >> Nitrobiphenyls and Bridged Nitrobiphenyls 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 SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> Specific Acetate Esters 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 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Quinoline Derivatives OR SN2 >> Nucleophilic substitution after nitrite formation OR SN2 >> Nucleophilic substitution after nitrite formation >> Nitroalkanes OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate Esters 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: "h"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules (GSH) by Protein binding potency

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Highly reactive (GSH) OR Highly reactive (GSH) >> 3-Alken-2-ones (MA) OR Moderately reactive (GSH) OR Moderately reactive (GSH) >> 2-Vinylpyridine (MA) OR Moderately reactive (GSH) >> Substituted 1-Alken-3-ones (MA) by Protein binding potency

Domain logical expression index: "j"

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

Domain logical expression index: "k"

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

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Alkaline Earth OR Halogens OR Metalloids OR Metals OR Rare Earth OR Transition Metals by Groups of elements

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Amine AND Anion AND Aromatic compound AND Cation AND Nitro compound AND Primary amine AND Primary aromatic amine AND Secondary amine AND Secondary aromatic amine AND Sulfonic acid derivative by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "n"

Similarity boundary:Target: Nc1ccc(Nc2ccc(N(=O)=O)cc2S(=O)(=O)O{-}.[Na]{+})cc1
Threshold=10%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Benzene/ Naphthalene sulfonic acids (Less susceptible) Rank C by Repeated dose (HESS)

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as 3-Methylcholantrene (Hepatotoxicity) Alert OR Nitrobenzenes (Hemolytic anemia with methemoglobinemia) Rank A OR Nitrobenzenes (Hepatotoxicity) Rank C OR Nitrobenzenes (Testicular toxicity) Rank C OR Not categorized by Repeated dose (HESS)

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of log Kow which is >= -3.99

Domain logical expression index: "r"

Parametric boundary:The target chemical should have a value of log Kow which is <= -1.5

Interpretation of results:

other: not irritating

Conclusions:

Sodium 2-[(4-aminophenyl)amino]-5-nitrobenzene-1-sulfonate was estimated to be not irritating to the eyes of New Zealand White rabbits.

Executive summary:

The ocular irritation potential of sodium 2-[(4-aminophenyl)amino]-5-nitrobenzene-1-sulfonate was estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor.

Sodium 2-[(4-aminophenyl)amino]-5-nitrobenzene-1-sulfonate was estimated to be not irritating to the eyes of New Zealand White rabbits.

Based on the estimated results, sodium 2-[(4-aminophenyl)amino]-5-nitrobenzene-1-sulfonate can be considered to be 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, sodium 2-[(4-aminophenyl)amino]-5-nitrobenzene-1-sulfonate 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 structurally related read across substances, 4-nitro-4’-aminodiphenylamine-2 -sulfonic acid [CAS: 91-29-2] and Disodium 4,4’–diaminostilbene–2,2’–disulphonate[CAS: 7336-20-1]. 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 for sodium 2-[(4-aminophenyl)amino]-5-nitrobenzene-1-sulfonate. Sodium 2-[(4-aminophenyl)amino]-5-nitrobenzene-1-sulfonate was not irritating to New Zealand White rabbit skin.

This result is supported by the experimental study summarized in GESTIS SUBSTANCE Database (information system in hazardous substance of the Berufsgenossenscheftn), 2017; for the structurally related read across substance, 4-nitro-4’-aminodiphenylamine-2-sulfonic acid [CAS: 91-29-2]. The study was conducted in accordance with OECD guideline No. 404. The animals were subjected to a single 4- hour exposure to 500 mg of the test substance, mixed into a paste with water and applied semi-occlusively to the mechanically depilated skin of the flanks. The findings were scored after 1, 24, 48 and 72 hours as well as 7 days in accordance with the Draize method. The average irritation scores according to the Draize scoring for erythema and oedema were 0.0.

Hence, 4-nitro-4’-aminodiphenylamine-2-sulfonic acid (CAS No:91-29-2) was considered to be not irritating to skin of female albino rabbits.

The above results are also supported by the experimental study summarized in SCREENING-LEVEL HAZARD CHARACTERIZATION Stilbene Fluorescent Brightener Intermediates U.S. Environmental Protection Agency Hazard Characterization Document, March 2012; for the structurally related read across substance, 4,4’–diaminostilbene–2,2’–disulphonate[CAS: 7336-20-1]. 500mg of the test chemical in water was applied to the skin of 3 male New Zealand White rabbits for 4 hours and observed for 7 days. The Draize scoring method was used. All scores were zero, with the exception of one (barely perceptible erythema) at 24 hours. The average irritation indices were 0, 0.3 and 0 in the three animals.

Since the animals failed to produced any irritation effects, disodium 4, 4’–diaminostilbene–2, 2’–disulphonate(CAS No: -7336–20–1) was considered to be non irritant on rabbit’s skin.

Based on the available data for the target and read across substances and applying the weight of evidence approach, sodium 2-[(4-aminophenyl)amino]-5-nitrobenzene-1 -sulfonate can be considered to be not irritating to skin.Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

Eye Irritation:

In different studies, sodium 2-[(4-aminophenyl)amino]-5-nitrobenzene-1-sulfonate 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 structurally related read across substances, 4-nitro-4’-aminodiphenylamine-2 -sulfonic acid [CAS: 91-29-2] and Disodium 4,4’–diaminostilbene–2,2’–disulphonate[CAS: 7336-20-1]. 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 sodium 2-[(4-aminophenyl)amino]-5-nitrobenzene-1-sulfonate. Sodium 2-[(4-aminophenyl)amino]-5-nitrobenzene-1-sulfonate was not irritating to New Zealand White rabbit eyes.

This result is supported by the experimental study summarized in GESTIS SUBSTANCE Database (information system in hazardous substance of the Berufsgenossenscheftn), 2017; for the structurally related read across substance, 4-nitro-4’-aminodiphenylamine-2-sulfonic acid [CAS: 91-29-2]. The study was performed in accordance with OECD guideline 405. About 100 μl of 4-nitro-4’-aminodiphenylamine-2-sulfonic acid was placed into the conjunctival sac of each rabbits and the results were recorded for 3 days. Slight reddening in only one of 6 animals was observed but this was reversible after 3 days.

Since the observed eye effects were fully reversible within 3 days ,the test chemical 4-nitro-4’-aminodiphenylamine-2-sulfonic acid (CAS No:91-29-2) was considered to be not irritating to rabbits’ eye.

The above results are also supported by the experimental study summarized in SCREENING-LEVEL HAZARD CHARACTERIZATION Stilbene Fluorescent Brightener Intermediates U.S. Environmental Protection Agency Hazard Characterization Document, March 2012; for the structurally related read across substance, 4,4’–diaminostilbene–2,2’–disulphonate[CAS: 7336-20-1]. 3 male New Zealand White rabbits received an ocular administration of 39 mg of disodium 4,4’-diaminostilbene-2,2’-disulphonate in one eye and were observed for 7 days following dosing. The treated eye was rinsed 24 hours following exposure. The untreated eye served as control. A conjunctival redness score of two (diffuse, crimson color, individual vessels not easily discernible) was observed in one rabbit at 1 hour and a conjunctival redness score of one (some blood vessels definitely hyperemic) was observed at 1 hour in the other two rabbits. Swelling score of one was observed in all rabbits after 1 hour of observation. All other scores were zero.

Disodium 4,4’-diaminostilbene-2,2’-disulphonate was not irritating to rabbit eyes in this assay.

Based on the available data for the target and read across substances and applying the weight of evidence approach, sodium 2-[(4-aminophenyl)amino]-5-nitrobenzene-1 -sulfonate can be considered to be not irritating to eyes.Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

Available studies for sodium 2-[(4-aminophenyl)amino]-5-nitrobenzene-1-sulfonate indicate that it is not likely to cause any irritation to eyes and skin. Hence,sodium 2-[(4-aminophenyl)amino]-5-nitrobenzene-1-sulfonate can be classified under the category “Not Classified” as per CLP regulation.