Registration Dossier

skin irritation :

In a prediction done by SSS (2017) using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor, the skin irritation potential ofTrisodium4-[[1-hydroxy-6-[[[[5-hydroxy-6-(phenylazo)-7-sulphonato-2-naphthyl]amino]carbonyl]amino]-3-sulphonato-2-naphthyl]azo]benzoate was estimated . It was estimated that Trisodium4-[[1-hydroxy-6-[[[[5-hydroxy-6-(phenylazo)-7-sulphonato -2-naphthyl]amino]carbonyl]amino] -3-sulphonato-2-naphthyl]azo]benzoate was not irritating to skin of rabbits.

Eye irritation :

In a prediction done by SSS (2017) using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor, the eye irritation potential of Trisodium4- [[1-hydroxy-6- [ [[[5-hydroxy-6-(phenylazo) -7-sulphonato-2-naphthyl]amino]carbonyl]amino] -3-sulphonato-2-naphthyl]azo]benzoate was estimated . It was estimated that Trisodium4-[[1-hydroxy-6-[[[[5-hydroxy-6-(phenylazo)-7-sulphonato -2-naphthyl]amino]carbonyl]amino] -3-sulphonato-2-naphthyl]azo]benzoate was not irritating to eye of rabbits.

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 predicted using OECD QSAR toolbox version 3.3 and QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: estimated data

Principles of method if other than guideline:

Prediction was done by using OECD QSAR toolbox v3.3

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material (IUPAC name): Trisodium 4-[[1-hydroxy-6-[[[[5-hydroxy-6-(phenylazo)-7-sulphonato-2-naphthyl]amino]carbonyl]amino]-3-sulphonato-2-naphthyl]azo]benzoate
- Common name: trisodium 4-[[1-hydroxy-6-[[[[5-hydroxy-6-(phenylazo)-7-sulphonato-2-naphthyl]amino]carbonyl]amino]-3-sulphonato-2-naphthyl]azo]benzoate
- Molecular formula: C34H21N6Na3O11S2
- Molecular weight: 822.673 g/mol
- Smiles notation: c12c(cc(c(c2S(=O)(=O)[O-])\N=N\c2ccc(cc2)C(=O)[O-])O)cc(NC(=O)Nc2cc3cc(S(=O)(=O)[O-])c(\N=N\c4ccccc4)c(c3cc2)O)cc1.[Na+].[Na+].[Na+]
-InChl:1S/C34H24N6O11S2.3Na/c41-27-16-19-14-24(11-13-26(19)32(53(49,50)51)29(27)39-38-22-8-6-18(7-9-22)33(43)44)36-34(45)35-23-10-12-25-20(15-23)17-28(52(46,47)48)30(31(25)42)40-37-21-4-2-1-3-5-21;;;/h1-17,41-42H,(H,43,44)(H2,35,36,45)(H,46,47,48)(H,49,50,51);;;/q;3*+1/p-3/b39-38+,40-37+;;;
- Substance type: Organic
-Physical sttate: Solid

Species:

rabbit

Strain:

not specified

Details on test animals or test system and environmental conditions:

No data available

Type of coverage:

not specified

Preparation of test site:

not specified

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

No data available

Duration of treatment / exposure:

24 hrs

Observation period:

24 hrs

Number of animals:

No data available

Details on study design:

No data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

24 h

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

no indication of skin reaction estimated

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" ) and ("g" and ( not "h") ) ) and ("i" and ( not "j") ) ) and ("k" and ( not "l") ) ) and ("m" and ( not "n") ) ) and ("o" and ( not "p") ) ) and ("q" and ( not "r") ) ) and ("s" and ( not "t") ) ) and ("u" and "v" ) )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as SN1 OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Aromatic phenylureas by DNA binding by OECD ONLY

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Aryl OR Azo OR Carboxylic acid OR Fused carbocyclic aromatic OR Naphtalene OR Phenol OR Sulfonic acid OR Urea derivatives by Organic Functional groups ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Aryl OR Azo OR Carboxylic acid OR Fused carbocyclic aromatic OR Overlapping groups OR Phenol OR Sulfonic acid OR Urea derivatives by Organic Functional groups (nested) ONLY

Domain logical expression index: "d"

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

Domain logical expression index: "e"

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

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Anion OR Aromatic compound OR Azo compound OR Carbonic acid derivative OR Carboxylic acid derivative OR Carboxylic acid salt OR Cation OR CO2 derivative (general) OR Hydroxy compound OR Phenol OR Sulfonic acid derivative by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as No alert found 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 >> Michael-type addition, quinoid structures OR AN2 >> Michael-type addition, quinoid structures >> Quinoneimines 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 >> Fused-Ring Primary Aromatic Amines OR Radical OR Radical >> Generation of reactive oxygen species OR Radical >> Generation of reactive oxygen species >> Thiols OR Radical >> Radical mechanism by ROS formation (indirect) or direct radical attack on DNA OR Radical >> Radical mechanism by ROS formation (indirect) or direct radical attack on DNA >> Organic Peroxy Compounds OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Primary Aromatic Amines 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 (indirect) OR Radical >> ROS formation after GSH depletion (indirect) >> Quinoneimines 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 >> Nucleophilic attack after carbenium ion formation OR SN1 >> Nucleophilic attack after carbenium ion formation >> Specific Acetate Esters OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation 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 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 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 by DNA binding by OASIS v.1.3

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Non binder, MW>500 by Estrogen Receptor Binding

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Moderate binder, NH2 group OR Moderate binder, OH grooup OR Non binder, impaired OH or NH2 group OR Non binder, non cyclic structure OR Non binder, without OH or NH2 group OR Strong binder, NH2 group OR Strong binder, OH group OR Very strong binder, OH group OR Weak binder, NH2 group OR Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as No alert found by Protein binding by OASIS v1.3

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Michael Addition OR Michael Addition >> Michael addition on conjugated systems with electron withdrawing group OR Michael Addition >> Michael addition on conjugated systems with electron withdrawing group >> alpha,beta-Carbonyl compounds with polarized double bonds OR Michael Addition >> Michael addition on conjugated systems with electron withdrawing group >> Cyanoalkenes by Protein binding by OASIS v1.3

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as No alert found by Protein binding alerts for Chromosomal aberration by OASIS v1.1

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Michael-type addition to quinoid structures OR AN2 >> Michael-type addition to quinoid structures >> Phenols by Protein binding alerts for Chromosomal aberration by OASIS v1.1

Domain logical expression index: "o"

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

Domain logical expression index: "p"

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

Domain logical expression index: "q"

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: "r"

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

Domain logical expression index: "s"

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

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Thiocarbamates/Sulfides (Hepatotoxicity) No rank by Repeated dose (HESS)

Domain logical expression index: "u"

Parametric boundary:The target chemical should have a value of log Kow which is >= -1.37

Domain logical expression index: "v"

Parametric boundary:The target chemical should have a value of log Kow which is <= 17.2

Interpretation of results:

other: not irritating

Conclusions:

Trisodium 4-[[1-hydroxy-6-[[[[5-hydroxy-6-(phenylazo)-7-sulphonato-2-naphthyl]amino]carbonyl]amino]-3-sulphonato-2-naphthyl]azo]benzoate was considered to be not irritating to rabbit skin.

Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor, the skin irritation potential of Trisodium4-[[1-hydroxy-6-[[[[5-hydroxy-6-(phenylazo)-7-sulphonato-2-naphthyl]amino]carbonyl]amino]-3-sulphonato-2-naphthyl]azo]benzoatewas estimated . It was estimated that Trisodium4-[[1-hydroxy-6-[[[[5-hydroxy-6-(phenylazo)-7-sulphonato -2-naphthyl]amino]carbonyl]amino] -3-sulphonato-2-naphthyl]azo]benzoatewas not irritating to skin of rabbits.

Endpoint conclusion:

no adverse effect observed (not irritating)

Reference

Endpoint:

eye irritation: in vivo

Type of information:

(Q)SAR

Adequacy of study:

other information

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 predicted using OECD QSAR toolbox version 3.3 and QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: estimated data

Principles of method if other than guideline:

Prediction was done by using OECD QSAR toolbox v3.3

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material (IUPAC name): Trisodium 4-[[1-hydroxy-6-[[[[5-hydroxy-6-(phenylazo)-7-sulphonato-2-naphthyl]amino]carbonyl]amino]-3-sulphonato-2-naphthyl]azo]benzoate
- Common name: trisodium 4-[[1-hydroxy-6-[[[[5-hydroxy-6-(phenylazo)-7-sulphonato-2-naphthyl]amino]carbonyl]amino]-3-sulphonato-2-naphthyl]azo]benzoate
- Molecular formula: C34H21N6Na3O11S2
- Molecular weight: 822.673 g/mol
- Smiles notation: c12c(cc(c(c2S(=O)(=O)[O-])\N=N\c2ccc(cc2)C(=O)[O-])O)cc(NC(=O)Nc2cc3cc(S(=O)(=O)[O-])c(\N=N\c4ccccc4)c(c3cc2)O)cc1.[Na+].[Na+].[Na+]
-InChl:1S/C34H24N6O11S2.3Na/c41-27-16-19-14-24(11-13-26(19)32(53(49,50)51)29(27)39-38-22-8-6-18(7-9-22)33(43)44)36-34(45)35-23-10-12-25-20(15-23)17-28(52(46,47)48)30(31(25)42)40-37-21-4-2-1-3-5-21;;;/h1-17,41-42H,(H,43,44)(H2,35,36,45)(H,46,47,48)(H,49,50,51);;;/q;3*+1/p-3/b39-38+,40-37+;;;
- Substance type: Organic
-Physical sttate: Solid

Species:

rabbit

Strain:

not specified

Details on test animals or tissues and environmental conditions:

No data available

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

No data available

Duration of treatment / exposure:

No data available

Observation period (in vivo):

No data available

Details on study design:

No data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: Not specified

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No indication of skin reaction estimated.

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

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

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as SN1 OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Aromatic phenylureas by DNA binding by OECD ONLY

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Aryl OR Azo OR Carboxylic acid OR Fused carbocyclic aromatic OR Naphtalene OR Phenol OR Sulfonic acid OR Urea derivatives by Organic Functional groups ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Aryl OR Azo OR Carboxylic acid OR Fused carbocyclic aromatic OR Overlapping groups OR Phenol OR Sulfonic acid OR Urea derivatives by Organic Functional groups (nested) ONLY

Domain logical expression index: "d"

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

Domain logical expression index: "e"

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

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Anion OR Aromatic compound OR Azo compound OR Carbonic acid derivative OR Carboxylic acid derivative OR Carboxylic acid salt OR Cation OR CO2 derivative (general) OR Hydroxy compound OR Phenol OR Sulfonic acid derivative by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as No alert found 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 >> Michael-type addition, quinoid structures OR AN2 >> Michael-type addition, quinoid structures >> Quinoneimines 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 >> Fused-Ring Primary Aromatic Amines OR Radical OR Radical >> Generation of reactive oxygen species OR Radical >> Generation of reactive oxygen species >> Thiols OR Radical >> Radical mechanism by ROS formation (indirect) or direct radical attack on DNA OR Radical >> Radical mechanism by ROS formation (indirect) or direct radical attack on DNA >> Organic Peroxy Compounds OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Primary Aromatic Amines 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 (indirect) OR Radical >> ROS formation after GSH depletion (indirect) >> Quinoneimines 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 >> Nucleophilic attack after carbenium ion formation OR SN1 >> Nucleophilic attack after carbenium ion formation >> Specific Acetate Esters OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation 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 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 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 by DNA binding by OASIS v.1.3

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as No alert found by Protein binding by OECD

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Direct Acylation Involving a Leaving group OR Acylation >> Direct Acylation Involving a Leaving group >> Acetates OR Acylation >> Direct Acylation Involving a Leaving group >> Anhydrides OR Michael addition OR Michael addition >> Polarised Alkenes OR Michael addition >> Polarised Alkenes >> Polarised alkene - amides OR Michael addition >> Polarised Alkenes >> Polarised alkene - cyano OR Michael addition >> Polarised Alkenes >> Polarised alkene - esters OR Michael addition >> Polarised Alkenes >> Polarised alkene - ketones OR Michael addition >> Polarised Alkenes >> Polarised alkene - pyridines OR Michael addition >> Polarized Azo Compounds OR Michael addition >> Polarized Azo Compounds >> Azocarbonamides OR SN2 OR SN2 >> SN2 reaction at sp3 carbon atom OR SN2 >> SN2 reaction at sp3 carbon atom >> Allyl acetates and related chemicals by Protein binding by OECD

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Not bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "l"

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

Domain logical expression index: "m"

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

Domain logical expression index: "n"

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: "o"

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

Domain logical expression index: "p"

Similarity boundary:Target: Oc1c2ccc(NC(=O)Nc3ccc4c(c3)cc(S(=O)(=O)O{-}.[Na]{+})c(N=Nc3ccc(C(=O)O{-}.[Na]{+})cc3)c4O)cc2cc(S(=O)(=O)O{-}.[Na]{+})c1N=Nc1ccccc1
Threshold=10%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of log Kow which is >= -1.35

Domain logical expression index: "r"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.19

Interpretation of results:

other: not irritating

Conclusions:

Trisodium4- [[1-hydroxy-6- [ [[[5-hydroxy-6-(phenylazo) -7-sulphonato-2-naphthyl]amino]carbonyl]amino] -3-sulphonato-2-naphthyl]azo]benzoate was considered to be not eye irritant on rabbit.

Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor, the eye irritation potential of Trisodium4- [[1-hydroxy-6- [ [[[5-hydroxy-6-(phenylazo) -7-sulphonato-2-naphthyl]amino]carbonyl]amino] -3-sulphonato-2-naphthyl]azo]benzoate was estimated . It was estimated that Trisodium4-[[1-hydroxy-6-[[[[5-hydroxy-6-(phenylazo)-7-sulphonato -2-naphthyl]amino]carbonyl]amino] -3-sulphonato-2-naphthyl]azo]benzoate was not irritating to eye of rabbits.

Endpoint conclusion:

no adverse effect observed (not irritating)

Endpoint conclusion:

no study available

Skin irritation:

In different studies, Trisodium 4-[[1-hydroxy-6-[[[[5-hydroxy-6-(phenylazo)-7-sulphonato-2-naphthyl]amino]carbonyl]amino]-3-sulphonato-2-naphthyl]azo]benzoate 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 human data for target chemical and its closely related read across substances Disodium 2,2'-([1,1'-biphenyl]-4,4'-diyldivinylene)bis(benzenesulphonate (27344-41-8) and 2,2'-Methylene-bis-(6-(2H-benzotriazol-2-yl)-4-(1,1,3,3-tetramethylbutyl)phenol) (103597-45-1) . 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 version 3.3 with log kow as the primary descriptor, the skin irritation potential of Trisodium4-[[1-hydroxy-6-[[[[5-hydroxy-6-(phenylazo)-7-sulphonato-2-naphthyl]amino]carbonyl]amino]-3-sulphonato-2-naphthyl]azo]benzoatewas estimated . It was estimated that Trisodium4-[[1-hydroxy-6-[[[[5-hydroxy-6-(phenylazo)-7-sulphonato -2-naphthyl]amino]carbonyl]amino] -3-sulphonato-2-naphthyl]azo]benzoatewas not irritating to skin of rabbits.

The above predicted data was supported by experimental study conducted by HERA targeted risk assessment of FWA-5, May, 2003 for the closely related read across substance Disodium 2,2'-([1,1'-biphenyl]-4,4'-diyldivinylene)bis(benzenesulphonate).

Disodium 2,2'-([1,1'-biphenyl]-4,4'-diyldivinylene)bis(benzenesulphonate was used as a test material to evaluate its skin sensitization potential.

The test was performed on 3 young adult male New Zealand White rabbits weighing 2.2 to 2.3 kg. They were housed individually in metal cages, were kept at a constant room temperature of 20±3 °C, at a relative humidity of 30-70%, and on a 12 hours light cycle day. The animals received ad libitum standard pelleted rabbit food (Nafag No. 814; Gossau, Switzerland) and water. Prior to treatment they were acclimatized for a minimum of 5 days. The test article was applied as a liquid formulation containing 21.3% FWA-5 in water.

About 24-hours before treatment an area of about 6 sq. cm was shaved on both flanks of each rabbit. Gauze patch of 2.5 x 2.5 cm covered with 0.5 mL of the test material was applied to one flank and a control patch to the contralateral flank. The patches were covered with an impermeable material and were fastened to the body of the rabbit with adhesive tape. The duration of treatment was four hours. The scoring of skin reaction was performed 1, 24, 48 and 72 hours after removal of the dressing. These scores were used in calculating the respective mean values for each type of lesion.

At one hour, erythema was observed in each animal (one with grade 2; two with grade 1) as was grade 1 edema. At 24-hours, no signs of erythema or edema were observed and the calculated primary irritation index was 0.00 (max.8.0). The substance did not cause any staining of the treated skin. No corrosive effects were noted on the treated skin of any animal at any observation time.

(Disodium 2,2'-([1,1'-biphenyl]-4,4'-diyldivinylene)bis(benzenesulphonate) when applied on the skin ofNew Zealand White rabbits in concentration 0.5ml of 21.3% in water . No corrosive effects were noted on the treated skin of any animal at observation time.(Disodium 2,2'-([1,1'-biphenyl]-4,4'-diyldivinylene)bis(benzenesulphonate) is considered to be not irritating to rabbit skin.

The above experimental result was further supported by experimental stud conducted by European Commission (EC) - Scientific Committee on Consumer Safety (SCCS) Opinion on 2,2'-Methylene-bis-(6-(2H-benzotriazol-2-yl)-4-(1,1,3,3-tetramethylbutyl)phenol) COLIPA No. S79 2013 for closely related read across substance 2,2'-Methylene-bis-(6-(2H-benzotriazol-2-yl)-4-(1,1,3,3-tetramethylbutyl)phenol) (103597-45-1)

2,2'-Methylenebis(6-(2H-benzotriazol-2-yl)-4-(1,1,3,3-tetramethylbutyl)phenol was used as test material to evaluate its skin irritation potential on Hartley-derived albino guinea pigs for 14 consecutive days.

Six animals per dose level received a 0.1 or 0.2 mL dermal application of the test item suspended on 0.5% (w/v) CMC in 0.1% (w/v) Tween 80 at 15, 40, or 65% (w/w). After approximately 24 hours, residual test item was removed. This procedure was repeated daily for a total of 14 exposure periods. Application sites were scored for signs of dermal irritation for up to 72 hours following the final test item removal on day 14.

Exposure to 15% formulations of test material resulted very slight erythema (1/6 test sites on two occasions, day 3 and day 8). No other signs of dermal irritation were noted at both dose levels after the last exposure on day 14.

Based on the available data for the target as well as it read across substances,it can be concluded that Trisodium4-[[1-hydroxy-6-[[[[5-hydroxy-6-(phenylazo)-7-sulphonato-2-naphthyl]amino]carbonyl]amino]-3-sulphonato-2-naphthyl]azo]benzoate was not irritating to skin; and itcan be classified under the category “Not classified” as per CLP regulation.

Eye irritation:

In different studies, Trisodium 4-[[1-hydroxy-6-[[[[5-hydroxy-6-(phenylazo)-7-sulphonato-2-naphthyl]amino]carbonyl]amino]-3-sulphonato-2-naphthyl]azo]benzoate 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 human data for target chemical and its structurally similar read across substance Pyranine; trisodium 8-hydroxypyrene-1,3,6-trisulfonate (6358-69-6) and disodium 5-amino-4-hydroxy-3-(phenylazo)naphthalene-2,7-disulphonate (3567-66-6) . 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 version 3.3 with log kow as the primary descriptor, the eye irritation potential of Trisodium4- [[1-hydroxy-6- [ [[[5-hydroxy-6-(phenylazo) -7-sulphonato-2-naphthyl]amino]carbonyl]amino] -3-sulphonato-2-naphthyl]azo]benzoate was estimated . It was estimated that Trisodium4-[[1-hydroxy-6-[[[[5-hydroxy-6-(phenylazo)-7-sulphonato -2-naphthyl]amino]carbonyl]amino] -3-sulphonato-2-naphthyl]azo]benzoate was not irritating to eye of rabbits.

The above predicted data was supported by experimental study conducted by The NSS Bulletin, Volume 46 Number 2: 21-33 - October 1984, A publication of the National Speleological Society for structurally similar read across substance Pyranine; trisodium 8-hydroxypyrene-1,3,6-trisulfonate (6358-69-6)

In an ocular irritation study conducted on mammals (species - not mentioned), Pyranine was observed to be non – irritating to eyes.Since there was no evidence of substantial toxicity, it was considered that Pyranine can be used safely for the angiography in the human eye.

The above experimental result was further supported by experimental study conducted by Scientific Committee on Consumer Safety (SCCS)-SCCP/1102/07 for 5-amino-4-hydroxy-3-(phenylazo)naphthalene-2,7-disulphonate (3567-66-6)

A study was conducted to determine the irritation potential of Acid Red 33 on rabbit eyes. 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 as well as it read across substances,it can be concluded that Trisodium4-[[1-hydroxy-6-[[[[5-hydroxy-6-(phenylazo)-7-sulphonato-2-naphthyl]amino]carbonyl]amino]-3-sulphonato-2-naphthyl]azo]benzoate was not irritating to eye; and itcan be classified under the category “Not classified” as per CLP regulation.

Based on the available data for the target as well as it read across substances,it can be concluded that Trisodium4-[[1-hydroxy-6-[[[[5-hydroxy-6-(phenylazo)-7-sulphonato-2-naphthyl]amino]carbonyl]amino]-3-sulphonato-2-naphthyl]azo]benzoate was not irritating to skin and eye; and it can be classified under the category “Not classified” as per CLP regulation.