Registration Dossier

Skin Irritation:

The dermal irritation potential of Octasodium 2,2'-[(2,2'-disulphonato[1,1'-biphenyl]-4,4'-diyl)bis[imino(6-chloro-1,3,5-triazine-4,2-diyl)imino(1-hydroxy-3-sulphonatonaphthalene-6,2-diyl)azo]] bisnaphthalene-1,5-disulphonate was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor.

Octasodium 2,2'-[(2,2'-disulphonato[1,1'-biphenyl]-4,4'-diyl)bis[imino(6-chloro-1,3,5-triazine-4,2-diyl)imino(1-hydroxy-3-sulphonatonaphthalene-6,2-diyl)azo]] bisnaphthalene-1,5-disulphonate was estimated to be not irritating to the skin of rabbits.

Based on the estimated result; Octasodium 2,2'-[(2,2'-disulphonato[1,1'-biphenyl]-4,4'-diyl)bis[imino(6-chloro-1,3,5-triazine-4,2-diyl)imino(1-hydroxy-3-sulphonatonaphthalene-6,2-diyl)azo]] bisnaphthalene-1,5-disulphonate 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 Octasodium 2,2'-[(2,2'-disulphonato[1,1'-biphenyl]-4,4'-diyl)bis[imino(6-chloro-1,3,5-triazine-4,2-diyl)imino(1-hydroxy-3-sulphonatonaphthalene-6,2-diyl)azo]] bisnaphthalene-1,5-disulphonate was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor.

Octasodium 2,2'-[(2,2'-disulphonato[1,1'-biphenyl]-4,4'-diyl)bis[imino(6-chloro-1,3,5-triazine-4,2-diyl)imino(1-hydroxy-3-sulphonatonaphthalene-6,2-diyl)azo]] bisnaphthalene-1,5-disulphonate was estimated to be not irritating to the eyes of New Zealand White rabbits.

Based on the estimated result; Octasodium 2,2'-[(2,2'-disulphonato[1,1'-biphenyl]-4,4'-diyl)bis[imino(6-chloro-1,3,5-triazine-4,2-diyl)imino(1-hydroxy-3-sulphonatonaphthalene-6,2-diyl)azo]] bisnaphthalene-1,5-disulphonate can be considered not irritating to the 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: Octasodium 2,2'-[(2,2'-disulphonato[1,1'-biphenyl]-4,4'-diyl)bis[imino(6-chloro-1,3,5-triazine-4,2-diyl)imino (1-hydroxy-3-sulphonatonaphthalene-6,2-diyl)azo]]bisnaphthalene-1,5-disulphonate
Molecular formula: C58H30Cl2N14Na8O26S8
Molecular weight: 1850.3 g/mol
Smiles Notation: [Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].c1(c(cc(cc1)Nc1nc(nc(n1)Cl)Nc1cc2cc(c(c(c2cc1)O)\N=N\c1c(c2cccc(c2cc1)S(=O)(=O)[O-])S(=O)(=O)[O-])S(=O)(=O)[O-])S(=O)(=O)[O-])c1c(cc(cc1)Nc1nc(nc(n1)Cl)Nc1cc2cc(c(c(c2cc1)O)\N=N\c1c(c2cccc(c2cc1)S(=O)(=O)[O-])S(=O)(=O)[O-])S(=O)(=O)[O-])S(=O)(=O)[O-]
InChI: 1S/C58H38Cl2N14O26S8.8Na/c59-53-65-55(61-27-7-11-31-25(19-27)21-45(105(89,90)91)47(49(31)75)73-71-39-17-15-35-37(51(39)107(95,96)97)3-1-5-41(35)101(77,78)79)69-57(67-53)63-29-9-13-33(43(23-29)103(83,84)85)34-14-10-30(24-44(34)104(86,87)88)64-58-68-54(60)66-56(70-58)62-28-8-12-32-26(20-28)22-46(106(92,93)94)48(50(32)76)74-72-40-18-16-36-38(52(40)108(98,99)100)4-2-6-42(36)102(80,81)82;;;;;;;;/h1-24,75-76H,(H,77,78,79)(H,80,81,82)(H,83,84,85)(H,86,87,88)(H,89,90,91)(H,92,93,94)(H,95,96,97)(H,98,99,100)(H2,61,63,65,67,69)(H2,62,64,66,68,70);;;;;;;;/q;8*+1/p-8/b73-71+,74-72+;;;;;;;;
Substance Type: Organic
Physical State: Solid

Species:

rabbit

Strain:

not specified

Details on test animals or test system and environmental conditions:

no data available

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

0.5 g

Duration of treatment / exposure:

24 hours

Observation period:

72 hours

Number of animals:

6

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 9 nearest neighbours
Domain logical expression:Result: In Domain

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

Domain logical expression index: "a"

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

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Alcohol, olefinic attach [-OH] OR Aliphatic Nitrogen, one aromatic attach [-N] OR Aliphatic Nitrogen, two aromatic attach [-N-] OR Amino Triazine/Pyrazine/Pyrimidine OR Aromatic Carbon [C] OR Aromatic Nitrogen OR Azo [-N=N-] OR Chlorine, aromatic attach [-Cl] OR Chlorine, olefinic attach [-Cl] 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 Sym-Triazine ring by Organic functional groups (US EPA) ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Aromatic amine OR Aromatic heterocyclic halide OR Aryl OR Aryl halide OR Azo OR Biphenyl OR Fused carbocyclic aromatic OR Overlapping groups OR Phenol OR Sulfonic acid by Organic Functional groups (nested) ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Aromatic amine OR Aromatic heterocyclic halide OR Aryl OR Aryl halide OR Azo OR Biphenyl OR Fused carbocyclic aromatic OR Naphtalene OR Phenol OR Sulfonic acid OR Triazine by Organic Functional groups ONLY

Domain logical expression index: "e"

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

Domain logical expression index: "f"

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: "g"

Referential boundary: The target chemical should be classified as Not known precedent reproductive and developmental toxic potential by DART scheme v.1.0

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Inorganic chemical OR Known precedent reproductive and developmental toxic potential OR Non-steroid nucleus derived estrogen receptor (ER) and androgen receptor (AR) OR Non-steroid nucleus derived estrogen receptor (ER) and androgen receptor (AR) >> Other non-steroidal estrogen receptor (ER) binding compounds (2b-2) OR Not covered by current version of the decision tree OR Organophosphorus compounds (1b) OR Toluene and small alkyl toluene derivatives (8a) by DART scheme v.1.0

Domain logical expression index: "i"

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

Domain logical expression index: "j"

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

Domain logical expression index: "k"

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

Domain logical expression index: "l"

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

Domain logical expression index: "m"

Similarity boundary:Target: Oc1c2ccc(Nc3nc(Nc4ccc(-c5ccc(Nc6nc(Nc7ccc8c(c7)cc(S(=O)(=O)O{-}.[Na]{+})c(/N=N/c7ccc9c(S(=O)(=O)O{-}.[Na]{+})cccc9c7S(=O)(=O)O{-}.[Na]{+})c8O)nc(Cl)n6)cc5S(=O)(=O)O{-}.[Na]{+})c(S(=O)(=O)O{-}.[Na]{+})c4)nc(Cl)n3)cc2cc(S(=O)(=O)O{-}.[Na]{+})c1/N=N/c1ccc2c(S(=O)(=O)O{-}.[Na]{+})cccc2c1S(=O)(=O)O{-}.[Na]{+}
Threshold=80%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log BCF max which is >= 0.96 log(L/kg wet)

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log BCF max which is <= 2.4 log(L/kg wet)

Interpretation of results:

other: not irritating

Conclusions:

Octasodium 2,2'-[(2,2'-disulphonato[1,1'-biphenyl]-4,4'-diyl)bis[imino(6-chloro-1,3,5-triazine-4,2-diyl)imino(1-hydroxy-3-sulphonatonaphthalene-6,2-diyl)azo]] bisnaphthalene-1,5-disulphonate was estimated to be not irritating to the skin of rabbits.

Executive summary:

The dermal irritation potential of Octasodium 2,2'-[(2,2'-disulphonato[1,1'-biphenyl]-4,4'-diyl)bis[imino(6-chloro-1,3,5-triazine-4,2-diyl)imino(1-hydroxy-3-sulphonatonaphthalene-6,2-diyl)azo]] bisnaphthalene-1,5-disulphonate was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor.

Octasodium 2,2'-[(2,2'-disulphonato[1,1'-biphenyl]-4,4'-diyl)bis[imino(6-chloro-1,3,5-triazine-4,2-diyl)imino(1-hydroxy-3-sulphonatonaphthalene-6,2-diyl)azo]] bisnaphthalene-1,5-disulphonate was estimated to be not irritating to the skin of rabbits.

Based on the estimated result; Octasodium 2,2'-[(2,2'-disulphonato[1,1'-biphenyl]-4,4'-diyl)bis[imino(6-chloro-1,3,5-triazine-4,2-diyl)imino(1-hydroxy-3-sulphonatonaphthalene-6,2-diyl)azo]] bisnaphthalene-1,5-disulphonate 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 the test chemical: Octasodium 2,2'-[(2,2'-disulphonato[1,1'-biphenyl]-4,4'-diyl)bis[imino(6-chloro-1,3,5-triazine-4,2-diyl)imino (1-hydroxy-3-sulphonatonaphthalene-6,2-diyl)azo]]bisnaphthalene-1,5-disulphonate
Molecular formula: C58H30Cl2N14Na8O26S8
Molecular weight: 1850.3 g/mol
Smiles Notation: [Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].c1(c(cc(cc1)Nc1nc(nc(n1)Cl)Nc1cc2cc(c(c(c2cc1)O)\N=N\c1c(c2cccc(c2cc1)S(=O)(=O)[O-])S(=O)(=O)[O-])S(=O)(=O)[O-])S(=O)(=O)[O-])c1c(cc(cc1)Nc1nc(nc(n1)Cl)Nc1cc2cc(c(c(c2cc1)O)\N=N\c1c(c2cccc(c2cc1)S(=O)(=O)[O-])S(=O)(=O)[O-])S(=O)(=O)[O-])S(=O)(=O)[O-]
InChI: 1S/C58H38Cl2N14O26S8.8Na/c59-53-65-55(61-27-7-11-31-25(19-27)21-45(105(89,90)91)47(49(31)75)73-71-39-17-15-35-37(51(39)107(95,96)97)3-1-5-41(35)101(77,78)79)69-57(67-53)63-29-9-13-33(43(23-29)103(83,84)85)34-14-10-30(24-44(34)104(86,87)88)64-58-68-54(60)66-56(70-58)62-28-8-12-32-26(20-28)22-46(106(92,93)94)48(50(32)76)74-72-40-18-16-36-38(52(40)108(98,99)100)4-2-6-42(36)102(80,81)82;;;;;;;;/h1-24,75-76H,(H,77,78,79)(H,80,81,82)(H,83,84,85)(H,86,87,88)(H,89,90,91)(H,92,93,94)(H,95,96,97)(H,98,99,100)(H2,61,63,65,67,69)(H2,62,64,66,68,70);;;;;;;;/q;8*+1/p-8/b73-71+,74-72+;;;;;;;;
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:

0.1g

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:

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 8 nearest neighbours
Domain logical expression:Result: In Domain

((((((((("a" or "b" or "c" or "d" ) and ("e" and ( not "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 "t" ) )

Domain logical expression index: "a"

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

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Alcohol, olefinic attach [-OH] OR Aliphatic Nitrogen, one aromatic attach [-N] OR Aliphatic Nitrogen, two aromatic attach [-N-] OR Amino Triazine/Pyrazine/Pyrimidine OR Aromatic Carbon [C] OR Aromatic Nitrogen OR Azo [-N=N-] OR Chlorine, aromatic attach [-Cl] OR Chlorine, olefinic attach [-Cl] 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 Sym-Triazine ring by Organic functional groups (US EPA) ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Aromatic amine OR Aromatic heterocyclic halide OR Aryl OR Aryl halide OR Azo OR Biphenyl OR Fused carbocyclic aromatic OR Overlapping groups OR Phenol OR Sulfonic acid by Organic Functional groups (nested) ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Aromatic amine OR Aromatic heterocyclic halide OR Aryl OR Aryl halide OR Azo OR Biphenyl OR Fused carbocyclic aromatic OR Naphtalene OR Phenol OR Sulfonic acid OR Triazine by Organic Functional groups ONLY

Domain logical expression index: "e"

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

Domain logical expression index: "f"

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 >> 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 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 Non-covalent interaction >> DNA intercalation >> Quinones OR Radical 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) >> 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 (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 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 >> 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 >> 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: "g"

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

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Non binder, impaired OH or NH2 group by Estrogen Receptor Binding

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 Non binder, non cyclic structure by Estrogen Receptor Binding

Domain logical expression index: "k"

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

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Non binder, without OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "m"

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

Domain logical expression index: "n"

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

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Not known precedent reproductive and developmental toxic potential by DART scheme v.1.0

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Inorganic chemical OR Known precedent reproductive and developmental toxic potential OR Non-steroid nucleus derived estrogen receptor (ER) and androgen receptor (AR) OR Non-steroid nucleus derived estrogen receptor (ER) and androgen receptor (AR) >> 4-alkylphenol-like derivatives (2b-3) OR Non-steroid nucleus derived estrogen receptor (ER) and androgen receptor (AR) >> Other non-steroidal estrogen receptor (ER) binding compounds (2b-2) OR Not covered by current version of the decision tree OR Organophosphorus compounds (1b) OR Polyhalogenated benzene derivatives (8c) OR Toluene and small alkyl toluene derivatives (8a) by DART scheme v.1.0

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Activated N-heterocycles AND Phenols by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Aromatic amines OR Inclusion rules not met OR Sulfonic acids or their salts by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "s"

Parametric boundary:The target chemical should have a value of log BCF max which is >= 0.963 log(L/kg wet)

Domain logical expression index: "t"

Parametric boundary:The target chemical should have a value of log BCF max which is <= 2.46 log(L/kg wet)

Interpretation of results:

other: not irritating

Conclusions:

Octasodium 2,2'-[(2,2'-disulphonato[1,1'-biphenyl]-4,4'-diyl)bis[imino(6-chloro-1,3,5-triazine-4,2-diyl)imino(1-hydroxy-3-sulphonatonaphthalene-6,2-diyl)azo]] bisnaphthalene-1,5-disulphonate was estimated to be not irritating to the eyes of New Zealand White rabbits.

Executive summary:

The ocular irritation potential of Octasodium 2,2'-[(2,2'-disulphonato[1,1'-biphenyl]-4,4'-diyl)bis[imino(6-chloro-1,3,5-triazine-4,2-diyl)imino(1-hydroxy-3-sulphonatonaphthalene-6,2-diyl)azo]] bisnaphthalene-1,5-disulphonate was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor.

Octasodium 2,2'-[(2,2'-disulphonato[1,1'-biphenyl]-4,4'-diyl)bis[imino(6-chloro-1,3,5-triazine-4,2-diyl)imino(1-hydroxy-3-sulphonatonaphthalene-6,2-diyl)azo]] bisnaphthalene-1,5-disulphonate was estimated to be not irritating to the eyes of New Zealand White rabbits.

Based on the estimated result; Octasodium 2,2'-[(2,2'-disulphonato[1,1'-biphenyl]-4,4'-diyl)bis[imino(6-chloro-1,3,5-triazine-4,2-diyl)imino(1-hydroxy-3-sulphonatonaphthalene-6,2-diyl)azo]] bisnaphthalene-1,5-disulphonate can be considered not irritating to the 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,Octasodium 2,2'-[(2,2'-disulphonato[1,1'-biphenyl]-4,4'-diyl)bis[imino(6-chloro-1,3,5-triazine-4,2-diyl)imino(1-hydroxy-3-sulphonatonaphthalene-6,2-diyl)azo]] bisnaphthalene-1,5-disulphonatehas been investigated for potential for dermal irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits along with predicted data for target chemicaland its structurally similar read across chemicals,Copper,[tetrahydrogen-3,3'-[(3,3'-dihydroxy-4,4'-biphenylylene)bis(azo)]bis[5-amino-4-hydroxy-2,7-naphthalenedisulfonato](4-)]di-,tetrasodium salt (7CI)(C.I Direct Blue 218)[CAS:28407-37-6], Hexasodium;4-amino-3-[[4-[[4-chloro-6-(3-sulfonatoanilino)-1,3,5-triazin-2-yl]amino]-2-sulfonatophenyl]diazenyl]-6-[[4-[[4-chloro-6-(3-sulfonatoanilino)-1,3,5-triazin-2-yl]amino]-2-sulfonatophenyl]hydrazinylidene]-5-oxonaphthalene-2,7-disulfonate(Reactive Green 19)[CAS:61931-49-5] and trisodium 5-amino-3-[(E)-2-(4-{4-[(E)-2-(7-amino-1-hydroxy-3-sulfonatonaphthalen-2-yl)diazen-1-yl]phenyl}phenyl)diazen-1-yl]-4-hydroxynaphthalene-2,7-disulfonate(Chlorazol Black BH)[CAS: 2429-73-4].The predicted data using the OECD QSAR toolbox has also been compared with the experimental data.

In a prediction done by SSS (2018) using the OECD QSAR toolbox v3.4 with log kow as the primary descriptor, the skin irritation potential was estimated for Octasodium 2,2'-[(2,2'-disulphonato[1,1'-biphenyl]-4,4'-diyl)bis[imino(6-chloro-1,3,5-triazine-4,2-diyl)imino(1-hydroxy-3-sulphonatonaphthalene-6,2-diyl)azo]] bisnaphthalene-1,5-disulphonate. Octasodium 2,2'-[(2,2'-disulphonato[1,1'-biphenyl]-4,4'-diyl)bis[imino(6-chloro-1,3,5-triazine-4,2-diyl)imino(1-hydroxy-3-sulphonatonaphthalene-6,2-diyl)azo]] bisnaphthalene-1,5-disulphonate was estimated to be not irritating to rabbit skin.

A study was performed (Hazardous Substances Databank [HSDB], U.S National Library of Medicine, last updated 2003) in rabbits to determine the dermal irritation potential of the structurally similar read across chemicals,Copper,[tetrahydrogen-3,3'-[(3,3'-dihydroxy-4,4'-biphenylylene)bis(azo)]bis[5-amino-4-hydroxy-2,7-naphthalenedisulfonato](4-)]di-,tetrasodium salt (7CI)(C.I Direct Blue 218)[CAS:28407-37-6]. The study was conducted as per 16 CFR 1500.41 &16 CFR 1500.3 Guidelines.6 New Zealand white rabbits were used for the study. After at least seven days of equilibration, the back and sides of each rabbit were clipped free of fur with an electric clipper. Rabbits with dermal lesions or irritation were replaced. One day after clipping, the left side of the spinal column was abraded (minor incisions which did not disturb the derma or produce bleeding). 0.5 g of the test material was applied to the intact and abraded skin of the back of the rabbits. The material was covered with dry surgical gauze, one inch square, two layers thick. The patches were secured with adhesive tape; the trunk was wrapped with impervious material. After 24 hours, the patches were removed. The dermal reactions were scored by the Draize technique at 24 and 72 hours. The primary dermal index was calculated.

No signs of erythema or edema were observed on the intact and abraded skin of the 6 rabbits after 24 and 72 hours of patch removal.

The Primary Irritation Index was calculated to be 0.0.

Based on the scores and observations, it was concluded that C.I. Direct Blue 218 [CAS: 28407-37-6] was not irritating to skin.

These results are supported by the experimental study summarized in Fiber Reactive Dyes Toxicological Profiles December 1981,PB83-168732; for the structurally similar read across chemical,Hexasodium;4-amino-3-[[4-[[4-chloro-6-(3-sulfonatoanilino)-1,3,5-triazin-2-yl]amino]-2-sulfonatophenyl]diazenyl]-6-[[4-[[4-chloro-6-(3-sulfonatoanilino)-1,3,5-triazin-2-yl]amino]-2 -sulfonatophenyl]hydrazinylidene]-5-oxonaphthalene-2,7-disulfonate(Reactive Green 19)[CAS:61931-49-5]. Reactive Green 19 was applied to the skin of rabbits and observed for signs of irritation (dose, duration not mentioned). No skin irritation effects were observed whenReactive Green 19was applied to rabbit skin.

Hence,Reactive Green 19can be considered to be not irritating to skin.

These results are further supported by the study summarized in OTS0215154, NTRL report, last updated 1983; for the structurally similar read across chemical,trisodium 5-amino-3-[(E)-2 -(4-{4-[(E)-2-(7-amino-1-hydroxy-3-sulfonatonaphthalen-2-yl)diazen-1-yl]phenyl}phenyl)diazen-1-yl]-4-hydroxynaphthalene-2,7 -disulfonate(Chlorazol Black BH)[CAS: 2429-73-4].6 New Zealand white rabbits were used for the study. The backs of the animals were clipped free of hair and the skin examined before testing. Only those animals without skin defects or irritation were used. Abrasions (minor incisions through the stratum corneum, but not sufficiently deep to disturb the derma) were made on one area of the backs while other area was left intact. The animals were immobilized in animal holders. 0.5 gm of a 50% w/v aqueous dilution of Chlorazol Black BH was applied under each of two one-inch square gauze patches to the prepared areas on the back of the animals. After the patches had been secured by adhesive tape, the entire trunk of each animal was wrapped with a plastic binder to keep the material in position and in contact with the skin for 24 hours. Following the 24 hours of exposure, the patches were removed; any remaining material was washed off the treated areas. The test sites were observed at 24 and 72 hours after removal of patches. The dermal reactions were scored by the Draize technique at 24, 72 hours and the Primary Irritation Index (PII) was calculated. The average values for erythema and eschar formation at 24 hours and 72 hours for the intact skin areas of exposure were added to the average values of the abraded skin areas of exposure at 24 hours and 72 hours (four values). Similarly, the average values for edema formation at 24 hours and at 72 hours for the intact and abraded skin areas of exposure were added (four values). The Primary Irritation Index is the total of the eight average values divided by four. According to the F.H.S.A method of testing, a Primary Irritant is a substance which produces a skin reaction resulting in a score of five or greater.

Chlorazol Black BH [CAS: 2429-73-4] when applied as a 50% w/v suspension with deionized water to the intact and abraded skin of New Zealand albino rabbits produced mild skin damage (abraded skin only) which persisted till 72 hours. No gross signs of local irritation were observed in the intact skin throughout the study. A deep bluish- purple was present at the abrasion of each animal at each reading; a light stain of similar color of the intact skin was observed at the 24-hour reading (all animals) and 48 hour reading (4 animals).

The Primary Irritation Index was calculated to be 0.50.According to F.H.S.A method of testing, Chlorazol Black BH [CAS: 2429-73-4] was considered to be not irritating to skin.

Based on the available data for the target and applying the weight of evidence approach, Octasodium 2,2'-[(2,2'-disulphonato[1,1'-biphenyl]-4,4'-diyl)bis[imino(6-chloro-1,3,5-triazine-4,2-diyl)imino(1-hydroxy-3-sulphonatonaphthalene-6,2-diyl)azo]] bisnaphthalene-1,5-disulphonate was 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,Octasodium 2,2'-[(2,2'-disulphonato[1,1'-biphenyl]-4,4'-diyl)bis[imino(6-chloro-1,3,5-triazine-4,2-diyl)imino(1-hydroxy-3-sulphonatonaphthalene-6,2-diyl)azo]] bisnaphthalene-1,5-disulphonatehas been investigated for potential for ocular irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits along with predicted data for target chemicaland its structurally similar read across chemicals, 1,5-Naphthalenedisulfonic acid, 2-[2-[6-[(4,6-dichloro-1,3,5-triazin-2-yl)methylamino]-1-hydroxy-3-sulfo-2-naphthalenyl]diazenyl]-, sodium salt (1:3) (REACTIVE ORANGE 4)[CAS: 12225-82-0] and Trisodium 7-[[4-chloro-6-[(4-sulphonatophenyl)amino]-1,3,5-triazin-2-yl]methylamino]-4-hydroxy-3-[(4-methoxy-2-sulphonatophenyl)azo]naphthalene-2-sulphonate(Reactive Red 33)[CAS: 12237-01-3]. The predicted data using the OECD QSAR toolbox has also been compared with the experimental data.

In a prediction done by SSS (2018) using the OECD QSAR toolbox v3.4 with log kow as the primary descriptor, the eye irritation potential was estimated forOctasodium 2,2'-[(2,2'-disulphonato[1,1'-biphenyl]-4,4'-diyl)bis[imino(6-chloro-1,3,5-triazine-4,2-diyl)imino(1-hydroxy-3-sulphonatonaphthalene-6,2-diyl)azo]] bisnaphthalene-1,5-disulphonate. Octasodium 2,2'-[(2,2'-disulphonato[1,1'-biphenyl]-4,4'-diyl)bis[imino(6-chloro-1,3,5-triazine-4,2-diyl)imino(1-hydroxy-3-sulphonatonaphthalene-6,2-diyl)azo]] bisnaphthalene-1,5-disulphonate was estimated to be not irritating to New Zealand White rabbit eyes.

This result is supported by the experimental studies summarized in Fiber Reactive Dyes Toxicological Profiles December 1981,PB83-168732; for the structurally similar read across chemicals,1,5-Naphthalenedisulfonic acid, 2-[2-[6-[(4,6-dichloro-1,3,5-triazin-2-yl)methylamino]-1-hydroxy-3-sulfo-2-naphthalenyl]diazenyl]-, sodium salt (1:3) (REACTIVE ORANGE 4)[CAS: 12225-82-0] and Trisodium 7-[[4-chloro-6-[(4-sulphonatophenyl)amino]-1,3,5-triazin-2-yl]methylamino]-4-hydroxy-3-[(4-methoxy-2-sulphonatophenyl)azo]naphthalene-2-sulphonate(Reactive Red 33)[CAS: 12237-01-3].

Reactive Red 33 and REACTIVE ORANGE 4were instilled in to the eyes of rabbits and observed for signs of irritation(dose, duration not mentioned). No irritation effects were observed when Reactive Red 33 and REACTIVE ORANGE 4were instilled into rabbit eyes. Hence, Reactive Red 33 andREACTIVE ORANGE 4can be considered to be not irritating to eyes.

Based on the available data for the target and applying the weight of evidence approach, Octasodium 2,2'-[(2,2'-disulphonato[1,1'-biphenyl]-4,4'-diyl)bis[imino(6-chloro-1,3,5-triazine-4,2-diyl)imino(1-hydroxy-3-sulphonatonaphthalene-6,2-diyl)azo]] bisnaphthalene-1,5-disulphonate was 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 Octasodium 2,2'-[(2,2'-disulphonato[1,1'-biphenyl]-4,4'-diyl)bis[imino(6-chloro-1,3,5-triazine-4,2-diyl)imino(1-hydroxy-3-sulphonatonaphthalene-6,2-diyl)azo]] bisnaphthalene-1,5-disulphonate indicates that it is not likely to cause severe irritation or corrosion to eyes and skin.

Hence, Octasodium 2,2'-[(2,2'-disulphonato[1,1'-biphenyl]-4,4'-diyl)bis[imino(6-chloro-1,3,5-triazine-4,2-diyl)imino(1-hydroxy-3-sulphonatonaphthalene-6,2-diyl)azo]] bisnaphthalene-1,5-disulphonate can be classified under the category “Not Classified” for skin and eye irritation as per CLP regulation.