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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Description of key information

Skin Irritation:

The dermal irritation potential of Tetrasodium 2,2'-[1,4-phenylenebis[carbonylimino[2-acetamido-4,1-phenylene]azo]]bis[5-[(4-sulphonatophenyl)azo] benzenesulphonate] was estimated using OECD QSAR toolbox version 3.4 with logPow as the primary descriptor.

Tetrasodium 2,2'-[1,4-phenylenebis[carbonylimino[2-acetamido-4,1-phenylene]azo]]bis[5-[(4-sulphonatophenyl)azo] benzenesulphonate] was estimated to be not irritating to the skin of New Zealand White rabbits.

Based on the estimated result; Tetrasodium 2,2'-[1,4-phenylenebis[carbonylimino[2-acetamido-4,1-phenylene]azo]]bis[5-[(4-sulphonatophenyl)azo] benzenesulphonate] 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 Tetrasodium 2,2'-[1,4-phenylenebis[carbonylimino[2-acetamido-4,1-phenylene]azo]]bis[5-[(4-sulphonatophenyl)azo] benzenesulphonate] was estimated using OECD QSAR toolbox version 3.4 with logPow as the primary descriptor.

Tetrasodium 2,2'-[1,4-phenylenebis[carbonylimino[2-acetamido-4,1-phenylene]azo]]bis[5-[(4-sulphonatophenyl)azo] benzenesulphonate] was estimated to be not irritating to the eyes of New Zealand White rabbits.

Based on the estimated result; Tetrasodium 2,2'-[1,4-phenylenebis[carbonylimino[2-acetamido-4,1-phenylene]azo]]bis[5-[(4-sulphonatophenyl)azo] benzenesulphonate] can be considered not irritating to the eyes and can be classified under the category “Not Classified” as per CLP regulation.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification
Justification for type of information:
data is from OECD QSAR toolbox v3.4 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 v 3.3
GLP compliance:
not specified
Specific details on test material used for the study:
- Name of test material: Tetrasodium 2,2'-[1,4-phenylenebis[carbonylimino[2-acetamido-4,1-phenylene]azo]]bis[5-[(4-sulphonatophenyl)azo] benzenesulphonate]
- IUPAC name: Tetrasodium 2-[(E)-2-{2-acetamido-4-[4-({3-acetamido-4-[(E)-2-{2-sulfonato-4-[(E)-2-(4-sulfonatophenyl)diazen-1-yl]phenyl} diazen-1-yl]phenyl}carbamoyl)benzamido]phenyl}diazen-1-yl]-5-[(E)-2-(4-sulfonatophenyl)diazen-1-yl]benzene-1-sulfonate
- Molecular formula: C48H34N12Na4O16S4
- Molecular weight: 1255.09 g/mole
- Smiles : [Na+].[Na+].[Na+].[Na+].c1(ccc(cc1)C(=O)Nc1cc(c(cc1)\N=N\c1c(cc(cc1)\N=N\c1ccc(cc1)S(=O)(=O)[O-])S(=O)(=O)[O-])NC(=O)C)C (=O)Nc1cc(c(cc1)\N=N\c1c(cc(cc1)\N=N\c1ccc(cc1)S(=O)(=O)[O-])S(=O)(=O)[O-])NC(=O)C
- InChl: 1S/C48H38N12O16S4.4Na/c1-27(61)49-43-23-33(11-19-39(43)57-59-41-21-13-35(25-45(41)79(71,72)73)55-53-31-7-15-37(16-8-31) 77(65,66)67)51-47(63)29-3-5-30(6-4-29)48(64)52-34-12-20-40(44(24-34)50-28(2)62)58-60-42-22-14-36(26-46(42)80(74,75)76)56-54-32-9-17-38(18-10-32)78(68,69)70;;;;/h3-26H,1-2H3,(H,49,61)(H,50,62)(H,51,63)(H,52,64)(H,65,66,67)(H,68,69,70)(H,71,72,73)(H,74,75,76);;;;/q;4*+1/p-4/b55-53+,56-54+,59-57+,60-58+;;;;
- 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:
shaved
Vehicle:
not specified
Controls:
not specified
Amount / concentration applied:
0.5 g
Duration of treatment / exposure:
24 hours
Observation period:
7 days
Number of animals:
2
Details on study design:
no data availableo
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
7 d
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
No signs of irritation observed

Estimation method: Takes mode value from the 5 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 ( not "k") )  )  and ("l" and ( not "m") )  )  and "n" )  and ("o" and "p" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Non-covalent interaction AND Non-covalent interaction >> DNA intercalation AND Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide and Aminoalkylamine Side Chain by DNA binding by OASIS v.1.4

Domain logical expression index: "b"

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

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Acylation involving an activated (glucuronidated) carboxamide group AND Acylation >> Acylation involving an activated (glucuronidated) carboxamide group >> Carboxylic Acid Amides AND Acylation >> Direct acylation involving a leaving group AND Acylation >> Direct acylation involving a leaving group >> Carboxylic Acid Amides AND Acylation >> Ester aminolysis AND Acylation >> Ester aminolysis >> Amides AND AN2 AND AN2 >> Michael-type addition to quinoid structures  AND AN2 >> Michael-type addition to quinoid structures  >> Carboxylic Acid Amides by Protein binding by OASIS v1.4

Domain logical expression index: "d"

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

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Acid moiety AND Amides AND Salt by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Non-covalent interaction AND Non-covalent interaction >> DNA intercalation AND Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide and Aminoalkylamine Side Chain by DNA binding by OASIS v.1.4

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 and Trihydroxybenzenes OR AN2 >> Carbamoylation after isocyanate formation OR AN2 >> Carbamoylation after isocyanate formation >> N-Hydroxylamines OR AN2 >> Michael-type addition on alpha, beta-unsaturated carbonyl compounds OR AN2 >> Michael-type addition on alpha, beta-unsaturated carbonyl compounds >> Four- and Five-Membered Lactones OR AN2 >> Schiff base formation OR AN2 >> Schiff base formation >> Dicarbonyl compounds OR AN2 >> Schiff base formation >> Polarized Haloalkene Derivatives OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation >> Geminal Polyhaloalkane Derivatives OR AN2 >> Shiff base formation after aldehyde release OR AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters OR AN2 >> Thioacylation via nucleophilic addition after cysteine-mediated thioketene formation OR AN2 >> Thioacylation via nucleophilic addition after cysteine-mediated thioketene formation >> Haloalkenes with Electron-Withdrawing Groups OR AN2 >> Thioacylation via nucleophilic addition after cysteine-mediated thioketene formation >> Polarized Haloalkene Derivatives OR No alert found OR Non-covalent interaction >> DNA intercalation >> Amino Anthraquinones OR Non-covalent interaction >> DNA intercalation >> Coumarins OR Non-covalent interaction >> DNA intercalation >> Fused-Ring Primary Aromatic Amines OR Non-covalent interaction >> DNA intercalation >> N-Hydroxyethyl Lactams OR Non-covalent interaction >> DNA intercalation >> Organic Azides OR Non-covalent interaction >> DNA intercalation >> Polycyclic Aromatic Hydrocarbon and Naphthalenediimide Derivatives OR Non-covalent interaction >> DNA intercalation >> Quinones and Trihydroxybenzenes OR Non-specific OR Non-specific >> Incorporation into DNA/RNA, due to structural analogy with  nucleoside bases    OR Non-specific >> Incorporation into DNA/RNA, due to structural analogy with  nucleoside bases    >> Specific Imine and Thione Derivatives OR Radical OR Radical >> Generation of ROS by glutathione depletion (indirect) OR Radical >> Generation of ROS by glutathione depletion (indirect) >> Haloalkanes Containing Heteroatom OR Radical >> Radical mechanism by ROS formation OR Radical >> Radical mechanism by ROS formation >> Organic Azides OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Amino Anthraquinones OR Radical >> Radical mechanism via ROS formation (indirect) >> Coumarins OR Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Geminal Polyhaloalkane Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> N-Hydroxylamines OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitro Azoarenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroaniline Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroarenes with Other Active Groups OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR Radical >> Radical mechanism via ROS formation (indirect) >> p-Substituted Mononitrobenzenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Quinones and Trihydroxybenzenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Specific Imine and Thione Derivatives OR SN1 OR SN1 >> Alkylation after metabolically formed carbenium ion species OR SN1 >> Alkylation after metabolically formed carbenium ion species >> Polycyclic Aromatic Hydrocarbon and Naphthalenediimide Derivatives OR SN1 >> Nucleophilic attack after carbenium ion formation OR SN1 >> Nucleophilic attack after carbenium ion formation >> Specific Acetate Esters OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Amino Anthraquinones OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Fused-Ring Primary Aromatic Amines OR SN1 >> Nucleophilic attack after nitrene formation OR SN1 >> Nucleophilic attack after nitrene formation >> Organic Azides OR SN1 >> Nucleophilic attack after nitrenium ion formation OR SN1 >> Nucleophilic attack after nitrenium ion formation >> N-Hydroxylamines OR SN1 >> Nucleophilic attack after nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitro Azoarenes OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitroaniline Derivatives OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> p-Substituted Mononitrobenzenes OR SN1 >> Nucleophilic substitution on diazonium ion OR SN1 >> Nucleophilic substitution on diazonium ion >> Specific Imine and Thione Derivatives OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> N-Hydroxylamines OR SN2 >> Acylation >> Specific Acetate Esters OR SN2 >> Acylation involving a leaving group after metabolic activation OR SN2 >> Acylation involving a leaving group after metabolic activation >> Geminal Polyhaloalkane Derivatives OR SN2 >> Alkylation, direct acting epoxides and related OR SN2 >> Alkylation, direct acting epoxides and related >> Epoxides and Aziridines OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation >> Haloalkenes with Electron-Withdrawing Groups OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation >> Polarized Haloalkene Derivatives OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation >> Polycyclic Aromatic Hydrocarbon and Naphthalenediimide Derivatives OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Haloalkanes Containing Heteroatom OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Sulfonates and Sulfates OR SN2 >> Alkylation, ring opening SN2 reaction OR SN2 >> Alkylation, ring opening SN2 reaction >> Four- and Five-Membered Lactones OR SN2 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Coumarins OR SN2 >> Direct acting epoxides formed after metabolic activation >> Quinoline Derivatives OR SN2 >> Direct acylation involving a leaving group OR SN2 >> Direct acylation involving a leaving group >> Acyl Halides OR SN2 >> DNA alkylation OR SN2 >> DNA alkylation >> Vicinal Dihaloalkanes OR SN2 >> Internal SN2 reaction with aziridinium and/or cyclic sulfonium ion formation (enzymatic) OR SN2 >> Internal SN2 reaction with aziridinium and/or cyclic sulfonium ion formation (enzymatic) >> Vicinal Dihaloalkanes OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Haloalkanes Containing Heteroatom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate Esters OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation >> Geminal Polyhaloalkane Derivatives OR SN2 >> SN2 at an activated carbon atom OR SN2 >> SN2 at an activated carbon atom >> Quinoline Derivatives OR SN2 >> SN2 at sp3 and activated sp2 carbon atom OR SN2 >> SN2 at sp3 and activated sp2 carbon atom >> Polarized Haloalkene Derivatives OR SN2 >> SN2 at sulfur atom OR SN2 >> SN2 at sulfur atom >> Sulfonyl Halides 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.1.4

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Acylation involving an activated (glucuronidated) carboxamide group AND Acylation >> Acylation involving an activated (glucuronidated) carboxamide group >> Carboxylic Acid Amides AND Acylation >> Direct acylation involving a leaving group AND Acylation >> Direct acylation involving a leaving group >> Carboxylic Acid Amides AND Acylation >> Ester aminolysis AND Acylation >> Ester aminolysis >> Amides AND AN2 AND AN2 >> Michael-type addition to quinoid structures  AND AN2 >> Michael-type addition to quinoid structures  >> Carboxylic Acid Amides by Protein binding by OASIS v1.4

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Acylation >> Acylation involving an activated (glucuronidated) ester group OR Acylation >> Acylation involving an activated (glucuronidated) ester group >> Arenecarboxylic Acid Esters OR Acylation >> Acylation involving an activated (glucuronidated) sulfonamide group OR Acylation >> Acylation involving an activated (glucuronidated) sulfonamide group >> Arenesulfonamides OR AN2 >> Michael-type addition to quinoid structures  >> Substituted Anilines OR AN2 >> Michael-type addition to quinoid structures  >> Substituted Phenols OR AN2 >> Nucleophilic addition at polarized N-functional double bond OR AN2 >> Nucleophilic addition at polarized N-functional double bond >> Arenesulfonamides OR Schiff base formation OR Schiff base formation >> Schiff base formation with carbonyl compounds OR Schiff base formation >> Schiff base formation with carbonyl compounds >> Aldehydes OR SN2 OR SN2 >> Interchange reaction with sulphur containing compounds OR SN2 >> Interchange reaction with sulphur containing compounds >> Thiols and disulfide compounds  by Protein binding by OASIS v1.4

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Inclusion rules not met by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Esters of organic sulfonic or sulfuric esters OR Ketones OR Phenols by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "l"

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: "m"

Referential boundary: The target chemical should be classified as Group 17 - Halogens I by Chemical elements

Domain logical expression index: "n"

Similarity boundary:Target: CC(=O)Nc1cc(NC(=O)c2ccc(C(=O)Nc3ccc(N=Nc4ccc(N=Nc5ccc(S(=O)(=O)O{-}.[Na]{+})cc5)cc4S(=O)(=O)O{-}.[Na]{+})c(NC(C)=O)c3)cc2)ccc1N=Nc1ccc(N=Nc2ccc(S(=O)(=O)O{-}.[Na]{+})cc2)cc1S(=O)(=O)O{-}.[Na]{+}
Threshold=40%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.00691

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.1

Interpretation of results:
other: not irritating
Conclusions:
Tetrasodium 2,2'-[1,4-phenylenebis[carbonylimino[2-acetamido-4,1-phenylene]azo]]bis[5-[(4-sulphonatophenyl)azo] benzenesulphonate] was estimated to be not irritating to the skin of New Zealand White rabbits.
Executive summary:

The dermal irritation potential of Tetrasodium 2,2'-[1,4-phenylenebis[carbonylimino[2-acetamido-4,1-phenylene]azo]]bis[5-[(4-sulphonatophenyl)azo] benzenesulphonate] was estimated using OECD QSAR toolbox version 3.4 with logPow as the primary descriptor.

Tetrasodium 2,2'-[1,4-phenylenebis[carbonylimino[2-acetamido-4,1-phenylene]azo]]bis[5-[(4-sulphonatophenyl)azo] benzenesulphonate] was estimated to be not irritating to the skin of New Zealand White rabbits.

Based on the estimated result; Tetrasodium 2,2'-[1,4-phenylenebis[carbonylimino[2-acetamido-4,1-phenylene]azo]]bis[5-[(4-sulphonatophenyl)azo] benzenesulphonate] can be considered not irritating to skin and can be classified under the category “Not Classified” as per CLP regulation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification
Justification for type of information:
data is from OECD QSAR toolbox v3.4 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 v3.4
GLP compliance:
not specified
Specific details on test material used for the study:
- Name of test material: Tetrasodium 2,2'-[1,4-phenylenebis[carbonylimino[2-acetamido-4,1-phenylene]azo]]bis[5-[(4-sulphonatophenyl)azo] benzenesulphonate]
- IUPAC name: Tetrasodium 2-[(E)-2-{2-acetamido-4-[4-({3-acetamido-4-[(E)-2-{2-sulfonato-4-[(E)-2-(4-sulfonatophenyl)diazen-1-yl]phenyl} diazen-1-yl]phenyl}carbamoyl)benzamido]phenyl}diazen-1-yl]-5-[(E)-2-(4-sulfonatophenyl)diazen-1-yl]benzene-1-sulfonate
- Molecular formula: C48H34N12Na4O16S4
- Molecular weight: 1255.09 g/mole
- Smiles : [Na+].[Na+].[Na+].[Na+].c1(ccc(cc1)C(=O)Nc1cc(c(cc1)\N=N\c1c(cc(cc1)\N=N\c1ccc(cc1)S(=O)(=O)[O-])S(=O)(=O)[O-])NC(=O)C)C (=O)Nc1cc(c(cc1)\N=N\c1c(cc(cc1)\N=N\c1ccc(cc1)S(=O)(=O)[O-])S(=O)(=O)[O-])NC(=O)C
- InChl: 1S/C48H38N12O16S4.4Na/c1-27(61)49-43-23-33(11-19-39(43)57-59-41-21-13-35(25-45(41)79(71,72)73)55-53-31-7-15-37(16-8-31) 77(65,66)67)51-47(63)29-3-5-30(6-4-29)48(64)52-34-12-20-40(44(24-34)50-28(2)62)58-60-42-22-14-36(26-46(42)80(74,75)76)56-54-32-9-17-38(18-10-32)78(68,69)70;;;;/h3-26H,1-2H3,(H,49,61)(H,50,62)(H,51,63)(H,52,64)(H,65,66,67)(H,68,69,70)(H,71,72,73)(H,74,75,76);;;;/q;4*+1/p-4/b55-53+,56-54+,59-57+,60-58+;;;;
- 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:
100mg
Duration of treatment / exposure:
24 hours
Observation period (in vivo):
72 hours
Duration of post- treatment incubation (in vitro):
no data available
Number of animals or in vitro replicates:
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 signs of 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" or "e" )  and ("f" and ( not "g") )  )  and ("h" and ( not "i") )  )  and ("j" and ( not "k") )  )  and ("l" and ( not "m") )  )  and ("n" and ( not "o") )  )  and ("p" and "q" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Non-covalent interaction AND Non-covalent interaction >> DNA intercalation AND Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide and Aminoalkylamine Side Chain by DNA binding by OASIS v.1.4

Domain logical expression index: "b"

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

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Acylation involving an activated (glucuronidated) carboxamide group AND Acylation >> Acylation involving an activated (glucuronidated) carboxamide group >> Carboxylic Acid Amides AND Acylation >> Direct acylation involving a leaving group AND Acylation >> Direct acylation involving a leaving group >> Carboxylic Acid Amides AND Acylation >> Ester aminolysis AND Acylation >> Ester aminolysis >> Amides AND AN2 AND AN2 >> Michael-type addition to quinoid structures  AND AN2 >> Michael-type addition to quinoid structures  >> Carboxylic Acid Amides by Protein binding by OASIS v1.4

Domain logical expression index: "d"

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

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Acid moiety AND Amides AND Salt by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "f"

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

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Direct Addition of an Acyl Halide OR Acylation >> Direct Addition of an Acyl Halide >> Acyl halide OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates >> Formamides OR Michael addition OR Michael addition >> P450 Mediated Activation of Heterocyclic Ring Systems OR Michael addition >> P450 Mediated Activation of Heterocyclic Ring Systems >> Furans OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Alkyl phenols OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Arenes OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Hydroquinones OR Michael addition >> Polarised Alkenes-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated amides OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated esters OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated ketones OR No alert found OR Schiff base formers OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal  OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal  >> Ethanolamines (including morpholine) OR SN1 >> Carbenium Ion Formation OR SN1 >> Carbenium Ion Formation >> Allyl benzenes OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation >> Aromatic nitro OR SN1 >> Nitrenium Ion formation >> Aromatic phenylureas OR SN1 >> Nitrenium Ion formation >> Primary (unsaturated) heterocyclic amine OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine OR SN1 >> Nitrenium Ion formation >> Unsaturated heterocyclic azo OR SN2 OR SN2 >> P450 Mediated Epoxidation OR SN2 >> P450 Mediated Epoxidation >> Coumarins OR SN2 >> SN2 at an sp3 Carbon atom OR SN2 >> SN2 at an sp3 Carbon atom >> Aliphatic halides OR SN2 >> SN2 at an sp3 Carbon atom >> Sulfonates by DNA binding by OECD

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as No alert found by Protein binding alerts for Chromosomal aberration by OASIS v.1.2

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Acylation involving an activated (glucuronidated) carboxamide group OR Acylation >> Acylation involving an activated (glucuronidated) carboxamide group >> Carboxylic Acid Amides OR Acylation >> Direct acylation involving a leaving group OR Acylation >> Direct acylation involving a leaving group >> Carboxylic Acid Amides OR AN2 OR AN2 >> Michael addition to the quinoid type structures OR AN2 >> Michael addition to the quinoid type structures >> Carboxylic Acid Amides OR AN2 >> Michael addition to the quinoid type structures >> N-Subsituted Aromatic Amines by Protein binding alerts for Chromosomal aberration by OASIS v.1.2

Domain logical expression index: "j"

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

Domain logical expression index: "k"

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

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Aryl AND Azo AND Benzamide AND Organic amide and thioamide AND Sulfonic acid by Organic Functional groups

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Alkyl arenes by Organic Functional groups

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Aryl AND Azo AND Benzamide AND Organic amide and thioamide AND Sulfonic acid by Organic Functional groups

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Triazine by Organic Functional groups

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.295

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.84

Interpretation of results:
other: not irritating
Conclusions:
Tetrasodium 2,2'-[1,4-phenylenebis[carbonylimino[2-acetamido-4,1-phenylene]azo]]bis[5-[(4-sulphonatophenyl)azo] benzenesulphonate] was estimated to be not irritating to the eyes of New Zealand White rabbits.
Executive summary:

The ocular irritation potential of Tetrasodium 2,2'-[1,4-phenylenebis[carbonylimino[2-acetamido-4,1-phenylene]azo]]bis[5-[(4-sulphonatophenyl)azo] benzenesulphonate] was estimated using OECD QSAR toolbox version 3.4 with logPow as the primary descriptor.

Tetrasodium 2,2'-[1,4-phenylenebis[carbonylimino[2-acetamido-4,1-phenylene]azo]]bis[5-[(4-sulphonatophenyl)azo] benzenesulphonate] was estimated to be not irritating to the eyes of New Zealand White rabbits.

Based on the estimated result; Tetrasodium 2,2'-[1,4-phenylenebis[carbonylimino[2-acetamido-4,1-phenylene]azo]]bis[5-[(4-sulphonatophenyl)azo] benzenesulphonate] can be considered not irritating to the eyes and can be classified under the category “Not Classified” as per CLP regulation.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation:

Various studies have been investigated to ascertain the dermal irritation potential of chemical, Tetrasodium 2,2'-[1,4-phenylenebis[carbonylimino[2-acetamido-4,1-phenylene]azo]]bis[5-[(4-sulphonatophenyl)azo] benzenesulphonate]. These include in vivo experiments in rabbits for the target chemical as well as 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], 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] andDisodium 6-hydroxy-5-[(4-sulfonatophenyl)diazenyl]naphthalene-2-sulfonate(Sunset Yellow FCF)[CAS: 2783-94-0]. The experimental results have also been compared with the predictions obtained from OECD QSAR toolbox.

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 test chemical, Tetrasodium 2,2'-[1,4-phenylenebis[carbonylimino[2-acetamido-4,1-phenylene]azo]]bis[5-[(4-sulphonatophenyl)azo] benzenesulphonate]. Tetrasodium 2,2'-[1,4-phenylenebis[carbonylimino[2 -acetamido-4,1-phenylene]azo]]bis[5-[(4-sulphonatophenyl)azo] benzenesulphonate] was estimated to be not irritating to skin of New Zealand White rabbits.

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 thestructurally 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.

The above studies are further supported by the experimental study summarized in BIBRA Report (1995), (Order No. BIBRA196GAR), 6 pp, for the structurally similar read across chemical, Disodium 6-hydroxy-5-[(4-sulfonatophenyl)diazenyl]naphthalene-2-sulfonate(Sunset Yellow FCF)[CAS: 2783-94-0]. Sunset Yellow FCF in petrolatum or as a aqueous solution was applied to the skin of rabbits and observed for signs of irritation (duration, dose, number of animals not mentioned). Sunset Yellow FCF did not cause any irritation to rabbit skin.

Hence, Sunset Yellow FCF can be considered to be not irritating to skin.

These results are also 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, Tetrasodium 2,2'-[1,4-phenylenebis[carbonylimino[2-acetamido-4,1-phenylene]azo]]bis[5-[(4 -sulphonatophenyl)azo] benzenesulphonate] 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:

Various studies have been investigated to ascertain the ocular irritation potential of chemical, Tetrasodium 2,2'-[1,4-phenylenebis[carbonylimino[2-acetamido-4,1-phenylene]azo]]bis[5 -[(4-sulphonatophenyl)azo] benzenesulphonate]. These include in vivo experiments in rabbits for the target chemical as well as its structurally similar read across chemicals, Trisodium 5-hydroxy-1-(4-sulphophenyl)-4-(4-sulphophenylazo)pyrazole-3-carboxylate(Tartrazine)[CAS: 1934-21-0] and Benzenesulfonic acid, 2,2'-(1,2-ethenediyl)bis[5-nitro-, disodium salt, reaction products with 4-[(4-aminophenyl)azo]benzenesulfonic acid, sodium salts(C.I. Direct Orange 39)[CAS: 1325-54-8]. The experimental results have also been compared with the predictions obtained from OECD QSAR toolbox.

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 for test chemical, Tetrasodium 2,2'-[1,4-phenylenebis[carbonylimino[2-acetamido-4,1-phenylene]azo]]bis[5-[(4-sulphonatophenyl)azo] benzenesulphonate]. Tetrasodium 2,2'-[1,4-phenylenebis[carbonylimino[2 -acetamido-4,1-phenylene]azo]]bis[5-[(4-sulphonatophenyl)azo] benzenesulphonate] was estimated to be not irritating to eyes of New Zealand White rabbits.

A study was performed by S.D. Gettings et.al, 1992 to determine the ocular irritation potential of the structurally similar read across chemical,Trisodium 5-hydroxy-1-(4-sulphophenyl)-4 -(4-sulphophenylazo)pyrazole-3-carboxylate(Tartrazine)[CAS: 1934-21-0].The study was performed according to a modification of the Draize test (Draize, 1959).

Tartrazine (FD & C Yellow No. 5) was prepared daily as a 3% (w/v) suspension in aqueous vehicle containing 0.5% (w/v) hydroxypropyl methylcellulose and 0.25% (w/v) laureth -10 acetate. Tartrazine (FD & C Yellow No. 5) 3% w/v in aqueous vehicle was administered once daily, for a total of 21 days, to the conjunctival sac of the right eye of New Zealand White Rabbits (6 of each sex/ group) at a dose volume of 30µl. Control animals (6 of each sex) received 30/µl of the vehicle daily. Ocular irritation was determined according to a modification of the Draize test (Draize, 1959). Interpretation of observations and assignment of scores were consistent with those described by the Consumer Product Safety Commission (1972).All eyes were scored for ocular irritation pretest (8 days, 24 hr and immediately prior to the initial dose) and approximately 24 hr after each treatment, prior to the next instillation of test material; on days 1, 3, 7, 14 and 21, the eyes were also evaluated for irritation 1 hr after treatment. In addition, all readily observable ocular structures were evaluated for eye stain and particle embedment 24 hr after each treatment.

No lethality or significant clinical signs, and no substance-related weight change were observed. Except slight conjunctival redness or discharge, that were seen sporadically in the eyes of the animals, all animals were free of significant signs of ocular irritation. No significant signs of eye staining or particle depositions were observed. At ophthalmoscopic examinations, no ocular abnormities were noticed.

Hence, FD&C Yellow No.5 (tartrazine) was not expected to cause any irritant effects following repeated exposure to rabbit eyes.

The above results are supported by the experimental study summarized in Scientific Committee on Cosmetology (seventh series),1988; for the structurally similar read across chemical,Benzenesulfonic acid, 2,2'-(1,2-ethenediyl)bis[5-nitro-, disodium salt, reaction products with 4-[(4-aminophenyl)azo]benzenesulfonic acid, sodium salts(C.I. Direct Orange 39)[CAS: 1325-54-8].

0.1 ml of 2% aqueous solution of C.I. Direct Orange 39[CAS: 1325-54-8] was instilled in the eyes of guinea pigs and observed for effects (dose duration and observation period not mentioned).

No signs of irritation were observed when guinea pigs were exposed to 2% aqueous solution of C.I. Direct Orange 39[CAS: 1325-54-8].

Hence, C.I. Direct Orange 39[CAS: 1325-54-8] can be considered to be not irritating to eyes.

Based on the available data for the target and applying the weight of evidence approach, Tetrasodium 2,2'-[1,4-phenylenebis[carbonylimino[2-acetamido-4,1-phenylene]azo]]bis[5-[(4-sulphonatophenyl)azo] benzenesulphonate] 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”.

Justification for classification or non-classification

Available data for Tetrasodium 2,2'-[1,4-phenylenebis[carbonylimino[2-acetamido-4,1-phenylene]azo]]bis[5-[(4-sulphonatophenyl)azo] benzenesulphonate] indicates that it is not likely to cause severe irritation or corrosion to eyes and skin.

Hence, Tetrasodium 2,2'-[1,4-phenylenebis[carbonylimino[2-acetamido-4,1-phenylene]azo]]bis[5-[(4-sulphonatophenyl)azo] benzenesulphonate] can be classified under the category “Not Classified” for skin and eye irritation as per CLP regulation.