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Description of key information

In a prediction done by SSS (2017) using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor, the skin sensitization 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 sensitizing to skin of guinea pigs.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Remarks:
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
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
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:
guinea pig
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
No data
Route:
epicutaneous, occlusive
Vehicle:
not specified
Concentration / amount:
Not specified
Day(s)/duration:
Not specified
Adequacy of induction:
not specified
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
not specified
Concentration / amount:
Not specified
Day(s)/duration:
Not specified
Adequacy of challenge:
not specified
No. of animals per dose:
Not specified
Details on study design:
Not specified
Challenge controls:
Not specified
Positive control substance(s):
not specified
Vehicle:
not specified
Concentration:
Not specified
No. of animals per dose:
Not specified
Details on study design:
Not specified
Reading:
1st reading
Group:
test chemical
Dose level:
Not specified
Clinical observations:
no indication of skin reaction estimated
Remarks on result:
no indication of skin sensitisation
Cellular proliferation data / Observations:
No indication of skin reaction estimated.

The prediction was based on dataset comprised from the following descriptors: "Skin Sensitisation"
Estimation method: Takes highest 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 ("l" and ( not "m") )  )  and ("n" and ( not "o") )  )  and ("p" and ( not "q") )  )  and ("r" and "s" )  )

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, 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, 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 High (Class III) by Toxic hazard classification by Cramer (original) ONLY

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as H-acceptor-path3-H-acceptor by in vivo mutagenicity (Micronucleus) alerts by ISS

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Hydrazine OR No alert found by in vivo mutagenicity (Micronucleus) alerts by ISS

Domain logical expression index: "n"

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

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Organic sulphonic salts OR Triphenylphosphonium salts by Eye irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "p"

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: "q"

Referential boundary: The target chemical should be classified as Group  3 - Lanthanoids OR Group 12 - Trans.Metals Zn,Cd,Hg OR Group 13 - Metals Al,Ga,In,Tl OR Group 2 - Alkaline Earth Be,Mg,Ca,Sr,Ba,Ra OR Group 9 - Trans.Metals Co,Rh,Ir by Chemical elements

Domain logical expression index: "r"

Parametric boundary:The target chemical should have a value of log Kow which is >= -1.36

Domain logical expression index: "s"

Parametric boundary:The target chemical should have a value of log Kow which is <= 13.4

Interpretation of results:
other: not skin sensitizing
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 skin sensitizing.
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 sensitization 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 sensitizing to skin of guinea pigs.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Skin sensitization:

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 skin sensitization to a greater or lesser extent. The studies are based on in vivo experiments in guinea pigs along with human data for target chemical and its structurally similar read across substancesD&C Green 8(6358-69-6) and closely related read across substancce Disodium 2,2'-([1,1'-biphenyl]-4,4'-diyldivinylene)bis(benzenesulphonate) (27344-41-8) . 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 sensitization 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 sensitizing to skin of guinea pigs.

The above predicted data was supported by experimental study conducted by Contact Dermatitis 2003: 49: 217–218 for thestructurally similar read across substancesD&C Green 8  (6358-69-6)

The sensitization potential of D&C Green 8 was determined by performing patch tests on humans. The dye was applied in Finn Chambers and read first at 2 or (more commonly) 3 days and again at 4–7 days. The reactions of the patients were graded as ‘?+ ‘ , ‘+’ and ‘++’ categories  9 patients were tested with the dye.No reactions were reported by all the patients. D&C Green 8 can be considered as a non- sensitizer in humans.

The above experimental data was further supported by experimental study conducted by HERA targeted risk assessment of FWA-5, May, 2003 for theclosely related read across substancce Disodium 2,2'-([1,1'-biphenyl]-4,4'-diyldivinylene)bis(benzenesulphonate) (27344-41-8)

Disodium 2,2'-([1,1'-biphenyl]-4,4'-diyldivinylene)bis(benzenesulphonate was used as a test material on30 (20 test and 10 control) female albino Guinea pigs to evaluate its skin sensitization potential .

 

The intradermal induction of sensitisation was performed with a 5% dilution of the test article in physiological saline and in an emulsion of Freund's Complete Adjuvant (FCA) / physiological saline.

 

The epidermal induction of sensitisation was conducted under occlusion with the highest non-irritating concentration of test article, 25 % in Vaseline. Two weeks after the epidermal induction application the challenge was completed by epidermal application of the test article at 25 % in Vaseline under occlusive dressing. The animals of the control group were induced with Vaseline and FCA/physiological saline and challenged similarly to those animals of the test group.

 

In this study none (0%) of the animals of the test group were observed with erythematous reactions after treatment with a non-irritant test article concentration of 25 % in Vaseline. No skin reactions were observed in the control group. Therefore, FWA-5 is considered to be a non-sensitiser

 

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 skin sensitizing ; and it can be classified under the category “Not classified” as per CLP regulation.

 

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

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 skin sensitizing ; and it can be classified under the category “Not classified” as per CLP regulation.