Trisodium [2-[[α-[[2-hydroxy-5-sulpho-3-[(2,5,6-trichloro-4-pyrimidinyl)amino]phenyl]azo]benzyl]azo]-5-sulphobenzoato(5-)]cuprate(3-)

Endpoint summary

Description of key information

Skin sensitization:

The skin sensitization potential of Trisodium [2-[[alpha-[[2-hydroxy-5-sulpho-3-[(2,5,6-trichloro- 4-pyrimidinyl)amino]phenyl]azo]benzyl]azo]-5-sulphobenzoato(5-)]cupra was estimated using OECD QSAR toolbox v 3.4 with logPow as the primary descriptor. Trisodium [2-[[alpha-[[2-hydroxy-5-sulpho-3-[(2,5,6-trichloro- 4-pyrimidinyl)amino]phenyl]azo]benzyl]azo]-5-sulphobenzoato(5-)]cupra was estimated to be not sensitizing to the skin of  guinea pig. Based on the estimated results, Trisodium [2-[[alpha-[[2-hydroxy-5-sulpho-3-[(2,5,6-trichloro- 4-pyrimidinyl)amino]phenyl]azo]benzyl]azo]-5-sulphobenzoato(5-)]cupra can be considered to be not sensitizing to skin and can be classified under the category “ Not Classified ” as per CLP regulation.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification

Justification for type of information:

Data is predicted using OECD QSAR toolbox version 3.4 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 v3.4

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 the test material: Trisodium [2-[[alpha-[[2-hydroxy-5-sulpho-3-[(2,5,6-trichloro- 4-pyrimidinyl)amino]phenyl]azo]benzyl]azo]-5-sulphobenzoato(5-)]cupra
- IUPAC name: Trisodium [2-[[alpha-[[2-hydroxy-5-sulpho-3-[(2,5,6-trichloro- 4-pyrimidinyl)amino]phenyl]azo]benzyl]azo]-5-sulphobenzoato(5-)]cupra
- Molecular weight: No data
- Molecular formula: C24H11Cl3CuN7O9S2.3Na
-substance type: organic
-physical state: solid
- Smiles:OS(=O)(=O)c1ccc2c(c1)C(=O)O{-}.[Cu]{2+}13N2=NC(c2ccccc2)N=N1c1cc(S(O)(=O)=O)cc(Nc2c(Cl)c(Cl)nc(Cl)n2)c1O{-}.3

Species:

guinea pig

Strain:

not specified

Sex:

not specified

Details on test animals and environmental conditions:

No data available

Route:

other: Not specified

Vehicle:

not specified

Concentration / amount:

Not specified

Day(s)/duration:

Not specified

Adequacy of induction:

not specified

No.:

#1

Route:

other: Not specified

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

Reading:

1st reading

Group:

test chemical

Dose level:

Not specified

Clinical observations:

Not specified

Remarks on result:

no indication of skin sensitisation

The prediction was based on dataset comprised from the following descriptors: "Skin Sensitisation"
Estimation method: Takes highest mode value from the 6 nearest neighbours
Domain  logical expression:Result: In Domain

((((((((("a" or "b" or "c" )  and ("d" and ( not "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 ( not "q") )  )  and ("r" and "s" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Michael addition AND Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals AND Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Arenes by DNA binding by OECD

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as SNAr AND SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds AND SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds >> Activated aryl and heteroaryl compounds by Protein binding by OASIS v1.4

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as SNAr AND SNAr >> Nucleophilic aromatic substitution AND SNAr >> Nucleophilic aromatic substitution >> Halo-pyrimidines by Protein binding by OECD

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.4

Domain logical expression index: "e"

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 >> 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 Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> Fused-Ring Primary Aromatic Amines 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) >> Geminal Polyhaloalkane Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitro Azoarenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroarenes with Other Active Groups OR Radical >> Radical mechanism via ROS formation (indirect) >> Polynitroarenes OR Radical >> ROS formation after GSH depletion (indirect) OR Radical >> ROS formation after GSH depletion (indirect) >> Haloalcohols OR Radical >> ROS formation after GSH depletion (indirect) >> Quinoneimines OR SN1 OR SN1 >> Carbenium ion formation OR SN1 >> Carbenium ion formation >> Alpha-Haloethers OR SN1 >> Nucleophilic attack after carbenium ion formation OR SN1 >> Nucleophilic attack after carbenium ion formation >> Specific Acetate Esters OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Fused-Ring 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 >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Polynitroarenes OR SN2 OR SN2 >> Acylation 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 by epoxide metabolically formed after E2 reaction OR SN2 >> Alkylation by epoxide metabolically formed after E2 reaction >> Haloalcohols OR SN2 >> Alkylation, direct acting epoxides and related OR SN2 >> Alkylation, direct acting epoxides and related >> Epoxides and Aziridines OR SN2 >> Nucleophilic substitution at sp3 Carbon atom 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 sp3-carbon atom OR SN2 >> SN2 at sp3-carbon atom >> Alpha-Haloethers OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 >> Nitroarenes with Other Active Groups by DNA binding by OASIS v.1.4

Domain logical expression index: "f"

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

Domain logical expression index: "g"

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

Domain logical expression index: "h"

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

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Highly reactive (GSH) OR Highly reactive (GSH) >> Alkyl vinyl sulfones (MA) by Protein binding potency

Domain logical expression index: "j"

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: "k"

Referential boundary: The target chemical should be classified as Known precedent reproductive and developmental toxic potential OR Metal atoms were identified OR Metals (1a) OR Not covered by current version of the decision tree OR Toluene and small alkyl toluene derivatives (8a) by DART scheme v.1.0

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Aromatic amine AND Aromatic heterocyclic halide AND Aryl AND Aryl halide AND Carboxylic acid AND Fused carbocyclic aromatic AND Fused saturated heterocycles AND Fused unsaturated heterocycles AND N-Alkyldiazene AND Phenol AND Pyrimidine AND Sulfonic acid AND Unsaturated heterocyclic fragment by Organic Functional groups

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Carboxylic acid ester by Organic Functional groups

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Aromatic amine AND Aromatic heterocyclic halide AND Aryl AND Aryl halide AND Carboxylic acid AND Fused carbocyclic aromatic AND Fused saturated heterocycles AND Fused unsaturated heterocycles AND N-Alkyldiazene AND Phenol AND Pyrimidine AND Sulfonic acid AND Unsaturated heterocyclic fragment by Organic Functional groups

Domain logical expression index: "o"

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

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Aromatic amine AND Aromatic heterocyclic halide AND Aryl AND Aryl halide AND Carboxylic acid AND Fused carbocyclic aromatic AND Fused saturated heterocycles AND Fused unsaturated heterocycles AND N-Alkyldiazene AND Phenol AND Pyrimidine AND Sulfonic acid AND Unsaturated heterocyclic fragment by Organic Functional groups

Domain logical expression index: "q"

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

Domain logical expression index: "r"

Parametric boundary:The target chemical should have a value of log Kow which is >= -17.6

Domain logical expression index: "s"

Parametric boundary:The target chemical should have a value of log Kow which is <= 0.438

Interpretation of results:

other: Not sensitizing

Conclusions:

Trisodium [2-[[alpha-[[2-hydroxy-5-sulpho-3-[(2,5,6-trichloro- 4-pyrimidinyl)amino]phenyl]azo]benzyl]azo]-5-sulphobenzoato(5-)]cupra was considered to be not sensitizing to guinea pig skin

Executive summary:

The skin sensitization potential of Trisodium [2-[[alpha-[[2-hydroxy-5-sulpho-3-[(2,5,6-trichloro- 4-pyrimidinyl)amino]phenyl]azo]benzyl]azo]-5-sulphobenzoato(5-)]cupra was estimated using OECD QSAR toolbox v 3.4 with logPow as the primary descriptor. Trisodium [2-[[alpha-[[2-hydroxy-5-sulpho-3-[(2,5,6-trichloro- 4-pyrimidinyl)amino]phenyl]azo]benzyl]azo]-5-sulphobenzoato(5-)]cupra was estimated to be not sensitizing to the skin of  guinea pig. Based on the estimated results, Trisodium [2-[[alpha-[[2-hydroxy-5-sulpho-3-[(2,5,6-trichloro- 4-pyrimidinyl)amino]phenyl]azo]benzyl]azo]-5-sulphobenzoato(5-)]cupra can be considered to be not sensitizing to skin and can be classified under the category “ Not Classified ” as per CLP regulation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Skin sensitization:

In different studies, Trisodium [2-[[alpha-[[2-hydroxy-5-sulpho-3-[(2,5,6-trichloro- 4-pyrimidinyl)amino]phenyl]azo]benzyl]azo]-5-sulphobenzoato(5-)]cupra has been investigated for potential for skin sensitization to a greater or lesser extent. The studies are based on in vivo experiments in guinea pig along with human data for target chemical Trisodium [2-[[alpha-[[2-hydroxy-5-sulpho-3-[(2,5,6-trichloro- 4-pyrimidinyl)amino]phenyl]azo]benzyl]azo]-5-sulphobenzoato(5-)]cupra and its functionally similar read across substance 2,7-Naphthalenedisulfonic acid, 5-[[4-chloro-6-[(3-sulfophenyl)amino]-1,3,5-triazin-2-yl]amino]-4-hydroxy-3-[2-[4-[[2-(sulfooxy)ethyl] sulfonyl]phenyl]diazenyl]-, sodium salt (1:4) (1405017-98-7). The predicted data using the OECD QSAR toolbox has also been compared with the experimental data.

The skin sensitization potential of Trisodium [2-[[alpha-[[2-hydroxy-5-sulpho-3-[(2,5,6-trichloro- 4-pyrimidinyl)amino]phenyl]azo]benzyl]azo]-5-sulphobenzoato(5-)]cupra was estimated using OECD QSAR toolbox v 3.4 with logPow as the primary descriptor. Trisodium [2-[[alpha-[[2-hydroxy-5-sulpho-3-[(2,5,6-trichloro- 4-pyrimidinyl)amino]phenyl]azo]benzyl]azo]-5-sulphobenzoato(5-)]cupra was estimated to be not sensitizing to the skin of  guinea pig. Based on the estimated results, Trisodium [2-[[alpha-[[2-hydroxy-5-sulpho-3-[(2,5,6-trichloro- 4-pyrimidinyl)amino]phenyl]azo]benzyl]azo]-5-sulphobenzoato(5-)]cupra can be considered to be not sensitizing to skin and can be classified under the category “ Not Classified ” as per CLP regulation.

The above predicted data was further supported by experimental data summarized in Contact Dermatitis volume 35 page no. 313 1996 by Bianca Maria Manzini et.al. 2,7-Naphthalenedisulfonic acid, 5-[[4-chloro-6-[(3-sulfophenyl)amino]- 1,3,5-triazin-2-yl]amino]-4-hydroxy-3-[2-[4-[[2-(sulfooxy) ethyl]sulfonyl]phenyl]diazenyl]-, sodium salt (1:4) was used as a test material to evaluate skin sensitization potential on healty skin of 321 patientsadmitted to Allergological Services.

 

  The test material was applied on the back of the patients which was installed in Finn chambers on Scanpor tape for the patch test in the concentration 5% on 119 patients and 10% on 193 patients diluted in petrolatum.

 

The exposure duration was 3 days and the observations were made 3 hrs after removal of the test material on day 4 .The test material produced no skin allergic reaction. Hence, 2,7-Naphthalenedisulfonic acid, 5-[[4-chloro-6-[(3-sulfophenyl)amino] -1,3,5-triazin-2-yl]amino]-4-hydroxy- 3 - [2-[4-[[2-(sulfooxy)ethyl]sulfonyl]phenyl]diazenyl]-, sodium salt (1:4) was considered to be not skin sensitizing.

Based on the available data for the target and read across substances and applying the weight of evidence approach,Trisodium [2-[[alpha-[[2-hydroxy-5-sulpho-3-[(2,5,6-trichloro- 4-pyrimidinyl)amino]phenyl]azo]benzyl]azo]-5-sulphobenzoato(5-)]cupra can be considered to be not sensitizing to skin.Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

 

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the available data for the target and read across substances and applying the weight of evidence approach,Trisodium [2-[[alpha-[[2-hydroxy-5-sulpho-3-[(2,5,6-trichloro- 4-pyrimidinyl)amino]phenyl]azo]benzyl]azo]-5-sulphobenzoato(5-)]cupra can be considered to be not sensitizing to skin.Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.