4-amino-3,6-bis[[4-[[4-chloro-6-[(3-sulphophenyl)amino]-1,3,5-triazin-2-yl]amino]-2-sulphophenyl]azo]-5-hydroxynaphthalene-2,7-disulphonic acid

Endpoint summary

Description of key information

Skin sensitization:

The skin sensitization potential of 4-amino-3,6-bis[[4-[[4-chloro-6-[(3-sulphophenyl)amino]-1,3,5-triazin-2-yl]amino]-2-sulphophenyl]azo]-5-hydroxynaphthalene  -2,7-disulphonic acid was estimated using OECD QSAR toolbox v3.4 with log Pow as the primary descriptor. 4-amino-3,6-bis[[4-[[4-chloro-6-[(3-sulphophenyl)amino]-1,3,5-triazin-2-yl]amino]-2-sulphophenyl]azo]-5-hydroxynaphthalene  -2,7-disulphonic acid was estimated to be not sensitizing to the skin of  guinea pig. Based on the estimated results, 4-amino-3,6-bis[[4-[[4-chloro-6-[(3-sulphophenyl)amino]-1,3,5-triazin-2-yl]amino]-2-sulphophenyl]azo]-5-hydroxynaphthalene  -2,7-disulphonic acid 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)

Remarks:

in vivo

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

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: predicted 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 test material: 4-amino-3,6-bis[[4-[[4-chloro-6-[(3-sulphophenyl)amino]-1,3,5-triazin-2-yl]amino]-2-sulphophenyl]azo]-5-hydroxynaphthalene -2,7-disulphonic acid
- IUPAC name: 4-amino-3,6-bis[(E)-2-[4-({4-chloro-6-[(3-sulfophenyl)amino]-1,3,5-triazin-2-yl}amino)-2-sulfophenyl]diazen-1-yl]-5-hydroxynaphthalene -2,7-disulfonic acid
- Molecular formula: C40H29Cl2N15O19S6
- Molecular weight: 1287.0571 g/mole
- Smiles : c1cc(cc(c1)S(=O)(=O)O)Nc2nc(nc(n2)Cl)Nc3ccc(c(c3)S(=O)(=O)O)/N=N/c4c(cc5cc(c(c(c5c4N)O)/N=N/c6ccc(cc6S(=O)(=O)O) Nc7nc (nc(n7)Cl)Nc8cccc(c8)S(=O)(=O)O)S(=O)(=O)O)S(=O)(=O)O
- Inchl: 1S/C40H29Cl2N15O19S6/c41-35-48-37(44-18-3-1-5-22(13-18)77(59,60)61)52-39(50-35)46-20-7-9-24(26(15-20)79(65,66)67)54-56-32-28(81 (71,72)73)11-17-12-29(82(74,75)76)33(34(58)30(17)31(32)43)57-55-25-10-8-21(16-27(25)80(68,69)70)47-40-51-36(42)49-38(53-40)45-19-4-2-6-23(14-19)78(62,63)64/h1-16,58H,43H2,(H,59,60,61)(H,62,63,64)(H,65,66,67)(H,68,69,70)(H,71,72,73)(H,74,75,76)(H2,44,46,48,50,52)(H2,45,47,49,51,53)/b56-54+,57-55+
- Substance type: Organic
- Physical state: Solid

Species:

guinea pig

Strain:

not specified

Sex:

not specified

Details on test animals and environmental conditions:

Data not available

Route:

other: Not specified

Vehicle:

not specified

Concentration / amount:

No data available

Day(s)/duration:

No data available

Adequacy of induction:

not specified

No.:

#1

Route:

other: No data available

Vehicle:

not specified

Concentration / amount:

No data available

Day(s)/duration:

No data available

Adequacy of challenge:

not specified

No. of animals per dose:

No data available

Details on study design:

No data available

Challenge controls:

No data available

Positive control substance(s):

not specified

Reading:

1st reading

Group:

test chemical

Dose level:

No data available

Clinical observations:

negative skin sensitization reaction estimated

Remarks on result:

no indication of skin sensitisation

The prediction was based on dataset comprised from the following descriptors: "A B C","S W A N"
Estimation method: Takes highest mode value from the 5 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 ( not "t") )  )  and ("u" and ( not "v") )  )  and ("w" and ( not "x") )  )  and ("y" and "z" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Acid moiety OR Anilines (Unhindered) OR Phenol Amines OR Phenols OR Triazines, Aromatic by Aquatic toxicity classification by ECOSAR ONLY

Domain logical expression index: "b"

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

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Michael-type addition to quinoid structures  OR AN2 >> Michael-type addition to quinoid structures  >> Substituted Anilines OR SNAr OR SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds OR SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds >> Activated aryl and heteroaryl compounds by Protein binding by OASIS v1.4 ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as 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 SN1 OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Fused-Ring Primary Aromatic Amines by DNA binding by OASIS v.1.4 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 by Estrogen Receptor Binding

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 Strong binder, NH2 group by Estrogen Receptor Binding

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND Group All Melting Point > 200 C by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as (!Undefined)Group CN Lipid Solubility < 0.4 g/kg by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND Group All Melting Point > 200 C by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as (!Undefined)Group CNHal Lipid Solubility < 400 g/kg by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND Group All Melting Point > 200 C by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Group C Vapour Pressure < 0.0001 Pa by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Activated N-heterocycles AND Aromatic amines AND Phenols AND Sulfonic acids or their salts by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "r"

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

Domain logical expression index: "s"

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

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as 3-Methylcholantrene (Hepatotoxicity) Alert by Repeated dose (HESS)

Domain logical expression index: "u"

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

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as Nitrophenols/ Halophenols (Energy metabolism dysfuntion) Rank B by Repeated dose (HESS)

Domain logical expression index: "w"

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

Domain logical expression index: "x"

Referential boundary: The target chemical should be classified as p-Alkylphenols (Hepatotoxicity) Rank A by Repeated dose (HESS)

Domain logical expression index: "y"

Parametric boundary:The target chemical should have a value of log Kow which is >= 3.28

Domain logical expression index: "z"

Parametric boundary:The target chemical should have a value of log Kow which is <= 5.28

Interpretation of results:

other: Not sensitizing

Conclusions:

4-amino-3,6-bis[[4-[[4-chloro-6-[(3-sulphophenyl)amino]-1,3,5-triazin-2-yl]amino]-2-sulphophenyl]azo]-5-hydroxynaphthalene  -2,7-disulphonic acid was considered to be not sensitizing to skin.

Executive summary:

The skin sensitization potential of 4-amino-3,6-bis[[4-[[4-chloro-6-[(3-sulphophenyl)amino]-1,3,5-triazin-2-yl]amino]-2-sulphophenyl]azo]-5-hydroxynaphthalene  -2,7-disulphonic acid was estimated using OECD QSAR toolbox v3.4 with log Pow as the primary descriptor. 4-amino-3,6-bis[[4-[[4-chloro-6-[(3-sulphophenyl)amino]-1,3,5-triazin-2-yl]amino]-2-sulphophenyl]azo]-5-hydroxynaphthalene  -2,7-disulphonic acid was estimated to be not sensitizing to the skin of  guinea pig. Based on the estimated results, 4-amino-3,6-bis[[4-[[4-chloro-6-[(3-sulphophenyl)amino]-1,3,5-triazin-2-yl]amino]-2-sulphophenyl]azo]-5-hydroxynaphthalene  -2,7-disulphonic acid 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, 4-amino-3,6-bis[[4-[[4-chloro-6-[(3-sulphophenyl)amino]-1,3,5-triazin-2-yl]amino]-2-sulphophenyl]azo]-5-hydroxynaphthalene -2,7-disulphonic acid 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 4-amino-3,6-bis[[4-[[4-chloro-6-[(3-sulphophenyl)amino]-1,3,5-triazin-2-yl]amino]-2-sulphophenyl]azo]-5-hydroxynaphthalene -2,7-disulphonic acid and its structurally similar read across substances 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) (CAS: 145017-98-7) and Tetrasodium 6-amino-4-hydroxy-3-[[7-sulphonato-4-[(4-sulphonatophenyl)azo]-1-naphthyl]azo]naphthalene-2,7-disulphonate (CAS: 2118-39-0). The predicted data using the OECD QSAR toolbox has also been compared with the experimental data.

The skin sensitization potential of 4-amino-3,6-bis[[4-[[4-chloro-6-[(3-sulphophenyl)amino]-1,3,5-triazin-2-yl]amino]-2-sulphophenyl]azo]-5-hydroxynaphthalene  -2,7-disulphonic acid was estimated using OECD QSAR toolbox v3.4 with log Pow as the primary descriptor. 4-amino-3,6-bis[[4-[[4-chloro-6-[(3-sulphophenyl)amino]-1,3,5-triazin-2-yl]amino]-2-sulphophenyl]azo]-5-hydroxynaphthalene  -2,7-disulphonic acid was estimated to be not sensitizing to the skin of  guinea pig. Based on the estimated results, 4-amino-3,6-bis[[4-[[4-chloro-6-[(3-sulphophenyl)amino]-1,3,5-triazin-2-yl]amino]-2-sulphophenyl]azo]-5-hydroxynaphthalene  -2,7-disulphonic acid 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 supported by experimental result summarized in Contact Dermatitis volume 35 page no. 313 1996 for structurally similar read across substance2,7-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) (CAS: 145017-98-7)

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.

The above experimental data was further supported by experimental result summarized in Environment and Quality of Life - Reports (Seventh Series) for Food Black 2 European Commission (EC) - Scientific Committee on Cosmetology (SCC) 1988Tetrasodium 6-amino-4-hydroxy-3-[[7-sulphonato-4-[(4-sulphonatophenyl)azo]-1-naphthyl]azo]naphthalene-2,7-disulphonate (CAS: 2118-39-0).

Tetrasodium 6-amino-4-hydroxy-3-[[7-sulphonato-4-[(4-sulphonatophenyl)azo]-1-naphthyl]azo]naphthalene-2,7-disulphonate was used as a test material to evaluate skin sensitization potential on guinea pig skin .The test material was given sub-cuteneously in the concentration 1 ml 0.05-0.1% in isotonic saline , 10 doses for 21 days . Challenge test was provided 14 days after induction . No skin allergic reactions were observed. Hence , Tetrasodium 6-amino-4-hydroxy-3-[[7-sulphonato-4-[(4-sulphonatophenyl)azo]-1-naphthyl]azo]naphthalene-2,7-disulphonate was considered to be not sensitizing to guinea pig skin.

 Based on the available data for the target as well as it read across substances;and applying the weight of evidence approach, it can be concluded that 4-amino-3,6-bis[[4-[[4-chloro-6-[(3-sulphophenyl)amino]-1,3,5-triazin-2-yl]amino]-2-sulphophenyl]azo]-5-hydroxynaphthalene -2,7-disulphonic acid was not sensitizing to skin. Itcan 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;and applying the weight of evidence approach, it can be concluded that 4-amino-3,6-bis[[4-[[4-chloro-6-[(3-sulphophenyl)amino]-1,3,5-triazin-2-yl]amino]-2-sulphophenyl]azo]-5-hydroxynaphthalene -2,7-disulphonic acid was not sensitizing to skin. Itcan be classified under the category “Not Classified” as per CLP regulation.