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Description of key information

Skin Sensitization:

The skin sensitization potential of 4,4'-[vinylenebis[(3-sulpho-4,1-phenylene)imino(6-chloro-1,3,5-triazine-4,2-diyl)imino]]bis[5-hydroxy-6-[(1-sulpho-2-naphthyl)azo]naphthalene-2,7-disulphonic] acid was estimated by SSS (2018) using OECD QSAR toolbox v3.4 with log kow as the primary descriptor. 4,4'-[vinylenebis[(3-sulpho-4,1-phenylene)imino(6-chloro-1,3,5-triazine-4,2-diyl)imino]]bis[5-hydroxy-6-[(1-sulpho-2-naphthyl)azo]naphthalene-2,7-disulphonic] acid was predicted to be not sensitizing to the skin of female guinea pigs.

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 from OECD QSAR toolbox v3.4 and the QMRF report has been attached
Reference:
Composition 0
Qualifier:
according to
Guideline:
other: Estimated data
Principles of method if other than guideline:
Prediction was done using OECD QSAR toolbox v3.4
GLP compliance:
not specified
Type of study:
guinea pig maximisation test
Test material information:
Composition 1
Specific details on test material used for the study:
- Name of test material: 4,4'-[vinylenebis[(3-sulpho-4,1-phenylene)imino(6-chloro-1,3,5-triazine-4,2-diyl)imino]]bis[5-hydroxy-6-[(1-sulpho-2-naphthyl)azo] naphthalene-2,7-disulphonic] acid
- IUPAC name: 4,4'-[vinylenebis[(3-sulpho-4,1-phenylene)imino(6-chloro-1,3,5-triazine-4,2-diyl)imino]]bis[5-hydroxy-6-[(1-sulpho-2-naphthyl)azo] naphthalene-2,7-disulphonic] acid
- Molecular formula: C60H40Cl2N14O26S8
- Molecular weight: 1700.482 g/mole
- Smiles c1ccc2c(c1)ccc(c2S(=O)(=O)O)/N=N/c3c(cc4cc(cc(c4c3O)Nc5nc(nc(n5)Cl)Nc6ccc(c(c6)S(=O)(=O)O)/C=C/c7c(cccc7S(=O)(=O)O)Nc8nc (nc(n8)Cl)Nc9cc(cc1c9c(c(c(c1)S(=O)(=O)O)/N=N/c1ccc2ccccc2c1S(=O)(=O)O)O)S(=O)(=O)O)S(=O)(=O)O)S(=O)(=O)O
- InChl: 1S/C60H40Cl2N14O26S8/c61-55-67-57(71-59(69-55)65-41-25-33(103(79,80)81)20-30-22-45(107(91,92)93)49(51(77)47(30)41)75-73-39-18-14-27-6-1-3-8-35(27)53(39)109(97,98)99)63-32-16-12-29(44(24-32)106(88,89)90)13-17-37-38(10-5-11-43(37)105(85,86)87)64-58-68-56(62)70-60(72-58)66-42-26-34(104(82,83)84)21-31-23-46(108(94,95)96)50(52(78)48(31)42)76-74-40-19-15-28-7-2-4-9-36(28)54(40)110(100,101)102/h1-26,77-78H,(H,79,80,81)(H,82,83,84)(H,85,86,87)(H,88,89,90)(H,91,92,93)(H,94,95,96)(H,97,98,99)(H,100,101,102)(H2,63,65,67,69,71)(H2,64,66,68,70,72)/b17-13+,75-73+,76-74+
- Substance type: Organic
- Physical state: Solid
Species:
guinea pig
Strain:
not specified
Sex:
female
Details on test animals and environmental conditions:
no data available
Route:
intradermal and epicutaneous
Vehicle:
not specified
Adequacy of induction:
not specified
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
not specified
Adequacy of challenge:
not specified
No. of animals per dose:
20
Details on study design:
no dataa available
Reading:
1st reading
Group:
test group
Clinical observations:
no reactions observed
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" or "d" )  and ("e" and ( not "f") )  )  and ("g" and ( not "h") )  )  and ("i" and ( not "j") )  )  and ("k" and ( not "l") )  )  and ("m" and ( not "n") )  )  and ("o" and ( not "p") )  )  and ("q" and ( not "r") )  )  and ("s" and "t" )  )

Domain logical expression index: "a"

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

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Alcohol, olefinic attach [-OH] OR Aliphatic Nitrogen, one aromatic attach [-N] OR Aliphatic Nitrogen, two aromatic attach [-N-] OR Amino Triazine/Pyrazine/Pyrimidine  OR Aromatic Carbon [C] OR Aromatic Nitrogen OR Azo [-N=N-] OR Chlorine, aromatic attach [-Cl] OR Chlorine, olefinic attach [-Cl] OR Hydroxy, aromatic attach [-OH] OR Hydroxy, sulfur 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 Sulfinic acid [-S(=O)OH] OR Sulfonate, aromatic attach [-SO2-O] OR Sym-Triazine ring  by Organic functional groups (US EPA) ONLY

Domain logical expression index: "c"

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

Domain logical expression index: "d"

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

Domain logical expression index: "e"

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

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >>  Michael-type addition, quinoid structures OR AN2 >>  Michael-type addition, quinoid structures >> Quinone methides 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 >> 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 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) >> 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 >> 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 nitrenium ion formation OR SN1 >> Nucleophilic attack after nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines OR SN2 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 by DNA binding by OASIS v.1.4

Domain logical expression index: "g"

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: "h"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Michael addition to the quinoid type structures OR AN2 >> Michael addition to the quinoid type structures >> N-Subsituted Aromatic Amines OR AN2 >> Michael addition to the quinoid type structures >> Substituted Phenols OR AN2 >> Michael-type addition to activated double bonds in vinyl pyridines OR AN2 >> Michael-type addition to activated double bonds in vinyl pyridines >> Ethenyl Pyridines 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 (!Undefined)Group All Aqueous Solubility < 0.000005 g/L AND (!Undefined)Group All Aqueous Solubility < 0.00002 g/L AND (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND (!Undefined)Group All log Kow < -3.1 AND (!Undefined)Group All log Kow > 9 AND (!Undefined)Group All Melting Point > 200 C AND Group All Molecular Weight > 650 g/mol by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as (!Undefined)Group CN Lipid Solubility < 0.4 g/kg OR (!Undefined)Group CNHal Lipid Solubility < 400 g/kg OR (N/A) OR Exclusion rules not met OR Group All Aqueous Solubility < 0.000005 g/L OR Group All Aqueous Solubility < 0.00002 g/L OR Group All log Kow < -3.1 OR Group All log Kow > 9 OR Group All Melting Point > 200 C OR Group C Aqueous Solubility < 0.0001 g/L OR Group C Aqueous Solubility < 0.0005 g/L OR Group C Melting Point > 55 C OR Group C Molecular Weight > 380 g/mol OR Group CHal Melting Point > 65 C OR Group CN Aqueous Solubility < 0.1 g/L OR Group CN log Kow > 4.5 OR Group CN Molecular Weight > 290 g/mol OR Group CNS Aqueous Solubility < 0.006 g/l OR Group CNS log Kow > 1.5 OR Group CNS log Kow > 3.6 OR Group CNS Melting Point > 200 C OR Group CNS Melting Point > 50 C OR Group CNS Molecular Weight > 620 g/mol by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Group 14 - Carbon C AND Group 15 - Nitrogen N AND Group 16 - Oxygen O AND Group 16 - Sulfur S AND Group 17 - Halogens Cl AND Group 17 - Halogens F,Cl,Br,I,At by Chemical elements

Domain logical expression index: "l"

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

Domain logical expression index: "m"

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

Domain logical expression index: "n"

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

Domain logical expression index: "o"

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

Domain logical expression index: "p"

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

Domain logical expression index: "q"

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

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Phenols (Mucous membrane irritation) Rank C by Repeated dose (HESS)

Domain logical expression index: "s"

Parametric boundary:The target chemical should have a value of log BCF max which is >= 2.58 log(L/kg wet)

Domain logical expression index: "t"

Parametric boundary:The target chemical should have a value of log BCF max which is <= 3.58 log(L/kg wet)

Interpretation of results:
other: Negative
Conclusions:
4,4'-[vinylenebis[(3-sulpho-4,1-phenylene)imino(6-chloro-1,3,5-triazine-4,2-diyl)imino]]bis[5-hydroxy-6-[(1-sulpho-2-naphthyl)azo]naphthalene-2,7-disulphonic] acid was predicted to be not sensitizing to the skin of female guinea pigs.
Executive summary:

The skin sensitization potential of 4,4'-[vinylenebis[(3-sulpho-4,1-phenylene)imino(6-chloro-1,3,5-triazine-4,2-diyl)imino]]bis[5-hydroxy-6-[(1-sulpho-2-naphthyl)azo]naphthalene-2,7-disulphonic] acid was estimated by SSS (2018) using OECD QSAR toolbox v3.4 with log kow as the primary descriptor. 4,4'-[vinylenebis[(3-sulpho-4,1-phenylene)imino(6-chloro-1,3,5-triazine-4,2-diyl)imino]]bis[5-hydroxy-6-[(1-sulpho-2-naphthyl)azo]naphthalene-2,7-disulphonic] acid was predicted to be not sensitizing to the skin of female guinea pigs.

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

Skin Sensitization:                                      

Various studies have been investigated to ascertain the degree of dermal sensitization caused by 4,4'-[vinylenebis[(3-sulpho-4,1-phenylene)imino(6-chloro-1,3,5-triazine-4,2-diyl)imino]]bis[5-hydroxy-6-[(1-sulpho-2-naphthyl)azo]naphthalene-2,7-disulphonic] acid. These include in vivo experiments in guinea pigs for the target chemical as well as its structurally similar read across chemicals, 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)( Reactive Red 198)[CAS: 145017-98-7] andTetrasodium 1-acetamido-2-hydroxy-3-(4-((4-sulphonatophenylazo)-7-sulphonato-1-naphthylazo))naphthalene-4,6-disulphonate(Brilliant Black 1)[CAS: 2519-30-4].The experimental results have also been compared with the predictions obtained from OECD QSAR toolbox.

The skin sensitization potential of 4,4'-[vinylenebis[(3-sulpho-4,1-phenylene)imino(6-chloro-1,3,5-triazine-4,2-diyl)imino]]bis[5-hydroxy-6-[(1-sulpho-2-naphthyl)azo]naphthalene-2,7 -disulphonic] acid was estimated by SSS (2018) using OECD QSAR toolbox v3.4 with log kow as the primary descriptor. 4,4'-[vinylenebis[(3-sulpho-4,1-phenylene)imino(6-chloro-1,3,5 -triazine-4,2-diyl)imino]]bis[5-hydroxy-6-[(1-sulpho-2-naphthyl)azo]naphthalene-2,7-disulphonic] acid was predicted to be not sensitizing to the skin of female guinea pigs.

This is supported by the results of the Patch tests performed by Bianca Maria Manzini et.al (Contact Dermatitis, 1996, 35, 313) on 312 consecutive patients to determine the allergic potential of the structurally similar read across chemical, , 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) (Reactive Red 198) [CAS: 145017-98-7].

312 consecutive patients underwent patch tests with reactive dyes to determine the allergic contact dermatitis potential.

The dyes tested were provided as powder by Hoechst and were dispersed in petrolatum. The dyes were applied to the healthy sin of the back with Finn Chambers, on Scanpor tape for 3 days and read at 3 hours after removal and at 4 days according to ICDRG Scoring pattern. The concentration used was 5% in 119 patients and 10% in 193 patients.

No positive allergic or irritant reactions were observed in the volunteers when tested with 5% and 10% concentration of the dye.

Hence, Reactive Red 198 can be considered to not sensitizing to human skin.

The above results are supported by the experimental study summarized in Joint FAO/WHO Expert Committee on Food Additives; (WHO Food Additives Series 16; IPCS INCHEM; 1975; for the structurally similar read across chemical, Tetra sodium 1-acetamido-2-hydroxy-3-(4-((4-sulphonatophenylazo)-7-sulphonato-1-naphthylazo))naphthalene-4,6-disulphonate (Brilliant Black 1)[CAS: 2519-30-4].

Since the guinea pigs did not elicit any sensitizing effect, the test chemical Brilliant Black 1 (CAS No: 2519-30-4) was considered to be not sensitizing to the guinea pigs.

Based on the available studies for the target as well as its structurally similar read across chemicals and applying the weight of evidence approach, 4,4'-[vinylenebis[(3-sulpho-4,1-phenylene)imino(6-chloro-1,3,5-triazine-4,2-diyl)imino]]bis[5-hydroxy-6-[(1-sulpho-2-naphthyl)azo]naphthalene-2,7-disulphonic] acid 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

Available data for 4,4'-[vinylenebis[(3-sulpho-4,1-phenylene)imino(6-chloro-1,3,5-triazine-4,2-diyl)imino]]bis[5-hydroxy-6-[(1-sulpho-2-naphthyl)azo]naphthalene-2,7-disulphonic] acid indicates that it is not likely to cause any dermal sensitization to skin.

4,4'-[vinylenebis[(3-sulpho-4,1-phenylene)imino(6-chloro-1,3,5-triazine-4,2-diyl)imino]]bis[5-hydroxy-6-[(1-sulpho-2-naphthyl)azo]naphthalene-2,7-disulphonic] acid can be considered to be not sensitizer to skin and can be classified under the category “Not Classified” as per CLP regulation.